Opinion

A new class of drugs is here – but India is dangerously inept at dealing with them

There is serious doubt over the competence of India’s regulatory regime for biosimilar drugs. If this isn't fixed soon, the biggest losers will be Indian patients.

A few weeks ago, the Indian pharmaceutical company Intas voluntarily “curtailed the distribution” of Razumab, a biosimilar drug used for treating macular degeneration, following reports that it caused severe inflammation of the eyes. The recall, coming barely two months after the drug’s launch, didn’t raise many eyebrows. Nor did it prompt any debate. It really should have.

While it’s appreciable that Indian companies are finally stepping up to their ethical and legal duty of withdrawing unsafe medicine, the episode raises serious questions about the competence of India’s regulatory regime for biosimilar drugs or biosimilars.

What are biosimilars?

For most of the last century, new drugs developed by the pharma industry were based on engineering chemical entities. These were relatively easy to reverse-engineer, giving us the whole industry of generic drugs. And for generic drugs to get marketing approval, they had to clear simple tests to prove their “equivalence” to their original, or “innovator”, counterparts.

Change set in during the 1980s when a breakthrough in the science of gene-splicing sparked off the biotech revolution in the US. For the first time, scientists could manipulate and modify genes to achieve stunning results. They could manufacture human insulin, create genetically modified crops, and ultimately build an entire new class of drugs called biologics.

The science of biologics is completely different from that of conventional chemical drugs. As Fortune magazine describes, biologics “are made using living cells that treat disease, usually by genetically modifying cells. They are big and very complex molecules, often 200 to 1,000 times the size of more common small-molecule drugs”. To explain with an example: aspirin, a small-molecule drug, is made of up 21 atoms, whereas the biologic drug Enbrel, which treats rheumatoid arthritis and plaque psoriasis, is made up of over 20,000 atoms.

As a result of this complexity, manufacturing a biologic is a challenging affair: even a small change in the manufacturing process can cause big changes in the drug’s efficacy. Equally difficult is the process of making an equivalent drug: companies have to find their own way to engineer living cells to provide the same results as the original. These imitations, called biosimilars, are relatively less expensive than the original biologics.

Given all this complexity, it has been necessary worldwide to create a whole new regulatory framework for authorising biosimilars. The kind of simple and limited clinical studies needed for chemical drugs simply don’t work for biological molecules. That is why the global standard for approving biosimilars has been to establish both safety and efficacy independently, because biosimilars are fundamentally different from biologics.

Did the industry drive the agenda?

In India, the regulatory framework for biosimilars was established in 2012 with the publication of the “Guidelines on Similar Biologics”. The drafters of the guidelines included the drug regulator Central Drugs Standard Control Organization, the Department of Biotechnology, academics, and surprisingly staff of major biotech companies, such as Biocon, Dr. Reddy’s and Roche.

This was a shocking conflict of interest. It is deemed reasonable worldwide to have the industry comment and provide input before the finalisation of regulations that affect public health. But never is the industry allowed to set the standards by which its products are regulated. Even the US Food and Drug Administration seeks public comment but only after the draft guidelines are published.

That conflict of interest was exacerbated by the fact that the guidelines didn’t prescribe rigorous standards needed to establish the safety and efficacy of biologics. For instance, they didn’t include tests assessing the ratio of heavy chain versus light chain of the protein included in the Certificate of Analysis, a legal document that the regulator evaluates for each batch of drug released.

Equally importantly, the guidelines didn’t mention if they were established under the provisions of the Drugs & Cosmetics Act, 1940. As per this law, all technical aspects of drug regulations should be referred to the Drugs Technical Advisory Board, a body with a wide representation of doctors, pharmacists, bureaucrats and researchers. The composition of this board is such that it is unlikely to be influenced by an interest group. It’s unknown if the board was consulted for the guidelines.

What’s also interesting is that the biologics guidelines were publicly announced at BIO, the largest biotechnology conference, in Boston, United States, in 2012. This was perhaps the first time that regulations drafted by Indian authorities for the purpose of regulating drugs in India were announced at an industry event abroad.

Together, these facts raise a crucial question: did the Indian biotech industry set the agenda for the Guidelines on Similar Biologics? This isn’t far-fetched. In 2012, India’s own parliamentary standing committee had accused the Central Drugs Standard Control Organization of acting under the influence of the industry which it is supposed to regulate.

In a sign of the ambiguity over the interpretation of the guidelines, Roche sued the Drug Controller General of India in 2014 along with the pharma companies Biocon and Mylan over the launch of a biosimilar of Roche’s breast cancer drug Herceptin. Besides questioning the approvals granted to the Biocon-Mylan biosimilar, Roche raised doubts over the conduct of clinical trials. All of these questions are now pending before the Delhi High Court, which last year issued a temporary injunction restraining Biocon and Mylan from launching their biosimilar into the market.

Does India have the expertise?

Still, the real challenge in creating a credible regulatory framework isn’t in the drafting of the law or guidelines. It lies in ensuring the regulator has the expertise – the staff competence, leadership and laboratories – to enforce the law. Unfortunately, India has almost no regulatory experience when it comes to complex regulatory approvals.

The two steps of a regulatory approval are the conduct of clinical trials followed by the evaluation of the data generated by those clinical trials. Even on the simple issue of conducting clinical trials, India has struggled to enforce the most basic ethical norm of informed consent. This had prompted the Supreme Court in 2013 to impose a temporary ban on all clinical trials in the country.

Part of the reason for this lack of experience in conducting clinical trials for new drug approval is that the Central Drugs Standard Control Organization depends on regulatory approvals granted in the West for approving drugs in India. The logic is simple: if it’s good enough for the West, we’ll allow it in India. This is why the CDSCO has almost never been the first regulator in the world to approve a new drug. For most of its existence, its only responsibility has been to approve generics, which, unlike new chemical entities, require only simple clinical studies on healthy human beings. Even evaluating the results of these studies is relatively simpler.

That is not the case for biosimilars: clinical trials are mandatory on patients and not just healthy volunteers. Since many biosimilars are being launched in India first, and not in the Western market, the Indian regulator has to actually evaluate data from full-fledged clinical trials to determine their safety and efficacy. Given that the regulator doesn’t have the expertise to conduct such evaluations for even conventional chemical drugs, can we expect it to do an effective job for the vastly more complex biosimilars?

Then there is also the issue of testing laboratories. As things stand, drug inspectors of both central and state governments draw samples from the market and send them to their labs. The government analysts at these labs are required, under Rule 44 of the Drugs & Cosmetics Rules, 1945, to have education in pharmacy or pharmaceutical chemistry or medicine or science. Molecular biology isn’t on this list. There is perhaps only one laboratory in the country, the National Institute of Biologicals in Noida, which has the expertise to test biologicals.

The alacrity with which the Central Drugs Standard Control Organization approved the biosimilar guidelines – and the controversies over them – leads one to question the regulator’s agenda. While the regulator must certainly respect the concerns of the Indian industry, it should not put them before the concerns of patients. If the Indian medical community loses faith in biosimilars because of poor regulation, Indian patients will have to cough up more for foreign imports. The ultimate culprit for this loss of faith will be the regulator.

The author is the executive chairman of Medassure Global Compliance Corporation.

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Swara Bhasker: Sharp objects has to be on the radar of every woman who is tired of being “nice”

The actress weighs in on what she loves about the show.

This article has been written by award-winning actor Swara Bhasker.

All women growing up in India, South Asia, or anywhere in the world frankly; will remember in some form or the other that gentle girlhood admonishing, “Nice girls don’t do that.” I kept recalling that gently reasoned reproach as I watched Sharp Objects (you can catch it on Hotstar Premium). Adapted from the author of Gone Girl, Gillian Flynn’s debut novel Sharp Objects has been directed by Jean-Marc Vallée, who has my heart since he gave us Big Little Lies. It stars the multiple-Oscar nominee Amy Adams, who delivers a searing performance as Camille Preaker; and Patricia Clarkson, who is magnetic as the dominating and dark Adora Crellin. As an actress myself, it felt great to watch a show driven by its female performers.

The series is woven around a troubled, alcohol-dependent, self-harming, female journalist Camille (single and in her thirties incidentally) who returns to the small town of her birth and childhood, Wind Gap, Missouri, to report on two similarly gruesome murders of teenage girls. While the series is a murder mystery, it equally delves into the psychology, not just of the principal characters, but also of the town, and thus a culture as a whole.

There is a lot that impresses in Sharp Objects — the manner in which the storytelling gently unwraps a plot that is dark, disturbing and shocking, the stellar and crafty control that Jean-Marc Vallée exercises on his narrative, the cinematography that is fluid and still manages to suggest that something sinister lurks within Wind Gap, the editing which keeps this narrative languid yet sharp and consistently evokes a haunting sensation.

Sharp Objects is also liberating (apart from its positive performance on Bechdel parameters) as content — for female actors and for audiences in giving us female centric and female driven shows that do not bear the burden of providing either role-models or even uplifting messages. 

Instead, it presents a world where women are dangerous and dysfunctional but very real — a world where women are neither pure victims, nor pure aggressors. A world where they occupy the grey areas, complex and contradictory as agents in a power play, in which they control some reigns too.

But to me personally, and perhaps to many young women viewers across the world, what makes Sharp Objects particularly impactful, perhaps almost poignant, is the manner in which it unravels the whole idea, the culture, the entire psychology of that childhood admonishment “Nice girls don’t do that.” Sharp Objects explores the sinister and dark possibilities of what the corollary of that thinking could be.

“Nice girls don’t do that.”

“Who does?”

“Bad girls.”

“So I’m a bad girl.”

“You shouldn’t be a bad girl.”

“Why not?”

“Bad girls get in trouble.”

“What trouble? What happens to bad girls?”

“Bad things.”

“What bad things?”

“Very bad things.”

“How bad?”

“Terrible!!!”

“Like what?”

“Like….”

A point the show makes early on is that both the victims of the introductory brutal murders were not your typically nice girly-girls. Camille, the traumatised protagonist carrying a burden from her past was herself not a nice girl. Amma, her deceptive half-sister manipulates the nice girl act to defy her controlling mother. But perhaps the most incisive critique on the whole ‘Be a nice girl’ culture, in fact the whole ‘nice’ culture — nice folks, nice manners, nice homes, nice towns — comes in the form of Adora’s character and the manner in which beneath the whole veneer of nice, a whole town is complicit in damning secrets and not-so-nice acts. At one point early on in the show, Adora tells her firstborn Camille, with whom she has a strained relationship (to put it mildly), “I just want things to be nice with us but maybe I don’t know how..” Interestingly it is this very notion of ‘nice’ that becomes the most oppressive and deceptive experience of young Camille, and later Amma’s growing years.

This ‘Culture of Nice’ is in fact the pervasive ‘Culture of Silence’ that women all over the world, particularly in India, are all too familiar with. 

It takes different forms, but always towards the same goal — to silence the not-so-nice details of what the experiences; sometimes intimate experiences of women might be. This Culture of Silence is propagated from the child’s earliest experience of being parented by society in general. Amongst the values that girls receive in our early years — apart from those of being obedient, dutiful, respectful, homely — we also receive the twin headed Chimera in the form of shame and guilt.

“Have some shame!”

“Oh for shame!”

“Shameless!”

“Shameful!”

“Ashamed.”

“Do not bring shame upon…”

Different phrases in different languages, but always with the same implication. Shameful things happen to girls who are not nice and that brings ‘shame’ on the family or everyone associated with the girl. And nice folks do not talk about these things. Nice folks go on as if nothing has happened.

It is this culture of silence that women across the world today, are calling out in many different ways. Whether it is the #MeToo movement or a show like Sharp Objects; or on a lighter and happier note, even a film like Veere Di Wedding punctures this culture of silence, quite simply by refusing to be silenced and saying the not-nice things, or depicting the so called ‘unspeakable’ things that could happen to girls. By talking about the unspeakable, you rob it of the power to shame you; you disallow the ‘Culture of Nice’ to erase your experience. You stand up for yourself and you build your own identity.

And this to me is the most liberating aspect of being an actor, and even just a girl at a time when shows like Sharp Objects and Big Little Lies (another great show on Hotstar Premium), and films like Veere Di Wedding and Anaarkali Of Aarah are being made.

The next time I hear someone say, “Nice girls don’t do that!”, I know what I’m going to say — I don’t give a shit about nice. I’m just a girl! And that’s okay!

Swara is a an award winning actor of the Hindi film industry. Her last few films, including Veere Di Wedding, Anaarkali of Aaraah and Nil Battey Sannata have earned her both critical and commercial success. Swara is an occasional writer of articles and opinion pieces. The occasions are frequent :).

Watch the trailer of Sharp Objects here:

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This article was published by the Scroll marketing team with Swara Bhasker on behalf of Hotstar Premium and not by the Scroll editorial team.