On March 19, 2019, the Ministry of Health and Family Welfare of India released the “New Drugs and Clinical Trials Rules, 2019.”[1] These rules included significant definitions, clarifications, opportunities, and expectations that, together, improved the clinical trial regulatory environment in India.
Several provisions are particularly notable: compensation provisions for death, permanent disability, and injury related to participation in a clinical trial; the DCGI through expert committee review, retaining the responsibility for determination of the quantum of compensation if any; publication by schedule for the amount of compensation; clarification of requirements for medical management of trial-related injury; procedure for post-trial access to investigational products determined to be beneficial to the participant; clarification of the requirement for audio- versus audiovisual recording of the informed consent process; definitions of academic trials and of vulnerable populations; certain provisions for research ethics committees; expedited review of the application for new clinical trials, including a 30 day review for any new drug that was discovered in India or will be manufactured and marketed in India; definition of special situations wherein the regulations for a new drug can be relaxed, abbreviated, or modified; introduction of pre- and post- submission meetings; penalties for non-compliance and the right of the aggrieved party to appeal; among other provisions.
Taken together, the rules constitute a significant advance for the country and encompass welcome clarifications for sponsors and investigators seeking to site clinical trials in India.
Initially created in 2006 by the World Health Organization, the African Vaccine Regulatory Forum (AVAREF) was created as an informal capacity building platform dedicated to improving the regulatory and ethical oversight of interventional clinical trials in Africa. In 2016, a revised governance structure was agreed upon and the remit of AVAREF was expanded to include all interventional clinical trials in Africa.
AVAREF seeks to enhance the efficiency and quality of regulatory and ethical reviews and inspections, develop and disseminate harmonized guidelines and approaches, protect participant and patient safety, and improve the timeliness of regulatory decisions for all trials. As a pan-African network, AVAREF is an important contributor to the African Medicines Regulatory Harmonization (AMRH) initiative and the future African Medicines Agency (AMA). Dr. Bierer was invited to describe the work of the MRCT Center and to participate in discussions of capacity building and regulatory systems strengthening.
The MRCT Center, in collaboration with Health Canada, conducted a 3-day training workshop in Ottawa, Canada, focused on Good Clinical Practice (GCP) and Multi-Regional Clinical Trials (MRCT), specifically the International Council of Harmonization (ICH) Guidelines ICH-E6(R2) and ICH-E17.
Seventy professionals from Canada participated in this successful in-depth and interactive training, including inspectors and reviewers from Health Canada as well as Canadian stakeholders from academia, hospitals, research institutes, CROs, and industry. Senior staff from Health Canada, Danish Medicines Agency, U.S. Food and Drug Administration (FDA), industry, and MRCT Center facilitated the interactive sessions. As one training participant said, “I’ve worked in this field for 13 years and this is the most helpful training I’ve been to.”
The objectives of the training were to:
Describe the standards of Good Clinical Practice (GCP) and key considerations in Multi-Regional Clinical Trials (MRCTs) design as set out in ICH E6(R2) and ICH E17 guidance, with particular focus on how the guidelines are applied by Health Canada.
Use case studies, to apply the changes of ICH E6(R2) addendum and ICH E17 to increase the acceptability of MRCT data by multiple regulatory authorities
Demonstrate practical approaches that Health Canada may take to fulfill the requirements of ICH E6(R2) and ICH E17 consistent with ICH standards
For Regulators:
Describe and demonstrate best practices to assess clinical trial regulatory submissions by Health Canada, including study design, data packages, essential documents, reports, and filings for alignment with ICH GCP and MRCT
Describe inspection methodologies that may be taken by Health Canada to assess clinical trial conduct for alignment with ICH GCP and MRCT standards, including review of corrective actions.
For other Stakeholders:
Gain better understanding and knowledge of Health Canada expectations with regards to compliance with the Canadian clinical trial regulations.
Gain better understanding and knowledge of Health Canada GCP inspection processes to better prepare for an inspection
The MRCT Center is an APEC (Asia-Pacific Economic Cooperation) Training Center of Excellence for MRCT and GCP inspection and is endorsed as a training partner by the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH).
Mr. Mark Barnes, MRCT Center Faculty Co-director, co-authored Will Consent be Disfavored as a Bases for Processing Personal Data in Clinical Research Under EU Data Protection Law? recently published by Bloomberg Law. The article may be accessed by navigating to his bio and scrolling to the bottom of the page for his publications.
In April 2018, the MRCT Center held a 3 1/2-day training workshop at the Harvard Faculty Club focused on Multi-Regional Clinical Trials (MRCT) and Good Clinical Practice (GCP) as an APEC (Asia-Pacific Economic Cooperation) Pilot Center of Excellence (CoE), and specifically on ICH-E17 and ICH-E6(R2).
Twenty-two professionals from twelve economies participated, and all but one were governmental regulators. Senior staff from the U.S. Food and Drug Administration (FDA), Health Canada, Health Products Regulatory Authority (HPRA) Ireland, Pharmaceuticals and Medical Devices Agency (PMDA) Japan, industry partners, PhRMA, and MRCT Center facilitated the interactive sessions. The training was co-hosted by the APEC Harmonization Center (AHC).
The objectives of the workshop were to:
Enhance regulatory cooperation in the APEC region on the evaluation and regulation of MRCTs
Demonstrate practical approaches to fulfilling the requirements of GCP as presented in ICH E6(R2)
Describe the concepts of MRCTs and key considerations in MRCT design as presented in ICH E 17 guidance
Increase the acceptability of MRCT data by multiple regulatory authorities
With near unanimity, the participants rated the program as “excellent,” including the organization of the training, the faculty lectures, case studies/breakout groups, question and answer and “ask the expert” sessions, and the course materials. The vast majority of participants agreed that the training increased their knowledge and understanding of MRCTs and GCP and that the knowledge or techniques gained from this training will be practically useful in their field. Participants found the faculty knowledgeable of their respective training topics and networking with other participants was helpful. Based on this training, participants envisioned what they will do differently when they go back to their place of work.
Faculty Director Barbara Bierer, MD, traveled to Mexico City, Mexico, in February to learn more about the national preparedness for clinical trials.
A number of changes have been introduced in the country that have served to decrease the times for review while improving human participant protections. Anyone interested in further information or to be involved, please contact mrct@bwh.harvard.edu.
