New Delhi: Indian drug inspectors have decided to advance a planned check of Indonesia’s PT Bio Farma, seeking to solve the mystery behind the contamination of some batches of a polio vaccine that now threatens to bring back a vaccine strain of polio believed to have been destroyed years ago.

The Indonesian company supplies the key starting material (KSM)—the active raw materials used in a vaccine that give it a therapeutic effect—to Indian manufacturers that make polio vaccines in oral forms. These drops, which carry weakened polio viruses, are given to children below the age of five under a government programme designed to build their immunity against the crippling disease.

“Four drug inspectors from CDSCO (Central Drugs Standard Control Organisation) will be travelling to inspect Indonesia’s PT Bio Farma. It provides KSM to the companies here to prepare polio vaccine. We were to leave on 29 October, but now have proposed to advance the trip," an official in the regulatory authority said on condition of anonymity. “The proposal is pending approval from the health ministry."

Since 29 September, when news of the contamination surfaced, regulators have been investigating how the type 2 strain of polio, believed to be long gone, found its way into vaccines made by Ghaziabad-based Bio-Med Pvt. Ltd.

The type 2 strain is thought to have been eradicated so long ago that the current polio vaccine no longer protects against it, and vaccine makers have been asked to remove it from the vaccine and destroy their stocks of the strain.

Traces of polio type 2 virus were found in some batches of polio drops given to children. The company was supplying polio vaccines for the government-run universal immunization programme. Around 50,000 vials—one vial has 20 doses—of contaminated vaccine are believed to have been used in Uttar Pradesh and Telangana.

In September inspectors of World Health Organization (WHO) found type 2 polio virus in sewage and stool samples in a development that threatens to rob India of its polio-free status.

According to Dr Sylvia Karpagam, a public health expert based in Karnataka, the oral polio vaccine batch containing the P2 strain has reached Uttar Pradesh and Telangana, endangering many of “those who have not received inactivated polio vaccine (IPV) and are exposed to strain 2 and are now at risk of getting vaccine-derived polio.

The bigger problem is that the virus can mutate and no one knows into what form—mild or virulent".

For a long time, polio vaccines carried three strains of viruses—type 1, type 2 and type 3, also called P1, P2 and P3, respectively—and were hence called trivalent vaccines. Worldwide, the second strain was withdrawn from vaccines several years ago on confirmation that it had been eradicated among humans.

India, which continued to use the trivalent vaccine for some more time, switched to bivalent vaccines in April 2016, joining the rest of the world, confident that the type 2 strain had been eliminated. The move also ensured that chances of vaccine-derived polio were minimized. With this, companies producing polio vaccines were supposed to destroy their stocks of strain 2. Therefore, the reappearance of the P2 strain comes as a shock and threatens to change India’s status as a polio-free nation.

As part of a larger investigation, Mint visited the Central Drugs Laboratory (CDL) located in Kasauli, a hill station in Himachal Pradesh, which tests vaccines before they are sent across the country. Although the health ministry has said there is no need to panic, questions remain over how the supposedly eradicated P2 strain entered some batches of the oral polio vaccine.

The contaminated batches were manufactured in March this year and sent to Kasauli for mandatory testing. At CDL Kasauli, vaccines are tested only for the viruses mentioned on the label.

This means testing is done on the assumption that what the manufacturer has mentioned on the label is accurate, so testing is limited to just the strains mentioned on the label.

If, for instance, the label mentions P1 and P3 strains, tests would be conducted only for those two strains, with none for P2.

According to CDL, this is the protocol, which it has duly followed. “The testing standards are set by Indian Pharmacopoeia Commission (IPC), an autonomous institution of the ministry of health and family welfare," said CDL Kasauli director Arun Bhardwaj. “All the samples are tested for their potency as per the label claim, before they enter the market for the consumers. We are following a due protocol."

According to CDL officials who did not want to be identified, if the Kasauli laboratory starts suspecting every batch and tests vaccines for every strain, no vaccine would reach the market since it’s a time-consuming process.

A visitor to Bhardwaj’s office has to pass by piles of empty boxes, bearing testimony to CDL’s huge workload. The director insists work is on track and that CDL is not short-staffed; yet, a large whiteboard in his office displaying the amount of work has not been updated since July. It says that a total of 4,105 vaccines were tested that month.

These include vaccines for MMR, rabies, hepatitis B, hepatitis A, yellow fever, influenza, Japanese encephalitis, varicella, measles and rotavirus. Polio accounts for the maximum, with 748 doses of the oral polio vaccine (OPV) tested in July.

“Samples from all over India from all the companies manufacturing vaccines come here for testing before going to the market," said Bhardwaj.

CDL Kasauli was established to ensure that the vaccines and antisera produced, distributed and imported into the country are safe, efficacious and potent. It is mandated to regulate the quality of vaccines produced indigenously for the domestic market, the government’s immunization programme, for exports and those imported into the country.

Every day, CDL Kasauli tests two batches of polio vaccines for potency. From the day news of the P2 strain surfaced until 4 October, a total of 16 batches had been tested.

“We need to investigate and find out what actually happened and how the contamination occurred," said WHO deputy director general Dr Soumya Swaminathan.

In India, there are four major manufacturers of the bivalent vaccine—Bio-Med (currently under the scanner), Bharat Biotech International, Panacea Biotec, government-owned Bharat Immunological and Biologicals Corp. Ltd (Bibcol) and Mumbai-based Haffkine Bio Pharmaceutical Corp. Ltd.

The contaminated doses were manufactured by the lesser known Bio-Med. About 150,000 contaminated vials are expected to have entered the government-run vaccination programme. The regulator is investigating how the type 2 strain was retained by the company even after the drug regulator had ordered manufacturers to completely destroy it by 25 April 2016.

“The first question is: Did the company stop and destroy P2 strain," asked Dr M.K. Bhan, former secretary in the department of biotechnology under the ministry of science and technology.

“The companies were also supposed to remove the virus from the cold chain and dispose of it," said Dr S. Eswara Reddy, drug controller general of India (DCGI).

The managing director of Bio-Med was arrested on 29 September after a first information report was filed by CDSCO and later released on bail last week.

Three drug inspectors have since been investigating Bio-Med’s plant and paperwork.

“It seems the company was not following good manufacturing practices (GMP) standards to the full extent. The company was not following certain quality parameters," said the official in the regulatory authority quoted earlier.

This is, however, not the first time Bio-Med has got into trouble with regulators. In March, CDL Kasauli found two batches of its Peda Typh typhoid vaccine to be substandard.

How then did Bio-Med continue supplying vaccines for the government? Experts say the problem lies with the bidding system under which the lowest bidder (L1) gets to supply the government. In this case, Bio-Med proved to be the L1.

In a recent tender floated to procure OPV vaccines after the virus debacle, there was a difference of a mere 14 paise per dose between L1 (Bio-Med) and the second-lowest bidder. According to documents seen by Mint, while Bio-Med quoted 4.73 for a dose, Bharat Biotech quoted 4.87, Bibcol 5.05 and Haffkine the most expensive at 121.80.

“This is a disaster. They can sell cheap because they don’t have quality assurance," Bhan said. “Price that we give to manufacturer must be reasonable without sacrificing the quality. We like to get cheap products, but it should not be held true for vaccines. The balance between quality and price is much needed."

The tender process has even become a bone of contention among companies. “Have we put lives of children in danger to save 14 paise,"asked a polio vaccine manufacturer, who lost the bid because he quoted higher, on condition of anonymity.

A spokesperson for Sanofi Pasteur, the world’s largest manufacturer of IPV, said: “At Sanofi Pasteur, it takes between 6-36 months to produce, package and deliver one single dose of vaccine. Seventy percent of the production time is dedicated to quality controls and thousands of tests are performed to make sure that the vaccine is of the highest quality."

“The amount of money that has been invested in the polio campaign will be of no use if the regulatory mechanisms and quality control measures are not of the highest quality," Karpagam said. “The regulatory body is equally liable for failing to adequately monitor the goof-up."

Some experts are hopeful, though. “With the current status that we have, children are adequately protected and hence we do not see any current threat of polio outbreak. India has a robust polio surveillance programme, it needs to be continued," said Dr Raj Shankar Ghosh, deputy director, vaccine delivery and infectious disease, at Bill and Melinda Gates Foundation.

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