Timely Resolution Of FDA Action Key For Indian Pharma's US Pipeline

Indian pharma's recent tryst with the US drug regulator may impact future pipeline from these plants, according to analysts.

The data shows that there were around 60 official action indicated (OAI) citations by the US Food and Drug Administration (USFDA) at Indian sites between November 2019 and November 2022. Particularly, in the past 12 months, five OAI classifications have been issued, of which two have been escalated to import alert. Motilal Oswal analysts showed in a recent report that in the calendar year 2022, around 4 plants have got import alerts from the FDA and there are at least 7-8 recent USFDA inspections conducted between August and November, which have not received any classification.

This is significant because the fate of these facilities now hang in balance until a final classification is announced by the FDA. Motilal Oswal analysts Tushar Manudhane and Sumit Gupta highlighted: “While the OAI classification is issued in approximately 90 days post-USFDA inspection, the timeline of regulatory action has reduced considerably.”

For instance, Glenmark Pharma’s Baddi site was inspected in June 2022 and was issued an import alert in October 2022. Even the Halol site was inspected in May 2022. Subsequently, it was issued OAI classification in August 2022. Recently, it was issued an import alert within six months of USFDA inspection.

After the USFDA inspectors visit a plant they typically either clear the plant or they issue what is called a Form 483 with their observations. Companies typically respond to the 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 (NAI). An import alert may follow a warning letter or OAI classification if the FDA is not satisfied with the remedial actions 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 it is placed under an import alert. A warning letter is an escalation of a form 483 (which notes adverse observations around quality and compliance of a facility that needs 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 the existing businesses as well, subject to exemption of certain products.

Sun Pharma’s Halol facility in Gujarat saw an OAI classification escalated to import alert over the past six months. “The import alert implies that a company would not be able to supply products from this site to the US market, until the facility becomes compliant,” Motilal Oswal said. Data from Motilal Oswal shows that recent warning letters or OAIs have taken anything between one year to 8-9 years to resolve.

Motilal Oswal thus notes: “Overall, 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 firms are, thus, focusing on de-risking their key products. Cipla, for example, said in the first week of November that they de-risked their chemotherapy drug Abraxane (estimated to be launched in the US in the first half of the calendar year 2023) because their Goa plant was under the FDA scanner. It had submitted responses to the FDA, and was waiting to hear from the regulator. “If Goa clears, then 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, MD and Global CEO, Cipla had said then.

By the third week of November, the FDA confirmed that Cipla’s Goa facility will 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 of them have also appointed consultants to help them grasp the regulatory requirements in the US.

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