Sterile Manufacturing Issues found at Canadian Manufacturer

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FDA sent a warning letter to Lernapharm (Loris) Inc. detailing the company’s lack of procedures to prevent microbiological contamination.

FDA sent a warning letter, dated Sept. 4, 2018, to Lernapharm (Loris) Inc. after an inspection of the company’s Montreal facility found deviations from current good manufacturing practices. Violations found included lack of written procedures, failure to investigate batch failures, and improper stability testing procedures. The inspection was performed from Dec. 4–12, 2017.

Specifically, the agency stated in the letter that the company had not established appropriate written procedures to prevent microbiological contamination of sterile products. The company had not adequately validated processes or tested the sterility of finished product batches. “Your firm lacks an adequate sterilization method. You have not demonstrated an ongoing state of control and your products, which purport to be sterile, are produced using manufacturing methods that are inappropriate to support this claim,” the agency stated.

Unexplained discrepancies in batches were not thoroughly investigated, according to FDA, after customer complaints regarding sterile products that were leaking. “Your investigation found that the (b)(4) seals leaked due to pinholes in the package caused by debris that had accumulated on the sealing (b)(4) of the packaging machine. However, your investigation did not include your assessment of the following: other potential contributors to the pinhole problem, such as packaging material integrity prior to production; risks that the leaking packages pose to patients and product quality, including lack of sterility; effectiveness of your corrective actions and preventive actions (CAPA); and full evaluation of scope and magnitude to determine impact of the manufacturing problems on other batches of (b)(4) and additional products you manufacture,” the agency stated. 


FDA requested the company perform comprehensive investigations into an additional 18 batches of product and provide the agency with an update on root-cause evaluations, an improved risk assessment, an assessment on package integrity, and an assessment of the company’s overall batch failure investigation system.


A lack of adequate programs for stability testing was also found. “For example, your stability studies did not include testing for sterility or container-closure integrity at least at expiry for your stability batches. You received multiple customer complaints of leaking (b)(4) containers and determined the root cause to be your sealing process. It is essential for products to maintain container-closure integrity throughout the labeled expiration period to assure their microbiological and chemical quality,” the agency stated.

The company also failed to use appropriate filtration systems in production areas and controls systems to prevent contamination or mix-ups. The agency asked the company to provide FDA with the company’s environmental monitoring procedures and data.

FDA placed the company on Import Alert 66-40 on April 24, 2018 and stated, “Until you correct all violations completely and we confirm your compliance with CGMP, FDA may withhold approval of any new applications or supplements listing your firm as a drug manufacturer.”

Source: FDA