One of the key determinants of high quality, safe and effective medicines is the role of a national drug authority in holding pharmaceutical manufacturers accountable for violating cGMP standards.
The recently released report on “Countering the Problem of Falsified and Substandard Drugs”1 from the Institute of Medicine of National Academies (IOM) is an excellent review of the current state of the manufacture of fraudulent medicines.
This report provides an excellent compilation of the drivers for adulteration and the impact of these substandard and falsified drugs on public health as well as a discussion about what drives the manufacturers and distributors of such adulterated drugs, the current state of technology for detection of these falsified and substandard drugs and the emerging standard code of practice for falsified and substandard drugs.
A key IOM observation relates to the role of national regulatory authorities. The report correctly observes that international quality standards for drug manufacture depend on the competence of the national regulatory authority.
Role of the Health Regulator in India:
In May 2012, a Standing Committee on Health and Family Welfare of the Indian Parliament produced an exhaustive report on the structure and functioning of the Indian Regulator, Central Drugs Standard Control Organization.2 This Report focuses on the manner in which regulatory approvals are sought for marketing of drugs for the Indian market and how the Drugs Controller General of India (DCGI) and the Central Drug Standards Control Organization (CDSCO) allegedly have failed to enforce the law, either through collusion or blatant negligence.
There are many serious observations in the Standing Committee report. However, one stands out: namely, the allegation that there is sufficient evidence of collusion between drug manufacturers and some officials at the CDSCO. It further states that it is difficult to believe that these irregularities merely were due to poor oversight or that they were unintentional.
The entire report is accessible online and makes for great reading. It is interesting to note that, as of almost one year after release of this report, no public action has been taken by the Ministry of Health on any recommendation made in this report. In fact, the only action noteworthy in this context is the public interest litigation filed by two non-governmental organizations in the Supreme Court of India alleging flaws in the regulatory framework governing clinical studies in India. As a consequence, the Supreme Court has imposed a temporary hold on any new approval of clinical studies for two months, effective January 22, 2013.
Response to the Ranbaxy case:
In the wake of the news about Ranbaxy pleading guilty to several criminal charges in the U.S., there have been demands for greater accountability from Indian regulator. There were reports in the Indian media that the Indian regulatory body is examining documents submitted by Ranbaxy to gain approval for marketing its drugs in India. It remains to be seen if there is any actionable outcome from this review.
In a recent interview with the media,3 the DCGI said Indian law governing marketing of drugs purely is based on science, while laws of other countries (unfortunately he did not name which ones) may be influenced by commercial interests. Having observed and participated in the work of the U.S. FDA for more than eight years in the prosecution of my case against Ranbaxy, this insinuation is totally false. The U.S. FDA is a science-based and data-driven organization, and the outcome of my case proves it. I wish this were true of other regulators across the world.
Equally absurd is the assertion there are differing standards when it comes to cGMPs. The amount of stability data needed to support a filing varies considerably among different countries. For example, some countries accept three months of initial stability data, while others require six or more months of data. This doesn’t mean the process by which they expect the manufacturer to study the shelf life, or the standards by which they expect the data to be analyzed to determine shelf life of their product are somehow different. It is exactly this type of approach that encourages manufacturers to have two different set of processes and quality standards: a stringent set of specifications for what they call “regulated markets” – which includes the U.S. and western Europe – and a “less stringent” set for what they call “rest of the world,” which, unfortunately, sometimes includes India. An interesting analysis of the current state of drug regulation in India was published earlier this year by Amir Attaran and Marvin Shephard in BMJ.4
Why do we care about the Drug Regulator in India:
It is the stated policy of the U.S. FDA to work collaboratively with national regulators of other countries to ensure product quality and safety. It is noteworthy that the U.S. FDA has no information-sharing agreement, confidential commitment or any other cooperative agreement with their regulatory counterpart in India. The question therefore to ask is what confidence do we have in a national regulator that has such a checkered past and that is tasked with overseeing the manufacture of medicines for domestic and international distribution? What do you think?