New Delhi: The Centre has banned 156 more fixed dose combination (FDC) drugs because they are “likely to involve risk to humans”, in the biggest crackdown on these drugs since 2018 when it prohibited 344 such combinations as “irrational”.
FDC drugs contain a combination of two or more active pharmaceutical ingredients (APIs) in a single form, usually manufactured and distributed in a fixed ratio.
The combination drugs banned through a notification on 12 August included several antibiotic combination medicines, used for fever, allergies, colds, skin disorders, and pain, among others, that are widely sold. ThePrint has a copy of the notification.
The newly banned FDCs include cetirizine and phenylephrine hydrochloride; levocetirizine and phenylephrine hydrochloride; paracetamol and pentazocine; paracetamol and mefenamic acid; and paracetamol, diclofenac potassium and caffeine anhydrous.
Some of the FDCs prohibited were also combinations of commonly used active pharmaceutical ingredients (API) with herbs such as ginkgo biloba as well as a mix of vitamins and enzymes.
The list also banned multi-enzyme complexes containing as many as 12-15 enzymes and over 20 formulations containing naphazoline, a decongestant commonly used in eye drops.
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‘Lack therapeutic justification’
The brands which are likely to be affected due to the latest ban are sold by pharma giants such as Cipla, Dr Reddy’s laboratories, Sun Pharmaceuticals, Torrent, and Alkem, among others.
ThePrint has reached these companies over email for their comments on the development. This report will be updated if and when their responses are received.
In the notification, the government has said that it feels that these FDCs are “likely to involve risk to human beings whereas safer alternatives to the said drug are available”.
It added that two committees — including one under the Central Drugs Standard Control Organisation’s (CDSCO) Drugs Technical Advisory Board (DTAB) — examined the FDCs and found that “there is no therapeutic justification for the ingredients contained” in the combination drug while they may involve “risk to humans”.
Exercising the power conferred by the section 26A of the Drugs and Cosmetics Act, 1940, the “Central Government hereby prohibits the listed FDCs’ manufacture for sale, sale and distribution for human use with immediate effect”, said the notification.
Dr Nilima Kshirsagar, who has headed the CDSCO committees based on whose recommendations the government has affected bans on FDCs in the past, said that most FDCs examined by her panels were found lacking in “therapeutic justification and were potentially harmful to patients”.
“In 2021, a DTAB panel which I had headed had submitted a report recommending ban on nearly 200 FDCs. I am not sure whether the 156 drugs banned now are from the same list but most FDCs could not prove safety or efficacy,” Kshirsagar, former chief of clinical pharmacology at the Indian Council of Medical Research (ICMR), told ThePrint.
In some cases, she said, the manufacturers did not even have any indications for the drug combinations they were selling, meaning it wasn’t clear which conditions they were meant to address.
Deep-rooted malaise
According to drug safety experts, irrational FDCs started hitting the Indian market in the 1980s, but it was only in 2012 — following a scathing report by a parliamentary standing committee — that the issue came under public scrutiny.
The committee had observed that some state licensing authorities had issued manufacturing licenses for several FDCs without prior clearance from the CDSCO, resulting in a flood of drug formulations not tested for efficacy and safety, putting patients at risk.
“What happens is while APIs A and B may have been tested separately for safety and efficacy, that does not mean that putting A and B together in a drug will make safe or effective too but that is exactly what drugmakers do in coming out with FDCs,” said pharmacologist Dr Santanu Tripathi, a former CDSCO committee member.
Under India’s Drugs and Cosmetics Act, only CDSCO can issue marketing licenses for a new drug. Drug combinations fall into that category.
However, Dr Tripathi explained, drugmakers convince state licensing authorities to approve manufacturing on FDCs on the ground that APIs used in the formulation are permitted separately by the CDSCO.
“The drugmakers do it in order to create new brands, which makes it easier for them to target doctors and patients and also circumvent price control,” Dr Tripathi said.
The ceiling price of APIs and formulations listed under the National List of Essential Medicines — mostly drugs used to treat common conditions such as fever, infection, heart disease, hypertension, skin diseases and anaemia, among others — is fixed by the government.
Following the 2012 parliamentary report, the CDSCO sought a list of FDCs approved by the state drug authorities and received 6,320 applications.
This led to the formation of a panel, led by veteran pharmacologist C. K. Kokate, to examine FDCs for their scientific rationale. Based on the first recommendations of this panel, the health ministry banned 344 FDCs in 2016.
However many pharma companies challenged this in the Supreme Court and based on the court’s direction, another DTAB sub-committee, headed by Kshirsagar, was formed. The panel backed Kokate committee’s recommendations and in 2018 the Centre finally, banned the 344 FDCs.
The Kokate committee had also looked into hundreds of other FDCs as well in three other lists, which were later referred to the Kshirsagar panel.
In 2021, Kshirsagar told ThePrint, the panel she was heading had suggested a ban on 200 more FDCs.
‘Decision lacks transparency’
Chinu Srinivasa, co-convenor of All India Drug Action Network (AIDAN), a patient rights group, which has advocated for careful scientific examination of FDCs, welcomed the latest move but also highlighted a lack of transparency in the decision.
“The government should put out the basis and recommendations of the expert panel based on which the decision has been made and also tell us whether the views by the companies have been heard,” he said.
Dr Tripathi, meanwhile, said the ban was not enough when the practice of state drug authorities permitting the manufacture of new FDCs still continues.
“I feel that merely banning one set of irrational FDCs is not enough. The companies doing that should also be penalised for selling drugs which do not have therapeutic justification and are mostly unsafe,” he stressed.
Several analyses have shown that FDCs now constitute a large share of the domestic drug market in India and the measures taken by the government, so far, to remove FDCs have been mostly ineffective.
A crucial study which came out last year, for example, found that in 2020, most of the antibiotic formulations sold in India were unapproved or banned.
(Edited by Sanya Mathur)
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