Indian drug regulator may expedite approval process for HIV drug pellets


Mumbai: Indian drug regulator, the Central Drugs Standard Control Organization (CDSCO), is likely to expedite the approval process for lopinavir and ritonavir pellets, used to treat HIV infections in children, to help avoid shortages of paediatric formulations for HIV in the country.

This development comes in the backdrop of the National Aids Control Organization (NACO) running out of stock of lopinavir and ritonavir syrup, as Cipla Ltd, the sole supplier, phased out production of the syrup in 2015 and replaced it with pellets. However, lopinavir and ritonavir pellets are not approved and registered in India as yet.

The company also did not participate in the tenders issued by NACO for procurement of the syrup due to delays in receipt of payments.

On 3 March, guardians of more than 600 HIV-infected children wrote a letter to Prime Minister Narendra Modi and ministry of health and family welfare to highlight the shortage of lopinavir and ritonavir syrup since January and seek resolution of the issue at the earliest.

NACO has placed an emergency order for the syrup with a Haryana-based company, Mcneil & Argus Pharmaceuticals Ltd, and the product will be available in the antiretroviral centres within the next few days, R.S. Gupta, deputy director general of NACO, said, adding that the agency has written to the Drugs Controller General of India (DCGI) to register lopinavir and ritonavir pellets in India.

Mcneil & Argus Pharmaceuticals manufactures the syrup only if there is a specific order and has supplied it only twice before, said G.D. Chhibber, chairman of the company.

While NACO has sourced the product from another vendor to deal with the crisis, a long-term solution would be to ensure that Cipla participates in the government tenders and the regulator approves the drug in pellet form, said a person associated with the Delhi Network of Positive People (DNP+), who did not wish to be named.

“We will consider expediting the approval for pellets and also waive off clinical trials requirement if the company applying for the product approval provides sufficient data on stability, safety and efficacy of the product,” DCGI G.N. Singh said.

Cipla had submitted an application last year for approval of lopinavir and ritonavir pellets in India but it was not accepted and the CDSCO insisted on conducting clinical trials as a pre-requisite for registration of the product.

Cipla’s global director for access and public affairs Denis Broun said, “As soon as the pellets were ready, we submitted a dossier to DCGI, but it was not accepted. We received approval from the US Food and Drug Administration and were able to commercialize the pellets in several other countries. We have re-submitted our dossier to DCGI and hope to have a rapid reply.”

Cipla stopped manufacturing lopinavir and ritonavir syrup about 18 months ago, when the new formulation (pellets) was approved by USFDA, Broun said.

“The syrup tasted really foul, had an alcoholic content of 42% (comparable to whisky) and required refrigeration. Pellets have no alcohol, no taste and can be kept at room temperature. The advantage of pellets was so obvious that we stopped manufacturing the syrup,” he added.

“Pellets are better than syrup but Cipla being the sole manufacturer should not have stopped production of syrup when no other alternative is available forHIV-infected children in the country,” said Paul Lhungdim, president of the patients group DNP+.

Paediatric AIDS affects only a small section of the population and hence very few manufacturers globally produce child-friendly doses of HIV medicines. In India too, several drug makers, including Aurobindo Pharma Ltd, Hetero Drugs Ltd and Macleods Pharmaceuticals, make HIV drugs for adults but are not into paediatric formulations, said the person associated with DNP+.

The letter to the PM mentioned that lack of prioritization by the CDSCO to provide permission for bioequivalence studies and registration of new child friendly fixed-dose combination formulations of HIV drugs is impacting the availability of essential paediatric medicines to the HIV programme in the country.

“Procurement of medicines needs to be timely and so do the payments by the government for the medicines that companies supply to NACO. Procurement and supply chain reforms for pharmaceuticals led by the Health Ministry are taking a long time,” the letter stated.

“Generic companies manufacturing ARV (antiretrovirals) sell them with a very thin margin and delayed payments easily make this margin negative. Cipla is not able to sell at a loss, even to the Indian government. We hope that NACO will regularize financial arrears and guarantee prompt payment in the future,” Broun said.

Once the company knew about the shortage, it set aside part of the production of lopinavir/ritonavir pellets so that they could become available for India and also immediately entered in discussions with the Global Fund for an exceptional financing of Indian children, Broun said. “The Global Fund reacted with remarkable speed and allowed their “rapid supply” facility to finance treatment for children for six months,” he said.

Cipla is currently finalizing a new formulation of antiretroviral drug, which will include four products in single formulation, which will take the form of tasteless granules. The company hopes to make it available in 2018, Broun added.