Pharmaceutical sector: Why India needs a regulatory pathway for biosimilar drugs

Yet another controversy is brewing in the biosimilar space with Swiss company Roche falling back on a time-tested strategy to leverage India’s inadequate regulatory laws to question the safety and efficacy of biosimilars manufactured by Indian competitors. This is the third time that Roche and its affiliates have deployed this strategy over the last two decades. A bit of context is necessary to understand this strategy and Roche’s success in deploying it in India.

First, it is important to understand the drugs in question. Biosimilars are copies of a class of drugs called biologicals. These are large molecule drugs which are generally manufactured with processes involving living organisms. These drugs include not just the century old anti-diphtheria serum which is produced by innoculating horses with diptheria toxin, but also the more recent biologics like trastuzumab, one of the first blockbuster biologicals manufactured with the aid of biotechnology.

Biologicals, unlike small molecule drugs, are not easy to reverse-engineer. Even when competitors succeed, these biosimilars that they manufacture are likely to vary from the original product, unless they get access to the exact cell lines used by the innovator.

This raises the question of whether it is possible for competitors to manufacture biosimilars that are therapeutically interchangeable with the original product; ie, can a doctor prescribe the (usually more affordable) biosimilar in place of the original biological?

This is a policy question that must be answered by a law that lays down clear scientific standards which provide a legal guarantee that biosimilars are as safe and efficacious as the original biological.

Countries like the United States responded to these challenges by enacting laws such as the Biologics Price Competition and Innovation Act of 2009 as part of the “Obamacare” reforms to create legal pathways for the launch of biosimilars which were aimed to reduce the astronomical prices at which biologics were being sold in the United States.

In India on the other hand, this critical regulatory issue has always been handled through ambiguous guidelines. For example, in 2012, the government announced the “Guidelines on Similar Biologics” and again in 2016, a new iteration of these rules was announced by the government.

There are two major problems with this legal approach adopted by India. First, the guidelines lack the force of law and by that we mean, the fact that neither government nor industry can be held liable for violating these guidelines. Only Parliament can enact law or specifically delegate the power to the government to create rules. The present guidelines on similar biologics are unable to trace their lineage to Parliament and hence lack the force of law.

Second, the existing biosimilar guidelines are poorly drafted, leaving the door open for innovators like Roche to raise a cloud of doubt over the launch of new biosimilars.

Returning to the most recent controversy, this pertains to clinical trials being conducted by an Indian company to test a biosimilar of Pertuzumab that was invented by Roche. Since comparator clinical trials have to be conducted in comparison to a “reference product”, which in this case is Roche’s product, the Indian company had to procure Roche’s products for their clincal studies.

Roche, which presumably keeps close track of the sales of its drugs (which are expensive and subject to stringent storage protocols) has now raised questions on how and where the Indian company accessed the “reference products” for the purpose of its clinical trials. Reporting on the issue states that Roche has complained to the regulator, the Central Drugs Standard Control Organisation, that the samples procured by the Indian company may be of “questionable quality”, “compromised” or “spurious”.

Given the drug regulator’s “see no evil, speak no evil and hear no evil” approach to its job, we are unlikely to receive a clear-cut answer to Roche’s complaint. This silence will ultimately affect the credibility of the biosimilar to be launched by the Indian company on conclusion of its clinical trials.

Oncologists treating cancer patients are unlikely to risk prescribing the new biosimilar to their patients meaning that patients (or their insurers) will have to cough up more for Roche’s drug. We have seen this happen in the past.

The same tactic has been employed on two previous occasions for two other biosimilars. The first instance was in 2001, when Dr Reddy’s Laboratories launched a biosimilar for Neupogen (India did not recognise pharmaceutical patents at the time allowing Dr Reddy’s Laboratories to launch biosimilars). At that time, Piramal, which held the exclusive rights for Roche’s drug in India, complained that Dr Reddy’s Laboratories was not just misrepresenting certain aspects of its biosimilar but also that there were serious issues of safety and efficacy with DRL’s product.

Anji Reddy recounted the episode in his autobiography, Unfinished Agenda, quoting a top executive of Piramal as saying, “it's a battle for safe and effective drugs for the patients – to ensure that doctors are not misled and get correct information from pharma companies”. While defending the biosimilar by Dr Reddy’s Laboratories, Anji Reddy also remarked that the controversy led to reduced sales of their product and that leading oncologists expressed their unwillingness to take the risk of prescribing DRL’s biosimilar in light of the allegations.

Roche used a similar playbook on multiple other occasions in the last decade to block the launch of biosimilars of its blockbuster breast cancer drug – trastuzumab, sold under the brand name of Herceptin. This time around, Roche sued multiple Indian companies launching biosimilars on the grounds that they were trying to misrepresent their products as being similar to Herceptin.

Roche’s case was weak but convincing enough to confuse the courts into action. A cycle of injunctions and appeals followed against the launch of biosimilars. But the real damage to these biosimilar manufacturers was occurring outside the courtroom and in hospitals. By framing the issue in terms of regulatory law, instead of patent law, Roche in all likelihood managed to cloud the credibility of these biosimilars in the minds of oncologists.

The company was betting on the fact that Indian doctors already have little faith in the quality of medicine in the Indian market. This lack of faith was evidenced most recently when the medical community rose in revolt to a mandate issued by the National Medical Commission to prescribe only generic drugs. The ultimate loser in this regulatory dysfunction are poor and hapless patients who need to pay more for medicine.

The only way to fix this recurring problem with the launch of new biosimilars and encourage greater competition in the market for very expensive biologics is for the Ministry of Health to introduce a comprehensive legislation that builds confidence, especially among the medical community, that all biosimilars launched in the Indian market have established their safety and efficacy.

In particular, the law should mandate the supply of reference products for clinical trials and categorically allow biosimilars to be marketed as being therapeutically interchangeable with the biological of which it is a copy as long as their safety and efficacy is clinically demonstrated. To be meaningful, these reforms will have to be accompanied by a comprehensive, bottom-up reform of India’s rickety drug regulator.

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