In what is considered to be one of the most stringent regulatory scrutinies ever, five US Food and Drug Administration (USFDA) inspectors audited Aurobindo Pharma's Unit 4 in Pashamylaram near Hyderabad. At the end of the surprise inspection, which took place over the course of ten days, they raised 14 observations in Form 483 that ran into 37 pages.
The Form 483 is issued by USFDA inspectors at the end of an inspection, where they list their observations related to any discrepancies in the current good manufacturing practice (cGMP).
The Unit 4 is no ordinary manufacturing plant - it produces injectables and ophthalmic medication and is crucial for Aurobindo Pharma's US business. USFDA, in its Form 483, picked holes related to deficiencies in procedures and practices related to controlled studies and monitoring conditions necessary for aseptic (or contamination free) processing.
"It would take 4 to 6 months of enhanced efforts to resolve the issues, in our view," Motilal Oswal said in its latest report on the company.
Unit 4 accounts for 7 percent to 8 percent of the drugmaker's US sales and has 47 abbreviated new drug applications (ANDAs) pending for approval. Aurobindo's US sales stands at around $1.5 billion. The year 2019 has been a forgettable one for the company when it comes to regulatory compliance.
Around eight sites belonging to the company have been inspected by the USFDA this year alone, of which Unit 11 has been issued a warning letter, while Units 1 and 9 have been classified as Official Action Indicated (OAI). According to FDA's definitions, OAI means "objectionable conditions were found and regulatory administrative sanctions by FDA are indicated" during inspections.
Three other plants have also received observations. The warning letter and OAIs were linked to the contamination of valsartan carcinogenic impurities.
Intensified regulatory risk
However, it isn't a bad year for Aurobindo Pharma alone. The regulatory risk has intensified for the entire Indian pharmaceutical industry over the past year.
Around 18 pharma companies have received USFDA warning letters for their Indian plants in 2019; these were more than half of the all the warning letters issued by the regulatory agency.
In 2018, out of the 68 warning letters issued by the USFDA, 10 were related to India. In 2017, India's share of warning letters was 17 out of the 79 handed out by the agency.
The facilities that got a warning from the USFDA include Mylan (Unit-8, active pharmaceutical ingredient (API) plant, near Visakhapatnam, Andhra Pradesh), Hospira, a unit of Pfizer (Irungattukottai plant near Chennai), Cadila Healthcare (Moraiya formulation plant, Gujarat), Torrent Pharma (Indrad plant, Gujarat), Glenmark (Baddi formulation plant, Himachal Pradesh), Lupin (Mandideep formulation, Madhya Pradesh), Aurobindo Pharma (API plant, Srikakulam, Andhra Pradesh), Indoco Remedies (Goa formulation plant), Strides Pharma (Puducherry plant), Jubilant Life Sciences (Roorke formulation plant, Uttarakhand), Emcure Pharmaceuticals (Hinjewadi facility in Pune), Lantech Pharmaceuticals (API plant, Srikakulam, Andhra Pradesh), CTX Lifesciences (API plant, Surat, Gujarat), Rxhomeo (Hyderabad plant, Telangana), Centurian Laboratories (formulation unit, Manjusar, Gujarat), Anicare Pharmaceuticals (formulations plant, Navi Mumbai, Maharashtra) Vipor Chemicals (API plant, Vadodara, Gujarat) and B. Jain Pharmaceuticals (formulation plant, Bhiwadi, Rajasthan).
A recurring theme, compliance woes include failure to establish and follow adequate procedures for production; failure to thoroughly investigate any unexplained discrepancy like failure of a batch or any of its components to meet any of its specifications; failure to establish an adequate quality control unit with the responsibility and authority to approve or reject all components, and discrepancies in following procedures for cleaning equipment and maintaining aseptic processing conditions.
"The regulators are upping the standard of the industry," Umang Vohra, MD and Global CEO of Cipla, recently told Moneycontrol.
Earlier, it was (DI) data integrity, now regulators point towards new potential problems that would rear their heads like contamination, impurities and cleaning, among others. Companies will have to re-gear to tackle these issues," Vohra added.
"Regulatory compliance is an ongoing process," said N Govindarajan, MD of Aurobindo Pharma.
"We work on improving systems and culture, we take help wherever needed (from outside consultants). We still need further improvement," Govindarajan added.