USFDA observations in 2022 focus on ancillary infra, written procedures

45% observations in 2022 around unavailability of written procedures and facility maintenance, ancillary infrastructure

Around 45 per cent of observations issued by the US drug regulator in 2022 were around unavailability of written procedures, facility maintenance and ancillary infrastructure, shows an analysis of Form 483s issued by the US Food and Drug Administration (USFDA), according to McKinsey.

The analysis shows that the nature of observations made in a Form 483 has been changing over the years. And, observations on issues such as laboratory control and core manufacturing processes have been on the decline.

This implies that core manufacturing processes at Indian sites are more or less stable and under control. And now, the regulatory focus is on ancillary functions and infrastructure.

The USFDA issues a Form 483 to a firm’s management after the conclusion of an inspection. When investigators observe any conditions, their judgement may constitute violations of the Food Drug and Cosmetic (FD&C) Act and related Acts.

Vikas Bhadoria, senior partner, McKinsey & Company, told Business Standard that in 2022, 45 per cent of observations witnessed by facilities were around unavailability of written procedures, facility maintenance and ancillary infrastructure.

“Root cause investigation also accounted for 15 per cent of the observations issued. Whereas in 2018, issues such as lab control and core manufacturing processes contributed to more than 20 per cent of the observations, it came down to just 12 per cent of the observations in 2022,” he added.

Bhadoria further added that observations on data reliability and good documentation practices were 5 per cent of the total observations analysed in 2022. “This is almost 50 per cent lower than the previous share of 11 per cent in 2018,” he said.

McKinsey has analysed the USFDA inspections database.Industry veterans said that the USFDA is focusing on ensuring that there are written guidelines for every process like cleaning of ducts, or starting and stopping of machines in case of a power failure.

India accounted for 48 per cent of the total abbreviated new drug applications (ANDAs) approved by the USFDA in 2022.

At over 530, the country ranks first in the number of USFDA-approved plants outside of the US.

The US imports $7.3 billion worth of pharmaceutical products from India. 

Rajiv Desai, senior technical advisor, quality and regulatory, at the Indian Pharmaceutical Alliance (IPA), said that companies that have a significant business in the US market have high stakes. So, ensuring quality compliance should be their top priority.  

“USFDA investigators constantly look for weak areas and expect quality systems to be upgraded at the manufacturing site.” Desai said. He added, “Now there is increased focus from the USFDA on engineering and infrastructure, including outsourcing activities,” he added. 

Data analysed by the IPA, which represents the top 24 drug firms in India, shows that out of the 52 inspections during 2023, 49 inspections resulted in VAI (voluntary action indicated) or NAI (no action indicated) status.

VAI implies objectionable conditions were found and documented but the agency is not prepared to take or recommend regulatory action. NAI implies no objectionable conditions or practices were found during the inspection (or the significance of the documented objectionable conditions found does not justify further action).

Therefore, in the first six months of 2023, only 6 per cent of the total inspections have resulted in OAI. This is comparable with the global inspections — out of 217 total global inspections in 2023, around 8 per cent resulted in OAI status.

Nature of observations in Form 483 by USFDA to Indian sites

2022

• 45% observations on unavailability of written procedures, facility maintenance, ancillary infra
• 15% observations on root cause investigation
• 12% observations - lab control, core manufacturing processes
• 5% observations - data reliability, good documentation practices

2018

• 20% observations on – lab control, core manufacturing processes
• 11% observations – data reliability, good documentation practices