On June 18, the Government of India suspended the manufacture for sale and distribution of two drugs — analgin and pioglitazone. The reasons for suspension were that the drugs are likely to involve risk to human beings and safer alternatives to the drug(s) are available.

Section 26 A of the Drugs and Cosmetics Act 1940 empowers the Central Government to “regulate, restrict or prohibit” any drug. There is no provision to “suspend” the manufacture for sale, sale or distribution. In both cases, minutes from relevant committees in the run-up to the suspension read thus: “(the committee) recommended that the marketing of the drug in the country should be put under suspension and the firm should be asked to generate adequate data in Indian scenario to consider the matter further.”

DATA INADEQUACY

One cannot gather evidence or “generate adequate data” if a drug is suspended — if suspension means that the drug is not legally available in the market. Clinical trial of suspended or bannable drugs has severe ethical problems, even if officially allowed. How many would volunteer to be a guinea pig for a clinical trial of a drug suspected to have problems?

In addition ‘suspending’ a drug, as contrasted to banning or prohibiting a drug, leaves the impression that the decision to suspend the drug can be reversed. It leads to unethical lobbying by pharma companies.

Indeed, aggressive lobbying may have led to a reversal of the order on pioglitazone and its formulations, which command a sale of Rs. 830 crore. On July 20, the media reported that suspension on analgin and pioglitazone is to be lifted soon. Nobody knows how “adequate data” was gathered in a matter of a month so as to reverse the decision. And that too Indian data.

All drugs banned in India since 1983 when Sec 26 A was introduced, were banned on the basis of ‘foreign’ data, not ‘Indian’ data. India does not as yet have a systematic process of adverse data collection that we can rely on to ban drugs — or even ‘suspend.’ So, what motivated the flip-flop? Obviously, considerations other than science.

The process belied the lack of a clear procedure on the part of the Government on the parameters for prohibiting/restraining a drug.

COMBINATION ISSUES

In the late 1970s, analgin was found to cause a severe fall of white blood cells — a potentially fatal condition. It was subsequently banned in several countries. It has a sale of Rs 100 crore in the Indian market. Analgin does not appear in the National List of Essential Medicines (NLEM). Therefore, it will not be under price control. And that seems to have motivated the move for revocation of suspension.

The other drug, pioglitazone, has attracted controversy. In the protocol of treatment of Type 2 diabetes, it is a drug that is to be followed after the utility of drugs like metformin and glimepiride have been exhausted. Its market is over Rs 800 crore, out of which only Rs 100 crore are of single ingredient, pioglitazone (which itself raises doubt whether it is being used sensibly as the third alternative). The balance of over Rs 700 crore are irrational (and likely harmful) fixed dose combinations of pioglitazone.

INDIAN CONTEXT

It is now clear from many studies that not an insignificant percentage of people using pioglitazone may end up getting bladder cancer. That does not mean it will or will not happen among Indian patients, too. We simply do not know because we have no Indian studies. Can these studies be done? Theoretically yes, but as pointed above it may be unethical, and will you have volunteers for such a trial? Unlikely.

In its Action Taken Note (on the 59th Parliamentary Committee Report) submitted to the Parliamentary Committee in December 2012, the MoHFW made the following commitment:

“It has since been decided that whenever a drug is banned due to adverse drug reactions in countries with well developed and efficient regulatory system, namely, the US, the UK, the EU, Australia, Japan and Canada, the manufacture, import and marketing of such drugs would be immediately put under suspension till the safety of the drug is examined and established in the country.”

Both the drugs, analgin and pioglitazone, were suspended on the basis of data generated in “well developed and efficient regulatory systems.” Why then attempt to go back on the suspension of these two drugs?

Indeed, a third drug, dextrpropoxyphene, was ‘suspended’ on May 23, 2013 — also on the basis of foreign data. The basis of suspension of the three drugs — dextrpropoxyphene, analgin and pioglitazone — was exactly the same, that is,, unacceptable serious adverse effects in countries with well-developed regulatory apparatus. Yet there is no talk of lifting the suspension order on dextropropoxyphene — flip-flop and inconsistent yardsticks at work.

The lack of a standard operating procedure for suspension/ban of drugs, and for revoking suspensions credibly is an added factor: Revocation has never been done before in the history of independent India. (We are not advocating the return of dextropropoxyphene.)

COST FACTOR

The originator of pioglitazone, Takeda Pharmaceuticals, has also issued additional warnings on pioglitazone, saying that it can cause fluid retention that precipitate or worsen congestive heart failure.

Takeda also says liver function tests must be done before starting pioglitazone and periodically thereafter. The upshot seems to be that pioglitazone is useful, but of doubtful safety. The alternative, although not of the same drug class, are gliptins and insulin, but these are costly compared to pioglitazone. And most people in India do not have refrigeration facilities to keep insulin cool in their homes.

If we ban pioglitazone, the problem of how to bring down the cost drastically of gliptins has to be addressed — and some gliptins are under patents. Nothing stops the Government in the meantime from reducing the complications of taking pioglitazone in unscientific fixed dose combinations with other anti-diabetics like metformin and glimepiride.

The only thing stopping the Government is lobbying from pharma companies that stand to lose Rs 700 crore of sales from irrational formulations of pioglitazone. And another Rs 100 crore from analgin.

(The author is with All India Drug Action Network.)

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