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WARNING LETTER

AG Hair Limited MARCS-CMS 638646 —


Delivery Method:
VIA UPS
Reference #:
320-23-05
Product:
Drugs

Recipient:
Recipient Name
Mr. Graham Fraser
Recipient Title
CEO
AG Hair Limited

14 King Edward Street
Coquitlam BC V3K 0E7
Canada

Issuing Office:
Center for Drug Evaluation and Research | CDER

United States


Warning Letter 320-23-05

November 28, 2022

Dear Mr. Fraser:

The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, AG Hair Limited, FEI 3002892007, at 14 King Edward Street, Coquitlam from June 20 to 24, 2022.

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

Because your methods, facilities, or controls for manufacturing, processing, packing, or holding 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).

We reviewed your July 15, 2022, response to our Form FDA 483 in detail. Your response is inadequate because it did not provide sufficient detail or evidence of corrective actions to bring your operations into compliance with CGMP.

During our inspection, our investigator observed specific violations including, but not limited to, the following.

1. Your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 CFR 211.192).

Your firm failed to adequately investigate a sample taken from your non-circulating, on-demand (b)(4) system. The sample was taken prior to manufacturing your (b)(4) drug product, lot (b)(4). The sample yielded an elevated bioburden count of (b)(4) CFU/mL (specification: not more than (b)(4) CFU/mL). You released the (b)(4) drug product without conducting a comprehensive investigation, including to document the root cause determination, and speciation and product impact assessment based on the recovered microorganisms.

Additionally, your firm failed to adequately investigate a customer complaint of (b)(4) irritation from the use of your (b)(4), lot (b)(4). Your investigation consisted of conducting a “panel test” involving four “participants,” who were all your employees, who used the (b)(4)1. You then determined that further investigation was not required after concluding that your employees exhibited no allergic reactions after using the (b)(4). No additional testing or evaluation of the lot was conducted.

In your response, you committed to updating standard operating procedures (SOPs) for managing complaints and deviations. Your response is inadequate. You failed to perform a retrospective review of previous investigations (including those associated with at least two lots of your (b)(4)) to ensure they were comprehensive and that adequate risk assessments were conducted. Further, you have not addressed how you will remediate your investigation system to determine the appropriate root cause, identify and implement appropriate corrective action and preventive action (CAPA) to prevent recurrence, and measure CAPA effectiveness.

Inadequate investigations may result in not identifying or mitigating the root causes of non-conformances and does not ensure consistent production of safe and effective drugs.

For more information about handling failing, OOS, out-of-trend, or other unexpected analytical results and documentation of your investigations, see FDA’s guidance document https://www.fda.gov/downloads/drugs/guidances/ucm070287.pdf.

In response to this letter, provide:

  • A comprehensive, independent assessment of your overall system for investigating deviations, discrepancies, complaints, OOS results, and failures. Provide a detailed action plan to remediate this system. Your action plan should include, but not be limited to, significant improvements in investigation competencies, scope determination, root cause evaluation, CAPA effectiveness, quality oversight, and written procedures. Address how your firm will ensure all phases of investigations are appropriately conducted.
  • A risk assessment for (b)(4) lots (b)(4) and (b)(4).

2. Your firm failed to establish laboratory controls that include scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that components, drug product containers, closures, in-process materials, labeling, and drug products conform to appropriate standards of identity, strength, quality, and purity (21 CFR 211.160(b)).

Your firm failed to establish adequate laboratory controls including microbiological testing and specifications for all of your non-sterile drug products. For example, your firm failed to conduct microbiological testing of your Hands Free Clean Hand Sanitizer Gel drug product prior to release. Additionally, while microbiological testing is conducted on your (b)(4) drug product prior to release; your standard plate count specification is not appropriate for the intended use of the product.

In your response, you committed to updating your microbiological test procedures and specifications. Your response is inadequate. You failed to commit to a plan to ensure your previously distributed drug products meet your updated microbiological test procedures and specifications. Your response did not include what actions you will take if your previously distributed drug products does not meet your updated microbiological test procedures and specifications.

In response to this letter, provide:

  • Appropriate microbiological lot release specifications (e.g., total counts, identification of bioburden to detect objectionable microbes, such as Burkholderia Cepacia Complex) for each of your drug products; current action/alert limits for total counts and objectionable organisms used for your (b)(4) system.
  • All microbiological test methods used to analyze each of your drug products and your (b)(4) system.
  • A summary of results from testing retain samples of all drug product lots within expiry. You should test microbiological quality (total counts and identification of bioburden to detect any objectionable microbes) of each lot. If testing yields an OOS result, indicate the corrective actions you will take, including notifying customers and initiating recalls.
  • A summary of all (b)(4) system results since the close of the inspection.

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)).

You failed to perform adequate identity testing for each component lot used in the production of your hand sanitizer drug products, including ethanol, your active pharmaceutical ingredient. Additionally, your active pharmaceutical ingredient, ethanol, is not tested for methanol content, and your procedures did not ensure that you test glycerin for presence of diethylene glycol (DEG).

In your response, you committed to updating component testing procedures and specifications. Your response is inadequate. You failed to provide a detailed plan to ensure that previously distributed drug products were manufactured with incoming components that meet your updated identity and impurity testing requirements.

Component testing is fundamental to quality. Without adequate testing, you do not have scientific evidence that your incoming components conform to appropriate specifications before use in the manufacture of drug products.

Products Containing Ethanol

You manufacture multiple drugs that contain ethanol. The use of ethanol contaminated with methanol has resulted in various lethal poisoning incidents in humans worldwide.

See FDA’s guidance document Policy for Testing of Alcohol (Ethanol) and Isopropyl Alcohol for Methanol, Including During the Public Health Emergency (COVID-19) to help you meet the CGMP requirements when manufacturing drugs containing ethanol at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/policytesting-alcohol-ethanol-and-isopropyl-alcohol-methanol-including-during-public-health.

Products Contain Glycerin

You manufacture products that contain glycerin. The use of glycerin contaminated with diethylene glycol (DEG) has resulted in various lethal poisoning incidents in humans worldwide.

See FDA’s guidance document Testing of Glycerin for Diethylene Glycol to help you meet the CGMP requirements when manufacturing drugs containing glycerin at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/testingglycerin-diethylene-glycol.

In response to this letter, provide:

  • The chemical and microbiological quality control specifications you use to test and release each incoming lot of components for use in manufacturing.
  • A description of how you will test each component lot for conformity with all appropriate specifications for identity, strength, quality, and purity. If you intend to accept any results from your supplier’s Certificates of Analysis (COA) instead of testing each component lot for strength, quality, and purity, specify how you will robustly establish the reliability of your supplier’s results through initial validation as well as periodic re-validation. In addition, include a commitment to always conduct at least one specific identity test for each incoming component lot.
  • A summary of results obtained from testing all components to evaluate the reliability of the COA from each component manufacturer. Include your SOP that describes this COA validation program.
  • A summary of your program for qualifying and overseeing contract facilities that test the drug products you manufacture.
  • Methanol, (b)(4), (b)(4), (b)(4), and test results for all hand sanitizer lots released and distributed.

Drug Production Ceased

We acknowledge your commitment to cease production of hand sanitizer drugs for the U.S. market. As of the date of this letter, your hand sanitizer drug products continue to be actively listed with the FDA. Additionally, shipments of your hand sanitizer drug products have entered the United States after you informed FDA of your decision to cease manufacturing these drug products. FDA has since placed your firm on Import Alert 66-40.

In response to this letter, clarify whether you intend to cease manufacturing and distribution of your hand sanitizer drug products to the United States. If your intent is to cease manufacturing and distribution of these products, delist all hand sanitizer drug products previously listed with FDA.

CGMP Consultant Recommended

Based upon the nature of the violations we identified at your firm, you should engage a consultant qualified as set forth in 21 CFR 211.34 to assist your firm in meeting CGMP requirements. The qualified consultant should also perform a comprehensive audit of your entire operation for CGMP compliance and evaluate the completion and efficacy of your corrective actions and preventive actions before you pursue resolution of your firm’s compliance status with FDA.

Your use of a consultant does not relieve your firm’s obligation to comply with CGMP. Your firm’s executive management remains responsible for resolving all deficiencies and systemic flaws to ensure ongoing CGMP compliance.

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 these violations and for preventing their recurrence or the occurrence of other violations.

FDA placed your firm on Import Alert 66-40 on October 28, 2022.

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 AG Hair Limited, 14 King Edward Street, Coquitlam 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, in that the methods and controls used in their manufacture do not appear to conform to CGMP within the meaning of section 501(a)(2)(B) of the FD&C Act, 21 U.S.C. 351(a)(2)(B).

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 3002892007 and ATTN: Rory Geyer.

Sincerely,
/S/

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

____________________________________

1 This warning letter does not address the legality of this practice.

 
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