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13 June 2012 EMA/330149/2012 Directorate

Overview of comments received on 'HMA/EMA Guidance document on the identification of commercially confidential information and protection of personal data within the structure of the marketing authorisation (MA) dossier – release of information after granting of a marketing authorisation'

Interested parties (organisations or individuals) that commented on the draft document as released for consultation.

Stakeholder no.

Name of organisation or individual

1 APIC (EUROPEAN CHEMICAL INDUSTRY COUNCIL) 2 AESGP – Association of the European Self-Medication Industry 3 AMGEN LTD 4 ASTRAZENECA and MedImmune 5 CFE SERBIA 6 DAIICHI SANKYO EUROPE GMBH 7 EFPIA-European Federation of Pharmaceutical Industries and Associations 8 EGA-European Generic Medicines Association 9 EGGVP-European Group for Generic Veterinary Products 10 EPDA-European Parkinson’s Disease Association 11 EPHA-European Public Health Alliance 12 EUCOPE-European Confederation of Pharmaceutical Entrepreneurs

13 EUROPABIO 14 GE HEALTHCARE 15 HAI EUROPE 16 IFAH-International Federation for Animal Health 17 INTERNATIONAL LEAGUE AGAINST EPILEPSY 18 IPFA-International Plasma Fractionation Association

Overview of comments received on 'HMA/EMA Guidance document on the identification of commercially confidential information and protection of personal data within the structure of the marketing authorisation (MA) after granting of a marketing authorisation'

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Stakeholder no.

Name of organisation or individual

19 LEO PHARMA A/S 20 MERCK SHARP & DOHME (EUROPE) INC 21 PFIZER 22 PSLG-Preclinical Safety Leadership Group and DMLG-Drug Metabolism Leadership Group

(IQ-International Consortium for Innovation and Quality in Pharmaceutical Development) 23 ROCHE 24 SANOFI and SANOFI PASTEUR


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1. General comments – overview on:

RELEASE OF PERSONAL DATA (E.G. CV, SIGNATURES, ETC)

CONTRACTUAL ARRANGEMENTS BETWEEN DIFFERENT COMPANIES

PERSONAL SECURITY OF INDIVIDUALS INVOLVED IN ANY WAY WITH STUDIES INVOLVING ANIMALS

Stakeholder no.

(See cover page)

General comment (if any) Outcome (if applicable)

1. APIC NO COMMENTS

2. AESGP AESGP in principle supports the efforts of the European Medicines Agency (EMA) and Heads of Medicines Agencies (HMA) towards appropriate transparency within the European regulatory framework in accordance with the EU Freedom of Information Act (Regulation (EC) No 1049/2001). In considering commercially confidential information (CCI), the specificities of the medicines should be taken into account. Non-prescription medicines are usually not patented and operate in a very competitive environment, including against non-medicinal products. When considering whether a document could be released or not, careful consideration should be given to potential unfair advantage given to competitors and in turn to the consequences this may have in terms of negative impact on investment, innovation and potential further applications and the viability of possible re-applications (in case of a withdrawal for example). A definition or clarification around what ‘CCI’ is missing from the draft document. It is important to set the context right and we suggest to

Agreed Agreed to add the definition of CCI explicitly to the document (it is currently included as a foot note).


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insert the following sentence (from the EMA policy on access to documents ref.EMA/110196/2006) “CCI shall mean any information which is not in the public domain or publicly available and where disclosure may undermine the economic interest or competitive position of the owner of the information”. Furthermore, we recommend that the useful clarification which was in the “EMA principles to be applied for the deletion of CCI for the disclosure of EMA documents” be re-introduced: “CCI is generally considered to fall broadly into two categories: - Confidential intellectual property, “know-how” and trade secrets (including e.g. formulas, programs, process of information contained or embodied in a product, unpublished aspects of trade marks, patents, etc.) - Commercial confidences (e.g. structures and development plans of a company).” These principles should be applied for deletion of commercially confidential information prior to publication or disclosure. Protection of commercially confidential Company data / information. In addition, disclosure of data AND information should consider confidentiality regarding planned line extensions / new indications. This would fall under “commercial confidences”.

Not agreed Refer to principle 41

1 When reference to principles is made, this relates to the Principles to be applied for the implementation of the HMA/EMA Guidance on the identification of CCI and PPD in MA Applications http://www.ema.europa.eu/docs/en_GB/document_library/Other/2012/03/WC500124537.pdf


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Process and identification of publishing CCI/PPD It is acknowledged that identification of CCI/PPD creates a considerable amount of additional workload within the authorities. This workload could be reduced if the applicant would take over responsibility for the first step in identification of CCI/PPD. This would also be in line with the already existing process of identification of CCI/PPD in EPARs before publishing. In addition, this would be aligned with processes of publishing this information on an international level e.g.: Japanese Guideline ‘Handling of Disclosure of Information Concerning Approval Evaluation of New Medicinal Products, 30-Mar-2011 PMDA Notification No. 0330011’. Here the identification of commercial confidential information is up to the applicant. Also within Europe, as much consistency as possible should be achieved regarding national legislation dealing with CCI/PPD topics. Consistency with other regulations should be watched Example: Disclosure on information on QPPV in the recently published Eudravigilance Access Policy. Invitation for industry proposals on specific CTD structure – should remain harmonised, at least on ICH level, i.e. no specific section for commercial confidential information and personal data: see: page 2, invitation for industry proposals. In principle, the benefit for this proposal is seen. However, we wonder if this can be achieved, keeping in mind the internationally harmonised CTD structure.

Agreed Agreed Agreed Refer to principle 16


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Information about natural persons allowing identification of the individual should not be published for reasons of data protection. This is not limited to CVs and signatures / signature statements but does also include any information about name and contact details (e.g. telephone numbers). In extreme cases, disclosure of such information could put these people at risk.

Refer to principles 5 and 6

3. AMGEN 1. There needs to be an explicit statement that this guidance is only applicable in the case of a positive opinion and subsequent approval and not applicable in case of a negative opinion or MAA withdrawal. Documents released in these situations could cause significant damage to the applicant in case of a later resubmission. 2. The document should define what will happen in a “case-by-case review.” We believe that in such instances particularly, it is very important that the MAH is consulted in advance of any release/disclosure of any EMA-held document and allowed to comment/agree on the data being requested and what is appropriate for release and offered the genuine opportunity to redact such document. This is in line with article 4(4) of Regulation 1049/2001, which sets out an obligation for the EMA to consult the MAH/third party concerned. 3. Regarding the release of Personal Data (CV, signature etc) we feel very strongly that names and signatures of individuals should not be released under any circumstances. This includes the signature for the statement in Module 1, sub-module 1.2, and the name and signature authorised for communication on behalf of the applicant; and individuals’ details found in Module 1 sub-module 2.1. In addition in Section 5 of Module 1 – Annexed Documents, names must be removed on the informed consent letter of marketing authorisation holder of

Refer to principle 10 Refer to principles 5 and 6


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authorised medicinal product. 4. Regarding contractual arrangements between different companies: Amgen consider that any details of contractual arrangements should be considered as Company Confidential Information (CCI). 5. Regarding the personal security of individuals involved in any way with studies involving animals: as for 3 above, we consider that any information allowing identification of such staff should be protected as personal data. It should not be released under any circumstances. 6. Regarding the proposed definition of CCI on page 1 and at footnote 1, we propose to explicitly refer to the possibility that disclosure of such information may undermine the protection of intellectual property, for instance by adding “(including intellectual property)” after “economic interest” (please note that article 4(2) of Regulation 1049/2001 makes such an explicit reference) . 7. Regarding finished product on pages 5 and 6, it is stated that, for “novel packaging or medical device”, “any confidentiality issue” “should be justified by the applicant”. We respectfully do not see any justification for reversing the burden of proof with respect to these aspects. We believe that the confidentiality duties and the disclosure rules should apply equally without making such a distinction. Inappropriate disclosure of information relating to packaging or medical device can also seriously harm the interest of a person.

Refer to principle 4 Refer to principle 5 Not agreed. The working definition of commercially confidential information has already been established across the European regulatory network. See EMA policy on access to documents ref. EMA/110196/2006. The principle is that all information is public. The confidentiality of information has to be proven. EMA policy on access to documents ref. EMA/110196/2006


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8. Regarding information on inspections on page 6, it is stated that “any information available at EudraGMP” cannot be considered as CCI. It is necessary in our view to add “publically” before “available”. We understand that EudraGMP has different levels of access and may indeed contain CCI. 9. At various instances, the document makes reference to the need, during case-by-case (CBC) analysis, not to disclose documents, if and when this can reveal commercial agreements between different companies (eg point 2.5.1.2 at page 15, point 4.4 at page 24, point 5.1 at page 25, point 1.3.4 at page 30, point 1.8.1 at page 32). Whilst we believe that any details of contractual arrangements should be considered as CCI (see also our general comment 4 above), it is not clear whether this reference is provided as an example or whether it is the intention to restrict the scope of the CBC analysis to this particular circumstance, which would not be appropriate in our view. We therefore suggest to each time add “for example” in the document to make it clear that inappropriate disclose of documents can also be inappropriate/harmful in other circumstances. For instance, the CBC analysis prior to disclosure of the details of the pharmacovigilance system must take into account the fact that such disclosure can harm the competitive position of the MAH. Also, information and documents about marketing authorizations applications for the same product outside the EEA shall in our view never be released/disclosed unless this is in the public domain or publically available (see also our specific comment on page 24 below).

Agreed Refer to principle 4


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10. The draft document does not indicate whether and how the EMA intends applying its new guidance and transparency policy to “old” MA dossiers (i.e. those relating to medicinal products approved prior to the new guidance/policy coming into effect). In light of the principle of legitimate expectations, we would have concerns about applying “retrospectively” the new guidance with respect to “old” dossiers, which have not been drafted by taking such guidance/policy into consideration or in other circumstances that the granting of “new” MA. We therefore suggest clarifying in the draft document that the recommendations only apply when the initial MA was granted after the entry into effect of the recommendations. We also suggest clarifying that the recommendations do not apply in the case the MA has been refused, or the application for MA withdrawn (see comment 1 above) or to the granting of access to documents filed in the context of other applications, such as for orphan designation, compliance with paediatric requirements or to the correspondence between the EMA/Medicines Agencies and the applicants.

Refer to principle 1 Refer to principle 2

4. ASTRAZENECA AND MEDIMMUNE

AstraZeneca (AZ) continues to be committed to support EMA/HMA’s objective with regard to transparency and therefore welcomes the opportunity to comment on this draft guidance. It is hoped that our response strengthens the guidance while protecting confidential information of patients, investigators and the intellectual property of those engaged in research. Please find below a summary of key points for consideration followed by general and detailed comments on the guidance. • It is important that data is disclosed in such a way that it is of public

Refer to principle 2 Comment noted – no change to document needed


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benefit and not harm. Further, it is important to ensure that decisions made by competent regulatory authorities based on sound scientific data are not undermined by misuse of that data, once it is disclosed to the public.

• The guidance does, to some extent, provide mechanisms to uphold these principles. However, it is suggested that further consistency and clarity is required; as well as clearly defined procedures for requesting and providing data.

• It should also be noted that a number of companies have already begun developing proposals with regard to appropriate data disclosure, which will provide greater transparency and additional context to the research being published for journal readers and researchers. Industry would welcome the opportunity to discuss these proposals further with EMA/HMAs.

• Consent For medical research, using identifiable human material or data, physicians must seek consent from patients for collection, analysis, storage and/or reuse of their data. Once in the public domain, industry cannot keep check on who will ‘re-use’ that information, and for what purpose, therefore the patient cannot be making an informed decision regarding re-use. • Withdrawn applications Industry generally objects to release of marketing authorisation application dossiers for withdrawn applications. Companies may still have a commercial interest in the product and may be performing additional analysis or generating more information to support the approval. In addition we object to disclosure of any data or studies not leading to an approved indication. The individual design and data

Comment noted – the revised document will be checked for consistency Comment noted. Refer to principle 5 Refer to principle 2


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collected that was insufficient to grant approval contributes to the further regulatory strategy. Therefore pre-mature disclosure of all dossier information would provide a significant commercial advantage to a competitor. Information about all clinical trials related to the approved or other indications is already available through public registries. General Principles in relation to the CTD Module 1 • Any names, contact details or signatures of individuals working for the company or as contractors or investigators should be redacted. Module 4 and non-clinical overview • We endorse the comments made by EFPIA’s nonclinical working group. Module 5 and the clinical overview We acknowledge the public interest in having access to clinical study data. It is our responsibility to show how our data were obtained and thereby aid in the understanding of our conclusions and treatment recommendations. AZ is willing to explore practical ways to share protocols and raw data for the purpose of conducting further research such as a well-planned and executed meta-analysis. We maintain that the sole responsibility for making binding and final decisions on the benefit and risk of a given medicine must reside with the competent regulatory authorities and that access to data does not lead to a parallel review process outside the regulatory framework. Industry is convinced that an emergence of a parallel and uncontrolled process, with no

Refer to principle 5 Noted While the concerns are noted, the EMA and HMAs are not in a position to prevent third parties from performing their own analyses.


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requirement for disclosure would represent a real threat to public health as hitherto well established treatments could be challenged on the basis of an ill planned or executed meta-analysis. In addition, public trust in the competence of Health Authorities would be undermined instead of enhanced as is the intended purpose of greater disclosure. When requests are made to access raw data a sound analysis plan needs to be developed and shared with all relevant stakeholders to avoid partisan or even biased approaches. When sharing such information requirements about personal data, protection and privacy must be respected. Although prospectively patients could be asked through the informed consent process to accept the sharing of personalized data with third parties, this may lead to a biased data set as only a subset of patients may give this agreement. Also, for completed studies, obtaining this authorization is biased data set as only a subset of patients may give this agreement. Also, for completed studies, obtaining this authorization is impractical if not impossible. It is therefore more sensible to create raw data sets that have been anonymized via clustering or categorization of data, or by removing non essential data. Routine disclosure of clinical study information (protocols, results) should be part of an established regulatory process. EudraCT already couples disclosure of new trials to the trial application process. This is more efficient and less prone to error than the voluntary pathway established in the US (www.clintrials.gov). This should lead to a more efficient and less error prone process. Such a framework should facilitate the disclosure of clinical study information volunteered by the sponsor. Format


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The CTD and therefore eCTD, has been expressly structured to facilitate the delivery, review, approval and lifecycle management of marketing authorisation application dossiers. Restructuring the eCTD in order to support the proposals laid out in the consultation would fundamentally undermine the eCTD as an effective vehicle for delivering quality submission dossiers for review. IP considerations To protect IP we encourage EMA to commit to communicating to the applicant, the date of publication of the dossier sufficiently in advance to allow redaction and/or patent filings.

Refer to principle 16

CFE INFO SERBIA (Association for help and support to people with Cystic Fibrosis in Serbia)

Our proposal refers to correction in sub module 1.9, meaning that information concerning clinical trials, those organized in institutions outside European Union, should be expanded for the Statement of the authorized person in the institution in which the trial is performed, that all participants of clinical trials should be informed that they are part of the trial, and that according to that they gave written consent for performing the trial. We also think that these data should be CBC (case by case analysis) and public available, at least the part referring to study and clinical centers, while the part referring to analytical clinical centers should stay CCI (Commercially Confidential Information).

This is standard practice according to GCP

DAIICHI SANKYO In this draft guidance document, all modules 3, 4, 5 are included in the scope of data disclosure. Each study reports can be considered as properties of the applicants, and accountability of the applicants could be achieved with disclosure of module 2 (summary of the data). From viewpoint of protecting the intellectual properties, module 3, 4, and 5 should be excluded from the scope of this information disclosure. At this time, the Policy document describes how the information in an

Not agreed. Refer to principles 17 and 18


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MAA dossier will be classified. There will be keen interest in the process document that describes how the information will be released and how, if at all, the owner of the information will be consulted during the process of releasing the information. Depending on status of publication, non-clinical and clinical information in MA dossier should be treated as “CCI (commercially Confidential Information). Researchers may face disadvantages when submitting manuscripts from disclosed non-clinical or clinical data (commercially Confidential Information). Researchers may face disadvantages when submitting manuscripts from disclosed non-clinical or clinical data.


EFPIA EFPIA welcomes and supports the European Medicines Agency (EMA) and Heads of Medicines Agencies (HMA) efforts to increase transparency within the European regulatory framework. We believe that enhanced transparency should facilitate and contribute to the EMA/HMA’s efforts to promote and protect the Public Health. We also believe that enhanced transparency is essential in maintaining overall public trust and confidence in the system for the regulation of medicines in Europe. It is important to agree a common European approach in this area and we would welcome further clarification in this regard (see comments made in relation to the fact that reference is made to national legislation in the draft guidance document). We also support EMA/HMA’s efforts to comply with the EU ‘public access

This guidance sets out the principles which EU regulators have agreed to apply. However in the event of legal challenge national legislation will take precedence.


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to documents’ legislation (Regulation (EC) No 1049/2001) that aims to ensure that “the administration enjoys greater legitimacy and is more effective and more accountable to the citizen in a democratic system”. This legislation is intended to provide public access to documents held by the European Institutions, while at the same time respecting the need to protect, amongst other things, the privacy and integrity of the individual, and commercial interest of a natural or legal person including intellectual property. In relation to the current draft guideline on the release of information from Marketing Authorisation (MA) dossiers following grant of a MA, we agree with HMA/EMA that there are significant challenges to address in identifying and separating the information that can be released, from the information which should be withheld. This is in part due to the size and complexity of MA dossiers, and the fact that much of the ‘commercially confidential’ and ‘personal data’ is intermingled with large amounts of other data throughout the dossiers (making redaction or extraction of such data difficult). In addition, we believe that there are three important issues that need to be in addressed before MA dossiers can be routinely disclosed to the public: • We are concerned that publication of clinical study reports at the time of MA approval may be regarded as ‘prior publication’, such that scientific journals will not accept or put on hold journal manuscripts. HMA/EMA should seek an understanding with editors that disclosure by authorities, to meet their obligations regarding public



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access to documents held by European and Member States Institutions , does not constitute ‘prior publication’. Alternatively, we propose that studies identified as ‘awaiting publication’ are not disclosed until the journal manuscript has been published, provided this happens in a reasonable time-frame. We suggest that HMA/EMA and industry together might consider discussing these options with Journal editors to explore how their way of working can be adjusted to the new reality of full transparency. • We are concerned that publication of certain CMC and non-clinical data following the EU approval will enhance the ability of non-innovators to obtain approval outside the EU based on the originator’s data. This would undermine the incentives that drive innovation and deliver medicines to patients. It is necessary to ensure that key CMC data is classified as CCI and we propose that non-clinical study reports are classified as CCI and therefore should not be disclosed. However, we support release of non-clinical summaries (with appropriate redactions). Already the release of all the clinical data (which will be the result of the EMA/HMA proposals) will impact on the way intellectual property rights are implemented and enforced worldwide. For instance, Regulatory Data Protection in international trade agreements must be understood in a manner that data that is obtained through regulatory agency transparency programs should not be relied on while the data protection period runs. • The release of a vast amount of data raises the challenge on regulatory agencies to make sure that current versions are released.

Refer to principle 17 Refer to principle 11 Noted


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For instance, the suggested pharmacovigilance measures suggested in the original application may have been revised during the regulatory review. Similarly, post-approval communications or measures may be important to mention when information from the original MAA is requested. When documents are proactively disclosed the appropriate links between original and current information is crucial. On a similar note, EMA/HMA should express caution how data can or cannot be reanalyzed by third parties. For example, it is important that the same standards apply for any subgroup analysis regardless who is conducting the analysis. Overtime we suggest that EFPIA and EMA/HMA monitor how data is used and reanalyzed. • The CTD and therefore eCTD have been expressly structured to facilitate the delivery, review, approval and lifecycle management of marketing authorisation application dossiers. Restructuring the eCTD in order to support the proposals laid out in the consultation document could undermine the eCTD as an effective vehicle for delivering quality submission dossiers for review. The proposal to group areas subject to redaction may improve efficiency for redaction but will lead to a significant revision in the structure of he CTD and therefore eCTD have been expressly structured to facilitate the delivery, review, approval and lifecycle management of marketing authorisation application dossiers. Restructuring the eCTD in order to support the proposals laid out in the consultation document could undermine the eCTD as an effective vehicle for delivering quality submission dossiers for review. The proposal to group areas subject to redaction may improve efficiency for redaction but will lead to a significant revision in the structure of the

While EMA/HMA understand the concerns expressed, how data is used and reanalysed is outside their control. Refer to principle 16


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CTD. It will also make the dossier very disjointed. Consideration would also have to be given to life cycle management activities i.e. the impact of such a grouping on the management of new/replacement documents within the eCTD structure. Given the structure of the CTD was agreed under ICH, we believe that there needs to be an ICH process to agree a redesign of the ICH Common Technical Document (CTD) to facilitate the release of information – a unilateral EU redesign of the CTD would undermine previous ICH agreements. • We agree with the title of the draft guidance document and the heading for the tables set out on pages 7-44, that the guidance currently for public consultation refers specifically to the release of information from a MA dossier after the granting of a MA. For reasons outlined under ‘specific comments on text’ in relation to paragraph 7 on page 3/44 we believe that this guidance should not apply to dossiers submitted to support an application for an MA where the application has been withdrawn or refused or to other formats or application types, or to correspondence between the Agency and the applicant. Our comments are intended to provide practical and constructive suggestions, on the basis that the above points can be adequately progressed, and to assist HMA/EMA in achieving our shared overall transparency objectives, as well as the specific obligations laid down in EU legislation. In conclusion, we welcome the release of this important draft guidance document for consultation and look forward to working with EMA/HMA to progress the new guidance.



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EGA The EGA supports the effort made by the Competent Authorities to

increase transparency and to best fulfil the legal obligations resulting from the revised pharmaceutical legislation. As an unquestionable principle, patients and healthcare professionals should have access to information which is important to them. Authorisation of medicinal products should be sufficiently transparent for society to build trust in the Competent Authorities’ decision making process. The area of the industry’s concerns is related to finding a right balance between transparency and commercially sensitive information. The EGA members trust that their assessment of what is considered commercially sensitive will be seriously taken into consideration in order not to undermine companies’ know-how, competitiveness and commercial contracts with their partners. The EGA fully agrees that the EMEA and National Competent Authorities (NCA) should have a common approach on what should be considered commercially confidential during the evaluation process of applications for marketing authorisations and on when the decision is made.

Agreed in principle

EGGVP The HMA together with the EMA have launched a draft document to give guidance and recommendations to competent authorities for the identification of confidential information contained in the marketing authorization dossiers. Following the invitation for consultation, EGGVP, the European Group for Generic Veterinary Products, takes this



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opportunity to express its views on a number general principles included in the access policy proposed. First, EGGVP considers the release of new guidance as not appropriate because, as a matter of principle, the full registration dossier should be regarded as a commercially confidential piece of information. Furthermore, EGGVP questions the benefits and interest for the general public in accessing detailed data contained in the registration dossiers (some examples are provided below). Directive 2004/28/EC was set up, among others, with the objective to create transparent and uniform rules for accessing public information included in the marketing authorization dossier of a veterinary product. In particular, Article 25, paragraph 3 of this Directive states that “the competent authority shall make the marketing authorisation publicly available without delay, together with the summary of product characteristics for each veterinary medicinal product that it has authorized”. EGGVP believes that the mentioned summary already contains the necessary information that could be of interest or beneficial for the general public, and therefore requests a full enforcement of Article 25, paragraph 3 of Directive 2004/28/EC as part of a solution to this problem. Experience shows that, although the majority of Member States have implemented this provision in their daily practice, there are still a number of national competent authorities that do not comply with it. In response to this concern, EGGVP kindly requests the HMA to provide a complete overview of this situation, by identifying which Member States are currently implementing Article 25, paragraph 3 of Directive 2004/28/EC in full.


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EPHA I am writing on behalf of the European Public Health Alliance (EPHA) in response to the public consultation launched by the Heads of Medicines Agencies (HMA) and European Medicines Agency (EMA) regarding the identification of commercially confidential information. We recognise the HMA/EMA effort to improve access to documents in the EU and are grateful for the chance to contribute to this consultation. EPHA – Europe’s leading NGO advocating for better health - is the European Platform bringing together public health organisations representing professional groups, patients, health promotion and disease specific NGOs and other health associations. EPHA's initial concern with the document is that in many cases, whether or not information can be released will be decided upon on a case by case basis. This risks leaving as little clarity as there is at the moment of in what situations, or what information, can be made publically available. There needs to be a clear and prominent clarification of this, and the process for decisions to be taken on a case by case basis should be made public. People who apply for a release of information must be clear on what the criteria are in place for the release on information and the grounds for rejection wherever necessary. There should also be a process put in place for appeals for or against releases, or decisions not to release, information. Finally, EPHA would to note that in order for patients to fully take part in the work of the Medicines Agency it is important that the EMA takes into account the language used. When sending out documents for consultations to a plurality of organisations, all acronyms and technical terms should be explained as fully as possible. The first time an

To the extent possible, EMA/HMA seeks to reduce the number of case by case decisions so that a truly common approach can be achieved. The comment with respect to acronyms is noted.


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acronym is mentioned its full version should also be given. This is important, because as a scientific body the Medicines Agency produces very technical pieces of work. However, the intended audience of this work is often patients, patient organisations, and the general public. It is therefore essential that the agency's work be clear, comprehensible, and concise in its communication with external stakeholders. There are a number of acronyms in this consultation document which are not explained making it difficult to comment on some sections. We wish the European Medicines Agency every success in analysing the consultation responses and in drafting revising the directive. It is my hope that the concerns brought forward in this letter will be helpful in drafting these documents. We would welcome the opportunity to discuss the issues raised in this letter in more detail.

EUCOPE EUCOPE appreciates the efforts of the European Medicines Agency (EMA) and the Heads of Medicines Agency (HMA) to strive for harmonization in the sensitive field of commercially relevant information. We welcome the opportunity to provide the perspective of our member companies. As a general remark we would like to point to the relation between freedom of information (FOI) requests and Regulatory Data Protection The question whether regulatory data protection of originators is jeopardized if competitors collect clinical trial data via FOI applications is increasingly debated. The Commission has taken a clear approach by initiating an infringement procedure against Germany which had granted a marketing authorization on the basis of FOI material (IP-10-536). Transparency and freedom of information

The concern raised by EUCOPE is acknowledged. However regulatory data protection is governed by separate legislation which also must be respected by HMA/EMA and/or be subject to the appropriate legal recourse.


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(FOI) are core values of good governance. However, a clear distinction between FOI and page 2 regulatory data protection has to be drawn in order to remain incentives for innovations. This is recognized by the Agreement on Trade Related Aspects of Intellectual Property Rights (TRIPS) where Article 39.3 underlines the importance of regulatory data protection and implements an obligation of Members to protect such data. The European Commission has rightfully pointed out that “it should be avoided that the use of Article 10a leads to a circumvention of data protection rules in the pharmaceutical acquis.” This objective can only be achieved if data collected via FOI applications cannot be used for marketing authorization applications during the time regulatory data protection exists. The Commission approach taken in a recent case should thus be followed by all agencies be it national or the EMA.

EUROPABIO EuropaBio's mission is to promote an innovative and dynamic biotechnology-based industry in Europe. EuropaBio, (the European Association for Bioindustries), has 62 corporate and 7 associate members operating worldwide, 2 Bioregions and 19 national biotechnology associations representing some 1800 small and medium sized enterprises. The Healthcare Council of EuropaBio includes 49 corporate members and 22 national associations who are involved in healthcare projects and healthcare applications of biotechnology. EuropaBio would like to thank the European Medicines Agency (“EMA”) and the Medicines Agencies for the opportunity to contribute to this public consultation on the identification of commercially confidential information (“CCI”) and protection of personal data (“PPD”) within the structure of the marketing authorisation (“MA”) dossier.

Noted.


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This issue directly affects EuropaBio’s members, in particular, when filing the documents which must accompany an application for MA for a biopharmaceutical medicinal product in the European Union (“EU”). In view of the importance of this consultation, we would have welcomed a longer consultation period. At EuropaBio, whilst we appreciate and support that EU citizens have a general right of access to documents, we are convinced that the public health authorities, and in particular, the EMA must carefully balance the various interests involved before responding positively to such requests for access. We firmly believe that, during the “balancing exercise”, due consideration must be given to the need to ensure sufficient protection of the interests, the competitive position and the intellectual property rights of biopharmaceutical companies (and other stakeholders). Without question, the EMA and the Medicines Agencies are aware that an inappropriate transparency policy can undermine the financial assumptions upon which the entire biopharma sector is founded and will discourage the further investments that are necessary for the continued success of the industry in developing new treatments for patients. This contribution is divided into general comments and specific comments on the draft document. General comments • EuropaBio would like to reiterate that the need to inform the users of the medicinal products (i.e. physicians, pharmacists, nurses and patients) should always be the primary rationale behind the

Agreed in principle. Agreed in principle. However community and national


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decision to make the content of regulatory MA dossiers publically available. • To ensure that no personal data and individual safety reporting records become publically available, we recommend that all appendices to clinical study reports are kept confidential. It should be noted that safety narratives can never be made publically available. • EuropaBio does not recommend the publication of any CMC or non-clinical study reports following EU approval, as this could give non-originators the ability to obtain approval outside of the EU, based on originators’ data. CMC and non-clinical summaries may be disclosed (with appropriate redactions). • EuropaBio would welcome efforts to increase the visibility of the identity of persons or legal entities making a request for disclosure. • The choice of an appropriate classification (CCI, CBC or ‘can be released’) will depend to a large extent on the status of a medicinal product in the lifecycle (i.e. whether the product is still being assessed by the competent regulatory authorities or already on the market). EuropaBio expects that – according to the title of the guidance – all suggested confidentiality classifications are set up in relation to the “Release of information after granting of a marketing authorisation”. • Whilst the draft document often refers to the need to carry out a case-by-case analysis (“CBC”), there is no indication of “how” such an analysis will be done in practice. In view of the complexity of such matters and of the balancing exercise itself, we consider that MA

legislation must be respected Refer to principle 5 Refer to principle 17 Refer to principle 11


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holders (and maybe other stakeholders) will need to be consulted by the authorities beforehand. The consent of MA holders and other data owners shall be obtained prior to any release/disclosure of a document falling in the category CBC, and they shall be provided with a genuine opportunity to redact such documents before disclosure. We therefore consider essential to clarify this point in the draft document, for instance, on page 4, where the meaning of the case-by-case analysis is described. Please note that when proposing classification as CBC hereunder, we always assume that the owner of the data/document will be consulted in advance. • More generally, we would welcome the opportunity to review and provide comments on the overall set of EMA guidance documents relating to its transparency policies prior to the public release and implementation. • The draft document seems to take the view that the confidentiality duties and the disclosure rules should apply differently with respect to finished products and novel packaging or medical devices (e.g. pages 5 and 6). We believe that such duties and rules should equally apply in all such circumstances. • The draft document does not indicate whether and how the EMA intends applying its new guidance and transparency policy retrospectively to “old” MA dossiers (i.e. those relating to medicinal products approved prior to the new guidance/policy coming into effect). In light of the principle of legitimate expectations, we would have reservations about applying “retrospectively” the new guidance with respect to “old” dossiers, which have not been drafted by taking such

Refer to principle 10 Agreed Refer to principle 1


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guidance/policy into consideration or in other circumstances that the granting of “new” MA. We therefore request clarifying in the draft document that the recommendations only apply when the initial MA was granted after the entry into effect of the EMA recommendations. We also suggest clarifying that the recommendations do not apply in the case the MA has been refused, or the application for MA withdrawn or to the granting of access to documents filed in the context of other applications, such as for orphan designation, compliance with paediatric requirements or to the correspondence between the EMA/Medicines Agencies and the applicants. Should this guideline apply retrospectively, the owner of the data should always be consulted prior to any release/disclosure, with the possibility to amend documents before publication. EuropaBio wishes to highlight that retrospective application of this guideline could increase the administrative burden on MA holders significantly. • The draft document contains specific considerations on PPD (at page 6) and envisages to release various documents that may contain the names, contact details, signatures and other personal data about persons authorised for communication on behalf of the applicant, qualified persons, experts, individuals involved in clinical trials, and other persons associated with, or involved in, the development and approval of medicines (e.g. pages 8-9, sub-module 1.2, pages 8-9, sub-module 1.2, page 9, sub-module 1.2 persons authorized for communication on behalf of the applicant, page 10, sub-module 2.5.3, page 13, sub-modules 2.4.2 (including Annex 5.4 letter of authorization for communication on behalf of the applicant/MAH), 2.4.3 (including Annex 5.4 letter of authorization for communication on behalf of the

Refer to principles 2 and 3 Refer to principle 3


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applicant/MAH) and 2.4.5, page 25, point 4, and pages 41-42, module 4, sub-module 4.2). We generally believe that the need to protect personal data should be more adequately reflected in the considerations on PPD, and that such personal data should not be released and should be redacted from such documents, which should therefore be classified as CBC and/or PPD. • At numerous occasions the draft document provides, often in the left columns, certain “justifications” for the proposed classifications (e.g. pages 15, 24, 25, 30, and 32). We agree that it is useful to provide examples, but feel that the example provided are not exhaustive and that there are other cases/circumstances where the proposed classification will also apply. We therefore suggest to add more relevant examples throughout the draft document and make it clear that they are provided for illustrative purposes (e.g. by adding each time “for instance”). We notably believe that the classifications CBC should also apply for the details of the pharmacovigilance system (regardless of whether or not the MAH and the qualified person belong to the same group of companies) and the Risk Management System, when the disclosure of such details may harm the interest or competitive position of the MA holder (and not only in case this would reveal commercial agreements between different companies). • Notwithstanding the importance of achieving transparency towards the Public, we wish to hereby draw the attention of the EMA HMA group that confidentiality is part of both directives governing GMO (both GMO deliberate release use (GMO-DR) and GMO contained use (GMO-CU) and is within the remit of Member States’ specific bodies

Refer to principle 5 Refer to principle 7 Refer to principle 8 Refer to principle 15


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which may not lie with the National Competent Authorities dealing with medicinal products . Therefore, with regards to disclosing GMO-related information gathered at time of pre-registration (for instance, within the context of clinical trials), of MAA submission and of post-registration, we consider of utmost importance that: o these GMO (DR/CU)-related stakeholders are consulted proactively by EMA HMA since they are most of the time not hosted by the medicines-related NCAs and o their recommendations are shared with the interested stakeholders (such as EuropaBio). Lastly, we consider that the public disclosure of such confidential information can be made only upon appropriate redaction and final endorsement by the MA holder.

GE HEALTHCARE Please find below comments from GE Healthcare on this draft guidance document released for public consultation. We highlight some sections of the MA that should be classified as ‘PPD’ instead of ‘can be released’ to prevent personal data such as names, signatures and cvs etc being publicly released. Information that could identify individuals within the applicant company or contract organisations associated within the MA should not be made publicly available.

Comment noted Refer to principle 5

HAI EUROPE and MIEF

HAI Europe and MIEF welcome the initiative to comment on the HMA/EMA guidance document on the identification of Commercially Confidential Information and Protection of Personal Data within the structure of the Marketing Authorisation (MA) Dossier. We have, however, identified serious shortcomings in the guidance document. Public accountability of regulatory decisions is only possible if the public has access to the evidence on which those decisions are


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based, and is provided with a rationale for decisions. There is an inherent risk that vital information of public relevance, would remain inaccessible to the public, were such a draft guidance document to be approved. When medicines agencies fail to publicly disclose important safety information to potential users and the public at large, they also fail to fulfill their mandate to contribute to rational medicine use, safeguarding and upholding public health. Lack of full public access to the body of available scientific evidence about the effects of medicines on human health leaves European citizens at greater risk for otherwise preventable harm. This is unacceptable. A broad definition of commercial confidentiality that puts commercial interests before human health is both inconsistent with EU regulations and almost certain to lead to otherwise preventable harm. Two steps are needed to prevent future harm: a precise and limited definition of commercial confidentiality and regulatory procedures that make transparency the norm and secrecy the exception. Legal obligations of the Medicines Authorities and the European Medicines Agency The European Union Treaty Declaration Nr 17 on the right of access to information clearly states that the ‘transparency of the decision making process strengthens the democratic nature of the institutions and the public's confidence in the administration.’ Both the European Medicines Agency and the Medicines’ Authorities at national level have a clear duty to uphold transparency and to communicate with the public. Their obligations are specified clearly and repeatedly in several regulations: • Regulation (EC) No 1049/2001 of the European Parliament and of the

Agreed


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Council of 30 May 2001 regarding public access to European Parliament, Council and Commission documents • Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Community procedures for the authorization and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency. (This regulation confirms that Regulation No 1049/2001 is applicable to the European Medicines Agency). • Regulation (EC) No 1367/2006 of the European Parliament and of the Council of 6 September 2006 on the application of the provisions of the Aarhus Convention on Access to Information, Public Participation in Decision-making and Access to Justice in Environmental Matters to Community Institutions and bodies • Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community Code relating to Medicinal Products for Human Use. Most notably, Article 12 of the regulation 1049/2001 recital reads that: ‘All rules concerning access to documents of the institutions should be in conformity with this Regulation.’ Therefore, any guidance document being put forward by the EMA and/or national MA concerning the disclosure of information should abide to current regulations on access to documents. Lack of compliance of the European Medicines Agency and the national Drug Regulatory Authorities with current regulations A full 10 years after Regulation 1049/2001 EC came into force, the European Medicines Agency and national Drug Regulatory Authorities are still not complying with current legislation. The draft guidance document being proposed contradicts current regulations and existing case law. In particular: A. Using article 4 of Regulation 1049/2001, which outlines exceptions to the law, as a stepping stone for this draft guidance document puts the onus on the non-disclosure of information, rather than on the public access to documents. It undermines the whole aim of the proposal. B. The concept of commercially confidential information being put

The EMA’s policy and approach is fully consistent with Regulation 1049/2001. It should be noted that Regulation (EC) No 1049/2001 of the European Parliament and of the Council of 30 May 2001 regarding public access to European Parliament, Council and Commission documents applies only to the EMA and not to Member States. Different legal provisions are in place at national level. A. It should be noted that Regulation (EC) No 1049/2001 of the European Parliament and of the Council of 30 May 2001 regarding public access to European Parliament, Council and


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forward is not compliant with official definitions. C. The notion of personal data, as presented in the draft document, constitutes a misinterpretation, and is, once again, not compliant with official recommendations. D. The reference to personal security of individuals involved in animal studies is pointless. A. Undue application of article 4 of Regulation 1049/2001 outlining exceptions In general, confidentiality is defined by way of exceptions: ‘In principle, all documents of the institutions should be accessible to the public. However, certain public and private interests should be protected by way of exceptions.’ (Regulation 1049/2001, recital, article 11) The exceptions that are applicable are further outlined under article 4 of the regulation, entitled ‘Exceptions’. The following are of relevance to this draft guidance document: 1. The institutions shall refuse access to a document where disclosure would undermine the protection of: (..) (b) privacy and the integrity of the individual, in particular in accordance with Community legislation regarding the protection of personal data. 2. The institutions shall refuse access to a document where disclosure would undermine the protection of: — commercial interests of a natural or legal person, including intellectual property (…) (Regulation 1049/2001, article 4) The draft guidance document is unsound in that it misuses the above-mentioned exceptions. In light of the objectives pursued in Regulation No 1049/2001, the exceptions as laid down in Article 4 should be interpreted and applied strictly. Nonconforming cases should not be generalised, as stated in article 4.6 clearly that reads: 6. If only parts of the requested document are covered by any of the

Commission documents applies only to the EMA and not to Member States. Different legal provisions are in place at national level. The EMA’s policy and approach is fully consistent with Regulation 1049/2001. B. We are not aware that there is an official definition of commercially confidential information. The version used in the preparation of this document has been agreed by the European regulatory network See EMA policy on access to documents ref. EMA/110196/2006 C. Refer to principle 5 D. We believe that there are circumstances in some countries where this issue may arise. See comment under A. above


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exceptions, the remaining parts of the document shall be released. Therefore, exceptions are only applicable to the confidential elements of a document, not to its entirety. Refusing access to entire documents based on the sole presence of an allegedly confidential element in the file name, as proposed in the draft guidance document, is injudicious. Case law decisions supporting the non-generalisation of exceptions 1 a) Exceptions cannot be applied to entire categories Case law invalidates the approach chosen in the draft guidance paper to, a priori, distribute documents according to different levels of confidentiality. Franchet and Byk v Commission The Court of First Instance has rejected as insufficient an assessment of documents by reference to categories rather than on the basis of the actual information contained in those documents, since the examination required of an institution must enable it to assess specifically whether an exception invoked actually applies to all the information contained in those documents. 1 b) A document concerning an interest protected by an exception is not sufficient to justify an overall exception T-2/03 Verein für Konsumenteninformation v Commission [2005] ECR II- 1121 Joined Cases T-110/03, T-150/03 and T-405/03 Sison v Council [2005] ECR II-1429 The examination required for the purpose of processing a request for access to documents made under the procedure provided for by Regulation No 1049/2001 regarding public access to European Parliament, Council and Commission documents must be specific in nature. The mere fact that a document concerns an interest protected by an exception is not sufficient to justify application of that exception. 1c) Each document requires an individual and concrete examination Case T-237/05 Éditions Odile Jacob SAS vs Commission [2010] The General Court concluded that the European Commission’s refusal to grant access to the documents under the exceptions in Regulation


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1049/2001 could not be justified and was an error of law. It ordered the Commission to produce all the documents requested with the exception of an opinion from the Commission’s legal service. The General Court stressed that in the case of a request for access, each document would need to be the subject of an individual and concrete examination. 1d) The institution is required to demonstrate specific and effective risks in disclosing the information Joined cases C-39/05 P and C-52/05 P Sweden and Turco vs Council [2008] ECR I-4723 It is insufficient, in principle, for a document to fall within an activity mentioned in Article 4(2) of Regulation No 1049/2001. The institution concerned must also supply explanations as to how access to that document could specifically and effectively undermine the interest protected by an exception laid down in that article. 1e) The risk invoked must be reasonably foreseeable Sweden and Turco v Council [2008] ECR I-4723 The application of an exception may, as a rule, be justified only if the institution has previously assessed whether access to the document could specifically and effectively undermine the protected interest. In addition, the risk of a protected interest being undermined must be reasonably foreseeable and not purely hypothetical. 1g) The risk should be weighed against the public interest in disclosure Case T-198/03 Bank Austria Creditanstalt v Commission [2006] ECR II- 1429 Case T-474/04 Pergan Hilfsstoffe für industrielle Prozesse v Commission [2007] ECR II-4225 Accordingly, the assessment as to the confidentiality of an item of information requires, on the one hand, that the individual legitimate interests opposing disclosure of the information be weighed against, on the other, the public interest in ensuring that the activities of the Community institutions take place as openly as possible. B. Definition of commercially confidential information It is interesting to note that the notion of commercially confidential information (CCI) contained in this consultation goes beyond the


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definition established by the EMA five years ago; when the agency issued a policy paper on Principles to be applied for the deletion of commercially confidential information for the disclosure of EMA documents (EMA/45422/2006). This document justifies the withholding of commercial information only in those cases where the release of information could ‘prejudice to an unreasonable degree the commercial interests’. The current proposal redefines CCI as: ‘any information which is not in the public domain or publicly available and where disclosure may undermine the economic interest or competitive position of the owner of the information’. This definition seems to rely solely on self-identification by the company of information that may undermine its economic interest or competitive position. Self identification is not adequate. On the contrary, companies should be required to produce information showing how the release of information would harm their position. In general, the default position should be that information is not commercially confidential and companies should have to prove that it is. A redefinition of the notion of commercially confidential information is essential to the improvement of transparency. The new EMEA policy should be based on the general principle of access to all documents, for complete transparency. In particular, all information about efficacy and safety is of public interest, and should therefore be publicly available, following the removal of any information that might identify individuals. This is in alignment with the current regulations which specify that public health protection is paramount to commercial confidentiality. The assessment of potential commercially confidential information on a case-by-case basis opens the door to subjective interpretation by the parties involved. When patient safety is at stake, it is essential to ensure objectivity.

We do not understand the reference to self-identification. The decision on what to disclose is made by the EMA or the NCAs.


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C. Personal data protection The Data Protection Working Party has been established by Article 29 of Directive 95/46/EC. It is the independent EU Advisory Body on Data Protection and Privacy. Its tasks are laid down in Article 30 of Directive 95/46/EC and in Article 15 of Directive 2002/58/ECi. This Working Party is responsible for making ‘recommendations to the public at large, and in particular to Community institutions on matters relating to the protection of persons with regard to the processing of personal data and privacy in the European Community.’ In its Opinion 4/2007 on the concept of personal data, article 29, the Data Protection Working Party clarified its definition of personal data. This opinion is particularly relevant to the draft guidance document, as it focuses specifically on pharmaceutical research data. It reads: (…)Recital 26 of the Directive 95/46 EC pays particular attention to the term "identifiable" when it reads that “whereas to determine whether a person is identifiable account should be taken of all the means likely reasonably to be used either by the controller or by any other person to identify the said person.” This means that a mere hypothetical possibility to single out the individual is not enough to consider the person as “identifiable”. If, taking into account “all the means likely reasonably to be used by the controller or any other person”, that possibility does not exist or is negligible, the person should not be considered as “identifiable”, and the information would not be considered as “personal data”. (…) Example No. 13: pharmaceutical research data Hospitals or individual physicians transfer data from medical records of their patients to a company for the purposes of medical research. No names of the patients are used but only serial numbers attributed randomly to each clinical case, in order to ensure coherence and to avoid confusion with information on different patients. The names of patients stay exclusively in possession of the respective doctors bound



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by medical secrecy. The data do not contain any additional information which make identification of the patients possible by combining it. In addition, all other measures have been taken to prevent the data subjects from being identified or becoming identifiable, be it legal, technical or organizational. Under these circumstances, a Data Protection Authority may consider that no means are present in the processing performed by the pharmaceutical company, which make it likely reasonably to be used to identify the data subjects. Hence, the identification number attributed to an individual in the framework of a clinical trial or an adverse event report should not be considered personal data as it cannot be used to trace back the individual’s identity. Similarly, the patient’s nationality and age are not sufficient elements, even when combined with the identification number, to track an individual. Therefore, the current consultation document’s proposal to consider these three elements to be confidential personal data is in contradiction with the recommendations of the competent body, the Data Protection Working Party. This proposal is all the more unacceptable as the three elements in question are of paramount importance in assessing the total number of adverse events and their frequency per country, and also for identifying pharmacovigilance patterns. The recent cases of narcolepsy after pandemic influenza vaccination (Pandremix) illustrate the importance of two factors in assessing vaccine-induced harms: ‘age’ (only children were concerned) and ‘nationality’ (Scandinavians were at a higher risk). Had these elements been absent from the analysis, then the drug-induced harm would not have been detected. In exceptional cases (patients suffering from a rare disease) should the combination of the three elements - date of birth, age and country - enable the direct or indirect identification of a natural person, then adequate measures should be implemented to

The principles outlined in HMA/EMA recommendations on Transparency (ref EMEA/743133/2009) will be applied


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revent that occurrence. If the date of birth is to be unavailable, the age of the patient suffering the adverse reaction, or participating in the clinical trial, should be released. As to the identification of EMA and DRA staff or scientific experts involved in the marketing authorisation process or related activities, such information should not be withheld. Without disclosing the identity of the individuals that have participated in the decision-making process, who sat at relevant committees, there is no possibility for the public to ascertain potential conflicts of interest. D. Personal security of individuals involved in animal studies The rationale brought forward to withhold documents is based on a subset application of personal data protection regulations. Yet, evidence from official sources casts a doubt on the likelihood of such a risk. EUROPOL’s 2010 ‘Terrorism Situation and Trends report’ identified but two attacks on individuals involved in animal studies, in the 27 European Member States. Both attacks targeted one company based in the United Kingdom. This low likelihood of events is not sufficient to warrant the non-disclosure of information relating to animal testing in medicines’ research and development. E. Encouraging transparency in medicines regulation across EU Member States While harmonised procedures can greatly reduce the bureaucratic burden on regulatory agencies, the priority should always be to have the appropriate checks and balances to ensure the highest standards of medicines quality, efficacy and safety. Above all, the practical orientations laid down in the guidance document should be harmonised to the highest existing transparency standard. Therefore, if a given national regulatory agency discloses publicly more information than other counterparts in the EU, that same agency should be used as a point of reference. The public should have access to a complete registry of all EMA documents, with a description of the aim of the document. Public

Please note that EMA publishes names and declarations of interest for all experts involved in scientific assessment. See comment under D above E. While efforts to achieve a harmonised approach across the European regulatory network are being made through this document, it must be accepted that there may be different legal frameworks in MSs which prevent this in practice as in the event of legal challenge national legislation will take precedence.


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accountability of regulatory decisions is only possible if the public has access to the evidence on which those decisions are based, and is provided with a rationale for decisions. Any decision and/or recommendation should be evidence-based and extensively referenced, in order to allow public scrutiny. Access to data of public interest Lack of full public access to the body of available scientific evidence about the effects of medicines on human health leaves European citizens at greater risk for otherwise preventable harm. Access to the following data is essential: • Clinical and non-clinical data (toxicology); • Information about quality that has an impact on the benefit/harm balance; • The qualitative and quantitative composition; • Details of the dosage form; • Primary and secondary packaging; • Information on the production process (that can impact on the medicines’ quality: excipient, impurities, and residues) • The periodic safety update reports (PSURs) as well as its assessment reports • Comprehensive register of clinical trials (completed, ongoing, stopped), including the protocols, detailed clinical data and results. • Public register of risk management plans and post-marketing studies. When information is not being disclosed by the EMA or national Medicines’ Authorities, a list of the documents being withheld should be published, containing an abridged summary of their contents. On a positive note, we welcome the release of information relating to modules 2.5 and 2.7, the Clinical Data and Clinical Summary, respectively. Furthermore, the disclosure of an up-to-date list of the marketing authorization documents is a positive development. Granting access to documents Dissemination is an important step, yet both the format and process through which the information is made available are equally important: • Acknowledgement of request within a very short period of time (e.g.,

See specific comments in the relevant sections of this guidance. The EMA has published a procedure for granting access to


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under a week). • Expectation of a response to a request within 30 days – extensions only granted under very exceptional circumstances and requests for extensions can be appealed by the person requesting the documents. Current regulations foresee 15 days, with extension of another 15 days. • Documents need to be provided in legible and easily up loadable/ downloadable format • All information made available online should be on a searchable format, so that users can retrieve it easily using key words. Lack of clarity about application to Variations This draft guidance document does not specify whether these practical orientations are also to be applied to Variations procedures. If so, it should be clearly indicated. Access to information is particularly relevant in variations type II (related to new indications), or other variations related to pharmacovigilance aspects

documents. See European medicines Agency policy on access to documents ref. EMA/110196/2006. It should be noted that other competent authorities may be subject to different administrative requirements and/or specific national legislation. The same principles will be applied for significant variations to MAs.

IFAH Europe IFAH-Europe issue with applying the human approach to veterinary MA dossiers The approach to classify each section of the human Common Technical Document (CTD) as CCI, PPD, ‘case-by-case’ or ‘can be released’ needs to be re-considered before we embark on a similar exercise with the veterinary Notice to Applicants (NtA, as based on Annex I to the veterinary Directive). First of all, the extent of granularity is higher in the CTD than in the NtA. Consequently, each section of the NtA is likely to contain a mix of information that falls under all 4 above criteria, i.e. CCI, PPD, ‘case-by-case’ or ‘can be released’; it will then be very difficult to label each section using only one of the 4 criteria. Secondly, the draft ‘human guidance’ (page 36) rightly stresses that information contained in sub-module 2.6 of the CTD for non-clinical



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summary “can be considered sensitive (related with animal protection issues)”. In fact, such remark applies to most parts of veterinary dossiers that contain names of veterinarians, test facilities location, etc…

IFAH-Europe proposed approach for veterinary MA dossiers IFAH-Europe believes that, in addition to what is already publically available, very little information contained in a veterinary MA dossier can actually be released; all is indeed likely to fall under the CCI or PPD criteria. Thus, and to answer requests for information, competent authorities should make the best use of already available sources of information as follows: S u m m a ry o f Pro d u ct s Ch a ra c t e r is t ics ( S m PCs ) p ro v id e in formation on the qualitative composition of VMPs; they are available for a high number of products from both HMA and EMA websites; European Public Assessment Reports (EPARs), especially the scientific discussion part, provide information on the quality, safety and efficacy data of centrally authorised products; a similar concept could be introduced for other products; Eu ro p e a n Pu b lic MRL As s e s s m e n t Re p o r t s ( EPMARs ) p ro v id e

information on maximum residue limits (MRLs); CVMP m e e t in g s p re s s r e le a s e s p ro v id e CVMP o p in io n s o n m e d ic in a l

products and MRLs, as well as information on referrals; CMDv m e e t in g s p re s s r e le a s e s provide information on products’ referrals; Eu d ra GMP d a t a b a s e g ive s a cce s s t o in fo rm a t io n on t h e m a n u fa c t u re r

responsible for batch release. All the above already constitute a remarkable source of publically


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available information, in a way that respects commercial confidentiality and personnel data protection. Veterinary competent authorities spend a considerable amount of resources to prepare and publish these, and it is difficult to see how agencies will be able to afford spending more time on releasing even more information. Thus, IFAH-Europe strongly believes that no further information should be proactively disclosed from veterinary MA dossiers, and that specific requests must be addressed individually in liaison with the relevant MA holder.

INTERNATIONAL LEAGUE AGAINST EPILEPSY

The International League Against Epilepsy (ILAE) is the world's preeminent association of physicians and other health professionals working towards a world where no person's life is limited by epilepsy. ILAE's mission is to ensure that health professionals, patients and their care providers, governments, and the public world-wide have the educational and research resources that are essential in understanding, diagnosing and treating persons with epilepsy. Antiseizure drugs are a matter of life and death for many of our patients. For most of our other patients, antiseizure drugs are essential for having at least a satisfactory quality of life and for being able to go to school, to drive or to work. In spite of available therapies, 1 in 3 patients with epilepsy continue to have seizures or intolerable side effects. As a result, many members of the ILAE are actively involved in pre-clinical and clinical studies of new antiseizure therapies. In many cases, our members contribute to the design and implementation of pivotal clinical trials and in other cases serve on Data Safety and Monitoring Boards and advisory panels for regulatory bodies, including in Europe.

Comments noted. No need to change guidance document.


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Given this level of involvement of our membership in the process of drug development and subsequent clinical use of those drugs, we welcome and support the efforts of the Heads of Medicines Agencies and European Medicines Agency to increase transparency with the public and professional communities of their operations as well as to increase the availability of information contained in marketing authorisation dossiers. Increased transparency in both of these areas will provide the public affected by epilepsy with the information they need and will help physicians more effectively treat their patients based on the best and most complete and current information, all of which will help ILAE fulfill its mission. Thank you for providing ILAE the opportunity to express our perspective on the HMA/EMA guidance document.

IPFA I can now inform you that IPFA is of the opinion that the topic of transparency is appropriately addressed in this document and that we have no further comments.

Comments noted. No need to change guidance document.

LEO PHARMA A/S LEO Pharma is, in general, supporting this draft guidance document. Clarification of some issues is needed. LEO Pharma would like to see consultation of the owner of documents, prior to release, for those parts of the dossier that are considered to be



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CBC (Case-by-case analysis). LEO Pharma is not in favour of publication/release of contractual arrangements between companies as they are deemed confidential. The parties to a contract are often bound by confidentiality obligations not only with respect to the outcome and the subject matter covered by the agreement (e.g. the project, services, etc.) but also with respect to the provisions stipulated in the agreement. A public disclosure would undermine a party’s bargaining power and have anti-competitive effects. The reference to document EMA/484118/2010 (P3/44, first bullet) is stating that “a common approach should apply for active publication and for disclosure upon request”. Can it be confirmed that release of documents that are part of the MA dossier will only be released after a request for access (i.e. reactive disclosure) and, in line with European Medicines Agency policy on access to documents (POLICY/0043, EMA/110196/2006), the originator will always be informed prior to disclosure that a request for access has been received?


MERCK SHARP & DOHME (Europe) Inc

We appreciate the efforts for a co-ordinated transparency policy across Europe and the need to simplify the release of information to the public by defining sections of the marketing authorisation dossier that could be released without further review. The proposal to group areas subject to case-by-case redaction may improve efficiency for redaction but may lead to a significant revision in the structure of the CTD into a part to be released, a part that needs redaction and a closed part (similar to the DMF). Although we can only speculate about the final guidance on this, we can't imagine that this can be done without revising the ICH



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guidance on the CTD. We generally object to the release of marketing authorisation application dossiers for withdrawn or refused applications. Companies may still have a commercial interest in the product and may be performing additional analysis or generating more information to support the approval. The individual design of the trials and the data collected that were insufficient to grant approval might also offer competitive advantage to other companies to obtain their approvals. However, we would like to stress that MSD remains committed to share clinical trial information through relevant clinical trial registries, conference presentations and journal articles. In addition, as of July 2011, MSD provides complete protocols for our clinical trial manuscripts of investigational and approved medicines and vaccines to journal editors on a confidential basis to assist with the review of the manuscript. If the journal accepts the manuscript, we allow the journal -- at its discretion - to post a redacted protocol on its website at the time of publication1. (http://www.merck.com/research/discovery-and-development/clinical-development/Merck-Guidelines-for- Publication-of-Clinical-Trials-and-Related-Works.pdf) In general, access to protocols or raw data should not lead to an undermining of data exclusivity or commercial interests but should only be driven by a public or scientific / medical interest in leveraging existing data to drive new knowledge. In such cases, we are willing to explore practical ways to share documents from the marketing

Refer to principle 2 We agree that access to documents should not undermine data exclusivity or commercial interests and that competent authorities should maintain responsibility for the benefit –risk evaluation after a scientific assessment. However regulatory authorities cannot prevent further use of data for other purposes.


http://www.merck.com/research/discovery-and-development/clinical-development/Merck-Guidelines-for-%20Publication-of-Clinical-Trials-and-Related-Works.pdf




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authorisation dossier when access to this data is for the purpose of conducting further research such as a well-planned and executed meta-analysis. However, it is important that competent regulatory authorities maintain their sole responsibility for making binding and final decisions on benefit – risk of a given intervention after a scientific assessment. There are currently no binding requirements or rigorous processes that guarantee that the qualifications of individuals conducting the analysis are assured or to justify the scientific adequacy of the analysis methods used. A parallel and uncontrolled process, leading to scientific or lay press statements about any findings prior to regulatory scrutiny would represent a real threat to public health as hitherto well established treatments could be challenged on the basis of an ill planned or executed meta-analysis. In addition, such statements could undermine public trust in the competence of Health Authorities. As such, we welcome that a statement regarding scrutiny of research requests by authorities is included in the documents. We recommend that before granting access to patient level data based on third party requests, the competent authority should review the analysis plan and share it with the marketing authorisation holders to avoid biased approaches. We would like to highlight that it is not possible to share personalised data due to legal requirements concerning personal data protection and privacy. Such authorisation must be obtained from the patients during the informed consent process. It is therefore only possible to create raw data sets that have been anonymized by clustering or categorization of data, or by removing non essential data.

Add comment on patient data – rules in Eudravigilance access apply Refer to principle 5 Refer to principle 5


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We object to the general statement that non-clinical information cannot be considered as commercially confidential per se. Non-clinical dossier components may contain information concerning innovation in the form of techniques, technologies, contracts, collaborations and basic science not previously published. Information on proprietary discovery platforms, technologies or collaborations that would damage future commercial utilization if released into the public domain may be contained in non-clinical summaries or study reports. For example, early development and pharmacology data often reflects candidate selection criteria which are company specific and therefore proprietary. Specific databases may be used to evaluate toxicities and disclosure can release proprietary data e.g. pharmacogenomic pattern recognition platforms. Proprietary RNA sequencing platforms or reagents may be used for bioanalytical assays and tools developed to describe or model studies based upon experimental data are also usually proprietary or their use is customized to the company. We would like to stress that personal data of employees of Industry must be protected and all names, contact details and signatures to letters, application forms or reports must be redacted. This relates to regulatory personnel as well as functional company staff such as QPPV, qualified person or person responsible for information. Our detailed comments on the table outlining the proposed classification are attached.


PFIZER INC Pfizer supports the EMA/HMA objective with regard to transparency and therefore welcomes the opportunity to comment on this draft guidance. We have a number of general and specific comments for consideration,


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set out below. These are aimed at strengthening the guidance and providing further clarity and consistency, where needed, in order to ensure that it provides a predictable and workable system, that best serves the interests of public health by appropriately balancing the transparency imperative with the vital interests of the innovative pharmaceutical industry and the regulatory system itself. General principles in relation to disclosure of clinical and non-clinical data from the MAA dossier Pfizer considers that disclosure of these data (especially, detailed and raw data that have not hitherto been routinely disclosed) without very careful consideration of the uses it may be put to, and the competitive implications, may have very negative consequences for the regulatory system and for the innovative industry in the EU. In view of the serious, far-reaching and irreversible potential consequences of the issues raised, Pfizer believes further discussion and collaboration is needed between regulators and industry as to how this information should best be presented and provided on a routine basis, before it is put into practice. Full disclosure of at least some (if not all) studies affords competitors (within and outside the EU), with clear insight and competitive advantage at an economic and competitive disadvantage of the applicant. Also, since such disclosure is likely to be regarded as “prior publication”, it may jeopardize publication in peer review journals. Such publication is clearly in the interests of medical science and public health, and therefore the position in this regard needs to be thoroughly examined, and as appropriate worked through with publishers of scientific journals, before that risk is taken.

Refer to principle 11 Refer to principle 17 Refer to principle 12


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Withdrawn Applications Pfizer is seriously concerned at the proposal to apply the same principles of disclosure to withdrawn and refused applications as to those which are successfully granted. This is because such applications may be resubmitted at a future point, for example pending further analysis, research or development work on the product in question. A company’s competitive and economic interests in continuing to develop a product, in these circumstances, are likely to be undermined by the disclosure of the detailed information from their prior MAA, over and above what is available in the public domain e.g. from clinical trial registries and the withdrawal assessment report, to the considerable benefit and advantage of their competitors. Case by Case Analysis It is not specified in the document which parties should be involved in a CBC (case-by-case) analysis. In any situation where the data being considered relate to the MAH, then they should be consulted (not just e.g. the Member State) This needs to be clarified in the document, in both the CBC section on page 4 and we would propose in a separate section as well. In addition, the MAH should be informed prior to supplying a 3rd party any information that it owns or that relates to it. This is consistent with Article 4(4) of Regulation EC (No.) 1049/2001 which states that:



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“As regards third-party documents, the institution shall consult the third party with a view to assessing whether an exception in paragraph 1 or 2 is applicable, unless it is clear that the document shall or shall not be disclosed.” In relation to the elements of the dossier / assessment report that may be made public based on a CBC analysis it will be very important that thorough consideration is given to the potential commercial/competitive harm that might result from disclosing such data. In general, where the tables indicate either a CBC analysis is needed or that there is an exception to the stated classification, this would benefit from a clearer explanation of the reasoning that might apply in this situation, and perhaps also examples to illustrate the point. It is also suggested that after a certain period has elapsed, a review takes place with the relevant stakeholders to assess whether commercial confidentiality is being correctly defined and managed under this guidance.

Refer to principle 10 We agree that a review after a certain period would be useful

PSLG-DMLG (IQ)

Preclinical Safety and Drug Metabolism Leadership Groups of the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) The recently formed IQ consortium is dedicated to developing the scientific basis for drug research and development policy. It has 24 member companies, and leadership groups representing the many scientific disciplines of pharmaceutical research and development. The


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Preclinical Safety Leadership Group (PSLG) and the Drug Metabolism Leadership Group (DMLG), the authors of this response, are two of those leadership groups.

Preclinical Safety and Drug Metabolism Leadership Groups of IQ welcome the opportunity to comment on this proposal, “HMA/EMA Guidance Document on the Identification of Commercially Confidential information and the Protection of the Persona Data within the Structure of the Marketing Authorization Dossier – Release of the Information after Granting of the Marketing Authorization.” The HMA/EMA have appropriately identified the primary concerns of Market Authorization Holders—personal data protection and commercially confidential information. PSLG and DMLG recognize the interests and concerns of the HMA/EMA 1—to avoid tedious, inefficient and labor-intensive redaction efforts and 2—to increase transparency of relevant safety and efficacy information to health care providers and recipients. The concerns of the Pharmaceutical Industry relate to 1—the privacy and security of their employees, who are making valuable contributions to medicine and public health, and 2—the protection of their proprietary technologies and strategies (innovations in the form of specialized techniques, animal models, study designs, etc) from competitors. As much of the preclinical information in the dossier is specific to the Market Authorization Holder’s unique innovations and strategies, IQ considers this information commercially confidential. The guidance’s definition of CCI does not acknowledge the proprietary nature of non-


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clinical efficacy and safety models, scientific data, analyses and analyses techniques, and other tools developed at substantial cost and resource expenditure by individual companies in their quests for successful new therapeutic agents. The definition of CCI should be expanded to include proprietary biological information, including pharmacology, DMPK, toxicology, models, methods, tools, databases, etc.) The Preclinical dossier contains details of investigative and mechanistic studies that have broad application to other drug development programs in the form of target validation, human risk assessment, species sensitivity, etc. The Market Authorization Holder’s systematic use of these tools, strategies, and decisions is important competitive intelligence, is based on years of prior drug development experience, and results in appropriate study design, unique endpoints or analyses, specific types of quality data, and greater success. Consequently, the PSLG does not support release of dossier components that would compromise this commercially advantageous information. The proposal of HMA/EMA specifies release of information “after granting of a marketing authorization”. It is therefore important to clarify that this proposal does not apply to release of this information for those products denied authorization or withdrawn after submission, or to correspondence between the sponsor and the agency, or subsequent submissions, such as for compliance with pediatric requirements. Clarification should also be made that this release would not extend to submissions prior to the date of this proposal or to those dossiers not in the CTD format. Detailed section by section responses are included in the comment section below, but are summarized as follows:

Refer to principle 17 Refer to principle 2 Refer to principles 1 and 3


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1. The HMA/EMA proposal to disclose documents of Sub-Module 2.4 of the MAA poses an acceptable compromise with respect to CCI and PPD. The information so disclosed is similar to that which may be disclosed by FDA under FOIA, but is more extensive and consistent in content as it is completely intact. As such, some otherwise proprietary strategy is revealed, however by the time of Market Authorization, much of the competitive advantage of the strategy has been realized. 2. HMA/EMA proposal to disclose documents included in Sub-Modules 2.6 and 4.2 poses an unacceptable level of risk for compromise of both CCI and PPD. 3. HMA/EMA proposal’s definition of CCI should be expanded to include proprietary biological information, including pharmacology, DMPK, toxicology, models, methods, tools, databases, etc.) 4. Clarity is needed that this proposal does not apply to release of this information for those products denied authorization or withdrawn after submission, or to correspondence between the sponsor and the agency, or subsequent submissions, such as for compliance with pediatric requirements, or to submissions made prior to the date of this proposal or to those dossier not in the CTD format. Nonclinical Dossier Components in the Common Technical Document that can contain such Commercially Confidential Information (CCI) or Protection of Personal Data (PPD) are specified here: 1. Sub-Module 1.4.2 (Non-clinical expert statement, p. 31) 2. Sub-Module 2.4 (Non-clinical Overview and Report on Non-clinical Data, p.36) 3. Sub-Module 2.6 (Non-clinical Summary, including pharmacology, pharmacokinetic, and toxicology written summaries,

Refer to principle 2 Refer to principles 5, 6, 17 and 18 Refer to principle 17


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tabulated summaries, and summary toxicology in tabular format) 4. Sub-Module 4.2 (Study Reports; p. 41-42; not stated, but as per Sub-Module 2.6 information provided herein can be considered sensitive) Detailed comments specifying the type of concern and suggested remediation or classification for each section are presented in the section for “Specific Comments on the Text”, below.

ROCHE The HMA/EMA draft guideline suggests that the commercial confidential information (CCI) and protection of personal data (PPD) should be concentrated in a single section within the CTD structure. Our concern with this proposal to revisit and modify the current CTD structure is the heavy impact which this will have on the eCTD lifecycle management for the products currently on the market. Depending on the changes, we will have most likely to start from scratch or create a consolidating sequence. Our alternative proposal, in order to avoid any potential issues with the eCTD lifecycle lifecycle management for the existing products, is to consider submitting a separate dossier which contains only the CCI and PPD information and which can be released to the public. This dossier will be submitted in the form of a NeeS style structure. It will be actually based on the original eCTD dossier, from which we will remove the confidential information and the XML backbone. It will be submitted on a seperate cd-rom at the same time as the original dossier.


SANOFI AND SANOFI welcomes this joint policy initiative from EMA/HMA to make


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SANOFI PASTEUR

systematically available and transparent to the public the documentary basis of Marketing Authorizations granted in the EU. We interpret this initiative as adequate to improve the overall transparency of the evaluation process, and its constitutive elements, as far as it does not infringe upon the existing legislation protecting commercial confidential information and personal data. Following the spirit of the European legislation and recent interventions from the EU Ombudsman, we understand that the main objective of this initiative will be to bring more insight on the process of approval for medicines in the European Countries. Subsequently, whilst we consider that timed* disclosure of clinical data and information is of the upmost importance; we also believe that there are certain documents which should still remain restricted concerning manufacturing/ quality elements and non-clinical studies. Restriction of certain publicly available information is a justified option in order to limit the potential misuse of CCI particularly outside of the EU. * For Clinical Trials results, opportunities for prior publication in peered review scientific journals should be preserved and encouraged. There is also the concern over the need to continue to keep strict confidentiality during all European Scientific Advice procedures and outcomes, to adequately protect ongoing commercially sensitive undisclosed projects. Moreover the Agencies have explicitly invited stakeholders to comment

Refer to principle 17 Refer to principle 11 Refer to principle 12. Refer to principle 14 Refer to principles 5 and 6


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specifically about the release of personal data, including company’s expert CVs and signatures, of contractual arrangements between companies and of personal data of individuals involved in studies on animals. Not only do we believe that publishing this type of information on the web will not add any substantial mean for better understanding the reasoning of evaluators nor the objective basis for approval. But, moreover, publishing these details could actually negatively impact companies and individuals. Avoiding possible misuse of published information: The information from the MA dossier that will be disclosed after an authorisation is granted must not lead to its possible misuse by an independent company in an attempt to circumvent any exclusivity periods of the reference product. Various regulatory pathways are available in the European legislation for registering a medicinal product. For some of them, there is no mention of the status of the regulatory data protection on the originator's data. Therefore these regulatory pathways may present a potential risk of circumvention of data and market exclusivity periods of the reference product. This situation concerns in particular the full mixed applications under Article 8(3) of Directive 2001/83/EC which included a combination of reports of limited non-clinical and/or clinical studies carried out by the applicant and of bibliographical references. With more and more data from the MA dossier for the reference product published, this regulatory pathway that allows the reliance on pre-clinical and clinical data of the reference product is of particular

Refer to principle 11 This is covered by specific legislation and it is not appropriate


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concern. In one recent example, a copy of a reference product (that was still under protection) was approved under this Article 8.3 full mixed application. In its application for MA, the applicant used information on the reference product obtained under freedom of information legislations. With the evolution of public disclosure of information included in applications for Marketing Authorisation, there is the need to reinforce in a legal text that an application for MA of a medicinal product containing a substance already authorised in the EU can only be submitted when the exclusivity period of the reference product has elapsed, regardless of the regulatory pathway used by the independent applicant. Today there is only a statement in chapter 1 of the Notice to Applicant saying that EPAR cannot be considered to supply sufficient information. The pharmaceutical companies need a legal certainty across all the Member States that a misuse of their data will not be possible and that the exclusivity periods for their innovative medicines will be respected. Criteria to identify PPD/CBC sections The process and rules to identify and select which information should be redacted for documents or sections classified as PPD and CBC must be clarified and well defined. These criteria must be publicly available and implemented uniformly by all the Competent Authorities. The MAH must systematically be consulted in this process. In case of disagreement between the MAH and the Competent Authority, a reconciliation procedure should be available.

to include it here. Refer to principle 10


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IFAH EUROPA The last sentence of the cover note to the draft human guidance (page

2) reads: “Such a system is already in place in other sectors and would save resources within the agencies when dossiers should be released without disclosing CCI and PPD.” It would be very useful to know what kind of system (for access to information) is already in place and in which sectors; such information could significantly contribute to the success of this exercise. National law: the § on top of page 4 of the draft human guidance reads: “This guidance document is intended to be a consensus document agreed by the whole network”, which we understand as an approach to be adopted by all. Nevertheless, the guidance continues with saying: “… it should be noted that national CAs/EMA have to follow their national legislation in terms of access to documents”, which appears to be contradictory. Also if HMA is to adopt a guidance jointly with EMA, each MS must commit to adapt its national law accordingly. This will ensure a predictable environment for the industry and the public. In the human draft guidance, specific feedback was also asked on the following: Re le a s e o f Pe r s o n a l Da t a ( e . g . CV, s ig n a t u re s e t c ) : t h e q u a lifica t io n

of any personal data (that can lead to identification of a person) as PPD, i.e. not for release, is supported. Co n t r a c t u a l a r r a n g e m e n t s b e t w e e n d iffe r e n t co m p a n ie s : a ll

information on third parties is regarded as CCI; thus it cannot be released. Pe r s o n a l s e cu r it y o f in d iv id u a ls in vo lve d in s t u d ie s w it h a n im a ls : a ll

the information on clinical centres or third parties involved in the manufacture of the clinical product is also regarded as CCI and cannot

To be considered in the context of the Vet specific document to be developed. Refer to principle 19


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be released. IFAH-Europe looks forward to receiving feedback to our proposed approach, especially now a joint CMDv/EMA working group has been formed with the objective to develop a parallel veterinary guidance (see: CMDv report for release, June and July 2011 at: http://www.hma.eu/151.html).

EUCOPE 2.2. Non-Clinical and Clinical Information We regard the approach taken in the Guidance according to which non-clinical and clinical information should not per se be regarded as commercially confidential information as inconsistent with the provisions of Directive 2001/83. These stipulate that a mere reference may be taken to the content of the authorization documents only after a period after 10 years. A fortiori, it follows that a prior publication is even less possible. Otherwise, other applicants within the EU and certainly outside the EU could circumvent the 10-year period. After 10 years, only a reference by the generic applicant is admissible, but no publication. A publication would in particular mean that other applicants from outside the EU could obtain authorizations using the original authorization documents without having any efforts and cost. Art. 10a of the Directive, does not allow any reference to the so-called ecotox data (Art. 8[3][ca] of the Directive). Therefore, such reference is prohibited even after the 10-year period. Contrary to the proposal in the Guideline with respect to information related to environmental risk assessments and risk management plans, a publication of such data would constitute an infringement of the Directive (regardless of the



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period). Furthermore, a free access to, and a free availability of, data for

competitors via publication by the authorities obviously would undermine the economic interest and competitive position of the owner of the information. The owner of the information had to bear all the cost and efforts to create such data on its own whereas his competitors may use such data in case of publication for marketing authorizations without such cost and efforts. A distortion of competition and a deterrence of innovation would be the result. Therefore, the approach taken in the Guidance according to which non-clinical and clinical information should not per se be regarded as commercially confidential information seems to us not only to be inconsistent with the Directive but also to be inconsistent with the definition of commercial confidential information provided by the Guidance (p. 3). The assessment under 2.2. that non-clinical and clinical results are not "per se" are commercially confidential information is therefore unacceptable. It also contradicts the assessment of the German Joint Federal Committee (GBA) in the field of the early benefit assessment, according to which the entire module 5 as well as decisions on applications for waivers or documents on counselling requirements are subject to confidentiality and are thus generally not published on the internet. Regarding the correct definition of commercial confidential information provided by the Guidance(p. 3) we take the view that only those parts of the authorization dossier which must be disclosed due to a specific legal basis (mandatory disclosures) could be excluded from the confidential results. These consist, however, only of certain parts of the data analysis. All other parts of the authorization dossier are per se


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commercially confidential information according to the definition of commercial confidential information. In no event, the (raw) information serving as a basis for the data analysis such as case report forms and data sheets to be submitted in accordance with Point 5.2.7 of Part 1 of Annex I to Directive 2001/83/EC may be published.


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1. Specific comments on text

[Add tables with specific comments as received from interested party.]

Stakeholder no. (To be completed by the Agency

Line no.

Comment and rationale; proposed changes Outcome

(To be completed by the Agency)

Cover Note (Pages 1-2)

EFPIA HMA/EMA

cover note “Request for specific and detailed feedback” Page 2/44, 1st para

Comment: In addition to the topics mentioned, we believe that the consultation should also be seeking specific and detailed feedback on the CCI proposals. This is one of the key exceptions defined in the Legislation, and it is essential that the guidance document accurately defines what information is CCI and what is not, throughout the various sections of the dossier.

Agreed

EFPIA HMA/EMA cover note “Facilitating responses to access to document requests – invitation for industry proposals” Page 2/44, 2nd and 3rd

Comment: EFPIA acknowledges the practical and resource challenges in relation to removing CCI and PPD information from dossiers prior to making them publicly available. We agree that one way of facilitating a more efficient and resource-sparing process would be to redesign the ICH CTD (and eCTD) dossier structure so that this information could be extracted more easily. However, given the complexity of the CTD dossier structure, the frequent intermingling of potential CCI/PPD information with other information, and the



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paragraph need to understand and maintain the links between different sets of information within the dossier, we believe that this will be a complex task. Furthermore, a unilateral (EU region) redesign of the ICH CTD dossier structure would run the risk of undermining the benefits achieved from implementing the single CTD dossier format across all ICH regions (and beyond). In addition, it seems likely that other regions will be facing similar issues in the future as they progress their own transparency initiatives. Consequently, we believe that the best way forwards would be to propose an ICH process to review the CTD dossier structure in relation to extraction of CCI and PPD information, and make proposals which could be agreed across all ICH regions. One further issue that is not covered in the draft guidance, but that needs to be addressed, is the issue of how the new guidance should be applied in the case of ‘old’ MA dossiers (i.e. those authorised prior to any revised guideline on CTD dossier structure coming into effect). Of course, the same principles with regard to CCI, CBC and PPD should apply for newer and older MA dossiers. Because such ‘old’ MA dossiers will not have been organised and constructed in accordance with the new policy, the workload for authorities will be significant if these are to be released proactively. We believe that EMA could meet its obligation in relation to these old dossiers by customised assessment and redaction of documents/dossiers, according to the principles of the new guidance, prior



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to release. EGGVP This is a

comment on the cover note page 2

1. Release of personal data (e.g. CV, signatures, etc.): any personal data should be seen as fully confidential and should not be disclosed. This includes not only CVs, signatures, etc., but also any personal data of people involved in the file development (employees’ information, CRO’s data, details of external experts, etc.). EGGVP requests that any information of this type remains 100% confidential. 2. Contractual arrangements between different companies: this is fundamental information in any company’s strategic plan and, therefore, its confidentiality must be extremely protected. In EGGVP’s view, inclusion of manufacturer’s data in the conditioning material (in cases where it is different from the marketing authorization holder) should also not be required. Since the marketing authorization holder holds full responsibility of the product, EGGVP suggests not including that information in the future. Alternatively, EGGVP would be in favor of publishing a positive list of GMP inspections carried on to APIS manufacturers. This information would be extremely helpful for the industry in order to make its choices upon assured suppliers / manufacturers. 3. Personal security of individuals involved in with studies involving animals: in bullet point 1 EGGVP already gives its opinion on this issue. Furthermore, EGGVP disagrees with the principle of

Refer to principles 5 and 6 Refer to principle 4 Refer to principle 5A


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making details on animal experiments publicly available. 4. EGGVP questions the benefits and/or advantages of making specific pieces of information available to the general public, i.e. types of application of a marketing authorization, bibliographic references, proofs of payment, name of the reference product for generic VMPs, etc. 5. PSURs contain detailed information that should only be made available to professionals. EGGVP believes that making the whole PSUR available to the general public can lead to incorrect interpretations and to situations of unnecessary social alarm. EGGVP suggests exploring other channels / systems of information. 6. Complete studies (i.e. ecotoxicity studies, residue studies…) should be treated as confidential information; their disclosure directly undermines the economic interest and competitive position of the owner of the information on the market. Again, EGGVP suggests exploring other channels / systems of information (i.e. the publication of a summary with main conclusions). In conclusion, EGGVP’s main position is that the marketing authorization dossier as such should be regarded as strictly confidential information and shall not be disclosed in any way. In particular, EGGVP

Refer to principle 5D and principles outlines in HMA/EMA Recommendations on Transparency (ref EMEA/743133/2009) Refer to principle 9 Refer to principle 5


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strongly opposes to any disclosure of personal data to the public. EGGVP also questions the benefits and/or interest for the general public in having access to detailed information from the registrations files, and believes it can lead to confusion, misinterpretation of information and unnecessary alarm of society. According to EGGVP’s opinion, Article 25, paragraph 3 of Directive 2004/28/EC already provides an appropriate legal framework for making the basic and necessary information available to the public, and therefore EGGVP advocates for a full implementation of this piece of legislation.

Introduction (Pages 3-6)

EGA Introduction

(page 3-6) A general point should be included to the introductory part that the parts of the dossier which refer to any contractual agreement between companies and all business partners should be treated as confidential. The names of employees, representatives, all business partners (e.g. CROs, contract manufacturers, suppliers, etc.) constitute essential trade secrets and should not be disclosed (CCI). In addition, company-related information referring to internal company structure, organisation, internal procedures etc. should be also treated as commercially sensitive (CCI)


EGA Point 3.1. In addition to personal data, the sales data included Such information is publicly available and cannot be


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PSUR in the PSURs are commercially sensitive and should be treated as confidential (CCI).

considered commercially confidential (See HMA/EMA recommendations on transparency ref. EMEA/743133/2009)

EFPIA Page 3/44 Comment : Although the adoption of a common approach for the active publication and disclosure upon request for access to documents after granting of a marketing authorisation is supported, the following should be well defined to ensure appropriate implementation: 1. Clear timelines, steps of these processes, including sufficient time for the review of all documents considered CBC by the owner of the data 2. Clear roles and responsibilities for the process of redaction of CCI and PPD information, including the responsibilities of the Health Authorities and owner of the data.

Refer to principle 10 EMA and National Competent Authorities will revise procedures in line with this guidance

EFPIA Page 3/44 Comment: Enhanced transparency in Europe is, in general, consistent with and supportive of international harmonisation initiatives and capacity building. However, we would point out that the impact of unilateral transparency initiatives in one region may have unintended consequences in other regions, and that currently Europe is in the lead in relation to release of information from MA dossiers. One aspect that may be important in this regard is in relation to the potential undermining of Intellectual Property rights and Regulatory Data Protection (RDP). The European Union has recognised the importance of RDP as an incentive to innovation by putting in place a system whereby the originator’s data cannot be relied upon to apply for approval of a generic product



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for eight years following approval of the originator product in the Union. Many countries outside the EU, however, do not yet have robust (or any) provisions to protect originators’ investment in their data. For this reason, the EU often seeks RDP commitments in trade agreements. Many clinical data are already, for good reasons, made available to the public, and overall we support the proposals contained within the draft guidance in the clinical area. However, the publication of certain CMC and non-clinical data in Modules 2, 3 and 4 under the current proposal is of particular concern. The publication of such data in addition to clinical data may enhance the ability of non-innovators to obtain approval in countries without robust RDP systems based on the originator’s data shortly after the originator obtains European approval. This would undermine the protection of the commercial interests of the innovator (including IP protection) and, because of the limited value of that data from a public interest perspective in comparison to the clinical data, there is no overriding interest in disclosure. Thus disclosure is not permitted under Regulation 1049/2001 Article 4.2.2

Refer to principles 11, 17 and 18

2 In addition, any use by a competitor of such data to obtain early registration of its product would constitute unfair commercial use. The disclosure of the data, without putting

in place steps to ensure the data are protected against unfair commercial use, is inconsistent with the obligations imposed by Article 39 of the TRIPS agreement. TRIPS Article

39.3 states: “Members, when requiring, as a condition of approving the marketing of pharmaceutical or of agricultural chemical products which utilize new chemical entities, the

submission of undisclosed test or other data, the origination of which involves a considerable effort, shall protect such data against unfair commercial use. In addition, Members

shall protect such data against disclosure, except where necessary to protect the public, or unless steps are taken to ensure that the data are protected against unfair


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We therefore believe that the CMC data and nonclinical study reports necessary to support product authorisation within Modules 2, 3 and 4 should be designated CCI.

EFPIA Page 3/44 Comment: MA dossiers contain very large amounts of data, including information relating to toxicity, safety, and adverse events. Some of this information, taken in isolation and viewed by individuals without the appropriate professional knowledge and experience to understand the information and place it within the context of the totality of the data available on the product, may be misinterpreted. This could raise unnecessary concerns for patients and their families and lead to discontinuation of treatment, or other undesirable outcomes. Furthermore the eCTD is generally submitted 1 year prior to the granting of a MA and therefore several modules might have been revised by the time the MA is granted, including the Product Information and the Risk Management Plan (RMP). Consequently, we suggest that in association with the release of information from ‘MA dossiers after approval’ EMA/HMA consider providing meaningful context to the information, including as a minimum the following:

To be considered when developing procedures for active publication

commercial use”. Unless the EU takes steps to ensure that the data are protected against unfair commercial use in third countries, the disclosure of the data would appear to be

inconsistent with the obligations imposed by Article 39 of the TRIPS agreement and would undermine the efforts of the EU to obtain RDP in trade agreements.


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• The information should be accompanied by a link or reference to the approved ‘Summary of Product Characteristics’ and ‘Patient Information Leaflet’ for the product. • The information should be accompanied by a caution about drawing conclusions about products based on isolated pieces of information sourced from dossiers, and indicating that the formal regulatory decision is based on an assessment of the totality of the data in the dossier. • In making MA dossier information available, EMA/HMA should also caution the public about not taking any action with regard to medications they may be taking before discussing their individual situation with their health care provider.

LEO PHARMA A/S P3/44 bottom line

Whereas the title of the document is clear regarding the scope of this guidance document (i.e. release of information from MA dossiers after granting a Marketing Authorisation), uncertainty is introduced in the text of the document when it is claimed on page 3 that “the principles outlined should be equally applicable to other formats and applications (e.g. Orphan designation, Paediatric Investigation Plans)”. Clarification is needed. LEO Pharma is of the opinion that the scope of the document should be limited to release of information from MA dossiers after granting a Marketing Authorisation.


EFPIA Page 3/44 and first paragraph on

Comment: EFPIA supports the development of a consensus document which represents a common European

Agreed


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page 4/44, paragraph starting with the sentence “this guidance document is intended…”

position accepted by all EU Competent Authorities. It is important to agree a common approach in this area, otherwise the de facto European position is the one adopted by the Authority that releases the greatest amount of information. Furthermore, multiple requests for the same information from different Agencies (“information shopping”) may be encouraged if Agencies adopt different approaches. However, the second sentence seems to imply that EMA and national Competent Authorities may be required to follow different approaches according to the applicable national or European legislation. If that is the case, it would be helpful to catalogue where such legislative differences may actually result in the disclosure of additional information over that which is agreed in the common European position.

EFPIA Page 3/44, Para 5

Comment: It would be helpful to provide the appropriate references for these documents (EMA/110196/2006 and EMEA/743133/2009) within the Guidance. Proposed change (if any): See above suggestion.

Agreed


Comment: It seems reasonable and appropriate that the principles defined for redaction of CCI and PPD within MA dossiers should also be applied to Regulator’s assessment reports; assuming that these are also released after the grant of a MA.

Agreed


Comment: We agree that the high level principles in relation to

Agreed


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the need for redaction of CCI and PPD information prior to release of MA dossiers may be applicable to other formats and dossier types. However, we would point out that what is considered CCI is highly dependent on the timepoint within the research, development, and marketing lifecycle of a product. Thus, the title of the guidance and the approaches set out in the tables on pages 7-44 within this guidance are specifically drawn up in relation to MA dossiers following the grant of an authorisation. The information that may be considered CCI may well be different for other formats and application types, such as for Orphan Designation and for Paediatric Investigation Plans (clearly both these types of submission are made prior to the subsequent grant of a MA), and for correspondence between the Agency and the applicant. In addition, CCI will be different within dossiers that have been withdrawn or refused MAs, than that within dossiers following the grant of a MA. For example, the company may wish to submit a new MA dossier for the same indication based largely on the data and studies included in the original MA dossier. In such cases these data and studies will be commercially sensitive until the MA is granted, and they should remain confidential until that time. In conclusion, we agree with the title of the draft guidance and the heading for the tables set out on pages 7-44, that the current guidance refers specifically to the release of information from a MA



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dossier after the granting of a MA. We believe that the current guidance should not apply to MA dossiers where the application has been refused or withdrawn, or to other formats or application types, or to correspondence between the Agency and the applicant, which should generally not be released. EFPIA detailed comments in relation to the tables set out on pages 7-44 of the document (structure of the marketing authorisation dossier) assume the draft guidance refers to the release of information after the granting of a MA.

DAIICHI SANKYO Section 1, classification criteria (Page 4)

Comment: The document proposes 4 criteria for the classification of data contained in the dossier. Given the problems that the pharma industry has had with members of the animal rights lobby groups (as acknowledged in the comment regarding sub-module 2.6), particularly where individuals have been targeted because of the relationship between their company and certain animal testing labs, should there be a fifth criterion introduced? This criterion would be applied to records that describe the business relationships that the owner of the information has and that may be potentially damaging for the company or it’s employees if this was made public. Note: that the criterion “CCI” specifies in the footnote that the “disclosure may undermine the economic interest or competitive position of the owner of the information”, whereas the proposal for a new criterion



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is aimed at damage to the company or individual employees of that company. Proposed change (if any): The EMA should add a fifth criterion, called something like “PCSI (Protection of Company Sensitive Information)” which means that the section may contain information about the business relationships between the owner of the information and third parties that may be damaging to the company or individual employees and should be redacted before release. This classification should apply to the whole of Module 4 and may also apply to information in Modules 2.4 and 2.6. This classification may also apply to business relationships in other Modules of the dossier.


ASTRAZENECA and MedImmune

Pg 4, Section 2

Comment: Despite identifying four criteria, in many cases there are then exceptions or deviations proposed. This does not give industry confidence that the criteria will be applied consistently across all products. - At present no development programme is identical and we would like to confirm how data submitted that adds to the data set will be handled if outside standard CTD headings. - The EMA and HMAs do not require Patient Line Listings but exceptionally these can be requested. How would this data be handled as it forms part of the CTD? We would strongly recommend these are not disclosed, and the proposal provided under



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module 5 is further explored as an alternative. - Various sections of the draft state information ‘Can be Released’. Industry needs to understand what criteria will be developed for this to ensure consistency across the EMA and HMAs. We strongly recommend that there is a formal agreement and consultation with the sponsor prior to disclosure. Proposed Change: Recommend the EMA/HMA proposes to standardise and ensure compliance with the redaction of all personal data from a dossier prior to release.


PFIZER INC Section 2

Comment: This section should be amended to state that in the case of the CBC classification, the owner of the data should be contacted in advance of the disclosure, and given the opportunity to comment whether any of the information in the proposed disclosure constitutes CCI. The view of the owner must be taken into account in making the decision whether to disclose information. (See further, general comments above.)


EFPIA Page 4/44, point 1

Comment: The term ‘section’ is not defined and we assume it could relate to a single word, a single sentence, or to a section of a document that runs to a number of pages. We suggest that the term ‘section’ be pragmatically and flexibly interpreted in order to ensure the effective redaction of the relevant information.

EFPIA Page 4/44, point 1, 2nd

Comment: No definition of ‘Personal Data’ is provided. We

Proposal accepted, text amended


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paragraph

propose that since this term has already been defined in EU legislation (i.e. Article 2 of Directive 95/46/EC; on the protection of individuals with regard to the processing of personal data and on the free movement of such data), this definition is included or referenced here, and is used to define the personal data that have to be protected (i.e. ‘personal data’ shall mean any information relating to an identified or identifiable natural person (‘data subject’); an identifiable person is one who can be identified, directly or indirectly, in particular by reference to an identification number or to one or more factors specific to his physical, physiological, mental, economic, cultural or social identity).

EFPIA Page 4/44, point 1, 3rd para

Comment: We believe that for sections classified as needing ‘Case by Case analysis’ the analysis should include review by the owner of the data, and that their views should be considered before reaching a final decision according to the provisions set forth in Article 4(4) of Regulation (EC) No 1049/2001. We also assume that the ‘Case by Case analysis’ will lead to the necessary CCI and PPD redactions, where appropriate. We suggest making these points clear in the guidance (“...a case-by-case review, including the opportunity for the owner of the data to provide comments and, where necessary, redaction prior to its eventual release.”) Proposed change (if any): CBC (Case-by-Case analysis): means that the section


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may have commercially confidential information or personal data, thus suggesting a case-by-case review including the opportunity for the owner of the data to provide comments and, where necessary, redaction prior to its eventual release.


EFPIA Page 4/44, point 2, 1st paragraph

Comment: As stated above, it should be clarified in this section that the tables set out on pages 7-44 specifically refer to the release of information from a MA dossier after the granting of a MA. Proposed change (if any): These recommendations apply to the granting of access to the MA dossier after approval, (delete: refusal or withdrawal of a marketing authorisation application)and to the disclosure of assessment reports.


LEO PHARMA A/S P4/44, “2. Additional Principles”

In the same way uncertainty is introduced when it is stated that “these recommendations apply to the granting of access to the MA dossier after approval, refusal or withdrawal of a marketing authorisation application”. Clarification is needed. LEO is of the opinion that the scope of the document should be limited to release of information from approved MA dossiers.


AESGP Page 4 Comments:


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Section 2.1

We agree on the general principle that detailed information on quality and manufacturing should be classified as CCI and general information can be disclosed. However, there may be exception to this general rule in which even general information can be deemed CCI, as clearly stated in the EMA document “principles to be applied for the deletion of commercially confidential information for the disclosure of EMA documents”. Proposed change (if any): “A general principle in the following question is that detailed information is commercially confidential but general information should be disclosed. However it is acknowledged that in certain circumstances, even a general description of a specific aspect could be regarded as commercially confidential, if justified.”

Agreed, see relevant section in the guidance document

EFPIA Page 4/44, Point 2.1

Comment: In this section it is stated for several types of information that “general information” is not commercially confidential, but the “details” are. We support the general principle that detailed quality and manufacturing information should be considered commercially confidential, but general information can be disclosed. It is important that this general principle is carried forward into the final guidance document. However, it is not always clear where the line will be drawn between “general” and “detailed” information. For example, in section 2.1.2., for the types of test



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methods and the fermentation and purification processes for active ingredients of biotechnology products, it is difficult to see how general statements can be made without disclosing specific confidential information, e.g. even general information on a purification process of a biological product will almost inevitably disclose the key features of the process. The distinction between what is classified as “general” and what is classified as “detailed” information needs to be clarified in the document. We recommend that any information related to fermentation and purification of biological products remains entirely confidential. Please refer to comments in later sections on what should be considered detailed and general information relating to quality and manufacturing.

LEO PHARMA A/S Page 4/44, “2.1 Information on the Quality”

Although LEO Pharma is in agreement with the general principle that detailed information is commercially confidential but general information should be disclosed, it is noted that it is not clear from the guidance document on what basis the assessment is made whether information is “detailed” or “general”. Therefore clear guidance is required as to when information will fall within or outside of either category since the consequences hereof can be far reaching.



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PFIZER INC Section 2.1., page 4

Comment: “A general principle regarding quality and manufacturing information is that detailed information is commercially confidential but general information should be disclosed.” The above statement would benefit from further clarity, in particular as to what information constitutes “general information”.


EFPIA Page 4-5/44, point 2.1.1

We agree with the statements in this section on what constitutes detailed and general information relating to composition and product development.


AMGEN LTD Module 1 Section 2.1.1 Composition and Product Development Page 5

Comments: Clarify the phrase ‘...unless disclosure is necessary for public health reasons.’ Proposed change (if any): Provide a few high level examples of situations of where the standard disclosure exceptions may be overruled.

To be reviewed in the light of experience

PFIZER INC Section 2.1.1., page 5

Comment: “The final qualitative formulation (composition) of the authorised product is not commercially confidential.” We query whether this conclusion would be correct in all cases. There will be instances where, for example, the purpose of certain excipients could be commercially confidential information, and not in the public domain. “Disclosure of names of manufacturers or suppliers

This is a specific EU legal requirement


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may be necessary for public health reasons (e.g. some biological products).” It is not clear why this should be the case. We would like to understand the rationale for this statement and which biologicals are impacted by this statement. In addition, if it is envisaged that disclosure of names of manufacturers or suppliers in other circumstances may be necessary for public health reasons, the types of situations and reasons should be specified.

EFPIA Page 5/44, point 2.1.2

Comment: In general, we support the recommendations on what should be considered detailed and general information for the active substance. For biotechnology products we would consider a detailed description of the type of producer cell line to be CCI. The information to be released should be limited to the nature of the cellular system, consistent with what is already included in section 2 of the SmPC, in accordance with the Guideline on Summary of Product Characteristics. This will become increasingly important as new cell lines are developed that have production advantages.

Agreed

SANOFI AND SANOFI PASTEUR

Page 5 Point 2.1.2 Active Substance 4th paragraph

Test methods for non-pharmacopoeial drug substances should be considered as CCI.

Agreed


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Page 5 2.1.2 Active Substance 5th and 7th paragraph

A clarification is required on the wording “general information on […] is not commercially confidential” as to what type of general information the Regulatory Authority is referring to. Some examples would be helpful. The applicant highlights that characterization is part of the knowledge of manufacturer during development studies for biological products. This information is not always publicly available. The method itself and the context of use may have commercial value besides the details of the characterization method.

AESGP Pages 5/6 (2.1.3) Last sentence

Comments: These aspects should be treated as CCI. Proposed change (if any): “Novel packaging or medical devices aspects are regarded confidential unless disclosure is necessary for public health reasons.”

Not agreed

PFIZER INC Section 2.1.3. page 6

Comment: “Concerning degradation products, qualitative and quantitative information is regarded as confidential unless disclosure is necessary for public health reasons.” Impurities controlled to ICH limits, or genotoxic impurities to agreed limits/threshold toxicological concern (TTC), should not constitute public health concerns.


Pg 6, section 2.2

Comment: Reference is made that detailed description of the pharmacovigilance system may be regarded as confidential. This is ambiguous, clarification is required.



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Proposed change (if any): Clarification is needed on what criteria lead to the classification of detailed description of the pharmacovigilance system not being considered confidential.


Pg 6, section 2.2

Comment: The environmental risk assessment (ERA) often includes data from other parts of the dossier which may be considered CCI. Whilst we support greater transparency in this area we would suggest that any such information should be included in a confidential appendix. Thus when ERA information is requested everything except the confidential appendix can be provided. Proposed change (if any): Change text to ‘‘This includes information related to environmental risk assessments and risk management, with the exception of any information which is deemed to be commercially confidential in other parts of the dossier.”


EFPIA Page 5/44, point 2.3

Comment: We agree with the statements outlined in this section on what constitutes detailed and general information relating to finished product.


DAIICHI SANKYO Section 2.2 (Page 6, Line 5-7)

Comment: Depending on status of publication, non-clinical Comment: Depending on status of publication, non-clinical information in MA dossier should be treated as “CCI (commercially Confidential Information). Researchers may face disadvantages when submitting manuscripts from disclosed non-clinical data.



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Proposed change (if any): Information encompassing non-clinical and clinical development of the medicinal product and the subsequent assessment by Competent authorities is not per se commercially confidential when this information has been already published by the applicant.


Comment: We are concerned that publication of clinical study reports immediately following approval may prevent some trials (particularly those finalised late in development such as the Phase 3 pivotal studies) being published in the peer reviewed scientific literature. Disclosure of study reports may be regarded as prior publication such that journals will not accept a journal manuscript – we do not believe that this would be in the best interests of science and patients. In order to avoid this situation we believe that EMA/HMA should invoke on a case by case basis the exception against disclosure for commercial interests, as defined in Regulation 1049/2001 Article 4.2. This Article applies to natural persons (i.e. the research authors) as well as legal persons (i.e. companies), and is applicable here. In other words the act of publication is a commercial interest/matter - the author (or other copyright owner) is exploiting his/her copyright in his/her article in negotiating with the journal to publish the new work – and journals won’t



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publish work/data that has been published before. Consequently, in such cases and with prior justification provided by the company, we believe that EMA should designate the affected study reports as CCI and withhold publication until such time as the journal manuscript has been published. We accept that this approach may prove to be burdensome for Regulatory Agencies, and should this be the case, an alternative might be for the publication of MA dossiers to be delayed until 12 months after the authorisation of the medicinal product. Finally, we suggest that HMA/EMA might also consider discussing this issue with Journal editors to explore how their needs might be best taken into account.


As mentioned in EFPIA’s “general comments” and as discussed in relation to page 3/44 of the draft guidance document, the publication of certain non-clinical data contained in non-clinical study reports will undermine the protection of innovator’s commercial interests. Furthermore, non-clinical dossier components may contain information concerning innovation in the form of techniques, technologies, contracts, collaborations and basic science not previously published.


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Information on proprietary discovery platforms, technologies or collaborations that would damage future commercial utilization if released into the public domain may be contained in non-clinical summaries or study reports. For example, early development and pharmacology data often reflects candidate selection criteria which are company specific and therefore proprietary. Specific databases may be used to evaluate toxicities and disclosure can release proprietary data e.g. pharmacogenomic pattern recognition platforms. Proprietary RNA sequencing platforms or reagents may be used for bioanalytical assays and tools developed to describe or model studies based upon experimental data are also usually proprietary or their use is customized to the company. Further detail on the multiple pieces of CCI and PPD information typically contained in non-clinical study reports and EFPIA’s position on the publication of non-clinical data are provided in relation to the classification proposed for sub-module 4.2 below.


AESGP Page 6 .2, first paragraph

Comments: The description of a MAH’s Pharmacovigilance system should be considered confidential and hence falling under CCI as these documents contain sensitive organisational information and business-related data. Proposed change (if any): “Organisational information submitted as part of marketing authorisation procedures, e.g. the detailed



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description of a MAH’s pharmacovigilance system, is may be regarded as confidential, depending on the level of detail of the information provided.”

HAI EUROPE and MiEF

Page 6

2.2 -The detailed description of a marketing authorisation holders’ pharmacovigilance system should not be regarded as confidential. It is unclear whether the outcomes of discussions at the level of Competent Authorities’ scientific committees or other scientific groups are being regarded as confidential. That should not be the case. 3.1 -It is not clear why information about the reporting country needs to be deleted from Periodic Safety Update Reports in order to ensure individual autonomy. That should not be the case.


AESGP Page 6 Section 2.2, second paragraph

Comments: For EMA, this matter is covered separately in the “EMA Policy on Documents” and the related “output table”, both published in November 2010. This broader and more general discussion should not be mixed up with the guidance document on identifying commercial confidential information within the structure of the MA dossier. Proposed change (if any): Delete the 2nd paragraph of section 2.2.

EMA plans to align these documents in the near future.

AESGP Page 6 Section 2.3

Information provided on the outcome of inspection should be limited to ‘high level’ information.

Agreed

PFIZER INC Section 2.3., page 6

Comment: The statement is quite general and could include also GLP and GCP in addition to GMP, this

High level information on the outcome of inspections at time


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should be clarified. The statement that “Information on the outcome of inspections (e.g. compliance/non-compliance/outstanding issues to be addressed) is not regarded as confidential…” requires clarification. Inspection findings, and their resolution, can be ongoing issues and there can be discussions between the competent authorities and inspected entity that last for some months or longer. Therefore clarity is needed regarding how the outcomes of inspections should be communicated, It is Pfizer’s view that only very high-level information should be disclosed, such as the inspectors’ recommendation regarding whether or not the data can be accepted in support of the evaluation and assessment of the application. Proposed change (if any): “Following the resolution of any dialogue between the competent authorities and the inspected entity and/or sponsor in relation to inspection findings, information on the outcome of inspections (i.e., the inspectors’ recommendation regarding whether or not the data can be accepted in support of the evaluation and assessment of the application) is not regarded as confidential.

of marketing authorisation is not considered confidential.

PFIZER INC Section 3, page 6

Comment: “In regard to the disclosure of personal data enclosed in the MAA, the general principle should be redacting sensitive data details. Information on technical or professional qualifications should only be disclosed in accordance with article 12



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of Directive 2001/83/EC.” Pfizer does not agree with this approach. Consistent with the principles of data privacy legislation, and in order to ensure that the security of individuals working in the pharmaceutical industry is protected (for example in light of the activities of certain animal rights campaigners) all personal data, not just sensitive personal data, should be exempt from disclosure. This includes redaction of the signatures of individuals from all documents – this should be clarified throughout the tables as well. Proposed change (if any): “In regard to the disclosure of personal data enclosed in the MAA, all personal data (within the meaning of EU data privacy legislation) should be exempt from disclosure and should be redacted. This includes redaction of the signatures of individuals from all documents. Information on technical or professional qualifications referred to in article 12 of Directive 2001/83/EC should only be disclosed to the extent that they do not identify or cannot be traced back to an individual person, and must be made anonymous.”



Comment: The environmental risk assessment (ERA) often includes data from other parts of the dossier which may be considered CCI. Whilst we support greater transparency in this area we would suggest that any



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such CCI or PPD information should be redacted. SANOFI AND SANOFI PASTEUR

Page 6 point 2.2 Non-clinical and Clinical Information

The important non clinical information being presented and discussed in the non clinical overview, it seems redundant to publish individual study reports, written summaries and tabulated summaries of non clinical studies. This will limit misuse of sensitive information (see p.36).



Pg 6, Section 3

Comment: Personal Data Protection (PPD) is taken very seriously by industry, and we go to considerable lengths to protect patients, employees and investigators involved in our research programmes, we are not confident in the methodology or robustness that will be applied to ensure that all personal identifiers will be effectively removed from a dossier. Proposed Change: With regard to redaction, please see comment above against page 4, section 2.


DAIICHI SANKYO Section 3 (Page 6)

Comment: The only specific example given in this section, under the heading Section 3.1, describes the access to information in a PSUR. It appears that this information has been specifically identified because of the existing EMA document relating to information requests relating to PSURs. However, the principles described for the PSUR are generally applicable to any instance about the provision of information that contains personal data.

Refer to principle 5 and existing HMA/EMA recommendations


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Proposed change (if any): The section should continue to state the points about protection of personal data. However, this should not specify this as something solely to do with PSURs, but be broadened to state this in terms of any document (clinical study reports, safety reports, etc.) that might contain personal data.

EFPIA Page 6/44, point 3

Comment: We agree that the general principle to be applied in relation to Personal Data enclosed within a MAA dossier is that all sensitive data should be redacted. However, we do not agree with the second sentence that states “Information on technical or professional qualifications should be disclosed in accordance with Article 12 of Directive 2001/83/EC” if this implies that such information will be made public. Article 12 states that 1) “the detailed summaries referred to in the last subparagraph of Article 8(3) are submitted to the competent authorities, they have been drawn up and signed by experts with the necessary technical or professional qualifications, which shall be set out in a brief curriculum vitae”, 2) these experts “shall justify any use made of scientific literature under Article 10a in accordance with the conditions set out in Annex I”, and that 3) “The detailed summaries shall form part of the file which the applicant submits to the competent authorities”.

Refer to principle 5 and existing HMA/EMA recommendations


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Thus, while Article 12 does provide for the inclusion of the names of the experts and their technical or professional qualifications within the MAA dossier, it does not provide any basis for mandating the public disclosure of this information. It should be noted that disclosure of the details of certain technical or professional qualifications could lead (by deduction) to the identification of the names of the corresponding experts. These concerns have been recognised previously, for example, in the UK MHRA document “Guidance on the Disclosure of Types of Human and Veterinary Medicines Information Held by the Human and Veterinary Regulatory Authorities”: http://www.mhra.gov.uk/home/groups/l-unit1/documents/websiteresources/con2033020.pdf). This document states: “Additionally, Section 38 of the FOI Act (Health and Safety) may apply to (for example) some Agency assessors, and external authors of expert reports working for companies that have been subject to attacks or intimidation by animal rights activists or other groups with vested interests. There are therefore, legitimate concerns that such information could be used to target named individuals (particularly where the information alludes to, or contains references to animal testing). This risk may also make it more difficult for Regulatory Agencies to recruit suitably qualified staff, thus

This is addressed in principle 5A

http://www.mhra.gov.uk/home/groups/l-unit1/documents/websiteresources/con2033020.pdf

http://www.mhra.gov.uk/home/groups/l-unit1/documents/websiteresources/con2033020.pdf


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hindering their ability to carry out their statutory duties with regard to human and animal, safety, health and welfare, and undermining the regulatory process. Therefore, in all relevant cases, Regulatory Agencies will redact the names and other identifying information relating to such individuals.” Furthermore, the possibility that any pharmaceutical company employees or experts might be subject to intimidation or attacks, because of their association with the company’s activities, cannot be excluded. Therefore, we believe that no information in relation to the names, or technical or professional qualifications of any company employees or experts (whether or not directly involved with animal testing) should be publicly disclosed; all such information should be classed as PPD.

Refer to principle 5A


Page 6 point 3

It should be ruled that names of responsible persons in the company or a company in charge of specific tasks will always be regarded as personal information and confidential. The information to be disclosed should be restricted to the position held and the professional qualification (example: pharmacist/qualified person).


EFPIA Page 6/44, point 3.1,

Comment: We welcome the acknowledgement that additional


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final two paragraphs

information may in some cases need to be redacted from PSURs, in order to ensure that patients cannot be identified.

Noted


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Stakeholder no.

(See cover page)

Specific comment (if any) Outcome (if applicable)

Module 1: Administrative information (pages 7-29)


Pg 7 - 29, Application, Cover Letter

Comment: It is unclear that the information to be disclosed is limited to the information provided by the applicant in the application form and does not extend to the dossier where more granular information is included. Specifically documentation included in the process is unclear. Proposed Change: Clarify exactly what this will include. Appears to duplicate information planned to be included in the EVMPD and discloses personal information on employees. Recommend that the application form and cover letter is not disclosed. The application form only indicates if the information is provided in the annex, and most of the annexes are already acknowledged to be CCI.

Clarification provided. See text in final guidance. Not accepted

EUROPABIO Module 1, page 7

Changes: Please amend page 7 of the draft document to clarify that the cover letter as such is classified as CCI and PPD and that only the information listed in the table may be disclosed, subject to the comments below. Comments: Cover letters should be informative documents.

See above


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Classifying such documents as CCI and PPD will provide the necessary safeguard to make them as informative as possible.

EFPIA Page 7/44 Application Cover Letter

Comment: It is assumed that it is not proposed to disclose the cover letter but only the information listed in the table. The meaning of “Documentation included in the process” is unclear. It is noted that some of this information is planned to be included (and maintained) in the EVMPD

See above.

EFPIA Structure of the marketing authorisation dossier

Comment: We agree with the criteria/justification column that there may be occasions where there is CCI, and so we suggest this section is classified as ‘CBC’.

Agreed. See text in final guidance

EUROPABIO Sub-module 1.1, page 8

Sub-module 2.1, page 35



Comments: We believe that the risk of having the table of content released (and the uncertainties associated with the proposed distinction between “detailed” and “non detailed tables”) may prevent applicants from creating “informative” tables, which provide a good overview of the content; any table, even non detailed ones, may contain CCI. Changes: Please amend page 8 of the draft document to classify any table of content, even if it is not detailed,

See above.


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as CBC. Same comments for (i) page 35 of the draft document – sub-module 2.1 – index – overall CTD table of contents of modules 2, 3, 4 and 5 and (ii) page 41 of the draft document – sub-module 4.1 – table of content; such tables may contain CCI and thus the need of a CBC classification. We would also recommend classifying Sub-module 5.1 on page 43 as CBC.

EFPIA Page 8/44, sub-module 1.1, index

Proposed change (if any): Replace “can be released” with “CBC”

See above.


Pg 8, sub module 1.1

Comment: Comprehensive table of contents is designated as can be released although acknowledged that contents may be confidential. Proposed Change: Not clear how this will be determined. Will further guidance be made available? Applies to all exceptions to the general criteria.

See above.


Pg 8, sub module 1.2, 2.4.2, 2.4.3, Annex 5.4

Comment: Statement and signature of any company employee should not be released. Name of person authorised to communicate on behalf of the applicant, is irrelevant after first approval. Proposed Change: This information should be redacted, please see comment above, against page 4, section 2.

Proposed change not accepted. See text in final guidance. Refer to principles 4, 5 and 6.

AESGP Page 8 Sub-Module

Information about natural persons allowing identification of the individual should generally not be

Agreed Refer to principle 5A


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1.2 published for reasons of data protection. This is not limited to CVs but does also include any information about name and contact details (e.g. telephone numbers). In section 2.4 “Marketing authorisation holder / Contact persons / Company” all information about contact persons should be classified as “PPD” as it is disclosing the name and contact details of individuals. This includes all information presented in subsections 2.4.2 – 2.4.5. The same applies to subsection 2.5.1.1 (contact person in the EEA for product defects and recalls). It is not necessary to disclose to third parties the identity of the person authorised for communication on behalf of the applicant. This would enable third parties to have insight into partnership, consultants, etc. Proposed change (if any): Signatures or signature statements should not be displayed and name should be confidential to public and requesters (Data Privacy).

See above See text in final guidance Refer to principle 6

GE HEALTHCARE Page 8, Sub-Module

Statement and Signature We propose PPD

Refer to principles 5A and 6


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1.2

DAIICHI SANKYO Section 1.2 (page 8-9/44)

Comment: Signatures and persons for communication on behalf of the applicant – These are personal data and should be set to PPD and/or, in case of using a CRO, can reveal industrial secrecy and are should therefore be set to CCI. Proposed change (if any): PPD/CCI


AMGEN LTD Module 1 Sub Module 1.2 Statement and Signature Page 9

Comments: The person authorised for communication on behalf of the applicant and original signature should be considered PPD. Proposed change (if any): Clarify text to ensure that the names and signature of the individual is considered to be PPD.

See above. Refer to principles 5A and 6


Changes: Please amend page 9 of the draft document to clarify that the name of the person authorised for communication on behalf of the applicant and the signature should be considered as PPD. Same comment for page 12-13 - MAH/Contact Person/Company.


GE HEALTHCARE Page 9, Sub-Module

Person authorised for communication on behalf of applicant, Original signature of Applicant



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1.2 We propose PPD

EFPIA Page 8-9/44, sub-module 1.2

Comment: Page 8-9, sub-module 1.2 – “Statement and signature”, “Person authorised for communication on behalf of the applicant”, “Original signature of the applicant” We welcome the classification of the name and CV of the qualified person for pharmacovigilance as PPD (section 2.4.4 of sub-module 1.2 and Annex 5.5). In line with this, the names and signatures included in sub-modules 1.2 should also not be released – they should be classed as PPD (see also comments on Page 6, point 3 above). Proposed change (if any): For names and signatures replace ‘can be released’ with “PPD”

Refer to principles 5A and 6 See text in final guidance

PFIZER INC Sub-module 1.2, page 9

Comments: the “person authorised to communicate on behalf of the Applicant” should not be released, nor should the original signature of the applicant. See above comments.


EUROPABIO Sub-module 1.2, point 1.3, page 9

Changes: Please amend page 9 of the draft document to clarify that the details of the qualitative change in declared active substance (not defined as active substances) shall be classified as CCI

Proposed change not accepted. The (E)PAR [(European) Public Assessment Report] would mention the qualitative change in the declared active substance applied for.


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EGA •Annex 5.1

Proof of payment

The bank details of a company should be treated as confidential (CCI). As fees may be paid by a business partner, the release of proof of payment can disclose the relationship between different commercial partners.

Amend classification to CBC See text in final guidance

EFPIA Page 10/44, Sub-module 1.2, Annex 5.2

Comment: The letter of consent from the MA holder will need the names and signature of individuals redacted (PPD), so we suggest this section is classified as CBC. Proposed change (if any): Replace “can be released” with “CBC”

Agreed See text in final guidance Refer to principle 6

EUROPABIO Sub-module 1.4, pages 9 and 10

Changes: Please clarify for all types of applications, including biosimilars, which kind of documents can be disclosed and which cannot, on pages 9 and 10. Point 1.4.4 on page 10 should be classified as CBC and the owner of the data shall always be consulted prior to any release.

For point 1.4.4 this information is not CCI after granting of MA. See text in final guidance

EGA •Annex 5.2 •2.4.2; •2.4.3; •annex 5.4

Documents disclosing the contractual agreements and/or partially containing personal data (PPD) to be treated as CCI:

• Annex 5.2- letter of consent from MAH • 2.4.2 and 2.4.3 and Person/Company

authorised for communication between the MAH and the competent authorities during

Agreed See text in final guidance


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and after MA AMGEN LTD Module 1

point 1.4.4 similar biological application page 10

Comments: We suggest detailing the specific information/documents which can be released. Proposed change (if any): add the information/document listed in the revision 9 of the Notice to Applicants for such applications, including about the reference medicinal product and the difference(s) compared to this reference medicinal product in terms of (i) change(s) in the raw material(s), (ii) change(s) in the manufacturing process(es), (iii) change in therapeutic indication(s), (iv) change in pharmaceutical form(s), (v) change in strength (quantitative change to the active substance(s)), (vi) change in route of administration(s) and (vii) others.

For point 1.4.4 this information is not CCI after granting of MA.

AESGP Page 10 Section 1.4.7 Article 10c

Comments : We fail to see the value in disclosing the letter of consent from the MAH in cases of informed consent applications.

The reference medicinal product is mentioned in the (E)PAR. The information is then in the public domain and can be released.

2. Marketing Authorisation Particulars (Pages 11- 23)

EUROPABIO Point 2.2.3,


Changes: Please amend the draft document at page 11 to ensure that the details of the container, closure and

Proposed changes not accepted.


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administration device(s), including the name(s) of their manufacturer(s), shall be classified as CCI.

EGA PROTECTION OF PERSONAL DATA (INDUSTRY SIDE) In line with the very strict policy of protecting the personal data of patients involved in clinical studies or in the reporting of adverse events, the same strict policy shall apply to the protection of personal information of the industry’s employees and representatives. Thus, the same classification (PPD) shall apply.

Proposed change not accepted. Refer to principles 5A and 6

EGA Parts of the dossier containing names of employers, representatives etc. •Sub-module 1.2 •Annex 5.3

Proposed change not accepted. Refer to principles 5A and 6

EUROPABIO Points 2.4.2, 2.4.3 and 2.4.5, Sub-module 2.4, page 13

Changes: The complete proprietary nonclinical strategy and program of the company may be revealed by release of Module 2.4 as it is an exact explanation of the entire nonclinical testing program, results, analysis, and conclusions. A case by case analysis for redactions would need to be made before verbatim release. Proposed change (if any): Replace with “CBC”.

This comment relates to Module 2.4, not point 2.4 of the application form. Refer to principle 17

AMGEN LTD Module 1 Comments: Once all names and signature have been Proposed change not accepted.


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Section 2.4 MAH/Contact Person/Company Annex 5.3 Page 12-13

removed from these documents, the remaining language is template text. Proposed change (if any): Consider classifying this section as PPD.


GE HEALTHCARE Page 13, Sub-Module 1.2, 2.4.2

Person/company authorised for communication on behalf of the applicant during the procedure in the Community/each MS We propose PPD if person


GE HEALTHCARE Page 13, Sub-Module 1.2, 2.4.3

Person/company authorised for communication between the marketing authorisation holder and the competent authorities after authorisation if different from 2.4.2 in the community/each MS We propose PPD if person



Pg 13, Module 1, sub-module 2.4.4 & Annex 5.5

Comment: Industry welcomes that personal information on the QPPV should be redacted. Proposed change (if any): We would recommend the same protection for all employees, i.e. PI of all employees is redacted. With regard to redaction, please Comment: Industry welcomes that personal information on the QPPV should be redacted. Proposed change (if any): We would recommend the



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same protection for all employees, i.e. PI of all employees is redacted. With regard to redaction, please see comment above, against page 4, section 2.

EPHA Points: 2.4.4.; 2.5.1.1; 2.5.1.2; pages 13.

Point 2.4.4 states that information about qualified persons in the EEA for Pharmacovigilance should be protected for integrity reasons. The reasons for this are not entirely clear, as in some Member States the information about who is responsible for the pharmacovigilance questions is made public and it is easy to find the curriculum vitae. Points 2.5.1.1 and 2.5.1.2 it is state that a case-by-case review should be made prior to its eventual release. It is therefore unclear why this would not be the case in 2.4.4.


EFPIA Page 13, sub-module1.2 sections 2.4.2, 2.4.3 and 2.4.5

Comment: We welcome the classification of the name and CV of the qualified person for pharmacovigilance as PPD (sub-module 1.2, sections 2.4.4 and Annex 5.5). In line with this, the names and signatures included in sections 2.4.2, 2.4.3 and 2.4.5 should also not be released – they should be classed as PPD (see also comments on Page 6, point 3 above). Proposed change (if any): Replace “can be released” with “PPD”


AESGP Page 13 Comments:


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Sections 2.4.2 – 2.4.5

The names of the respective people/companies listed should not be disclosed as these data should be covered by data privacy protection (e.g. CV of qualified person for pharmacovigilance). This could put the people under unnecessary pressure and in more extreme cases at personal risk. Proposed change (if any): PPD applies to all categories; names should be kept confidential and should not be displayed to public and requesters (Data Privacy).


DAIICHI SANKYO Sections 2.4.2 and 2.4.3 (page 13/44) including annexes 5.4 (see also page 25/44)

Comment: Persons/companies authorized for communication of behalf of the applicant of MAH - These are personal data and should be set to PPD (same as for the Qualified person in the EEA for Pharmacovigilance in section 2.4.4 page 13) and/or, in case of using a CRO, can reveal industrial secrecy and are should therefore be set to CCI. Proposed change (if any): PPD/CCI


EGA Documents disclosing the company’s specific data:

•Annex 5.7 –


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Justification for more than one manufacturer responsible for batch release

It is sufficient to disclose the name of the manufacturer responsible for the batch release. As the justification contains strategic company information and relates to the company’s internal organisation, should be classified as CCI.


AESGP Page 14 Annex 5.7

Comments: There is no need to make publicly available the justification for more than one manufacturer responsible for batch release; this would make available data relating to the internal organisation of a company and at its worst would facilitate industrial espionage.


AMGEN LTD Module 1 annex 5.6 pages 14 and 15

Comments: this reference to annex 5.6 appears twice in the draft document

It’s because both point 2.5.1 on page 14 and point 2.5.2 on page 15 both refer to annex 5.6.

EGA •2.5.1.1 Contact person in the EEA for product defects recalls

Personal data of the person in the EEA for product defects recalls should not be disclosed (PPD)


PFIZER INC Section 2.5.1.1., page

Comment: “Contact person in the EEA for product defects and recalls”. This should be PPD for the

Refer to principles 4 and 5A


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15

reasons explained above.

EFPIA Page 15/44 Comment: We welcome the classification of the name and CV of the qualified person for pharmacovigilance as PPD (sub-module 1.2, sections 2.4.4 and Annex 5.5). In line with this, the names and signatures included in sub-module 1.2, section 2.5.1.1 should also not be released – they should be classed as PPD (see also comments on Page 6, point 3 above). Proposed change (if any): Replace “CBC” with “PPD”

Proposed change not accepted. Refer to principles 5A and 6 See text in final guidance

AESGP Page 15 Comments: See comment for Sections 2.4.2-

DAIICHI SANKYO Section 2.5.1.1 (page 15/44)

Comment: Contact person in the EEA for product defects and recalls should be set to PPD instead of CBC (same as for the Qualified person in the EEA for Pharmacovigilance in section 2.4.4 page 13) Proposed change (if any): PPD

Proposed change not accepted. Refer to principles 5A and 6 See text in final guidance

EGA •2.5.1.2 Batch control testing arrangement

Arrangements within the same company/ group are related to company’s internal organisation. Thus, as in the case of third party involvement, the arrangements shall not be disclosed (CCI).

See text in final guidance


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AESGP Page 15 Section 2.5.1.2

Comments: Process for case-by-case assessment is lacking. The MAH should be contacted in such case in application of article 4(4) of Regulation (EC) No 1049/2001”


AESGP Page 20 Section 2.5.3

Comments: Proposed change (if any): Release of information as published in SmPC only, all other information should be CCI.

This information is considered CCI, apart from the biotech medicinal products if the same information is declared in the Annex II to the MA.

EUROPABIO Point 2.5.3, Sub-module 2.5, page 20

Changes: Please clarify at page 20 of the draft document that only the name and address of manufacturers of active biological substances (which appear in the SPC) can be released, but not more detailed information.

See above. For biotech products information on name and address of the manufacturer of the active biological substances are not in the SPC but in Annex II to MA. This information will also be released from the application form.

EFPIA Page 20, sub-module 1.2, section 2.5.3

Comment: Although we recognize that the manufacturers of biological drug substances are currently required to be declared in Annex II of the Commission Decision, we do not believe that disclosing this information is necessary for the protection of Public Health, as is claimed in the draft guidance document. The manufacturer must have GMP certification and this is the way that Public Health is protected. The information to be released from section 2.5.3 should be identical to that made available in Annex II of the Decision.

Not agreed. See above and text in final guidance


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Proposed change (if any): “Exception: the manufacturers of biological substances are declared in Annex II of the Commission DecisionSPC in addition to the Manufacturer Responsible for Batch Release. After the marketing authorisation or a variation, both the informations should be published as an abstract on the Official Journal as their public disclosure is necessary for the protection of public health.”

EGA Clinical Trials • 2.5.4

Contract companies used for clinical trials

• Sub-module

1.9

• Sub-module 2.5

• Sub-module 2.7

• Sub-module 5.3

In principle, information disclosed about BE/BA and other clinical studies shall not exceed that available in the EudraCT. This means that the name of CROs involved in studies, equally as it is proposed for study analytical and clinical centers, shall not be disclosed. In case of the sponsor being different to the MAH/applicant, disclosure of the sponsor shall be on a CBC basis (after agreement with MAH).



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AMGEN LTD Module 1 – section 2.5.3 Manufacturer(s) of the active substance(s) and site(s) of manufacture Page 20

Comments: The text is ambiguous in the exception of manufacturers of biological substances (natural biological products vs recombinant biotechnology derived products). Only the name and address of manufacturers of active biological substances appear in the SPC, not more detailed information. Proposed change (if any): Clarify the text to ensure that this information is considered to be commercially confidential for recombinant biotechnology derived products. Consider adding “name and address of the” before “manufacturers” and “active” before “biological substances”.

For biotech products it’s only the information in the SPC that can be released, i.e. name and address. Any other information in point 2.5.3 is CCI, also for biotech products.

PFIZER INC Section 2.6.1, page 22

Comment: The grade of the API/excipient, and the purpose of an excipient should be CCI, because disclosure of this kind of information can enable competitors to recreate, by deduction, the manufacturing process of the applicant.

Proposed change not accepted. The grade of the API or excipient should in general not be mentioned at this point in the application form, neither should the purpose of the excipient. If the grade is relevant, it will be mentioned in the SPC and then it can also be released.

HAI EUROPE and MiEF

Page 22

2.5.4 - Information about the study clinical centre and the study analytical centre should be publicly released as particular centres may have affiliations with industry that could create conflicts of interest. 2.6 – The full qualitative and quantitative composition of a medicine must be publicly available, on public health grounds.

Refer to principle 4 The qualitative composition and the quantitative composition of the active ingredient are public information


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3. Scientific Advice (Page 23)

AESGP Page 23

Section 3 Comments: The contents of scientific advice and the information provided are sensitive data and disclose the company's ongoing or future development projects. Therefore, the extent of information made available requires careful consideration and input from the applicant/MAH. Proposed change (if any): please insert: “note: this information is subject to prior verification by the applicant/MAH”


EUROPABIO Module 3, page 23 Point 14

Changes: Please amend the draft document at pages 23 and 28 to clarify that only the information that scientific advice(s) were given by the CHMP for the product concerned and the dates thereof can be released. The scientific advice itself and details about any scientific advice given by the CHMP or by national competent authorities should be considered CCI.

Refer to principle 14.

PFIZER INC Part 3 Scientific Advice, page 23

Comment: Scientific advice sought in the course of drug development is considered to be CCI, since the originator’s competitive and economic position could be seriously undermined by competitors making use of this information in developing their own competing

This part of the application form is only a tick box. The actual scientific advice is in annex 5.14. Refer to principle 14


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medicinal products. Any CCI has to remain so. It is stated that “detailed information” is not contained in this section, without further explanation. Therefore clarity as to what exactly would be released here is needed In general, scientific advice given for any compound, indication or new formulation etc, that is still under development, should not be released (see further below, comments on part 14,page 28). Proposed change (if any): Explanation of the “detailed information” which is not covered.

GE HEALTHCARE Page 23, Sub-Module 1.2.3

Scientific Advice We propose CBC – copies of scientific advice received are to be included and which may contain both CCI and PPD.


4. Other Marketing Authorisation Applications (Page 24)

AESGP Page 24

Section 4.1.1 Comments: What is meant by "... "pending" applications are already finalised in the other MSs..." ?

If the pending applications are finalised and information thereby publicly available, then the information will no longer be CCI and can therefore be released.

HAI EUROPE and MiEF

Page 24

4.1.1 - In general once an application is filed for a new drug in any Member State or with the EMA the names of the product and the Member State(s) should be publicly

Refer to HMA/EMA recommendations on transparency ref. EMA/484118/2010


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disclosed to allow for public participation/scrutiny in the approval process.

DAIICHI SANKYO Section 4.1.1 (page 24/44)

Comment: The status of pending applications in other member states (even if only done when approval is given) changes frequently so the information will probably never be actual. We question the value of this information.

Comments noted.

EPHA

Point 4.1.3 Under point 4.1.3 the guidelines produced by the HMA and EMA if one European Member State refuses, suspends or withdraws the Marketing Authorisation for a product this information is not relayed to other Member States or the EMA. This is not an acceptable situation as it risks guarding secret information which could have a clear detrimental impact on public health. If one competent authority has grave enough concerns about a medicine as to take such measures, this should be a concern for all Member State competent authorities and the reasons for the action should be presented so that other member states can take their own decisions. This point was underlined by Mr Guido Rasi, Executive Director General-Designate of the EMA at his Parliamentary Hearing on 13 July 2011. It is also in line with the early warning ‘drug alert’ system introduced by the WHO following the thalidomide catastrophe in european public health alliance a.i.s.b.l. 49-51 rue de Trèves – Box 6 1040

According to art. 23 of directive 2001/83/EC the MAH is obliged to forthwith inform the competent authority of any prohibition or restriction imposed by the competent authorities of any country in which the medicinal product is marketed or of any other new information which might influence the evaluation of the benefits and risks of the medicinal product concerned. Likewise if a competent authority as a result of pharmacovigilance data considers that the MA should be suspended, revoked or varied, it shall forthwith inform the EMA, the other MS and the MAH, cf. art. 107 of the directive.


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Brussels, Belgium - Tel +32 2 230 3056 Fax +32 2 233 3880 E-mail : [email protected] Web-site : www.epha.org 1961. If one country suspected or found risks with a medicine it calls and informs the WHO, which in turn sends information to other drug regulatory agencies.

DAIICHI SANKYO Section 4.1.3 (page 24/44)

Comment: The status of refused/suspended/revoked applications in other member states may changes over time so the information will probably never be actual. We question the value of this information.

Comments noted.

PFIZER INC Part 4.2 – 4.3, Page 24

Comment: The MAH should be consulted in addition

to the MS, consistent with the changes proposed in

the General Comments section, and section 2 above.

Proposed change (if any): ‘… the MS and the MAH should be consulted.’


AMGEN LTD section 4.1.1 Page 24

Proposed change (if any): Consider this section as CCI.

Proposed change not accepted This information can be released if the “pending” MA applications are already finalised in the other EEA Member

http://www.epha.org/


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State(s) (MS). Therefore, there is a need to consult the MS in question and section is indicated as CBC. NO change in the draft Guidance

AMGEN LTD Module 1 Section 4 Other Marketing Authorisation Applications –

Comments: This information is considered to be CCI until such a time when the other MA is granted and when the information is in the public domain or publically available.

The draft Guidance outlines in which cases information can be regarded as “CBC” or “Can be released”. NO Change in the draft Guidance.

AMGEN LTD Module 1 Section 4 Other Marketing Authorisation Applications Section 4.4 Page 24

Comments: Information about ongoing applications outside the EEA (including dates of filing) should be considered CCI. Proposed change (if any): Consider this section as CCI.

Proposed change not accepted. The classification CBC in the Guidance is satisfactorily reflected.

5. Annexed Documents (Pages 25- 29)

AESGP Page 25 Section 5

Comments: It remains unclear why these data (e.g. proof of payment or informed consent letter) need to be disclosed at the request of third parties. For further



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items please also see our comment for Sections 2.4.2-2.4.5 (page 13)

HAI EUROPE and MiEF

Page 25

5 - The CV of the qualified person for pharmacovigilance should be publicly available so that the public and professionals can be assured that this person has the necessary training and independence to carry out the job.


PFIZER INC Section 5.4, page 25

Comment: It should also be clarified that PPD should not be disclosed, such as the signatures of individuals.


DAIICHI SANKYO Annex 5.4 (page 25/44) (see also page 13)

Comment: Persons/companies authorized for communication of behalf of the applicant of MAH - These are personal data and should be set to PPD (same as for the Qualified person in the EEA for Pharmacovigilance in section 2.4.4 page 13) and/or, in case of using a CRO, can reveal industrial secrecy and are should therefore be set to CCI.

Refer to principle 5 and 6

EFPIA Page 25, point 4

Comment: The letter of authorization for communication on behalf of the applicant/MAH will need the names and signatures of individuals redacted (PPD). Proposed change (if any):


AESGP Page 28 Annex 14

Comments: The contents of a Scientific Advice by CHMP or any member state is sensitive data, regardless of whether

Refer to principle 14 See text in final guidance


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it is related to the indication approved or not. See also our comment above

AMGEN LTD Module 1 Section 5 Annexed documents 14 Scientific Advice given by CHMP and/or by member states Page 28 See also page 23

Comments: In our view, only the information that scientific advice(s) were given by the CHMP for the medicinal product concerned, the dates thereof and the reference of the advice(s) can be released; this is in essence the information listed at point 3.1 of Module 1. The copy of the scientific advice itself (Annex 5.14), even if it relates to the authorised indications, and details about any scientific advice given by the CHMP or by MSs should be considered CCI. Due account should also be taken to the need not to undermine the EMA decision-making process. For instance, there may be differences or inconsistencies between the scientific advice(s) and the final CHMP opinion. Proposed change (if any): Consider this section as CCI or breakdown section further to allow categorisation for CCI and Can be released etc. Replace the example provided (text starting by “eg if the procedure is finalized ... then the advice can be disclosed”) and replace by another one, which takes the above considerations into account. Ensure the any scientific advice provided regarding unauthorised indication is categorised as CCI. Note that we are assuming that the listing in the category CBC implies that the person concerned will always be consulted in advance of any release of



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relevant documents and offered the possibility to redact them. (see also our general comment 2 above)

EUROPABIO Module 5, page 28

Changes: Please amend the draft document at pages 23 and 28 to clarify that only the information that scientific advice(s) were given by the CHMP for the product concerned and the dates thereof can be released. The scientific advice itself and details about any scientific advice given by the CHMP or by national competent authorities should be considered CCI.


EFPIA Page 28, point 14 (Scientific advice)

Comment: This section is marked as “CBC”. This is a real concern because Scientific Advice often contains key CCI (especially when requested at early stage). For example, Scientific Advice often covers several indications, and subsequently at the time of initial authorisation one indication may be approved, and the others not. Also, Scientific Advice often covers several product formulations different to the one approved, and their disclosure may reveal critical company R&D strategies. Scientific Advice may also contain technical background information and give insights to development or testing strategies (even in the case of clinical SA) which is CCI. It is unclear how EMA will manage the publication of information on Scientific Advice (SA) without risking the inadvertent disclosure of CCI. We believe that



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information on Scientific Advice should be considered as likely to be CCI and therefore that the MAH should systematically be consulted prior to publication of a SA (or part of a SA). Proposed change (if any): Need to add: “However often contains CCI. Information considered to be CCI by the MAH will be redacted”

PFIZER INC Section 14, page 28

Comment: See comments above on part 3 Scientific

Advice, page 23.

Proposed change (if any): ‘…“Depends on the content of the scientific advice given (e.g. if the procedure is finalised and if the advice relates to the authorised indications, then the advice could be disclosed). In general, scientific advice given in relation to an application (indication, new formulation etc) still under development would not be released.”


HAI EUROPE and MiEF

Page 28

14 – The Scientific advice given by the CHMP and/or Member States should always be publicly available to enable public scrutiny.


DAIICHI SANKYO Annex 17 (page 28/44)

Comment: The mock-ups used for initial submission might be

Not agreed


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modified during the procedure. Outdated mock-ups should not be disclosed.

AMGEN LTD Module 1 Sub-Module 1.2 point 19 list of names page 29

Comments: Invented names are generally protected by trade mark rights Proposed change (if any): delete (likely this is a typo) “not” in the sentence “Invented names are not under trade mark register protection”


Sub-module 1.3 Product Information (Page 29-30)

PFIZER INC Section 1.3.3.

Specimen, page 30

Comment: Please clarify what would be subject to release here. Proposed change (if any):



Pg 30, sub-module 1.3, 2.3 and 4, product information

Comment: It is not clear why mock-ups should be subject to disclosure when final pack is available. Companies may introduce innovative packaging to prevent fraud and counterfeiting that could be disclosed by publishing mock-ups. Readability testing is complex and we are not sure why this is subject to disclosure. Proposed change (if any): Recommend 1.3.2 to 1.3.4 are not released.


EGA •1.3.4 Readability

In any case, the name of company performing the readability test shall not be disclosed.

Not agreed See text in final guidance


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testing EFPIA Page 30/44,

Sub-module 1.3; 1.3.2. Mock –up

Comment: Companies may introduce innovative packaging to prevent fraud and counterfeiting that could be disclosed by publishing mock-ups and therefore should be considered CCI. Proposed change (if any): Recommend 1.3.2 is “not released” if it contains information that aim to prevent counterfeiting.


EUROPABIO Point 1.3.2, Sub-module 1.3, page 30

Changes: Please amend the draft document at page 30 -1.3.2 mock-up - to classify this entire section as CBC. Comments: We believe that the disclosure of the mock-up can undermine the protection of the interests of biopharmaceutical companies (e.g. by disclosing innovative packaging or safety features required to prevent fraud and counterfeiting).

Not agreed

EPHA Point 1.3.4 EPHA finds it unfortunate that commercial agreements between different companies, and the risk of the release of information could disclose such commercial agreements, will prevent the release of information. For example point 1.3.4 on page 30 of the consultation document states that justification for



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failure to submit the test results of the readability test cannot be released if the test sponsor and MHA do not belong to the same group of companies as it could disclose a commercial agreement between these companies. It is in the public interest that the reasons for not submitting the readability test be publically available.

HAI EUROPE and MiEF

Page 30

1.3.4 - The justification for the failure to submit the tests results of the readability test should be accessible. There is no public health rationale in protecting commercial interests by withholding this information.


HAI EUROPE and MiEF

Page 31

1.3.5 - Information about the experts – The CV of the experts should be publicly available so that the public and professionals can be assured that the experts have the necessary training and independence to carry out their tasks.


EFPIA Page 30/44 1.3.5

Comment: Suggest considering replacement of “SPC” with “SmPC” in the table (and wherever possible in the NTA) Proposed change (if any): Replace “SPC” with “SmPC”

Not agreed

Sub-module 1.4. and sub-module 1.5 (Page 31)


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EFPIA Page 31/44, sub-module 1.4 Information about the Experts

Comment: We agree that the information about the experts should be classified as PPD. The table, however, refers to point 3 on page 6/44 of the draft guidance document, which suggests that this information (“information on technical or professional qualifications”) could be released. Point 3 should be revised, as proposed in the comments above. Proposed change (if any):

See text in final guidance Refer to principles 5A and 6

PFIZER INC Sub-module 1.4., page 31

Comment: We support this section being classified as PPD - names and CVs of experts should be protected. Proposed change (if any):


PSLG/DMLG (IQ) Submodule 1.4.2

Comment: Submodule 1.4.2 contains personal information of the nonclinical expert including their CV (location of employment, qualifications, experience) and signature. Proposed change (if any): Classify this section as PPD—do not release

Not agreed See text in final guidance Refer to principles 5 and 6

AESGP Page 31 Sub-Module 1.4

Comments: See our comment for Sections 2.4.2-2.4.5 (page 13)

See above.

AESGP Page 31 Comments: Comment not accepted.


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Sub-Module 1.5

The information should routinely not be disclosed as this pertains to the company’s regulatory strategy

No Change to the draft Guidance.

Sub-modules 1.6 and 1.7 (Pages 31-32)

EUROPABIO Sub-module

1.6, page 31 Changes: Please amend the draft document at page 31, sub-module 1.6 - Environmental Risk Assessment (ERA) to classify this entire section as CBC. We notably believe that (i) the name of the expert(s) doing the ERA should be redacted (notably to protect their identity from groups who may be opposed to animal testing), (ii) the detailed ERA may contain CCI (eg internal production or marketing forecast data), (iii) the full reports for the required laboratory testing should be considered CCI to compensate the costs incurred by sponsors, and (iv) the details of the study reports should be redacted from the references section of the ERA. Comments: We believe that the release of such information/document may undermine the protection of the interests and competitive position of our members. Changes: For GMO-related medicinal products, the ERA section is critical and contains confidential information by nature. Moreover, since a) the GMO-related ERA is



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assessed by expert(s) who sit(s) neither with EMA, nor with HMA, nor w/ NCAs and b) the EMA needs to proactively redact confidential information from the EPAR before it release (3), we recommend that the EMA-HMA consult the relevant parties as explained in the general comments.


Pg 31, sub-module 1.6

Comment: Industry supports greater transparency of information relating to the environmental risk assessment (ERA). However some ERAs may contain CCI, for example detailed information on identity of human metabolites and detailed epidemiological data which may be considered commercially sensitive. For new applications this information could be included in a confidential Appendix to the ERA. However, for existing ERA’s for licensed products some CBC redaction would be necessary to remove such information. Similarly, study reports may contain personnel data and potentially some CCI. If study reports are to be made available how will IP be protected? It should not be possible for a competitor to use these reports for their own MAA without permission from the originator.

See above (on ERA) Refer to principle 15

3 ENVIRONMENTAL RISK ASSESSMENTS FOR MEDICINAL PRODUCTS CONTAINING, OR CONSISTING OF, GENETICALLY MODIFIED ORGANISMS (GMOs) (Module 1.6.2) [EMEA/CHMP/BWP/135148/2004 ] (p8/17) “By day 300,The EMEA finalises the European Public Assessment Report (EPAR), including an account of the M1.6 assessment (after deletion of any confidential information).” http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003806.pdf

http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003806.pdf


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Scientific advice, rapporteur questions and applicant responses may also contain information deemed to be CCI which should not be released. Proposed change (if any): Change criteria to ‘Can be Released’ (except for and information included that is deemed confidential in other parts of the dossier - this information may be included in a confidential appendix). ASTRAZENECA and MedImmune

EFPIA Page 31/44, sub-module 1.6 Environmental risk assessment

Comment: We agree that the Environmental Risk Assessment document itself can be released (with appropriate PPD/CCI4 redaction), but that the associated study reports should be classified as CCI and should not be released (for the same reasons discussed below in relation to Non-clinical study reports). An example of CCI in an environmental risk assessment report (ERA) is provided in a foot note below. It should also be noted that ERAs often contain details about the sources and suppliers of some components of the products, confidential marketing data aimed at calculating the predicted environmental concentration, etc. Proposed change (if any):

See above (on ERA) Refer to principle 15

4 Detailed information on the identity of human metabolites for example may be CCI ; for new applications this information could be included in a confidential appendix to the ERA ; however for existing ERA for already authorised products some CBC redaction would be necessary to remove such information


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Environmental risk assessment report can be released after appropriate redaction of CCI/PPD. Associated study reports are CCI

Sub-module 1.8 Information relating to Pharmacovigilance (Page 32)

AESGP Page 32

Sub-Module 1.8

Comments: The names of the respective persons/companies listed should not be disclosed as these data should be covered by data privacy protection (e.g. CV of Qualified Person for Pharmacovigilance). Review of the complete risk management plan (section 1.8.2) will facilitate competition ;this may again lead to reduced efforts in developing new drugs. See comment for Module 1.2 Annex 5.7


EGA •Sub-module 1.8 pharmacovigilance system

Detailed data on the company’s pharmacovigilance system shall be treated as confidential not only in the case of third party involvement but also within the same company/ group as the data are related to the company’s internal organisation.


EFPIA Page 32/44 Sub-module 1.8 Item 1.8.1 Pharmacovigilance system

Comment: It is currently unclear what information will be included in a MA dossier in relation to the pharmacovigilance system as defined in the new pharmacovigilance legislation. However it is expected to primarily contain information on the personnel involved in pharmacovigilance activities and on



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organisational matters i.e. information that is considered to be PPD. Furthermore, during the transition period to the new requirements under Regulation (EU) 1235/2010 and Directive 2010/84/EU, where a detailed description of pharmacovigilance system (DDPS) is still in place this should be considered PPD as this document typically contains the contact details and CV of the QPPV and other pharmacovigilance personnel as well as significant detail regarding the organisational arrangements relation to pharmacovigilance. Proposed change (if any): Suggest any details provided under this sub-module be categorised PPD.

PFIZER INC Sub-module 1.8.1.,page 32

Comment: See comments relating to section 2.2, page 6 above.


PFIZER INC Section 2.2., page 6 / sub-module 1.8. page 32

Comment: In the first paragraph, it is stated that information related to i.e. risk management plans is not per se considered to be commercially confidential, but the PV systems may be considered confidential. Further, on page 32 it is stated the PV system is CBC, whereas the risk management system can be released. We would note in this respect that the current

Refer to principles 5 and 7 See text in final guidance


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detailed description of the pharmacovigilance system (DDPS) contains manufacturer’s organization details and technology details, as well as general pharmacovigilance and product-specific contractual arrangements, i.e. information that is considered CCI. Moreover, requested details on the EUQPPV, including personal details and CV, are PPD. It is unclear which parts, if any, of the DDPS could be considered CBC. In general, the DDPS should be classified as CCI/PPD. As regards the new pharmacovigilance legislation, the information included in the MA dossier is expected to primarily contain information on the personnel involved in pharmacovigilance activities and on organisational matters i.e. information that is considered to be PPD and CCI. Proposed change (if any):

HAI EUROPE and MiEF

Page 32

1.8.1 – Information on the Pharmacovigilance system should always be made available.



Pg 32, sub-module 1.8, Pharmacovigilance system

Comment: Releasing the Risk Management System in its entirety places sensitive information in the public domain and currently industry does not know the requirements under the new EU pharmacovigilance System and therefore cannot at this stage agree that the system master file can be disclosed. It will



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contain specific information that may require redaction. This is also inconsistent with Pg 6, section 2.2 where the Risk Management System is considered confidential. Proposed change (if any): This should be CCI and PPD until guidance is finalised. We recommend it is still retained within the Eudravigilance system, as the information is routinely updated the information included in the original application will be not maintained.

EGA •1.8.2 risk management system

Document shall be redacted before the release by deleted data which are related to the company’s internal organisation or any other business cooperation


EFPIA Page 32/44 Sub-Module 1.8, item 1.8.2 Risk-management system

Comment: The Risk Management Plan defined in the new pharmacovigilance legislation refers to the Risk management system. The new pharmacovigilance legislation (Regulation (EU) 1235/2010 Article 26 & Directive 2010/84/EU Article 106) indicates that each Member State and the European Medicines Agency shall set up and maintain medicines web-portals, through which they shall make publicly available summaries of risk management plans (RMPs) for medicinal products authorised in the European Union.



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It is apparent that the intention of these RMP summaries is to improve transparency and communications. Therefore, it is reasonable to assume that they should be written in such a way as to be understood by members of the general public. Furthermore this summary will relate to the final/authorised RMP and not to the initial RMP. Therefore to combine the objective of enhanced transparency and good communication practice it would seem appropriate to make public this summary alongside the more detailed information in the dossier after deletion of any PPD or CCI. This will also ensure that there is consistency in the information released on the same topic. Proposed change (if any): See above suggestion

EUROPABIO Sub-module 1.8, Point 1.8.2, page 32

Changes: Please amend the draft document at page 32 - Sub-Module 1.8, item 1.8.2 - Risk Management Plan (RMP) - to classify this entire section as PPD and CBC. Comments: We notably believe that the RMP may contain personal data (e.g. individual adverse experience case report data or details about personnel involved in pharmacovigilance and risk management) and CCI (eg discussion of joint ventures and other contractual



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relationships with other companies for pharmacovigilance/risk management purposes or forecasts and market research data or copyrights on literature articles and other resources), which shall thus not be released.

Sub- module 1.9 Information related to clinical trials (Page 33)

EFPIA Page 33/44,

sub- module 1.9 Information related to clinical trials

Comment: We agree with the classification proposed for this sub-module. Consistent with previous comments it should also be clarified that the name of the person signing the statement and his/her signature should be considered PPD. Proposed change (if any): See above suggestion

Refer to principles 4, 5 and 6. See text in final guidance

HAI EUROPE and MiEF

Page 33

Sub-module 1.9 - There is no reason why the name of the API manufacturer should be hidden. It should be able to be disclosed as well as the rest of the information about clinical trials performed outside of the EC.

See principles 3.1.2 and 3.4 in the introduction to the final guidance

Sub-module 1.10 Information related to Paediatric (Page 34)


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Pg 34, sub-module 1.10

Comment: It’s unclear from the document whether the PIP elements are considered confidential until the overall MAA is completed vs completion of the PIP process. The request for transparency of the PIP partial compliance check is duplicative of the request for final PIP compliance report and should only be released after granting of an MAA as it may contain confidential pre-clinical, pharmaceutical development, clinical information or other proprietary information . Publication of PIP results prior to MAA assessment provides for development data release ahead of MAA which is company confidential. Proposed change (if any): Clarify whether compliance check refers to ‘partial compliance check’ at time of MAA or ‘full compliance check’ at time of PIP completion. Change classification of PIP compliance report to CCI.


EFPIA Page 34/44, sub-module 1.10 Information related to Paediatric

Comment: The content of the final bullet relating to the ‘Overview table of the PIP results’ is of concern. Any information which may relate to a possible future application, and might therefore reveal a company’s development strategy, should be considered CCI. Such information should therefore be redacted. Proposed change (if any):



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“CBC Documents published at the EMA’s website can be disclosed. Other documents should be analysed in a cases by case basis, in order to decide if they can be disclosed or not. If the procedure is finalised and if it is related to the same indications and if there is no CCI, then “can be released”.


Comment: It should be highlighted in this section that the potential for harm to the data owner’s economic interests or competitive position could be undermined through disclosure. With reference to the last bullet and as a general principle, any results for a not yet approved product (assessment ongoing or data still to be submitted), and any data that are expected to be part of future applications, as well as the company’s development strategy, should be considered CCI. The disclosure of dossiers for approved PIPs provide a clear opportunity for economic and competitive advantage for competitors, to the corresponding disadvantage of the applicant, in providing an insight into the development strategy (formulations indications, rationales etc) for the product in question, that could not lawfully be obtained by other means.

Not agreed Refer to principle 3

AESGP Page 34 Sub-Module

Comments: See comments for Section 3 ‘scientific advice’, which



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1.10 apply also for the PIP documentation.

Module 2. Summary/Overview (Pages 35-37)


Pg 35, Module 2

Comment: Signature of applicants can be released? This should remain classified as ‘confidential information’. Proposed change (if any): Revise wording accordingly throughout this section.


HAI EUROPE and MiEF

Page 35

It is not clear why the summary of sub-module 2.1 is not to be fully accessible. That should not be the case.



Changes: Please amend the draft document at page 35 - to classify Sub-Module 2.2 - introduction, as CBC, since such introduction may contain CCI.

The general introduction to the medicinal product should include its pharmacological class, mode of action and the proposed clinical use. In general the introduction should not exceed one page. Such information cannot be considered confidential, especially after granting of a marketing authorisation.

EFPIA Page 35/44, sub-module 2.3

Comment: We agree with the proposed classifications of CBC and CCI for the information in the Quality Overall Summary that can be disclosed.

Noted


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ROCHE Sub-Module

2.3 Comment: Statement should be added in the right column Proposed change (if any): Please add: “For new biologic active substances belonging to the class of recombinant proteins/ polypeptides, their derivatives, or products of which they are components (e.g. conjugates), information on the amino acid sequence has to be treated as confidential”.


PFIZER INC Sub-module

2.3., page 35

Comment: The CV and name of the relevant expert is PPD and therefore should not be released. As stated above, the purpose for an excipient should be CCI, and the text should be clear about this. The comments in this section would benefit from further clarity since they are not well written at present.

Refer to principle 5 Agreed

EUROPABIO Sub-modules 2.4 and 2.5, page 36

Changes: Please amend the draft document so that both sections are marked CBC. Comments: This will provide flexibility while protecting the interests of our members.

Refer to principles 17 and 18 See text in final guidance


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GE HEALTHCARE Page 36, Sub-Modules 2.4 and 2.6

Information in this section is likely to be CCI. There could be novel assays or technology contained in these sections. In addition, details of the preclinical strategy would be CCI.


PFIZER INC Section 2.4 and 2.6, page 36

Comment: The information in both sub-modules 2.4 and 2.6 can be highly sensitive in view of animal protection issues (as acknowledged in the text only in relation to sub-module 2.6). In both such cases, this sensitive information should be regarded as CCI. Proposed change (if any):


EUROPABIO Module 2, Sub-module 2.6, page 36

Changes: Please amend the draft document at page 36 -Module 3 Sub-Module 2.6 - to classify this entire section as CBC. Comments: We believe that the disclosure of information or documents relating to non-clinical issues, even in the form of summaries, can undermine the protection of the interests of our members, including intellectual property. This is especially the case for SMEs. It could also present a threat from animal activists.

Refer to principles 17 and 5A

AMGEN LTD Module 3 Sub-Module 2.6 page 36

Comments: The release/disclosure of information or documents relating to non-clinical issues, even in the form of summaries, can seriously undermine the protection of the interests of a natural or legal



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person, including intellectual property. Such release/disclosure may lead to a situation where the person concerned is not able to protect an invention by way of patents. Also, the example provided, namely “animal protection issues”, whilst relevant, seems slightly anecdotal in comparison to the potential negative impact of an inappropriate disclosure of such information/documents by the EMA. Proposed change (if any): Consider this section as CBC and to provide other examples or to delete the example provided. Note that we are assuming that the listing in the category CBC implies that the person concerned will always be consulted in advance and offered the possibility to redact the relevant document(s).

PSLG/DMLG (IQ) Submodule 2.62.6.1, 2.6.3, 2.6.4, 2.6.6 Nonclinical Written Summaries

Comment: For Submodule 2.6 Nonclinical Written Summaries, for the most part these sections are summaries of study results, however, details of study design and methods are generally included. The design and methods can include techniques and technologies that are commercially advantageous to the Market Authorization Holder and will be applied in subsequent unrelated drug development programs. Disclosure of these technologies/techniques that result from extensive investment by the company



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would devalue the investment and discourage further similar investment and innovation. Proposed change (if any): Classify these sections as CCI—do NOT release.

PSLG/DMLG (IQ) Submodule 2.6 2.6.2, 2.6.4, 2.6.5, 2.6.7 Nonclinical Tabular Summaries

Comment: Submodule 2.6, for the most part is tabular summaries of study results, however, it can include the names or external partner organizations (CROs and academic institutions) and details of proprietary methods. These contractual arrangements or methods (techniques and technologies) are commercially advantageous to the Market Authorization Holder and will be applied more broadly to other unrelated drug development programs. Disclosure of this information, which is the result of extensive investment by the company, would devalue the investment and discourage further similar investment and innovation. Proposed change (if any): Classify these sections as CCI-do NOT release.

Refer also to principles 4 and 17

AMGEN LTD Module 3 Sub-Module 2.7 page 37

Comments: the release/disclosure of information or documents relating to clinical issues, even in the form of summaries, can seriously undermine the protection of the interests of a natural or legal person, including intellectual property. Such release/disclosure may



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lead to a situation where the person concerned is not able to protect an invention by way of patents as a result of such /release/disclosure (eg because it no longer meets the statutory patentability criteria of novelty). Proposed change (if any): Consider this section as CBC Note that we are assuming that the listing in the category CBC implies that the MAH will always be consulted in advance and offered the possibility to redact the relevant document(s).

DAIICHI SANKYO SUB-MODULE 2.4, 2.5, 2.6 and 2.7 (Page 36-37

Comment: These sub-modules should be treated as “CBC (Case-by-Case analysis) since the applicants are not able to prepare and submit manuscripts from disclosed data. If the MA dossier includes unpublished data, these sections or reports should be protected in terms of protecting intellectual property of the applicant. Proposed change (if any): change “CAN BE RELEASED” to “CBC”



Comment: Patient narrative numbers would be in ‘Sub-module 2.7.4. Summary of clinical safety’, and should be considered sensitive information (PPD), and so we disagree that they can always be released with no redaction needed. We propose that this section is

Refer to principle 5. See text in final guidance


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CBC.

Proposed change (if any): 2.7.4 Summary of clinical safety Replace “can be released” with “CBC because may contain PPD”


Comment: In relation to the ‘Sub-module 2.7.5. References’, we would point out that actual references are not included in this section (just the list of references). The references themselves are contained in Sub-module 5.4.

Proposed change (if any): Replace “References” with “List of references” or “Reference list” or “Literature references”


ROCHE Sub-Module 2.7 - 2.7.1.

Summary of biopharmaceutics and associated analytical methods Comment: This section can contain information on proprietary bioanalytical methods (like the CSR in Section 5.3) Proposed change (if any): Label this section as Case-by-Case



Changes: Please amend the draft document at page 37 - Sub-Module 2.7 - to classify this entire section as CBC.



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Comments: Whilst we appreciated that clinical trial summaries and references may be disclosed in registries, we believe that the disclosure of information or documents relating to clinical issues, even in the form of summaries, can undermine the protection of the interests of our members, including intellectual property (eg copyrights of natural persons on articles for publication in scientific journals). This is especially the case for SMEs.

ROCHE Sub-Module 2.7 - 2.7.2.

Summary of clinical pharmacology studies Comment: This section can contain information on proprietary bioanalytical methods (like the CSR in Section 5.3) Proposed change (if any): Label this section as Case-by-Case



Comment: The purpose and rationale for the disclosure of the Table of Contents (TOC) for Module 3 is not clear. The guidance states that “generally the TOC can be disclosed, but if the contents are detailed there might be CCI”. We would anticipate that what could be considered a “detailed TOC” might be open to interpretation, leading to variable and potentially inappropriate application of the CCI rules. We therefore recommend that the TOC for Module 3 be

Agreed CBC


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classified as CCI.

Proposed change (if any): Replace “CBC” with “CCI”

Module 3. Quality (Pages 37-40) PFIZER INC 22 Sub-module

3.1., page 37

Comment: It should be considered that since the structure of the table of contents may reveal formulation and manufacturing process details, this should be classified as CCI and should not be disclosed.

Agreed CBC


Pg 38 & 39, sub-module 3.2

Comment: CCI applying to the detail of analytical methods on pgs 38 and 39 should also apply to any in-vitro methodology described elsewhere, e.g. sub-section 2.7.1 ‘Summary of biopharmaceutics and associated analytical methods’. Proposed change (if any): CCI criteria to be applied to sub-section 2.7.1, and any other section referencing in-vitro methodology.

Not agreed. See principle 3.1.2 in the introduction to the final guidance

DAIICHI SANKYO

SUB MODULE 3.2 3.2.S.1 and 3.2.P.1 (Page 38-39)

Comment: Since nomenclature, structure and general properties of the active substance, and qualitative composition on the medicinal product can be released based on sub-module 2.3, the whole information in Module 3 may be CCI. This would help reducing additional masking procedure for Module 3.

Not agreed. See principles 3.1.2 and 3.4 in the introduction to the final guidance


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Proposed change (if any): Change complete Module 3 to CCI

EFPIA Page 38/44, sub-module 3.2.S – Active substance

Comment: Other than the comment below in relation to ‘Section 3.2.S.1.3 – General Properties’, we agree with the classification for disclosure/non-disclosure of information relating to active substance in sub-module 3.2. It is important that this classification is carried forward into the final guideline. Proposed change (if any):

Agreed

ROCHE Sub-Module 3.2.S.1

General information Comment: Statement should be added in the right column Proposed change (if any): Please add: “For new biologic active substances belonging to the class of recombinant proteins/ polypeptides, their derivatives, or products of which they are components (e.g. conjugates), information on the amino acid sequence has to be treated as confidential”.


EFPIA Page 38/44, sub-module 3.2.S;Section 3.2.S.1.3 – General Properties

Comment: We believe that this section may contain detailed information on the product which is considered CCI and therefore should not be released (i.e. aggregation, quaternary structure, etc.). This section should therefore be labelled CBC (or CCI). Proposed change (if any): Replace “can be released” with “CBC (or CCI)”

Partially agreed See text in final guidance

PFIZER INC Sub-module 3.2.S.1.3., page 38

Comment: We have experience of requests for discussion on polymorphism in section 3.2.S.1.3. If we are to continue to provide proprietary physical information in this section, the relevant subsections

Not agreed Section 3.2.S.1.3 contains the general properties of the active


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should be CCI and should not be disclosed. Proposed change (if any):

substance. We do not regard this information as CCI.

EFPIA Pages 39-40/44, sub-module 3.2.P-Drug Product

Comment: We are in general agreement with the classification for the disclosure/non-disclosure of information relating to drug product outlined in this section. We would recommend that rather than stating ‘Partial suppression of information:…’, the guidance should be more specific and state ‘The qualitative composition on the medicinal product can be disclosed; but the quantitative….’ It is important that the overall classification included in this section, incorporating the proposed change, is carried forward into the final guideline. Proposed change (if any): “Partial suppression of information: The qualitative composition on the medicinal product can be disclosed; but the quantitative composition should be regarded as CCI since it reveals industrial secrecy.”


PFIZER INC Sub-module 3.2.P.1., page 39

Comment: As mentioned above, any details of the API and excipients need to be classified as CCI. Only information that is already publicly available from the label and package insert should be disclosed. No details on the process, e.g. solvents used for granulation etc., should be disclosed since this is CCI. The text should be clarified accordingly. Proposed change (if any):

Agreed.

HAI EUROPE and MiEF

Page 39 and 40

The names and amounts (e.g., in parts per million) of any excipients should be released so that people who may be allergic to them will be aware of the

This information is already given in the SPC/ PIL/PAR.


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contents of the medicines that they will be taking.

EFPIA Page 40/44 sub-modules 3.2.A and 3.2.R

Comment: Although not clearly delineated, it is our understanding that documents in these sections would be considered CCI and we would support such a classification. Proposed change (if any): “CCI: this information refers to the manufacturing process of the medicinal product and therefore can reveal industrial secrecy”

This is already the criteria/description for this section.


Changes: Please amend page 40 - Module 3 Sub-Module 3.3 - literature references of the draft document to classify this entire section as CBC. Comments: Whilst it is appreciated that the information in this section is already publically available, we believe that the disclosure of a collection of literature articles, in the context of an MA application, may enable third parties to elude CCI and thus the classification as CBC is appropriate to properly balance such interests. We also consider that EMA should avoid disclosures that may make publications in scientific journals more difficult.

See text in final guidance Refer to principle 13


In addition, the list of references for Module 3 should be considered either CCI or CBC due to the fact that references could provide an insight into the manufacturing process or product that is considered confidential.


PFIZER INC Sub-module Comment: The list of references for Module 3 See text in final guidance


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3.3., Literature References, page 40

should be considered either CCI or at least CBC due to the fact that they could provide competitors with an insight into the manufacturing process/product development, to the economic and competitive disadvantage of the applicant. Proposed changes (if any):


AMGEN LTD Module 3 Sub-Module 3.3 Literature References Page 40

Comments: Although it is acknowledged that the information in this section is already publically available, taken as a collection of literature articles and in the context of an MAA it may be possible to elude CCI. Proposed change (if any): Consider the contents of the literature reference as CCI.


Module 4. Non-clinical study reports (Pages 41- 42)


Pg 41 Sub-module 4.1 and 4.2

Comment: Please refer to separate document on Pre-clinical

No separate document was submitted


Changes: Please amend page 41 - Module 4 Sub-Module 4.2 Study Reports - of the draft document to classify this entire section as CBC.

Not agreed See text in final guidance Refer to principle 17


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Comments: We consider that it is not appropriate for all non-clinical study reports to be released and that it is necessary to remove from such reports any information the disclosure of which may undermine the interest or position of our members. For instance, non-clinical study reports may contain information concerning innovation in the form of techniques, technologies, contracts, collaborations and basic science not previously disclosed and the disclosure of such information could prevent future commercial utilisation by our members.

PSLG/DMLG (IQ) Module 4 Comment: Every toxicology study report, particularly those that are conducted as required by GLP, will contain the names of study personnel and often contain their signatures. Release of this information would link these personnel and their location as specified in the study reports to animal study work and make them vulnerable to the actions of individuals or groups that oppose regulated animal research in pharmaceutical development. In addition, the information contained in the nonclinical study reports identifies the location of study conduct and assay conduct and therefore relationships with specific vendors. The methods sections of reports contain details of technologies and techniques that are proprietary and/or of significant competitive advantage. Release of the information on techniques and technologies, relationships with vendors, and specific personal information would compromise the scientific investment for innovation, relationships with commercial vendors, and information specific to individual scientists.

Not agreed Refer to principles 5 and 6 See text in final guidance Refer to principle 17


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More specifically, • In study reports, PPD (names, titles, and affiliations of study personnel and reviewers and partner organizations) is located on multiple pages throughout the documents, because of regional requirements that principle investigators and other collaborators sign their contributions to the overall study report (e.g. pathologists report, toxicokinetics report). • This section contains technologies and tactics of the overall non-clinical strategy that are viewed as both confidential and proprietary as they confer competitive advantage. For example: In recent years individuals and invested substantial resources to de-risk their candidate drug nominations and reduce attrition post 1st GLP dose for unanticipated non-clinical adverse findings. A successful non-clinical de-risking strategy can confer substantial advantage and is thus CCI. • Details of individual study designs are viewed as confidential by some companies because they have invested to develop and refine in these designs and consider them proprietary (e.g. CCI) • Details of study results, including individual animal data, are viewed as both confidential and proprietary and thus as CCI. • Details of study analyses, including use of proprietary historic incidence/range values, statistical designs are viewed as both confidential and proprietary. Proposed change (if any): Reclassify these sections as PPD and CCI—do NOT release.

PFIZER INC Sub-module Comments: The same comments as above for 2.4 See above.


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4.2, page 41 - 42

and 2.6 (page 36) apply. Proposed change (if any):

EFPIA Pages 41-42/44, Module 4 Nonclinical Study Reports, sub-module 4.2

Comment: We have major concerns over the proposal to release the Non-clinical study reports contained in Sub-module 4.2. Firstly, we are concerned that the release of full Non-clinical study reports (in association with the release of clinical study reports and detailed CMC data), will enhance the ability of non-innovator companies to obtain regulatory approvals outside the EU based on the originator’s data/EU dossier. As discussed above (in particular in relation to page 3/44 of the draft guidance document), such disclosure will undermine the protection of the innovator’s commercial interests. Secondly, Non-clinical study reports often contain multiple pieces of CCI and PPD information which should not be released (i.e. detailed information products under development, Certificates of Analysis, names of individuals involved in the study, e.g. study directors, report authors, principal investigators, etc - see footnote for detailed examples5). To ensure effective redaction of such information at the study report level would be a complex and highly resource intensive process. Thirdly, as mentioned above in relation to point 2.2 of the draft guidance non-clinical reports may contain information on proprietary discovery and the release of such reports may prevent the protection of inventions by patents should such patent protection


5 - Methodology main contain information on proprietary discovery platforms, technologies or collaborations that would damage further commercial utilization if released into the public domain - Early development and pharmacology data often reflects candidate selection criteria which can be considered to be company specific and therefore proprietary, etc


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not have been sought or obtained yet. Consequently we believe that all Non-clinical study reports contained in Sub-module 4.2 should be designated CCI and not released. However, in order to facilitate the overall objective of enhanced transparency, including enhanced transparency for the content of the Non-clinical sections of the dossier, we support the release of the Non-clinical Overview included in Sub-module 2.4 after appropriate redaction of any PPD or CCI. We believe this interpretative overview would provide sufficient detail for interested parties. If HMA/EMA do not concur with this position and think that more detail is required, EFPIA would not object to releasing the text studies summaries and/or the CTD Tables (subject to appropriate redaction) included in sub-module 2.6. The Tabulated Summaries provide detailed information on each study in a highly structured format, and this should facilitate the efficient redaction of CCI and PPD information. Proposed change (if any): The phrase “can be released” should be replaced with “CCI”

Not agreed. See above.

GE HEALTHCARE Page 41, Sub-Module 4.2

We propose CCI and PPD. CCI for the same reasons as in Module 2.4 and 2.6, plus information about CRO’s, facilities and academic collaborators used by the MAH. There will be names and signatures of Study Directors, Study Monitors and Institutions involved in animal studies and these should not be publicly available.

See above. Refer to principles 5 and 6

EGA Non-clinical Trials

The name of partners involved in performing non-clinical studies should not be disclosed.

See above. Refer to principle 5


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• Sub-module 2.4 • Sub-module 2.6 • Sub-module 4.2

DAIICHI SANKYO MODULE 4 NONCLINICAL STUDY REPORTS (Page 41-42)

Comment: For countries where patent protection is not available or not long enough due to long development period for various reasons, third party companies could apply IND/NDA using non-clinical study reports and clinical study reports released by this procedure. These reports are all produced by the originator company with significant investment, and proprietary to the company. The release of such information could discourage the originator companies to develop and commercialize new treatments in countries where such IND/NDA is possible (e.g. China).

See above. Refer to principle 11

AMGEN LTD Module 4 Sub-Module 4.2 Study Reports Page 41

Comments: We consider that it is not appropriate for all non-clinical study reports to be released and that it is important to remove any information that may undermine the interest or position of a natural or legal person, including intellectual property such as patents. Proposed change (if any): Consider this section as CBC. Note that we are assuming that the listing in the category CBC implies that the person concerned will always be consulted in advance and offered the possibility to redact the relevant document(s).


AMGEN LTD Module 4 Sub-Module

Comments: Although it is acknowledged that the information in this section is already publically



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4.3 Literature References Page 42

available, taken as a collection of literature article and in the context of an MAA it may be possible to elude CCI. Proposed change (if any): Consider the contents of the literature reference as CCI.

Module 5. Clinical study reports (Pages 43-44)

Stakeholder Section of the

guidance

Comments from the Stakeholder


Changes: Please amend this section so that only information contained in EudraCT may be automatically released. Other types of information should be classified as CBC.



Changes: Please amend page 43 – Sub-Module 5.3 - Clinical Study Reports - of the draft document to classify this entire section as CBC. Comments: We consider that it is not appropriate for all clinical study reports to be released and that it is necessary to remove from such reports any information the disclosure of which may undermine the interest or position of a natural or legal person, including intellectual property. We firmly believe that such a change in classification (from CAN BE RELEASED to CBC) is necessary to adequately protect the interests of our members, including their intellectual property rights (e.g. medical use patents



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or copyrights on articles for publication in scientific journals). This is especially the case for SMEs.


Pg 43 Sub-module 5.3.1 and 5.3.2

Comment: Detailed information about human metabolites and their evaluation (including methodology) during development is considered company confidential as recognised on pg 22, 2.5.4 of the Guidance. Proposed Change: Should be changed to CBC for all sections of sub-module 5.3.



Pg 43 Sub-module 5.3.1 and 5.3.2

Comment: It is not clear throughout this document how EMA and HMA intend to remove all relevant personal data Proposed Change: See general comments and proposed dialog with industry on solutions.

Refer to principles 5A, 5B and 5C

AMGEN LTD Module 5 Sub-Module 5.3 Clinical Study Reports Page 43

Comments: We consider that it is important to remove any information on contractual arrangements/personal data which may be described in either the Annex’s or the main study report which it is not appropriate to release. The release/disclosure of such reports may lead to a situation where the person concerned is not able to protect an invention by way of patents (eg relating to second/further medical use claims), notably on the ground that such invention no longer meets the statutory patentability criteria of novelty.



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Proposed change (if any): Consider this section as CBC. Note that we are assuming that the listing in the category CBC implies that the person concerned will always be consulted in advance and offered the possibility to redact the relevant study reports.

DAIICHI SANKYO MODULE 5 CLINICAL STUDY REPORTS (Page 43-44)

Comment: For countries where patent protection is not available or not long enough due to long development period for various reasons, third party companies could apply IND/NDA using nonclinical study reports and clinical study reports released by this procedure. These reports are all produced by the originator company with significant investment, and proprietary to the company. The release of such information could discourage the originator companies to develop and commercialize new treatments in countries where such IND/NDA is possible (e.g. China).


DAIICHI SANKYO Sections 4.2 and 5.3 (pages 41, 42 and 43/44)

Comment: All reports can contain personal data relating to investigators (PPD) and/ or methods developed/ owned by sponsor/CRO (CCI) or shows relation to CRO (CCI). This should be aligned for all relevant sections.

Not agreed See text in final guidance. Refer to principles 4 and 5


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Proposed change (if any): PPD for investigators, CCI for methods not publicly available and information on CRO.

EFPIA Page 43/44, sub-module 5.3 Clinical study reports

Comment: The draft guidance has rightly identified this section as sensitive (it is identified as CBC). Sub-module 5.3 may indeed potentially contain critical CCI in particular with respect to bio-analytical methods developed/owned by the MAH and not publicly available. This sub-module may also contain validation reports, as well as the SOPs of the clinical readout tests provided separately from CSRs. Some of them contain CCI as well as personal data on patients/subjects. In addition, these reports may contain information on external parties who have performed these studies and therefore in effect describe contractual agreements between companies. We propose that this kind of information is marked as CCI and/or PPD. Information on study design (protocol and amendments: statistical analysis) is of public interest and can be disclosed provided any CCI or PPD information it may contain is deleted. The same principles should be applied to the appendices. Proposed change (if any): It must be made clear that all reports in sub modules 5.3.1 to 5.3.7 are marked CBC because they may



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all contain PPD and CCI HAI EUROPE and MiEF

Page 43 It is not clear why sub-module 5.3 which concerns clinical study reports, of relevance to public health, should not be fully accessible. That should not be the case.

Agreed See text in final guidance

EFPIA Page 44/44, sub-module 5.4 Literature references

Comment: The actual references are included here (i.e. not the List of References). We agree that this should say that these cannot be released due to copyright issues.
