WARNING LETTER
Analytical Food Laboratories, Inc.
MARCS-CMS 687513 —
October 10, 2024
Delivery Method:
VIA UPS
Reference #:
320-25-04
Product:
Drugs
Recipient:
Recipient Name
Ms. Shannon Colleen Villanueva
Recipient Title
Chief Executive Officer
Analytical Food Laboratories, Inc.
860 Greenview Drive
Grand Prairie
,
TX
75050
United States
Issuing Office:
Center for Drug Evaluation and Research (CDER)
United States
Warning Letter
320-25-04
October 10, 2024
Dear Ms. Villanueva:
The U.S. Food and Drug Administration (FDA) inspected your contract testing laboratory, Analytical Food Laboratories, Inc., FEI 3005057567, at 860 Greenview Drive, Grand Prairie, Texas, from May 7 to 17, 2024.
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, the drug products you tested 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 May 31, 2024 response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondences.
During our inspection, our investigators observed specific violations including, but not limited to, the following.
1. Your firm failed to establish and follow required laboratory control mechanisms, and 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(a) and 211.160(b)).
Lack of method validation
Your firm failed to adequately validate the analytical methods used to test your customers’ drug products. For example, you conducted assay testing of over-the-counter (OTC) drug products,
(b)(4)
oral solution and
(b)(4)
tablets, but indicated during the inspection that your firm did not have written procedures for the assay method and had not validated the test methods you used.
Inadequate system suitability
Your high-performance liquid chromatography (HPLC) analyses for drug products lacked an appropriate system suitability determination, as outlined in USP <621>, prior to sample injections. To determine whether your HPLC system is “working” you injected a “
(b)(4)
” (referred by you as a
(b)(4)
) and observed whether
(b)(4)
appeared within the expected retention time window. However, you failed to demonstrate how your approach is equivalent to or better than the USP system suitability requirements.
Inadequate growth promotion testing
Your firm failed to adequately establish and follow procedures for growth promotion testing of your microbiological media to assure suitability before use. For example, growth promotion tests for media batches 06-19-23-3 and 06-19-23-5 were performed with only one indicator microorganism, Staphylococcus aureus, and did not include the other challenge microorganisms listed in USP <61>. Both media were subsequently used to test a sample of
(b)(4)
tablets.
Between January 2022 and May 2024, you performed chemical and/or microbiological testing on at least
(b)(4)
of your customers’ drug samples. Your customers rely on your laboratory data for critical information regarding the quality of their drugs. Thus, it is important that both your test methods and growth media are properly validated, and that you use suitable analytical methods to enable your customer to make proper decisions (e.g., lot disposition). Results generated using unvalidated methods can mislead your customers and may put patients at risk.
In your response, you provide a validation report for the test method for guaifenesin, pseudoephedrine hydrochloride, and dextromethorphan hydrobromide, and committed to completing the validation of the remaining test methods. You also provided a procedure outlining your chromatographic practices that includes a requirement to perform system suitability. Additionally, you committed to revising your growth promotion procedure to include all test strains per USP requirements.
Your response is inadequate. You did not provide sufficient details regarding your corrective actions, including a complete validation protocol and study results. Additionally, you did not perform a retrospective risk assessment to determine the potential effect of these deficiencies, such as non-validated test methods, inadequately qualified growth media, and failure to perform system suitability on the validity of the test results for the drug product samples.
Refer to FDA’s guidance documents
Q2(R2) Validation of Analytical Procedures and Analytical Procedures and Methods Validation for Drugs and Biologics
for general principles and approaches for method validation at https://www.fda.gov/media/161201/download and https://www.fda.gov/media/87801/download, respectively.
In response to this letter, provide:
A comprehensive, independent assessment of your laboratory practices, procedures, methods, equipment, documentation, and analyst competencies. Based on this review, provide a detailed plan to remediate and evaluate the effectiveness of your laboratory system.
A retrospective assessment of prior testing to assure suitability of all analytical methods for the last 3 years of drug chemical testing, and a commitment to notify customers of any deficiencies.
A retrospective risk assessment of prior testing to assure suitability of all growth media for the last 3 years of drug microbiological testing to ensure reliable microbial enumeration and appropriate identification of objectionable microorganisms including, but not limited to,
Burkholderia cepacia complex
, and a commitment to notify customers of any deficiencies.
2. Your firm’s quality control unit failed to exercise its responsibility to ensure drug products manufactured are in compliance with CGMP, and meet established specifications for identity, strength, quality, and purity (21 CFR 211.22).
Your quality unit (QU) lacked adequate oversight of your contract testing operations. For example, your QU failed to adequately:
control the issuance and reconciliation of uncontrolled loose forms used for documenting laboratory testing, equipment uses, and calibrations.
review laboratory records to ensure completeness, including documentation of blank, sample, and mobile phase preparations.
Furthermore, while your quality manual, “Manual of Quality Policies for Analytical Food Laboratories” and SOP PRO42-1, “Quality Department Responsibilities” referenced 21 CFR 58.35, your procedures did not detail how your operations would meet 21 CFR parts 210 and 211 requirements.
In your response, you commit to discontinuing the use of uncontrolled loose forms and capturing all forms in bound logbooks or qualified electronic systems. Further, you note that you are drafting a procedure for documenting mobile phases, solutions, and standards in laboratory notebooks.
Your response is inadequate because you did not address the full scope and impact of the deficiencies such as uncontrolled loose forms and inadequate documentation practice on the validity of your test results and the associated risks to drug product quality.
In response to this letter, provide:
A comprehensive assessment and remediation plan to ensure your QU is given the authority and resources to effectively function. The assessment should also include, but not be limited to:
o A determination of whether procedures used by your firm are robust and appropriate.
o Provisions for QU oversight throughout your operations to evaluate adherence to appropriate practices.
o A complete and final review of the laboratory record for each drug sample and its related information before the QU disposition decision.
o Oversight and approval of investigations and discharging of all other QU duties to ensure validity of the laboratory test results of drug products without having negative impact on identity, strength, quality, and purity of your customers’ drug products.
A comprehensive independent assessment of documentation practices used throughout your laboratory operations to determine where documentation is insufficient. Include a detailed corrective action and preventive action plan that comprehensively remediates your firm’s documentation practices to ensure you retain attributable, legible, complete, original, accurate, contemporaneous records throughout your operation.
An independent assessment that summarizes the potential impact on product quality of the inadequate documentation.
A comprehensive, independent assessment of your change management system. This assessment should include, but not be limited to, your procedures to ensure changes, such as changes to or deviations from a validated test method, are justified, reviewed, investigated, and approved by your QU. Your change management program should also include provisions for determining change effectiveness.
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/media/71023/download.
Responsibilities of a Contract Testing Lab
FDA considers contractors as extensions of the manufacturer’s own facility. Your failure to comply with CGMP may affect the quality, safety, and efficacy of the drugs you test for your clients. It is essential that you understand your responsibility to operate in full compliance with CGMP, and that you inform all your customers of any out-of-specification results or significant problems encountered during the testing of these drugs.
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.
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 3005057567 and ATTN: Emily Wu.
Sincerely,
/S/
Francis Godwin
Director
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research
Content current as of:
11/05/2024
Regulated Product(s)
Drugs