Mumbai: In a fresh crackdown reported last week, the government banned 156 medicines that were made from “irrational” combinations of two or more drug ingredients.
The gazette notification issued Aug. 12 by the health ministry said there is no therapeutic justification for those ingredients and that may involve risk to human beings. “Hence in the larger public interest, it is necessary to prohibit the manufacture, sale or distribution” of such fixed dose combinations (FDCs).
Some of the drugs in that list had as many as eight ingredients.
Among the most popular medicines blocked are combinations of paracetamol injection and mefenamic acid, tramadol and paracetamol with caffeine and taurine and cold and allergy drug cetirizine with terbutaline, ambroxol and guaiphenesin. Several other medicines have combinations with antibiotics like azithromycin, cefixime and amoxicillin. Large companies reported to be affected by this decision include Torrent, Dr. Reddy’s, Sun Pharma, Cipla and Alkem.
This is the second major action that the government initiated as part of its efforts in the last few years to clean up and revamp the drug regulatory procedure for approval of new products. The first move came in 2016 when about 344 products were ordered to be withdrawn, those prominently included popular cough syrups and painkillers.
That decision came following a report by a high-powered government committee set up under Professor Chandrakant Kokate. The mandate for the committee was to understand the safety and efficacy of thousands of combinations of medicines that were approved by state level drug authorities.
However, a long list of companies had then rushed to the courts to challenge the decision. Damage controlled, the court favoured some companies that paved the path for reintroduction of their drugs while others did so with minor tweaks in their ingredients.
A significant change that came with increased scrutiny was that the approval process for new drugs moved from the state level regulatory agencies to the central regulatory authority – the Drug Controller General of India. That meant a centralized system that closely consider scientific factors to approve or dismiss an application.
However, that in isolation, may clearly not be a fool proof or sufficient step to control the flooding of irrational combinations in the market. Indian drug makers have developed great expertise in chemistry but the big question looms: Do such combinations stand a chance to be approved by drug regulators in markets like the US or EU? That may need several steps of clinical trials, comparative studies with existence drugs and a rigorous review process by a panel of experts.
Experts believe with a few exceptions, much of the combination drugs launched in India may have less to do with convincing therapeutic rationale or benefits for patients and more to gain an edge over the competition. To push the doctor to write prescriptions for such drugs based on thin evidence is another skill.
Also, the idea of robust pharmacovigilance is barely seen in India. If only patients were educated through mass campaigns and knew about the adverse event reporting framework and doctors took time out to share their feedback with authorities, tracking and examination process to weed out irrational combinations would have been a lot simpler and transparent.
Therefore, the drug approval process needs to get stringent and based on scientific evidence, a global scanning of approved drugs and finally the risk-benefit ratio over existing alternatives. If the state regulators had not approved thousands of such drugs in the first place there would have been no need to ban them.
At the same time, it needs to be emphasized that not all drug combinations are irrational or devoid of ample therapeutic justification. HIV drugs cocktails as also many anti-cancer drugs work better when combined.
While the regulatory process has its flaws, there is another problem in the approach of the homegrown companies. For most, India has turned out to be the hot destination for growth. That rush is noticeable for a major reason.
Roughly two decades ago leading companies struck big opportunities that were unfolding in the US. They made windfall profits from launches of generic drugs. Costly court battles against multinational drug makers made it all worth. Then a decade later came the phase of declining returns. Multiple companies moved in and crashed the prices of generic drugs sold in the US, litigation costs shot through the roof, costs for ANDA filings saw a sharp rise and most critically, manufacturing sites came under the scrutiny of the US FDA. All this made the US business risky, unattractive and profit margins started to shrink.
Business reviews found the US market viable only in specialised products with high barriers for competition. The complexity was tough to crack, and the go-to-market strategy was way different from the pure generics play and needed more cash burn for promotion of brand and specialized field staff.
That shifted the focus back to India. From the time about two decades ago when a leading executive in an Indian company had said “we don’t see much in India,” to now when India is seen as a formidable market for long term growth, the change is interesting to say the least. No problem with that.
Just that like the US regulators, their Indian counterparts should be stricter on compliance standards. By doing so they will gain the respect and dignity from the Indian industry. The larger goal of serving the patients better can be achieved more meaningfully.
