Here’s What U.S. FDA Found At Sun Pharma’s Halol Plant — Exclusive

US FDA has issued a Form 483 with 10 observations to Sun Pharma for its Halol facility in Gujarat.

<div class="paragraphs"><p>Drug pills arranged for a photograph. (Photo:&nbsp;Michał Parzuchowski/Unsplash)</p></div>
Drug pills arranged for a photograph. (Photo: Michał Parzuchowski/Unsplash)

The U.S. health regulator has flagged production-related quality control and procedural lapses, as well as deficient equipment and laboratory standards, at the Gujarat facility of India’s largest drugmaker.

The U.S. Food and Drug Administration conducted a good manufacturing practices inspection of Sun Pharmaceutical Industries Ltd.’s Halol facility—the formulations or final drugmaking unit for generics—from April 26 to May 9, 2022, according to an exchange filing. The FDA has issued a Form-483, a kind of inspection letter, with 10 observations, the filing stated without disclosing the details.

BQ Prime obtained a copy of the observations from the U.S. FDA. Here’s a summary of the observations:

Production System

  • Procedures designed to prevent microbial contamination of drug products did not include adequate validation of aseptic process. The procedures performed for injectable suspension is a high-risk manually intensive dispensing and compounding process. Deficiencies were identified in the media filling process (that could lead to rejection or recall of batches) and the review videos for the media filling.

  • Aseptic processing areas that include manually intensive operations were not identified as high-risk for microbial cross-contamination.

Facility And Equipment System

  • Equipment and utensils are not cleaned, maintained and sanitized, especially production equipment used to manufacture certain dosage drug products. There is no assurance that products manufactured by this equipment are free from contamination.

  • Equipment used for manufacturing causes solution filled in vials to appear blackish from contamination. This due to friction and damage caused by variability in quality of parts by equipment manufacturer. There is failure to prevent usage of damaged equipment.

  • Absence of separate areas to prevent contamination and provide adequate protection between aseptic drug processing and the operators.

Laboratory Control System

  • Written stability program is not followed. The quality control lab failed to test stability of over 200 samples within the defined time frame. Out of specification result was noted for about 147 of total 215 stability samples tested with delay.

  • Quality unit failed to implement adequate controls to prevent cross-contamination of microbial samples prior to or during testing. Lab controls lack appropriate plans designed to assure that drug products conform to appropriate standards.

Quality System

  • Quality unit failed to fulfill responsibilities as per standard operating procedures. It also failed to take timely market action in accordance with drug recall procedure (failure to recall non-confirming batches and recall initiated close to expiry).

  • Failure to review unexplained discrepancy of a batch or its components and release of batch based on passing finished product results and historical stability data. Seven different instances including contaminated API, ceiling water leaks and inadequate root cause analysis of customer complaints were identified.

  • Employees engaged in manufacturing and processing of a drug product lack adequate training to perform visual inspection of drugs manufactured.

Sun Pharma has yet to respond to BQ Prime’s emailed queries.

The company, in the filing, however, said it’s preparing the response to the observations, which will be submitted to the U.S. FDA within 15 business days. “The company is committed to addressing these observations promptly. It remains committed to working closely with the U.S. FDA and continues to enhance its GMP (good manufacturing practices) compliance on an ongoing basis.”

Abdul Puranwala, pharma analyst at Elara Capital, said less than 5% U.S. generic sales come from Sun Pharma’s Halol plant. It has certain repeat observations from the 2019 inspection and “if timely resolution is not done, they could even extend to a warning letter”, he told BQ Prime. “In worst case of the issue getting escalated to an import alert, then all exports from the plant would have to be stopped.”

According to Vishal Manchanda, pharma analyst at Nirmal Bang, “Halol is an important plant for Sun pharma for its existing sales but large part of the growth that we forecast in the U.S. over the next two years comes from its specialty portfolio, which is not dependent on Halol.”

“Hence, even if the Form 483 does translates into OAI (official action indicated) status being maintained on the plant, we do not expect a material negative impact on earnings prospects,” he told BQ Prime. “New product approvals from the plant, however, will get hampered.”

Shares of Sun Pharma have risen 1.9% since May 10, when the observations were issued, compared with a 2.56% decline in the Nifty 50.