One of the great revelations about India’s drug regulatory framework during the pandemic was the fact that it simply does not know how to approve new drugs. Many of the new drugs approved by the Drug Controller General of India such as Favipiravir, Itolizomab and Virafin never found mention in the government’s own treatment guidelines for Covid-19.
Quite often, the Drugs Controller General of India kept dropping phrases such as “emergency use authorisation”, “clinical trial mode” and others while approving these new drugs and vaccines despite the lack of adequate clinical trial data, except that none of these phrases actually find a mention in the law.
The process was so chaotic that at one point, Biocon’s head for regulatory affairs and the Drugs Controller office contradicted each other on the provision of law under which the company’s drug Itolizumab was approved for treating Covid-19.
The government’s decision in July to introduce the Drugs, Cosmetics & Medical Devices Bill, 2022, to replace the colonial-era drug regulatory law, was an excellent opportunity to fix the broken drug regulatory process.
The main concern, however, is that the head of the drafting committee for the new law was the incumbent Drugs Controller General of India VG Somani, who presided over the chaotic drug approvals during the pandemic. It is, therefore, no surprise that the new law does nothing to curb the vast discretionary powers that exist with the Drugs Controller to approve new drugs.
The need for safeguards
Before proceeding to critique the new law, some history and context may be useful.
Until the Thalidomide tragedy – a drug for treating nausea in pregnant women that led to birth defects – of the late 1950s, most countries did not require pharmaceutical companies to actually prove the safety and efficacy of any drugs that they marketed.
A domestic inquiry by the American Senate into the eye-popping profit margins of the pharmaceutical industry led to the Kefauver-Harris Amendments in 1962, introducing for the first time a requirement to demonstrate the efficacy for all new drugs.
The United States already had a safety requirement in its law since 1938 because of which Thalidomide had never been approved in the country, saving it from the horrors of deformed babies that were born in Europe in the thousands due to the drug being prescribed to pregnant mothers to combat nausea.
The new efficacy rules required clinical trial evidence to be generated in a controlled setting. Over the decades, as scientific methodologies were fine-tuned and improved, the double-blind randomised clinical trial became the gold standard to generate clinical evidence required to establish the safety and efficacy of new drugs.
Over the years, American law has been constantly reviewed to make transparency the bedrock principles of regulation, so much so that even clinical trial data is now required to be made public.
India incorporated only some of these elements into the Drugs & Cosmetics Rules, 1945, in the year 1988. Legally speaking, new drugs could now be approved only after completing three phases of clinical trials, except there was ample evidence that the Drugs Controller was approving drugs that had either not completed the three phases of clinical trials or alternatively were evaluated in poorly-designed clinical trials that failed to meet the standards of modern science.
Multiple red flags
The transgressions came to light in the first decade of this century when multiple doctors repeatedly flagged drugs approved by the Drugs Controller for strange indications despite not being approved anywhere else in the world. For example, a drug originally approved as an antihistamine to treat allergies was approved additionally as an “appetite stimulant” for children.
The 59th report of the Parliamentary Standing Committee on Health and Family Welfare delved deep into matter only to discover that many of the drug approval files were missing. The committee concluded that, “There is sufficient evidence on record to conclude that there is collusive nexus between drug manufacturers, some functionaries of CDSCO [Central Drugs Standard Control Organisation] and some medical experts.”
A subsequent internal inquiry ordered by the government and headed by Dr Tribhuban Mohapatra resulted in a report that went missing until we fought a legal battle with the Drugs Controller for two years, after which we got an unsigned copy of the report. The Mohapatra Committee described the approvals by the Drugs Controller as “arbitrary, whimsical and inconsistent” with the law.
Opaque system
The public flogging of the Drugs Controller by the Parliamentary Committee resulted in the establishment of subject expert committees. These bodies consisted of expert doctors for different fields who would provide recommendations to the Drugs Controller on whether or not to approve a new drug.
The functioning of these subject expert committees is opaque. Very often their membership is not made public and as a result it is difficult to determine if the doctors in the committee have any financial conflict of interest.
Similarly, the deliberations of the committee are not released in the form of a verbatim transcript. Rather, a summary of 150 words of the committee’s recommendations are published and even those are apparently susceptible to manipulation as has been alleged by the Central Bureau of Investigation in the corruption case filed against Biocon and a senior drug controller in June.
This summary – a mere 150 words – is the only publicly available information explaining the rationale for approving a new drug to the people of the country. This, when regulators in the United States and Europe release thousands of pages of their own assessment of new drug applications. The European Medical Agency releases the European Public Assessment Report on approving new drugs.
Yet, as India witnessed during the pandemic, the Drugs Controller was approving new drugs in a whimsical manner, often when Phase III clinical trials were not complete or the data from such trials was not publicly available.
The Drugs Controller refused to share basic information, such as the composition of one of the subject expert committees, until a parliamentary question in March last year left it with no choice. The basic precepts of modern science and regulation appear to have been lost on the Drugs Controller.
Carte blanche for DCGI
Despite all of the above being well known within the government and public health circles, the New Drugs, Cosmetics and Medical Devices Bill, 2022, drafted by the committee headed by the current Drugs Controller, has not instituted a single worthwhile reform.
Incredibly enough, the bill is entirely silent on the process to be followed by the Drugs Controller while approving a new drug. There is nothing in the proposed law about a new drug having to go through rigorous clinical trials in controlled settings.
It is silent on the requirement for the Drugs Controller to publish the regulator’s justification for approving the drug or for appointing experts to advisory committees and their mode of functioning.
All that the new law contains on the subject of new drug approvals is Section 41(3), which states, “No person shall manufacture for sale of any new drug except in accordance with the permission or approval issued by the Central Licensing Authority in such manner as may be prescribed.”
Simply put, the drafting committee wants to reserve the power to determine this billion- dollar question with the bureaucracy through its rule-making process.
As if this was not bad enough, the drafting committee has had the audacity to include a provision, Section 41(4), which gives the Drugs Controller carte blanche to “abbreviate, defer or waive off such pre-clinical and clinical data requirements for approval of such new drug relating to life threatening or serious diseases or rare disease of special relevance to the country.”
Union Health Minister Mansukh Mandaviya should not sign off on this law. The drafting committee has betrayed the spirit and intent with which it was tasked with the responsibility of drafting a new law. The minister should junk this bill and constitute a new committee of external experts actually interested in protecting public health rather than their own turf.
Dinesh Thakur was the whistleblower in the Ranbaxy case. Prashant Reddy T is a lawyer specialising in drug regulation and intellectual property.