Biosimilars need to be regulated better

The health ministry must form a committee of external experts to draft legislation to regulate the biosimilar industry, crucial for public health and trade

According to recent press reports, public health groups, primarily concerned with access to medicine issues, have urged the health ministry to ease regulatory requirements for the introduction of biosimilars into the Indian market.

Unlike small-molecule generics, biosimilars are subject to much stricter regulatory requirements worldwide. For instance, to gain approval in most jurisdictions, a generic version of a small-molecule drug like paracetamol needs to demonstrate that its dissolution rate is the same as the innovator drug, which has already undergone clinical trials. This involves conducting bioequivalence studies where the generic drug is administered to healthy human volunteers and their blood and urine samples are periodically analysed to examine the drug’s dissolution rate. In the past, such bioequivalence studies were not obligatory in India, contributing to the widespread scepticism among Indian doctors regarding the quality of most generic drugs available in the market.

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The approval process for a biosimilar (a copy of a biologic like trastuzumab) is, however, significantly more complicated. The reason for this is that biologics are manufactured from living cells that are genetically modified using biotechnology. It is impossible to make identical replicas of a biologic without access to the original cell lines. At best, competitors can come up with a similar drug. Because of their molecular size and complexity, the only way to certify the safety and efficacy of biosimilars is to evaluate them through a similar regulatory process as the innovator drug, which means replicating animal studies for toxicity and clinical trials for safety and efficacy. All of this is expensive and complicated, and therefore the entry of biosimilars will result in marginal price erosion in the market when compared to the deep price cuts with the entry of traditional small-molecule generics.

While it is natural for the pharmaceutical industry to lobby for reducing regulatory requirements, it is relatively rare for public health groups, which have traditionally focused on “access” issues, to lobby on such regulatory issues. This, however, is beginning to change as many of these groups realise that price and regulatory requirements are intrinsically linked. In an ideal world, regulatory requirements should not be influenced by considerations of affordability because drugs that are not adequately tested for safety and efficacy will not work. What use is a cheap drug that does not work to cure a disease?

However, drug affordability is an emotive issue that can be used relatively easily to drown out advocates for regulations that guarantee the safety and efficacy of drugs. We say this from our own practical experience in advocating for stronger regulatory laws. Our most vocal opponents have not been the generic pharmaceutical lobby, as we expected, but public health groups that are willing to sacrifice scientific rigour at the altar of affordable drugs. Given the haloed existence of these public health groups, their word carries more credibility, even among the media, without addressing obvious conflict of interest issues or links between these groups and the pharmaceutical industry. For example, on the issue of bioequivalence testing, which is the standard across the world to ensure therapeutic equivalence of small molecule generics with innovator brands, some public health groups have actively spread misinformation, claiming it is unnecessary and a conspiracy to make it tougher for affordable generics to enter the market. Similarly, even after Ranbaxy pleaded guilty to multiple felony counts under American law and agreed to pay $500 million in penalties for supplying adulterated drugs to the American market, many public health groups in India claimed the American regulatory action was part of a conspiracy to defame the Indian pharmaceutical industry. Another set of public health groups amplified the Ranbaxy defence in the Indian market, which was that they were caught for “mere documentation issues”—this when Ranbaxy was found to be fabricating essential safety and quality data for drugs.

Thus, it is important for the government to ensure that the issues raised by public health groups are subject to rigorous scientific scrutiny. The mere fact that other countries have modified their regulations, as claimed in the letter by public health groups, may not be a good enough reason to change Indian regulations, especially given the scale of data integrity problems we have witnessed in both the Indian clinical research industry and the pharmaceutical industry.

Further, it is important to pay attention to the fine print. For example, a letter by the public health groups refers to the UK doing away with a few requirements for approvals of biosimilars; a close reading, however, would reveal that the UK has allowed for case-by-case waivers, not blanket waivers. These are important nuances that are often ignored by public health groups during their advocacy efforts.

In our opinion, the more pressing issue when it comes to biosimilars is the fact that the entire industry is regulated by a set of guidelines that have no binding legal force. In fact, those guidelines, which were published in 2016, do not even qualify as “law”. Simply put, the Central Drugs Standard Control Organisation (CDSCO), which has no rule-making powers in this regard, whipped up a set of guidelines in consultation with the Department of Biotechnology to regulate a multi-billion-dollar industry with a significant impact on public health. Other democracies have tackled the issue through legislation. The health ministry should seriously consider setting up a committee with external experts to draft legislation to regulate the biosimilar industry, which is strategically important for India from the perspective of both public health and trade.

(The writers are co-authors of The Truth Pill: The Myth of Drug Regulation in India)