The unit, located in Washington state, operated by Jubilant’s US-based subsidiary Jubilant HollisterStier, was inspected by the regulator between April 15 and May 10, 2013.
The USFDA said in the letter that it was aware of unexplained increased levels of unspecified impurities in a product, whose name was not stated in the letter. The company has dealt with the issue by withdrawing batches of the product from the market and reducing its expiry date.
“Although your initial actions are appropriate, it is essential that your firm also implements corrective actions to ensure the quality of the finished drug product throughout the product lifecycle. Your firm does not appear to have adequate control of the (production process). Your firm cannot assure product quality by reducing the expiry without understanding the root cause of the increased (unspecified material),” USFDA’s district director Gerald Bromley, Jr said in the warning letter.
It also said the company failed to establish appropriate written procedures, designed to prevent microbiological contamination of drug products, supposed to be sterile.
Jubilant had shut down certain production lines (filling lines SVP Line 1 and SVP Line 2) used to manufacture aseptically-filled injectable drug products in April 2013, in order to upgrade some systems.
The USFDA pointed out that the company’s procedure lacks provisions for evaluating the effect of significant maintenance shutdowns and whether acceptable conditions are restored to certain classified areas before operations are restarted.
“Your firm acknowledges the lack of an adequate, documented evaluation of the effect of major equipment and facility modifications... Your response is inadequate because you do not commit to conducting media fill process simulations to assure the aseptic processing operations are acceptable after major shutdown activities,” the letter said.
The regulator has asked the company’s management to undertake a comprehensive evaluation of global manufacturing operations to ensure compliance with current Good Manufacturing Practice regulations.
“The items listed above, as well as other deficiencies our investigators found, lead us to question the effectiveness of your current quality system to achieve overall compliance with cGMP at your facility. It is apparent that you have not implemented a robust quality system at your firm,” the USFDA said.
The Noida-based company had informed the BSE of the warning letter on December 5, saying the facility located in the Washington contributed 7%, or R195.51 crore, to consolidated sales and 4%, or R20.72 crore, to consolidated Ebitda of the company during H1 FY14. It had reported total revenue of R2,793 crore and an Ebitda of R518 crore during the same period.
The Spokane plant is a contract manufacturing facility and Nomura analyst Saion Mukherjee said that the brokerage’s forecast of a 5% constant currency growth in FY15 and FY16 may be under risk in case the warning letter is not resolved, and new approvals are halted. “With no growth in constant currency terms, we estimate the impact on FY15-16 earnings forecasts at 2.5%,” Mukherjee wrote in a report dated December 5.
Jubilant HollisterStier’s Montreal site had also received a warning letter dated February 20, 2013, citing cGMP violations. The issues identified in the Montreal warning letter included points such as failure to thoroughly investigate any unexplained discrepancy in a batch to meet specifications any of its specifications and the company distributing finished products despite the failure of the batch to meet acceptance criteria during visual inspection.