India To Weed Out Over 300 Fixed-Dose Combos; Next Round In Court
This article was originally published in Scrip
India has clamped down on the country's burgeoning market for irrational fixed-dose combinations (FDCs), weeding out more than 300 such products – a move that is seen as denting the industry sharply but being welcomed by physicians given the lack of therapeutic rationale for most of these medicines and the growing challenge of drug resistance in the case of anti-infectives.
Pfizer and Abbott, whose top cough syrup brands have been covered under the ban, have, however, already moved court against the government's action. Pfizer has secured interim relief from the Delhi High Court on March 14.
India's ministry of health and family welfare has already prohibited the manufacture, sale and distribution for human use 344 FDCs deemed likely to involve "risk to human beings" and where safer alternatives are available.
The matter was examined by an expert committee appointed by the central government and the panel recommended that these FDCs have "no therapeutic justification", government notifications, dated March 10 and now publicly available, said.
It is, however, not immediately clear how pipeline stocks will have to be dealt with.
The ban covers products across segments such as respiratory, pain, diabetes and cardiology and is expected to impact over INR38bn ($572m) of the Indian market in value terms, according to early estimates from AIOCD AWACS, a market research agency that tracks retail sales. The respiratory, anti-diabetics, pain/analgesics and anti-infectives segments are among those badly hit, the agency's data suggested.
Pfizer and Abbott are among those staring at big dents, with their cough syrup brands Corex and Phensedyl respectively to be pulled off the market, though both firms have sought legal relief. Among the Indian firms, Macleods, Mankind, Alkem, Ipca and Glenmark are some of those affected.
Early on March 14, Pfizer informed the Bombay Stock Exchange that it had "discontinued" the manufacture and sale of Corex with immediate effect, following the government prohibition concerning the chlopheniramine maleate + codeine syrup. The US firm, though, maintained that Corex has a "well-established" efficacy and safety profile in India for more than 30 years. Corex reported sales of INR1.76bn for the nine months ended December 2015.
"Pfizer makes every effort to maintain the highest standards of regulatory and quality compliance in the manufacture and distribution of Corex cough syrup. The company is exploring all available options at its disposal," it said.
The Pfizer stock ended more than 8.6% lower on the BSE on March 14.
Late March 14 Indian time, Pfizer confirmed having received an interim injunction "suspending the operation" of the notification banning the manufacture and sale of the FDC of chlopheniramine maleate + codeine syrup till the next date of hearing.
"We are awaiting the order from the Delhi High Court," the company added.
Abbott said that it had reviewed the notification and is concerned about the "unilateral approach" in prohibiting the manufacture, sale and distribution of certain FDCs that have already been approved for use by the Drugs Controller General of India (DCGI).
"We are evaluating the notification and exploring all available options," Abbott said.
Industry Response
Industry bodies swung into action, questioning the seeming unilateral action of the ministry in the case of some products.
Ranjana Smetacek, Director General, Organisation of Pharmaceutical Producers of India (OPPI), which represents foreign firms, told Scrip that a list of FDCs has been under technical review for some years now, mostly due to concerns around the "irrational" definition of these products.
"These concerns did not extend to codeine formulations, which have also now been brought under this notification. Codeine formulations are approved by the US FDA and available across many countries. The codeine products in the notification have been approved by the DCGI and safely and effectively used in India for years. What is more, some of these formulations do not presently have alternatives," Smetacek told Scrip.
Others like Dilip Shah, secretary general of the Indian Pharmaceutical Alliance (IPA), which represents leading domestic firms, said that the IPA was not against the ban of irrational combinations keeping in mind patient interest, but underscored that such action must follow due process of law laid down in the Drugs and Cosmetics Act.
"The IPA looks for a rule-based, stable and transparent regulatory regime -one that is free from knee-jerk reactions to criticism from any and all quarters. Unfortunately the current list includes some items which were not examined by the expert committee. Even in respect of items that were referred to the committee, the process of law is circumvented," Shah said.
Part of India's irrational FDC problem is also on account of India's regulatory structure that permitted state drug authorities to issue licences for new drugs including FDCs without the prior approval of the DCGI.
"The loophole is not yet fully plugged as some state authorities do not comply with the DCGI directions as the Drugs and Cosmetics Act has empowered them to grant manufacturing licenses," Shah told Scrip.
India had some years ago instructed state authorities to cancel manufacturing licences for combination formulations that are "new drugs" not yet approved by DCGI. [
Physician Speak
While physicians contacted by Scrip welcomed the government ban in general, they also referred to implementation and monitoring challenges and "distress" to patients who have been on some of the FDCs for long periods.
"Such FDCs should never have been approved in the first place; once approved, companies should have been asked to show clinical data and justify such combinations. It's going to be quite challenging for some patients - those who have been on triple combinations etc," one leading endocrinologist told Scrip. The list of banned FDCs includes several metformin combinations including with atorvastatin, metformin + pioglitazone + glimepiride and gliclazide + metformin, among others.
There have been some reports of smaller firms expressing concern over the costs of trials to justify long available FDCs.
Others, though, said it was time irrational FDCs were taken off the market also in the backdrop of the huge problem of antimicrobial resistance in the country. They said that it was bad enough to have antibiotics available in India across the counter without proper prescriptions and that irrational FDCs only made things worse.
India had earlier included a new provision, Schedule H1, to the Drugs and Cosmetics Act that aimed to curb the indiscriminate use of certain third- and fourth-generation antibiotics, certain habit forming medicines and anti-TB drugs, though experts have generally referred to how implementation aspects remain sketchy.