How Maiden and other Indian pharma firms exploited WHO certification process

Late on October 8, three days after the news broke that four of its adulterated cough syrups were likely responsible for killing 66 kids in Gambia, Maiden Pharmaceuticals, a company with its registered office in Delhi and its manufacturing facility in Haryana, broke its silence and said it was “shocked” at the development.

The cough syrups, which were being exported only to the West African nation by the firm, were found to be adulterated with diethylene glycol (DEG) and ethylene glycol, according to the World Health Organisation.

These two chemicals, fatal for humans beyond a minuscule limit, are not permitted in a pharmaceutical product but mass poisonings with its adulteration have happened on many occasions in different parts of the world, including India.

Clarifying that the company was fully cooperating with authorities in investigations, Maiden Pharma insisted that it had been diligently following the protocols laid down by the regulators.

Remarkably, a one-page statement issued by the drug maker claimed it was certified under the WHO-Good Manufacturing Practices (WHO GMP) norms.

This claim, though misleading—WHO itself does not issue any such certification—is a common feature on the letterheads of many drug makers.

The Certificate of Pharmaceutical Products (CoPP) issued by India’s national regulator, which allows a drug maker to manufacture and also export a product, assures that a plant complies with minimum standards of procedure and processes of pharmaceutical production as prescribed by the world health agency.

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Every CoPP certificate, at least on paper, guarantees that a drug maker follows good manufacturing practices for specified pharmaceutical products.

However, the certificate issued—following joint inspection by its authorities, in collaboration with state drug regulators, in no way guarantees that all products produced there are of standard quality, say experts, and as such, holds little value.

Regulated vs unregulated market

Pharmaceuticals expert C M Gulhati explained that from the exports’ point of view, the world is divided into two: regulated and unregulated markets, with about 35 countries, mainly in Western Europe and North America, falling in the first category.

When a country like the US, for instance, has to issue a licence to a drug manufacturer unit in India, the US Food and Drug Administration gets the facilities “spot inspected” without notice.

“There are very strict random checks of products exported to the US too, once they reach there,” said Gulhati, adding that in contrast, unregulated markets such as most African nations—barring South Africa to an extent—seldom check the drugs exported for quality.

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This unfortunately means that while drug makers in India are more careful about the drugs that go to developed countries, they are far more lax in what is supplied to low- and middle-income countries and often take “advantage of the regulatory oversights”, he added.

A scientific paper published in 2014 by Indian and American researchers, based on assessment of the quality of 1,470 antibiotic and tuberculosis drug samples from India sold in Africa, India, and five mid-income non-African countries, provides probably the only empirical evidence proving this, though.

The researchers found that 10.9 percent of those products failed a basic assessment of active pharmaceutical ingredients (API), and the majority of the failures are substandard (7 percent) as they contained some correct API but the amount of API was under-dosed.

“The distribution of these substandard products is not random: they are more likely to be found as unregistered products in Africa than in India or non-African countries,” the authors had noted.

The Indian government had come down heavily on the research report, calling it “motivated”.

Moneycontrol tried reaching drug controller general of India V G Somani and Haryana food and drug administrator Wazeer Singh Goyat to seek their responses on these observations but they were not available for comments despite multiple attempts.

An email seeking response from the Indian Drug Manufacturers’ Association, a network of generic drug makers in the country, has also not elicited any response so far either.

WHO’s role

Sources in the India office of the UN body explained that while the agency does not have any direct role to play in CoPP issued to drug makers in India, it is independent of inspections done only for on-boarding pharmaceutical products from a company for pre-qualification programme for supply to United Nations agencies.

The inspections carried out by WHO are far stricter than the ones carried out by the Central Drugs Standard Control Organisation (CDSCO) for issuing CoPP, pointed out Chinu Srinivas, another pharmaceutical expert associated with the All India Drug Action Network, a grouping of non-government organisations working to rationalise the use of medicines.

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In response to a query by Moneycontrol, the WHO said in an email that "the stated manufacturer is authorized and regulated by the State Drugs Controller, Haryana, India". This manufacturer has not been inspected nor any of its products assessed in any way by the WHO, the world health agency said.

Understaffing, corruption big concerns

A parliamentary standing committee report on the CDSCO’s functioning that came out in 2013 said that its mission was to “meet the aspirations….demands and requirements of the pharmaceutical industry”, instead of protecting public health.

The situation since, despite the committee putting on record the gross irregularities in its functioning, has remained as bad.

Gulhati, for instance, pointed out that random inspections by central and state drug regulators at least twice a year at every drug manufacturing unit in India—there are about 10,000 of them—are mandated as per the rules prescribed under the Drugs and Cosmetics Act, 1940, but that rarely happens.

“India’s CDSCO has less than 200 drug inspectors on its rolls. In comparison, the USFDA has over 10,000. One can imagine the seriousness with which the business of issuing CoPP and then carrying out inspections of plants and quality monitoring of finished products is taken here,” said Gulhati, who has also worked with the WHO in the past.

According to Srinivas, while it may be difficult to establish, on many occasions, CoPP may be issued even without carrying out proper inspections.

Quality, last priority?

In addition, states are competing with each other to promote pharmaceutical production in their own backyard, offering tax incentives and in many cases deciding only to procure medicines produced locally for government programmes.

It’s rather left to the manufacturer’s conscience to ensure that the drugs manufactured, either for consumption locally or for export, would be of standard quality, which sometimes results in instances of substandard products reaching the market, conceded a health ministry official, citing problems such as shortage of manpower to test every batch of a drug produced in a plant.

But according to public health activist Dinesh Thakur, that may be a ridiculous argument.

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“If drug manufacturers have a very high degree of ethics, instances of toxic substances getting mixed in the medicines or substandard drugs getting produced would not happen routinely,” he said, adding that India’s regulator and the government cannot escape their responsibility.

If some countries, such as African nations, are not so diligent in testing the quality of medicines coming from India, it's all the more important for Indian regulators to keep an eye on what's being exported from drugmakers here, said Thakur.