In the budget session of the Indian Parliament in 2012, the Parliamentary Standing Committee on Health and Family Welfare, which has its members 30 MPs from across the political spectrum, had tabled a damning report on the state of drug regulation in India. The report, which is probably the first ever comprehensive study of the Indian drug framework focuses on the functioning of the Indian drug regulator and also the manner in which local clinical trials were being routinely waived by the drug regulator without any cogent reasoning.
On the point of local clinical trials, the parliamentary panel examined three specific points: (1) The importance of local clinical trials for India; (2) the regulatory requirements for local clinical trials in the DCR, 1945 and (iii) the manner in which local clinical trials were being waived.
Given the scathing and eloquent critique by the Panel report, the writer has extracted in whole, the relevant statements made by the Panel:
(i). The importance of local clinical trials for India:
The committee had the following to state on the issue of local clinical trial in India: “ the basic purpose of Phase III trials is to determine if there are any ethnic differences that can alter the metabolism, efficacy and safety of the drug when administered to patents of different ethnicities living in India. There is evidence that the effect of some drugs can vary among various ethnic groups. For example, the blood levels reached after intake of lipid lowering agent rosuvastatin are for far higher in Asians, compared to Europeans and North American Caucasians, Hispanics and Blacks needing lowering of dosage. Failure to lower dose in Indians can result in severe toxicity including life threatening muscle injury leading to fatalities. Hence, testing drugs in the Indian ethnic groups is of paramount importance before approving any drug of foreign origin”.
It should also be noted that the lack of local clinical trials is a global problem not limited to India. While studying the AIDs situation in Africa, All Party Parliamentary Group (APPG) of the United Kingdom complained of “missing information” for the African patients infected with the HIV +ve virus since most clinical trials were designed for the mark of developed countries. In pertinent part the report stated “ As well as missing medicines and diagnostics there is missing data about the suitability of some of the existing medicines for a developing country context. Clinical trials are often designed with a view to registration in the developed world, to capture maximum commercial benefits.
It may help to mention, that there has been a long standing demand even within the U.S. , for making available clinical trial information as per various subsets including sex, race, and ethnicity. In response, the U.S. enacted in July 2012 , the Food and Drug Administration (FDA), Safety and Innovation Act (FDASIA) which “makes available information about differences in safety and effectiveness of medical products according to demographic subgroups such as sex, age, racial and ethnic subgroups, to health care providers, researchers and patients”.
The new requirement however extends to only reporting requirements and does not extend to mandatory clinical trials on a more diverse range of patient groups.
(ii) The regulatory requirements for local clinical trials in the DCR, 1945:
On the point of re-examining Indian regulatory requirements, the Committee had this to say :” The Committee is of the view that taking into account the size of our population and the enormous diversity of ethnic groups there is an urgent need to increase the minimum number of subjects that ought to be included in Phase III pre-approval clinical trials to determine the safety and efficacy of New Drugs before marketing permission is granted. In most Wwestern countries the required numbers run into thousands. However since major objective in India is to determine the applicability or otherwise of the data generated overseas to Indian population, the requirement should be re-assessed and revised as per principles of medical statistics so that major ethnic groups are covered. A corresponding increase in the number of sites so as to ensure a truly representative sample spread should also be laid down in black and white. Furthermore, it should be ensured that sites selected for clinical trials are able to enroll diverse ethnic groups. For domestically discovered drugs, the number of subjects should be revised as well. This can be easily achieved by changes in the Good Clinical Practice (GCP) guidelines.
If the above recommendation of the Committee is accepted by the GOI, and it is hard to see as to how the Government is going to ignore such a recommendation, the regulatory authorities will have to re-examine why and how innovator firms will carry out local clinical trials when they have no way to prevent free riders from entering the markets on the basis of such data thereby corroding the competitive advantage of the innovator firms. As explained earlier, this question is all the more pertinent given the high threshold for pharmaceutical patent protection in India(3).
(iii) The manner in which local clinical trials were being waived:
While studying the manner in which the Indian drug regulator was conducting local clinical trials on the Indian population, the Committee noted, and shockingly so, that a total of 31 new drugs were approved for the Indian market in the period of 30 months without any local clinical trials being conducted in India. The local clinical trials were reportedly waived on the basis of the “public interest” provision in Rule 122A &B. When the Regulator was asked for the basis of determining “public interest” to waive local clinical trials, it was not given a satisfactory answer. In pertinent part, the report states “ The Ministry explained that under the rules, DCGI has the power to approve drugs without clinical trials in “Public Interest.
