article 58 · 5/6/2008 · 3. “article 58” opinions article 58 of regulation (ec) no. 726/2004...
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Article 58:
A route to scientific opinion
Eric PelfreneEMEA
Open forum on Key Issues on TB Drug Development New Delhi
5-6 May 2008
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Agenda1. EU Registration procedures2. EMEA3. “Article 58” Opinion principles4. “Article 58” Procedure & Evaluation5. “Article 58” EU experiences 6. Other peculiarities of “Article 58”
procedure
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1. EU Registration Systems in 2008
-1 National Regulatory Authority (e.g. Spain) performs assessment of MAA and issues…-1 National authorisation(= RMS)
-up to 26 other National Regulatory Authorities can “mutually recognise” the Spanish assessment (=CMS)
- Managed at EMEA by single scientific committee
- Generates binding scientific opinion- Max. 210 days to Opinion- Peer review system Final Decision
- 1 marketing authorisation valid EU- 1 Trade name- 1 common Product information
- Transparent system (e.g. EPAR) - Access to potentially 500 million users
LondonBrussels
- Parallel submissions in RMS and CMS
- RMS performs assessment- Peer review system by CMS
(90 days):-Assessment report-SPC, PL and labelling
-RMS and CMS grant Marketing authorisations after agreement (in 30 days)- Only, If no authorisation has been granted
CENTRALISEDMRP DECENTRALISED
NATIONAL
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2. EMEAThe EMEA is conceived as an interface of co-operation and co-ordination of Member States’activities with respect to medicinal products
Opening EMEA London – Jan 1995- Manages centralised procedure- Network for scientific advice/scientific opinions and evaluation which generates scientific opinionsfor EU Marketing Authorisations and “Article 58”…
- Coordination pharmacovigilance, inspection - Transparency/information and databases together with MSs and other interested parties all over the EU
Partnership with the European Commission in Brussels which issues Pan European marketing authorisation
LondonBrussels
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3. “Article 58” Opinions
EU Regulation
EU Regulation
(EC) No. 726/2004
(EC) No. 726/2004
EU Regulation
EU Regulation
(EC) No. 2309/93
(EC) No. 2309/93
repealed by
repealed by
Pre-submission PrimaryEvaluation
ClockStop
SecondaryEvaluation
Opinion
Decision
PostAuthorisation
D.1D.120
D.121
D.210D.277
Rap/Co-RapDay 80 Assessment
Reports
LoQ Answers
AssessmentReport on answers
D. 180 Hearing?
-Ph.Vigilance-Variations-Extensions-Renewal
Scientific Advice
Rap/Co-Rap
Centralised ProcedureCentralised Procedure
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3. “Article 58” Opinions
Article 58 of Regulation (EC) No. 726/2004
“1. The Agency may give a scientific opinion, in the context of cooperation with the World Health Organization, for the evaluation of certain medicinal products for human use intended exclusively for markets outside the Community. For this purpose, an application shall be submitted to the Agency in accordance with the provisions of Article 6. The Committee for Medicinal Products for Human Use may, after consulting the World Health Organisation, draw up a scientific opinion in accordance with the provisions of Articles 6 to 9. The provisions of Article 10 shall not apply.
2. The said Committee shall establish specific procedural rules for the implementation of paragraph 1, as well as for the provision of scientific advice.”
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3. “Article 58” OpinionsWhy ?Why ? Scope ?Scope ?
• Responds to the unavailability of medicinal products whose Marketing Authorizations are no longer in place in EU for commercial reasons but are still of use for countries outside the EUoutside the EU
• Access to essential medicines for countries lacking the regulatory capacity for assessing new medicinal products for their markets
• Responds to the need to protect protect publicpublic health and to give scientific scientific assistance to nonassistance to non--membermember countries in the context of cooperation with WHO while at the same time allowing rapid accessrapid access to those countries for important new important new medicinal products
• Vaccines used or of possible use in the WHO Expanded Programme On Immunization (EPI)
• Vaccines for protection against a WHO public health priority disease
• Vaccines that are part of a WHO managed stock pile for emergency response
• Medicinal products for WHO target diseases such as HIV/AIDS, malaria, tuberculosis, lymphatic filariasis(elephantiasis), trachoma, leishmaniasis, schistosomiasis, African trypanosomiasis(sleeping sickness), onchocerciasis (river blindness), dengue fever, Chagas disease, leprosy
medicinal products
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3. “Article 58” Opinions CHMP Guideline
http://www.emea.europa.eu/pdfs/human/regaffair/557904en.pdfhttp://www.emea.europa.eu/pdfs/human/regaffair/557904en.pdf
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4. “Article 58” Procedures
Adoption of CHMP SCIENTIFIC OPINION
Adoption of CHMP OPINION
D210
Centralized Procedure Article 58
ELIGIBILITY
PRE SUBMISSION
SUBMISSION VALIDATION
PRIMARY EVALUATION
SECONDARY EVALUATION
CLOCK STOP
D0
D1
D120
D121
COMMISSION DECISION
EC Decision Making ProcessEC Decision Making ProcessTranslation check of production informationTranslation check of production information
TexteWHO
EXPERTISE
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4. “Article 58” Evaluation“Art. 58” EVALUATION PROCEDURE MIRRORS the PROCEDURE for medicinal products intended to be marketed in the EU (BUT NO EC DECISION!) i.e.:
as for EU medicines taking into account possible adjustments as appropriate (e.g. stability, RMP etc..) - In absence of EU/ICH guidelines, or otherwise justified, WHO guidelines apply
Possibility to accept exceptionally old NTA format if justified
Not mandatory
Further to WHO recommendations
With consultation of relevant WPs/SAG
Possible nomination WHO Experts to be involved in Assessment review
and Observers from WHO and observers from NCAs may attend relevant WPs, CHMP plenary discussions
SCIENTIFIC ADVICE
Similar DATA REQUIREMENTS & EVALUATION STANDARDS
Submission CTD
Invented Name
Eligibility by CHMP
REVIEW PROCESS TIMELINES
RAPPORTEUR APPOINTMENT PROCESS
EXPERTS’ NOMINATION
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5. “Article 58” Scientific Opinions – EU experiences
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5. “Article 58” Scientific Opinions – EU experiences
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5. “Article 58” Scientific Opinions – EU experiences
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5. “Article 58” Scientific Opinions – EU experiences
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5. “Article 58” Scientific Opinions – EU experiences – Art.58 Certificate
http://www.emea.europa.eu/Inspections/index.html
http://www.emea.europa.eu/Inspections/index.html
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5. “Article 58” Scientific Opinions – EU experiences – Art.58 Certificate
http://www.emea.europa.eu/Inspections/Certificates.html
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5. “Article 58” Scientific Opinions –EU experiences – Art.58 Certificate
EMEA Certificates of Medicinal Products (CPPs) adopted under Art. 58 of Reg. 726/2004:
For a product for which an application has been submitted under Art. 58 of Reg. (EC) No. 726/2004, once validated by EMEA
• either under evaluation[no product information incl. but composition, GMP status of allsites can be incl.] or• once the opinion has been adopted by the CHMP
According to WHO rules/guidelines Only upon request from of Applicant/Scientific
Opinion Holder(s) with the exception of Anti-counterfeiting activities, where request from developing countries MSs can be made
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5. “Article 58” Scientific Opinions – EU experiences – Art.58 Certificate
This Certificate will stipulate that:
• the specific medicinal product is intended exclusively for markets outside the European Union[i.e. No EU MA]
• MP has undergone an evaluation procedure = Centralised procedure [w/o EC decision, no EU MA]
• GMP status of all manufacturing sites [for finish product, batch release, quality control sites, labelling, etc…]
•includes latest Product information[SPC mandatory, rest labelling and EPAR upon request]
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5. “Article 58” Scientific Opinions – EU experiences – Art.58 Certificate
Requesting EMEA Certificates of Medicinal Products:
All requests for certificates submitted by e-mail should be sent to [email protected]. Requests that are sent to the e-mail addresses of EMEA staff members may be delayed. Questions and comments about the EMEA Certificates of Medical products are also welcome at [email protected].
Other questions, not related to the EMEA Certificates of Medicinal Product, should be sent to [email protected].
General Information:Notification on new Application FormNotification on Arrangements for Requesting Certificates - December 2007 What's new for Certification - 8 November 2005 Notification on Increase of the Administrative Charges for EMEA of Certificates of Medicinal Products Notification on Stopping Legalisation of Certificates of Medicinal Products from 1 Nov 2005 Information package Rev 8Questions and Answers
Send all queries regarding this content to:
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6. Other peculiarities of “Article 58” procedure
• Inspection during the evaluation:– Co-ordination pre-opinion inspections (GMP, GCP ,…) ?
•Manufacturers located in the EEA :– Supervisory Authority = Competent Authority of Member State that granted the manufacturing
authorization•Manufacturers located outside the EEA :
– Competent Authority of the Rapporteur's Member State
• Post-marketing follow-up:– Implementation of Risk Management Plans ?– Implementation of changes post opinion at national level ?– Adverse Events reporting / collection ?
• EU awareness of specific problems due to differences between the EU and developing countries:– Organisation of health care systems and ADRs reporting systems?– How to inform the patients?– How to communicate with health care professionals?
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OTHER ?Lymphatic filariasis,
Trachoma,,Dengue fever, leprosy..etc.
ANTI-MALARIA(3 WHO/CHMP Art.58
Eligibility granted – 5 under discussion)
HIV/AIDS(3 SOs adopted)
Combination vaccines
(3 WHO/CHMP Art.58 Eligibility granted – 1 Art.58 start/2SAs)
ANTI-LEISHMANIOSIS
(1 WHO/CHMP Art.58 Eligibility granted)
7. “Article 58” pipeline
ANTI-ONCHOCERCIASIS
(1 WHO/CHMP Art.58 Eligibility granted)