FDA Issues Warning Letter to Nowrez & Ismail Shukri Company

Nowrez & Ismail Shukri Company, Amman, Jordan, received a Warning Letter from the US Food and Drug Administration for “significant” violations pursuant to section 704(a)(4) of the FD&C Act. These violations include:

• Failure to have, for each batch of drug product, appropriate laboratory determination of satisfactory conformance to final specifications for the drug product, including the identity and strength of each active ingredient, prior to release (21 CFR 211.165(a)). FDA noted, for example, certificates of analysis (COA), including (4)% Isopropyl Rubbing Alcohol, did not include an appropriate assay test for active ingredient content or microbiological testing.

• Failure to establish and follow an adequate written testing program designed to assess the stability characteristics of drug products (21 CFR 211.166(a)). According to FDA, Nowrez & Ismail Shukri’s records and information provided did not demonstrate that the company has an adequate stability program for the OTC drug products that it manufactures. For example, Nowrez & Ismail Shukri initially provided a stability test report which noted three years of stability data for (b)(4) batch of (b)(4)% Isopropyl Rubbing Alcohol that was tested between 2017 and 2020. But when FDA recently asked for data to support the expiry period for each drug product formula, Nowrez & Ismail Shukri responded with stability data for (b)(4) batch of (b)(4)% Isopropyl Rubbing Alcohol that was tested between 2017 and 2020. The stability data provided failed to show appropriate chemical and microbiological testing was being performed on an ongoing basis to support the (b)(4) expiry period for the OTC drug products shipped after 2017 to present.

• FDA said Nowrez & Ismail Shukri failed to test samples of each component for identity and conformity with all appropriate written specifications for purity, strength and quality (21 CFR 211.84(d)(1) and 211.84(d)(2)).

Based on the records and information provided, FDA said the company did not demonstrate that it is adequately testing the identity of incoming components used in the manufacture of OTC drug products. “Your response indicates that you do not test your active ingredient, isopropyl alcohol, for methanol,” wrote FDA in the Warning Letter. “Relying solely on supplier’s certificate of analysis (COA) for identity testing is insufficient. Without adequate testing you do not have scientific evidence that your raw materials conform to appropriate specifications prior to use in the manufacture of your drug products. As a manufacturer, you have a responsibility to sample, test and examine drug components before use in production to assure adequate quality, including testing for the presence of methanol in isopropyl alcohol.”

FDA noted that the use of ethanol or isopropyl alcohol contaminated with methanol has resulted in lethal poisoning incidents nationally. In the Letter, FDA included the link, Policy for Testing of Alcohol (Ethanol) and Isopropyl Alcohol for Methanol, at https://www.fda.gov/media/173005/download.

FDA concluded that if Nowrez & Ismail Shukri intends to resume manufacturing drugs for the US market, it should engage a consultant qualified as set forth in 21 CFR 211.34 to assist in meeting CGMP requirements before resuming drug manufacturing operations. FDA said the qualified consultant should also perform a comprehensive six-system audit of the company’s entire operation for CGMP compliance and evaluate the completion and efficacy of all CAPAs before Nowrez & Ismail Shukri pursues resolution of its compliance status per FDA’s guidance document, Quality Systems Approach to Pharmaceutical CGMP Regulations at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/quality-systems-approach-pharmaceutical-current-good-manufacturing-practice-regulations.