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Warning Letter 320-24-53

July 11, 2024

Dear Mr. Shukri:

Your facility is registered with the United States Food and Drug Administration (FDA) as a manufacturer of over-the-counter (OTC) drug products. FDA has reviewed the records you submitted in response to our September 12, 2022, and February 26, 2024 requests for records and other information pursuant to section 704(a)(4) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) for your facility, Nowrez & Ismail Shukri Company, FEI 3009721234, at Sahab, King Abdullah II Street, No 22, Amman, Jordan.

This warning letter summarizes significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals. See Title 21 Code of Federal Regulations, parts 210 and 211 (21 CFR, parts 210 and 211).

Because your methods, facilities, or controls for manufacturing, processing, packing, or holding of drugs as described in your responses to our 704(a)(4) requests do not conform to CGMP, your drug products are adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 351(a)(2)(B)).

Following review of records and other information provided pursuant to section 704(a)(4) of the FD&C Act, significant violations were observed including, but not limited to, the following:

1. Your firm failed 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)).

Based on the records and information provided, you did not demonstrate that you conducted adequate finished drug product testing on your OTC drug products. For example, the certificates of analysis (COA) you provided, including your (b)(4)% Isopropyl Rubbing Alcohol, did not include an appropriate assay test for active ingredient content or microbiological testing.

Full release testing, including strength and identity testing of the active ingredient, must be performed before drug product release and distribution. Without adequate testing, you do not have adequate scientific evidence to assure that your drug products conform to appropriate specifications before release.

2. Your firm failed to establish and follow an adequate written testing program designed to assess the stability characteristics of drug products (21 CFR 211.166(a)).

The records and information you provided did not demonstrate that your firm has an adequate stability program for the OTC drug products that you manufacture. For example, your firm 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. When asked recently to provide data to support the expiry period for each drug product formula, your firm responded with stability data for (b)(4) batch of (b)(4)% Isopropyl Rubbing Alcohol that was tested between 2017 and 2020. The stability data you provided failed to show appropriate chemical and microbiological testing was being performed on an ongoing basis to support the (b)(4) expiry period for your OTC drug products shipped after 2017 to present.

3. Your firm 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, you did not demonstrate that you are adequately testing the identity of incoming components used in the manufacture of your OTC drug products. Your response indicates that you do not test your active ingredient, isopropyl alcohol, for methanol.

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.

The use of ethanol or isopropyl alcohol contaminated with methanol has resulted in lethal poisoning incidents nationally. See FDA’s guidance document, Policy for Testing of Alcohol (Ethanol) and Isopropyl Alcohol for Methanol, at https://www.fda.gov/media/173005/download.

CGMP Consultant Recommended

If your firm intends to resume manufacturing drugs for the U.S. market, you should engage a consultant qualified as set forth in 21 CFR 211.34 to assist your firm in meeting CGMP requirements before resuming drug manufacturing operations. The qualified consultant should also perform a comprehensive six-system audit of your entire operation for CGMP compliance and evaluate the completion and efficacy of all CAPAs before you pursue resolution of your firm’s 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.

Conclusion

The violations cited in this letter are not intended to be an all-inclusive list of violations that exist at your facility. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations.
FDA placed your firm on Import Alert 66-40 on July 3, 2024.

Correct any violations promptly. FDA may withhold approval of new applications or supplements listing your firm as a drug manufacturer until any violations are completely addressed and we confirm your compliance with CGMP. We may re-inspect to verify that you have completed corrective actions to any violations.

Failure to address any violations may also result in the FDA continuing to refuse admission of articles manufactured at Nowrez & Ismail Shukri Company, FEI 3009721234, at Sahab, King Abdullah II Street, No 22, Amman, Jordan, into the United States under section 801(a)(3) of the FD&C Act, 21 U.S.C. 381(a)(3). Articles under this authority that appear to be adulterated may be detained or refused admission.

This letter notifies you of our findings and provides you an opportunity to address the above deficiencies. After you receive this letter, respond to this office in writing within 15 working days. Specify what you have done to address any violations and to prevent their recurrence. In response to this letter, you may provide additional information for our consideration as we continue to assess your activities and practices. If you cannot complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion.

Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov. Identify your response with FEI 3009721234 and ATTN: Joseph Lambert.

Sincerely,
/S/

Francis Godwin
Director
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research