Janifha Evangeline | Saturday, 04 June 2022
After a break of 24 months, the US Food and Drug administration resumed its onsite inspections of drug manufacturing units outside its borders including countries like India. The US Food and Drug Administration has been following this practice in order to ensure that all the medicines that come into the country follow the set standards.
However, in March 2020 most of the inspections were put on hold. This was the period when the COVID-19 pandemic hit all the countries across the globe. “We are getting inputs from companies on the USFDA move," said Sudarshan Jain, secretary-general, Indian Pharmaceutical Alliance, a lobby group of large generic drug companies. In the second month of 2022, officials of the US Food and Drug Administration stated that their agency is going to start inspections that would include surprise inspections in the country. In the month of March 2022, the USFDA inaugurated its offices in Mumbai & Delhi intending to safeguard pharma exports from India.
Therefore, the pharma plant inspections have started to increase again after almost a 2-year break. This was reflected in the inspection that was conducted recently at Zydus Lifesciences in the month of March and also a warning letter that was sent to Aurobindo Pharma earlier in 2022. The US Food and Drug Administration would have a busy year in the country as the backlog of redressals from previous inspections and pending plant & product applications are on the rise. Earlier, the total number of US Food and Drug Administration plant audits in our country reached 239 for medication quality assurance, in the year 2019.
Prior to the COVID-19 pandemic, around 80 inspections were conducted between the months of January and March, while there were only 5 in 2021. The rise in audit inspections may be a cyclical increase or can be linked to the changing & evolving standards in pharmaceutical manufacturing. In such waves, the Official Action Indicated (OAI) classification of the inspected manufacturing plants increases from five to six percent in a normal year to a high of twenty-six percent. While OAI is the least favourable outcome from an inspection, VAI and NAI are better outcomes.
Regulatory action is envisaged in plant inspections that lead to OAI classifications Most of the pharma enterprises can anticipate inspections
throughout their factories, owing to the 2-year pause in inspection activity. It was reported that based on an examination of previous reviews & results, Lupin and Aurobindo may be more vulnerable, while Cipla, Sun Pharma, Biocon & Dr. Reddy’s might be at reduced risk. Furthermore, regulatory action is envisioned only in plant inspections which result in Official Action Indicated classifications, and new product approvals from these plants might be delayed. In case the faults that are mentioned in the inspection are not addressed satisfactorily, a warning letter is given to that plant.
Post earning an Official Action Indicated (OAI), in the month of November 2021, Aurobindo got a warning notice in the month of January for its Unit 1, while Lupin got its warning notice in June 2021 for its factory in Somerset, New Jersey. Also, Manideep Unit 1 got a warning notice in September 2021. Biocon is subjected to regular inspections owing to the new product clearance process, however, the company typically performs well. Also, until February 2020, Cipla had a spotless record but its Goa factory received a warning notice.
What is USFDA’s Form 483? The Indian pharma organizations adhere to the norms as any departure may hit their export adversely. In one such inspection that was conducted in the month of May at Sun Pharma’s Halol facility, Form 483 was issued by the US FDA team, and the share price of Sun Pharmaceutical Industries was reduced by 4% the next day after Form 483 was issued. Therefore, the ten observations made in Form 483 were not good news for Sun Pharmaceutical Industries.
The firm stated that it was preparing a response to the observations and that would be submitted within fifteen business days to the US Food and Drug Administration. Observations are being made when the investigators find that either the conditions/practices observed show that any drugs, cosmetics, food items, or devices have been adulterated or if in their judgment the aforementioned products are being packed or prepared or even held under conditions in which they might become adulterated or rendered injurious to health.
The way ahead The companies which have been inspected should respond to Form 483 in writing and present their corrective action plan as well. The USFDA expects that subsequently, the organization will implement said plan expeditiously. The pharma companies of India are worried about the rise in warning letters and OAIs from the USFDA, which would lead to delays in product launches and push up regulatory uncertainty as well as compliance costs.
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