The USFDA on Wednesday said that it had resumed physical inspections of some manufacturing sites in India deemed “mission critical” for the US market. The US regulator began the inspections in January.
“It’s (the inspections) part of our risk-based model... based on criteria set forth by CDER (Center for Drug Evaluation and Research) and ORA (Office of Regulatory Affairs),” said Christopher Middendorf, Director, USFDA India Office, speaking at the 6th India Pharmaceutical Forum, 2021 organised by the Indian Pharmaceutical Alliance (IPA).
“So, we have defined the mission critical... for example, if we have a shortage of Covid-related therapy or if we have a pre-approval for a drug that is in short supply,” Middendorf said.
He added that the USFDA has put in place stringent protocols for in-person inspections. “We have to remember that our inspectors are also vulnerable to Covid-19. We don’t want to be carriers and have our staff get sick out on an inspection; that doesn’t benefit anyone,” Middendorf said.
Faster approval for some drugs
Middendorf said the USFDA may grant approval without inspection for a pre-approval inspection (PAI) if a drug belongs to an already approved profile class and the manufacturer has a Good Manufacturing Practices (GMP) track record.
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PAI is triggered when companies file for marketing authorisation of a drug in the US market.
“We’re getting back to the pre-approvals. There are some things we can do about pre-approvals. And so if you already have that profile class approved and you have a good GMP record, we have the option of approval without inspection and maybe having a post-approval (inspection),” Middendorf said.
“Now (if) it’s a new profile class or an innovator drug, it’s going to require an inspection by the USFDA,” he added.
To be sure, unlike regulators in Europe and the UK, the US is yet to begin virtual inspections.
“On alternative options, the CDER hasn’t published anything specific but they are reviewing the feasibility of all avenues to try and mitigate what Covid-19 has done to in-person inspections,” Middendorf said.
Middendorf said the regulator was reviewing electronic records of manufacturing sites under Section 704(b) of the federal Food, Drug and Cosmetics Act (FD&C Act).
The USFDA paused all inspections, both domestic and foreign, in March 2020 following the outbreak of Covid-19. While it resumed prioritised domestic inspections last July, it took the agency another six months to resume overseas inspections.
Delay in approvals a concern
Meanwhile, approvals related to complex generics and biosimilars, critical to the revenue growth and profitability of Indian drug companies, have been hit. Companies that have completed remediation of OAIs (official action indicated) and warning letters have had to face a long wait in having a USFDA re-inspection of their facilities. This, in turn, has delayed resolution of regulatory issues and product approvals. Imports account for about 60 percent of drugs consumed in the US, with India and China accounting for a big chunk.
The US currently faces a shortage of about a hundred drugs. These are mostly injectable drugs used in hospital settings. There are also shortages of drugs widely used in the treatment of severe Covid-19, such as Dexamethasone injections, Zinc Acetate Capsules, and commonly used anti-hypertension pills such as Methyldopa.
It is difficult to pinpoint which drugs are mission-critical for the US, but several Indian drug companies, including Zydus Cadila, Lupin, Aurobindo Pharma, Dr Reddy’s and Sun Pharma produce many key drugs consumed in that country.