Libby Laboratories, Inc. - 708259 - 06/27/2025

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Warning Letter 320-25-87

June 27, 2025

Dear Ms. Libby:

The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, Libby Laboratories, Inc., FEI 2912388, at 1700 Sixth Street, Berkeley, California, from March 11 to 14, 2025.

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 April 1, 2025 response to our Form FDA 483 in detail.

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

1. Your firm failed to conduct for each batch of drug product, appropriate laboratory testing, as necessary, required to be free of objectionable microorganisms (21 CFR 211.165(b)).

You manufacture over-the-counter (OTC) sunscreen and (b)(4) drug products. Your (b)(4) antiseptic is labeled for hospital use only and used to prepare skin prior to surgery. You released your (b)(4) drug product batches without testing for microbiological quality. For example, the batch record for finished product batch (b)(4), manufactured in September 2024 and distributed to a children’s hospital, only lists finished drug product tests for (b)(4) assay, color, odor, appearance, and percentage of (b)(4).

Without testing each batch prior to release, you did not have scientific evidence that all drug product batches were free of microbial contamination that is objectionable in view of its intended use.

In your response, you state that your (b)(4) product contains (b)(4) and (b)(4), which are bactericidal. You indicate that you “think that the requirement to have finished product tested for presence of objectionable microorganisms is not necessary.” You commit to testing your finished drug product for objectionable microorganisms prior to releasing any future batches.

Your response is inadequate. You did not provide an appropriate scientific basis to support that your finished drug products are free from microbial growth or survival. Additionally, you did not provide any retrospective testing to support the quality of your drug products currently on the market.

In response to this letter, provide the following:

• A list of chemical and microbiological specifications, including test methods, used to analyze each batch of your drug products before batch disposition decisions.
  o An action plan and timelines for conducting full chemical and microbiological testing of retain samples to determine the quality of all batches of drug products distributed in the United States that are within expiry as of the date of this letter.
  o A summary of all results obtained from retain samples from each batch. If such testing reveals substandard quality drug products, take rapid corrective actions, such as notifying customers and product recalls.

2. Your firm failed to conduct at least one test to verify the identity of each component of a drug product. Your firm also failed to validate and establish the reliability of your component supplier’s test analyses at appropriate intervals (21 CFR 211.84(d)(1) and 211.84(d)(2)).

You failed to perform adequate identity testing of each component lot used in the manufacture of your OTC drug products, such as (b)(4) and (b)(4). You also relied on your suppliers’ certificate of analysis (COA) for components, such as (b)(4), and (b)(4), without establishing the reliability of the suppliers’ test analyses at appropriate intervals.

Furthermore, we note that you used (b)(4) purchased from a local grocery store as a component in the manufacture of your drug products for which you only conducted organoleptic assessment, including color, odor and appearance. This practice is unacceptable for pharmaceutical manufacturing. At a minimum, you must use purified water (refer to USP General Chapter <1231> Water for Pharmaceutical Purposes) to manufacture your topical, non-sterile drug products. Pharmaceutical water must be suitable for its intended use and routinely tested to ensure ongoing conformance with appropriate chemical and microbiological attributes.

(b)(4)

You failed to adequately test each shipment of each lot of (b)(4) for identity, a component at high-risk of (b)(4) or (b)(4) contamination. Identity testing for (b)(4) and certain other high-risk drug components includes a limit test in the United States Pharmacopeia (USP) to ensure the component meets the relevant safety limits for levels of (b)(4) or (b)(4). Because you did not perform identity testing on each shipment of each lot using the USP identification test that detects these hazardous impurities, you failed to assure the acceptability of this component for use in the manufacture of your drug products.

The use of ingredients contaminated with (b)(4) or (b)(4) has resulted in various lethal poisoning incidents in humans worldwide. See FDA’s guidance document (b)(4) to help you meet the CGMP requirements when manufacturing drugs containing ingredients at high-risk for (b)(4) or (b)(4) contamination at (b)(4)

(b)(4)

You failed to adequately test your incoming (b)(4), used as an active pharmaceutical ingredient, for (b)(4). The use of (b)(4) contaminated with (b)(4) has resulted in various lethal poisoning incidents in humans worldwide. See FDA’s guidance document (b)(4).

Without adequate testing, you do not have scientific evidence that components 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.

In your response, you state that you plan to use contract laboratories to perform the identity tests for (b)(4) and (b)(4). You also plan to test your drug components in-house or via a contract testing laboratory using compendial test methods or test methods from the manufacturers’ COA.

Your response is inadequate because you fail to address the full scope and impact of the CGMP deficiencies as well as the associated risks to drug product quality, including batches already in distribution. Your response also lacked adequate information on how you will evaluate the suitability of your in-house laboratory or contract laboratories to perform testing of your drug components.

In response to this letter, provide the following:

• A comprehensive, independent review of your material system to determine whether all suppliers of components, containers, and closures, are each qualified and the materials are assigned appropriate expiration or retest dates. The review should also determine whether incoming material controls are adequate to prevent use of unsuitable components, containers, and closures.
• 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 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 standard operating procedure that describes this COA validation program.
• A commitment to provide (b)(4) and (b)(4) test results, no later than 30 calendar days from the date of this letter, from testing retains for all lots of high-risk drug components used in the manufacture of drug products. Alternatively, if a retain of a component lot is unavailable, perform retain sample testing of all implicated finished drug product batches for the presence of (b)(4) and (b)(4).
• A full risk assessment for drug products that are within expiry which contain any ingredient at risk for (b)(4) or (b)(4) contamination (including, but not limited to, (b)(4)). Take prompt and appropriate actions to determine the safety of all lots of the component(s) and any related drug product that could contain (b)(4) or (b)(4), including customer notifications and product recalls for any contaminated lots. Identify additional appropriate corrective action and preventive action (CAPA) that secure supply chains in the future, including, but not limited to, ensuring that all incoming raw material lots are from fully qualified manufacturers and free from unsafe impurities. Detail these actions in your response to this letter.
• Provide scientific justification to demonstrate the (b)(4) you use is suitable for use in drug manufacturing operations. If you determine the (b)(4) you used to manufacture drugs was not suitable, provide a detailed risk assessment addressing the potential effects on the quality of all drug product lots currently in U.S. distribution and within expiry. Specify actions you will take in response to the risk assessment.

Quality Systems

Your firm’s quality systems are inadequate. See FDA’s guidance document Quality Systems Approach to Pharmaceutical CGMP Regulations for help implementing quality systems and risk management approaches to meet the requirements of CGMP regulations 21 CFR, parts 210 and 211 at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/quality-systems-approach-pharmaceutical-current-good-manufacturing-practice-regulations.

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 evaluate your operations and to assist your firm in meeting CGMP requirements.

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

Correct any violations promptly. Failure to promptly and adequately address this matter may result in regulatory or legal action without further notice including, without limitation, seizure and injunction. Unresolved violations may also prevent other Federal agencies from awarding contracts.

Failure to address violations may also cause FDA to withhold issuance of Export Certificates. 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 address any violations.

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 2912388 and ATTN: Emily Wu.

Sincerely,
/S/

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