India is fast becoming a major center for clinical trials and drug development. The increase in activity has lead the FDA to establish international offices in Mumbai and New Delhi in 2008. FDA states that their mission in India is in part: “… engaging with Indian counterpart regulatory authorities to ensure the timely exchange of information regarding clinical trials that are conducted that support marketing applications in the U.S…” Growing interest in India comes with many questions. What is the history of drug development in India? What type of regulatory structure does India have? What is the infrastructure for clinical trials and drug development? In this Guest Commentary by Jacquie Mardell she gives an overview and discusses some of the benefits, and challenges, of conducting clinical trials in India. GxP Perspectives is fortunate to have a number of readers in India. In fact, after the United States, the country with the most members of the GxP Perspectives LinkedIn group is India. I invite them and others to comment and share their insights about clinical trials in India.
Changes in Indian Clinical Trials Processes Cause for Renewed EnthusiasmIndia has become an attractive destination for clinical trials, combining many of the elements western sponsors require: a vibrant urban health care milieu staffed by English speaking professionals with first class medical credentials; an advanced clinical trial infrastructure thanks to the long-standing presence of big pharma companies and major CROs who trained local monitors and project managers in current GCP methodology; the wide availability of high-speed Internet access in offices and hospitals enabling instant remote data capture; and of course relatively easy access to large numbers of willing patients with the conditions western sponsors want to study, such as cardiovascular disease, metabolic diseases such as type 2 diabetes and many types of cancers.
By the early 2000’s, there remained just two significant challenges in conducting Indian clinical trials from the western sponsor’s perspective: shaky intellectual property protection and a long, opaque regulatory process for obtaining clinical trial approval. The former has been resolved by India’s participation as a signatory in WTO’s TRIPS agreement and subsequent harmonizing amendment of her own patent laws in 2005. The approval problem was addressed in late 2006 when India’s regulatory authority, the Drugs Controller General of India (DCGI) and the Central Drugs Standard Control Organization (CDSCO), the Indian regulatory authority, introduced a two track process allowing rapid approval of clinical trials that were part of a global development program.
So we’re all set, right? Sadly, the reality and the promise have not quite met. The DCGI’s office underwent a change at the top shortly after the new approval process was put in place and clinical trial approvals languished for months, against published expectations of 90 days. Despite having well placed regulatory liaisons in New Delhi, CROs can obtain little information to give sponsors, who in turn became disillusioned with the process once again, even with the enticing prospect of all those treatment-naive patients and proven rapid enrollment rates once the trial eventually started.Into this rather frustrating situation has come reason to hope. Recently the CDSCO has signaled an interest in providing more transparency and greater accountability among all parties by releasing several new guidances that harmonize Indian regulatory processes with other clinical trial countries. First, Schedule Y-1 (the Indian counterpart to Title 21 of the Code of Federal Regulations) was amended to require all CROs working in India to register with the authorities to conduct clinical trials (scroll down in the link for English). This requirement has rather more teeth than the FDA’s move in 2009 to require IRB registration, as the authority can reject a CRO’s application.
Secondly, CDSCO this summer published a draft guidance to clarify and streamline the process for obtaining permission to import drugs in small quantities, fewer than 100 doses per patient, for use in clinical trials. This will differentiate from the large quantity application process already in place. Should this draft become a final rule, it would encourage sponsors and CROs to be more precise with their drug calculations on the import license, and to make contingency plans should they wish to expand an existing trial. Despite this apparent additional hurdle, the draft is intended to provide for more uniformity of decision making by the reviewers, and is not expected to change operational policies CROs already have in place.
Finally, CDSCO issued a final guidance on clinical trial inspection procedures effective November 2010, a kind of bioresearch monitoring manual. As with the small quantity test license draft, this guidance provides clear expectations for inspectors and sponsors in preparing for, conducting and reporting an inspection at a clinical trial site or a CRO/sponsor facility, as well as follow up and response actions.Taken together with the recent introduction of an Indian clinical trials registry listing all clinical trials and sites in India, these changes though incremental, signal CDSCO’s desire to improve oversight of clinical trials and provide clarity for the sponsors and CROs who conduct them. There is even a glimmer of hope that the clinical trial approval process itself might be addressed soon, as October will see a change to the DCGI, India’s top drug official who ultimately approves all applications. Reasonable, reliable approval intervals combined with all the other attractive clinical trial attributes and recent improvements, India is truly an important solution in the quest for high quality clinical data.
Anhvita BioPharma Consulting, Inc. (Pvt Ltd)
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Central Drugs Standard Control Organization
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A comment worth reading from Anusha Reddy Mirayala: “In addition to the above mentioned changes made in Indian clinical trial process.I would like adding the following points
The ministry of health & family welfare, India has constituted a 12 new dug advisory committees to assist the DCGI in the matters related to review and regulatory approval of new drugs and clinical trials (except INDs), chalking a roadmap for proper development of new drugs.
Also the agency has come up with the draft guidance on approval of clinical trials and new drugs in july this year. which will help the industry to submit the required documents in a more realistic manner and also eases the agency review process in a systematic way.”
Article from Healthcare Management in India by Dr. Arun Bhatt, From guidelines to law
Article from Bio Spectrum on New DCGI expected to takeover in November
Thanks to our readers in India!
On the Blogroll: Compliance Zen discusses Building Compliance in India
Rebar Interactive has 22 great GCP websites, and more.
Tufts Center for the Study of Drug Development: Article on Protocol Amendments: One third can be avoided.
Drug shortage at hospitals could be deadly, by Linda A. Johnson, The Associated Press
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