Ipca Laboratories Ltd.'s two units may face regulatory action after U.S. drug regulators found objectionable conditions at the facilities, according to Nomura.
The pharma company's Ratlam and Pithampur facilities may remain classified as 'offical action indicated', after their recent inspections by the U.S. Food and Drug Administration, Nomura said.
This would mean that the inspection found some objectionable conditions at the facilities, for which regulatory action should be recommended by the U.S. FDA.
The agency had issued a Form-483 with 11 observations for Ipca's Ratlam active pharmaceutical ingredients and eight observations for Indore formulations sites. "Both sites have been under import alert since 2015," Nomura said in its July 3 report.
"We do not expect a resolution and the facilities may remain classified as 'Official action indicated' in the near term," it said, even though this was the first site inspection post the imposition of the import alert. The brokerage is not factoring in any upside from the U.S.
However, unlike past inspections, there were no issues with data integrity at the facilities, Nomura said. "The inspection highlights inadequacies in current operating procedure and in the case of Ratlam, it also highlights lack of procedures."
Shares of the company were trading 0.21% higher, compared to a 0.41% rise in the benchmark Sensex as of 12:26 p.m. on Tuesday.
Nomura On Ratlam API Facility
The observations cover both lack of systems and process and also depth of existing systems, and process in almost equal proportion, the brokerage said. "Additional inspection will be required in due course, before the site is cleared," the report said.
The following eleven observations were noted:
The observation is related to 'out-of-specification' test results and deviations. Investigation and identification of root cause for OOS test results are not comprehensive or adequately justified.
Certain batches of APIs, that were sold in domestic and international markets, failed the stability test. The quality unit did not notify the regulatory authority and customers and didn't undertake market recall.
The company rework or reprocess APIs and the same were released in the market, without carrying out appropriate stability tests.
Failure to establish optimal processing conditions to ensure consistency of product. For instance, the validation for an API was done in 2018. Later in 2021/2022, multiple OOS results were noted for the API. This indicates gaps in the earlier validation process and the need to revalidate the process.
The firm did not do proper testing of a possible contaminant for a product distributed in the U.S. market. The standard operating procedure of equipment cleaning is not scientifically justified to ensure cross contamination of drug substance is prevented.
The test method to establish the level of impurity was inappropriate.
Quality control test method to establish level of impurity with high-performance liquid chromatography/gas chromatography is inappropriate.
The batches supplied to the U.S. market during the Covid-pandemic (the company was provided exemptions) were not appropriately certified by the third-party consultant. There is no documented evidence that the third-party consultant reviewed audit trails to certify batches.
There is deficiency in verification of pH meter used in lab.
Ipca establishes the purity and strength of APIs manufactured at the site by comparing it against the in-house qualified secondary standards (not the primary standard). The inspectors note that this process of qualification is deficient (lack of scientific rationale).
Complete use, maintenance and cleaning record of major equipment was missing.
Nomura On Pithampur Formulations Facility
The observations primarily highlight inadequacies in the current system and processes, the report said. "We think Ipca would be required to further tighten controls on processes before the site is approved."
The following eight observations were noted:
Invalidating OOS test results, without properly identifying the root cause for products supplied to non-US markets. Or even when root cause was identified, it wasn't satisfactory, as per the inspectors.
Hold time studies were not comprehensive. The inspectors highlight this as a concern in the backdrop of 12 OOS results, of which 10 were eventually invalidated.
The UV (ultraviolet) method is used for dissolution testing of drug products. The suitability of the testing method was not verified. Hence, all the data analysed with this test method are invalid, as per inspectors.
Maintenance and cleaning of the equipment is not appropriate, which could lead to contamination of drug products. Scratch marks were found inside equipment.
Test procedures using an autosampler for dissolution studies were not appropriate. Three instances were noted.
The company's quality control lab uses computerised LES (Laboratory Execution System) to document and perform analysis. As per SOP, all the test methods in the system are expected to be named appropriately, based on the products being tested. The inspectors observed that many procedures in the system were not named appropriately.
This relates to gowns worn by operators in the manufacturing unit. As per inspectors, the gowns worn were not proper. They were unclean, damaged or torn.
As per SOP, the corrective action and preventive action implemented in response to a customer complaint is required to be checked for its effectiveness. The company implemented a CAPA to address a customer complaint. However, complaints resurfaced later, indicating that the CAPA implemented was not effective. The company did not investigate and develop a new CAPA.
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