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Cytespace Research Pvt. Ltd.

Learn India: Challenges at the Site and Potential Solutions Cyte News

Volume 5, Dec 25, 2015

Introduction: As the year 2015 is ending, I think this is a perfect opportunity for us to reflect back, review the year constructively and take forward the learning in 2016 to make it a better year for the Clinical Research industry in India. First of all, my sincere thanks to all the Clinical Trial Sites including Ethics Committees, who have worked diligently in coping with implementation of numerous regulatory changes and at the same time keeping the patient’s interest at forefront to ensure that we continue to offer option of newer treatment / research option for patients to consider. My sincere thanks to Pharmas & CROs, who kept faith in India’s capability to provide good research data not only by getting global studies to India but also performing India specific studies. Last but not the least; I would like to thank the Regulators, who are continuously making all the required efforts to

ensure that we have correct checks and balances in place to protect patient’s rights and safety to participate in Clinical Trials. Year 2015 has been an exciting year with some welcome regulatory changes to promote Clinical Trials in India. At the same time, we could hear a lot of buzz (in the right direction) around Risk Based Monitoring (RBM) and India getting strengthened to process clini-cal trial data in the area of DM, Bios, MW and safety. As we work on creating better ways to monitor the sites to function in most efficient way, we need to work in an inclusive way to help sites understand their role in making RBM successful. We need to invest in sites, which is the “source of the clinical trial data” to generate clean data at the first time rather than making additional cleaning efforts downstream. Once again thank you all for your support to Cytespace, as we continue to strengthen our Site Centric Model by supporting the sites with People, Process and Technology. Also looking forward to working with Pharmas/CROs towards implementation of RBM to make the Clinical Trial process more efficient and hence making newer drug affordable to patients.

I appreciate your contribution to our success this year. I wish you peace, joy, and fulfillment in 2016. Happy New Year!

India’s Central Drugs Standard Control Organization (CDSCO)

issued four new circulars on 10 Nov’15 that all seek to help pro-

mote clinical research on the subcontinent. –

To deliberate stakeholders concerns and the way forward relat-

ing to some issues on conduct of clinical trials in India, two

meetings were held on 20.08.2015 and 06.10.2015 under the

Chairmanship of Secretary, Ministry of Health and Family Wel-

fare in which experts including Secretary, D/o Health Research &

Director General Health Services were present.

Circular 1: Requirement of permission for conduct of trials for

academic/research purposes that are non-regulatory in nature,

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Our sincere thanks to Clinical Trial Sites, who provided their views on challenges faced. Here we are trying to capture a few of them and also talk about “potential solutions”. The proposed solutions may not be the best and suitable for each setup and hence we highly encourage all Clinical Trial Sites to contribute by writing to cytexpression@cytespace.com which can be further collated and shared in the upcoming volumes. Development of SOPs –Though schedule Y has mandated site SOPs from beginning not many sites have laid down their pro-cess for Clinical Trials. Instead they are dependent on sponsor/CRO for the guidance towards any such process. On the contra-ry at times in a single institute there are more than one SOPs, either because they are not aware about the existent SOP or they create a new SOP as per their respective trials. The Govern-ment institutes may have an additional challenge as no authority is designated to create standard processes which again lead to no processes at site. Potential Solution: The investigators conducting trials at a site could agree on the development of SOP and expert opinion can be obtained from external organisations in case required. As the challenge at Government site is beyond control at times to devel-op SOP for entire institute, one of the lateral solutions could be to create SOPs at department level. Thereafter a copy of site SOP could be submitted to EC so that there are minimal chances for creation of multiple SOPs at same site. Infrastructure – All sites are mandated to record AV consenting, however sites are facing challenge w.r.t this in terms of either managing too many recording devices or adhering to the individ-ual requirements of each sponsor & hence this leads to develop-ment of more than one process for the same activity each time.

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Mr. Bhavesh Acharya Head-Site Solutions, India

At the outset, Cytespace would like to share our journey so far, as we end year 2015 with a few metrics that we are proud of. We are grateful for our work with you in 2015, and we look for-ward to working together in the New Year. Happy 2016!

Cities 35+

Access to the Sites 500+

Studies 55

Customers 40

Subjects 3000+

Subject Visits 16000+

% Subject Visits within Protocol 95 %

Customer Satisfaction Index (CSI) 97.6%

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Cytespace Research Pvt. Ltd.

Potential Solution: The sites shall develop SOPs along with spec-ifications on the type of AV consenting instrument they would be using, so that by default they would be following the same prac-tice for each trial instead of working as per sponsor/CRO’s recom-mendation using multiple AV consenting devices. Dealing with Ethics Committee – The Ethics Committee plays a vital role in reviewing and providing their opinion on the trial applications by safeguarding the rights of subjects. However there are multiple challenges in communicating with EC as either the trial applications are not considered on time due to in-frequent EC meetings or at times the processes are so complex that it takes more than usual time to approve a trial. At few sites EC terminated the study at the site after receiving global safety notifications (as per regulations), wherein a few deaths had re-ported from other countries (though not because of study drug). Potential Solution: It is fine for ECs to take cautious approach in their opinion. However reaction like above to discontinue ongoing subjects receiving study drug may impact their safety. A part from conducting regular training on ICH-GCP and Schedule Y & it’s amendments for EC, there is a requirement of a common fo-rum between regulators and EC for them to interact and share learning. This will help EC work not only independently but with more confidence, as more responsibilities are being given to Insti-tutional ECs. Feasibility and Site Selection – In recent past, India has seen lot of feasibility and Site Selection Visits being conducted at the site and most of those studies could not start either because of regu-latory delay or sponsor took India off the list for some reasons. In these cases, sites do not get paid for all their efforts from feasi-bility to start-up activities in spite of investing time & efforts in this phase. Moreover, these feasibilities and SSVs block the PI’s availability to take more trials, if the final decision of trial con-duct is not conveyed on time. Potential Solution: It is highly recommended that the sponsors/CROs pay to sites for their efforts in start-up phase irrespective of the outcome of the study initiation. Also, timely communication shall be sent to the investigator which would create more healthy and professional environment between site and sponsor/CRO. In turn, sites shall also have a process in place where in a defined timeline is set for customers to respond back to feasibilities/SSV so that their response is not awaited for indefinite time. There could be many other potential challenges at site; however the motive is to concentrate on solutions rather than only chal-lenges. A definite continuous support would be provided by the existing market leaders in the industry to sites, however at the same time it’s high time for sites to stand, walk and run on self-created path.

- Ms. Akanksha Jain Site Solutions Manager—Cytespace

Learn India: Challenges at the Site and Potential Solutions Round the Corner

How will you get the accreditation faster?

In the coming days, CDSCO will make compulsory for sites to obtain accreditation to conduct clinical trials. Based on the study of the current draft of the accreditation standards, if a site has robust pro-cesses and documentation in the following area, it will help the site to obtain the accreditation faster and smoothly – have an upper-hand over the competitors: 1. A document describing various facilities, equipment,

their calibration, performance check and maintenance including the medical emergency facilities.

2. An SOP explaining the training of site staff and the maintenance of training records; training topics should include, at least, ICH GCP, Schedule Y, regulatory amend-ments & site SOPs.

3. SOP on SOP: Procedure for the preparation, review, approval, distribution, and revisionof site standard oper-ating procedures

4. It has been always our primary aim to protect the rights and safety of the subjects recruited in clinical studies (or of all the patients, not only subjects!). Now, for accredi-tation purpose the site should explain the process. A document describing site activities for subject identifica-tion and recruitment, informed consent, protection of confidentiality and privacy will help the assessor (from the accreditation body) to understand these aspects and will facilitate the accreditation.

5. There will be a focus on how site manages the investiga-tional products (receipt, storage, dispensing, accounting & destruction), the materials (e.g. lab kits), the biological specimens, etc. A detailed SOP explaining the manage-ment of IP will be very helpful, not only for the accredita-tion process but also for regulatory inspections.

6. An archival policy mentioning the storage facilities of study documents or the terms and conditions for utiliz-ing third party vendors.

A more systematic strategy reminds the practice and require-ment in the pharmaceutical manufacturing industry – preparing and maintaining a “Site Master File” covering such aspects. Once prepared, it’s very easy to maintain and update. A defined responsibility for a site staff to manage the “Site Master File” will help to ComplyWell. Let us start performing the gap analysis and fixing the gaps to avoid the delays in accreditation whenever it becomes compul-sory! And then - ComplyWell!

- Satyam Kothari Director, ComplyWell Solutions, Ahmedabad.

Quiz

For conducting Biosimilar studies, which of the following is true a) No clinical trials are required b) Phase II studies are not required c) PK/PD studies are not required d) All of the above

You may send your answers to below mentioned email.

Email— Cytexpression@cytespace.com

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Cytespace Research Pvt. Ltd.

Empowering Trial Sites

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If you have any business enquiry/ ideas/suggestions/feedback, please send them at below address:

For Business related: info@cytespace.com

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Ideas/Contribution with respect to CyteXpression: cytexpression@cytespace.com

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Accelerated Clinical Trials Through

High Performance Sites

Enchanched Patient Safety,

Compliance and Data Quality

Reduced Spend, Increase Efficiency

at Trial Sites

With an objective of providing complete solutions to the sites for conduct of clinical trials. Cytespace has lately introduce Cytestream (www.cytestream.com), our proprietary 21 CFR Part 11 compliant Clinical Trial Management Software (CTMS). Subject Visits Management is an integral part of the Cytestream. All Clinical Trial Sites can make use of this functionality:

One can track all Subject Visits, Missed Visits, Unscheduled Visits and can do overall analysis of the site.

Upcoming Subject visits automatically gets trigger once have any scheduled visit.

Similarly, Site can utilize this module to track upcoming Subject Visits Schedule, it creates an automated trial calendar and can

view by day, week or period.

One can record all procedures done and can add relevant notes.

PI/SSE/CRC can get automated email reminders for upcoming patient visits.

Contact Us

it was decided that the permission of DCGI shall not be re-

quired in such trials, provided that the trials were approved

by the respective Ethics Committee and they are not for reg-

ulatory submissions. However, the Ethics Committee of the

respective Institution may take a view in this regard. They

should inform DCGI about the cases where permission of

DCGI was not required. In case, no objection was received

from DCGI within 30 days, the clearance of DCGI may be

presumed.

Circular 2: Requirement of NOC from DCGI for addition of

new clinical trial site or Investigator in clinical trial it was

decided in the meeting that the respective Ethics Committee

after due diligence can approve proposal for addition of site

(s) and Investigator(s) and no NOC from DCGI in the normal

course, should be necessary. However, the applicant would

inform DCGI about any such addition/deletion and thereaf-

ter if no objection was received from DCGI it would be

deemed to have the concurrence of CDSCO.

Circular 3: Issues regarding the repetition of preclinical/

toxicological studied, the recommendation of IND Committee and

DTAB were noted in the meeting that if a new drug was already ap-

proved outside India after conducting pre-clinical/toxicological stud-

ies on animals, such studies are not required to be repeated while

approving their proposal for import/manufacture in India unless

there were specific written concerns.

Circular 4: The requirement of approval of Review Committee on

Genetic Manipulation (RCGM) under Department of Biotechnology

for r-DNA derived drugs like Insulin, Monoclonal antibody etc, it was

decided in the meeting that the applicant may submit parallel appli-

cation to RCGM and DCGI seeking approval to conduct clinical trial.

However, DCGI shall complete the scrutiny of application and issue

permission.

- Ms. Asha Nair Site Solutions Manager—Cytespace