Timely resolution of FDA action crucial to Indian pharma's US pipeline

Analysts say overall risks remain high for US generics business

The Indian pharmaceutical industry’s recent tryst with the US drug regulator may impact future pipelines, observe analysts.

Data shows that there were about 60 official action indicated (OAI) citations by the US Food and Drug Administration (USFDA) at Indian sites between November 2019 and November 2022.

For the most part, in the past 12 months, five OAI classifications have been issued, of which two have been escalated to ‘import alert’.

Research analysts at Motilal Oswal revealed in a recent report that in Calendar 2022, around four plants have got import alerts from the FDA and there were at least seven to eight USFDA inspections conducted between August and November that did not receive any classification.

This is significant because the fate of these facilities now hangs in balance until a final classification is announced by the FDA.

Analysts Tushar Manudhane and Sumit Gupta of Motilal Oswal highlighted: “While the OAI classification is issued in approximately 90 days after USFDA inspection, the timeline of regulatory action has reduced considerably.”

For instance, Glenmark Pharmaceuticals’ Baddi site was inspected in June this year and issued an import alert in October. Even the Halol site was inspected in May this year. Subsequently, it was issued OAI classification in August. Recently, it was issued an import alert within six months of USFDA inspection.

After the USFDA inspectors visit a plant, they either clear the plant or issue what is called Form 483 with their observations. Companies typically respond to queries raised by the regulator within a stipulated time frame. Eventually, the FDA issues the final classification of the site – which could be OAI, warning letter voluntary action indicated (VAI) or no action indicated. An import alert may follow a warning letter or OAI classification if the FDA is not satisfied with the remedial action taken by the company.

OAI implies objectionable conditions were found and regulatory action should be recommended, whereas a VAI implies objectionable conditions were found and documented but the agency is not prepared to take or recommend regulatory action.

Exports from a facility stop if placed under import alert.

A warning letter is an escalation of Form 483 (which notes adverse observations around the quality and compliance of a facility that need to be addressed by the manufacturer) by the USFDA. The regulatory actions of OAI or warning letter cease new product approvals from the site. Additionally, import alert stops existing businesses as well, subject to the exemption of certain products.

Sun Pharmaceutical Industries’ Halol facility in Gujarat saw an OAI classification escalated to import alert over the past six months.

“The import alert implies that a company will not be able to supply products from this site to the US market until the facility becomes compliant,” said Motilal Oswal.

Data from the brokerage shows that recent warning letters or OAIs have taken anything between a year and eight/nine years to resolve.

Motilal Oswal thus notes: “Overall, the risk to the US generics business remains elevated. The successful product review, as well as approval, should be supported with robust compliance requirements for better visibility and consistent growth in the US generics segment.”

Drug companies are thus focusing on derisking their key products.

Cipla, for example, said in the first week of November, that it derisked its chemotherapy drug Abraxane (estimated to be launched in the US in the first half of the Calendar 2023) because its Goa plant was under FDA scanner. It had submitted responses to the FDA and was awaiting word from the regulator.

“If Goa clears, we can launch this product in the first half of next calendar year, and if it does not clear immediately, then the launch can be in the second half of the year. We are filing this product from another site,” Umang Vohra, managing director and global chief executive officer, Cipla, had then said. 

By the third week of November, the FDA confirmed that Cipla’s Goa facility would continue to remain under OAI status.

A senior executive of a drug firm said that Indian drug firms continue to work closely with the FDA, and most have also appointed consultants to help them grasp the regulatory minutiae in the US.

“China and India have the highest number of inspections, excluding the US. Therefore, the number of actions is also high,” he said, adding that a company does not know in advance about an impending USFDA audit.