FDA 就微生物检验数据记录缺陷向 Eurofins SF Analytical Laboratories 发出警告信 320-27-05

Delivery Method:

VIA Electronic Mail

Reference #:

320-27-05

Product:

Drugs

Recipient:

Recipient Name

Mr. David Riggs

Recipient Title

President - EFSA Cluster

Eurofins SF Analytical Laboratories, Inc.

2345 South 170th Street
New Berlin, WI 53151
United States

(b)(4)

Issuing Office:

Center for Drug Evaluation and Research (CDER)

United States

October 6, 2026

WARNING LETTER
Reference number: 320-27-05

To Mr. David Riggs:

This warning letter advises you of significant violations observed during a U.S. Food and Drug Administration (FDA) inspection of your facility. Promptly address the violations described herein without delay including ensuring that appropriate resources are allocated to fully address the violations and prevent their recurrence. This is not intended to be an all-inclusive list of the violations that exist at your facility. It is your responsibility to ensure that your firm complies with all requirements of federal law, including FDA regulations. Failure to adequately address violations may result in regulatory or legal action without further notice including, without limitation, seizure and injunction.

FDA Inspection

Violations were observed and documented during an inspection of your contract testing laboratory, Eurofins SF Analytical Laboratories, Inc., FDA Establishment Identifier (FEI) 3014704316, at 215 Witmer Road, Horsham, Pennsylvania, from June 1 to 3, 2026. This inspection was conducted under FDA’s statutory authority and public health responsibilities to protect the public from unsafe, ineffective, and poor quality drugs.

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 June 22, 2026, response to our Form FDA 483 in detail.

Violations of the Federal Food, Drug, and Cosmetic Act

The following are violations identified during our inspection and review. As a reminder, this is not an all-inclusive list of violations at your facility.

1. Your firm failed to ensure that laboratory records included complete data derived from all tests necessary to ensure compliance with established specifications and standards (21 CFR 211.194(a)).

Your firm conducts microbiological analyses of components and drug products for your customers.

You perform (b)(4) pour plate methods for microbial enumeration of (b)(4) samples. During the inspection, our investigator observed that your microbiologist failed to record the (b)(4) results when they were assessed as too numerous to count (TNTC), recording only the pour plate counts. The investigator also noted that while the (b)(4) for the pour plate samples was cracked and desiccated, the pour plate counts were recorded as within acceptable limits. When (b)(4) plates are desiccated and cracked, the media can no longer reliably support uniform microbial growth. A result recorded from a compromised plate, even one that falls within specification, cannot be considered valid, as the physical condition of the media may have suppressed or obscured actual microbial recovery.

Additionally, your data review procedure is deficient in that it does not require secondary verification when an initial plate count is recorded as 0 colony forming units (CFU), creating a systemic gap where microbial growth can go undetected. During the inspection, the investigator identified a colony on a plate recorded as 0 CFU by your analyst. Further, several samples with desiccated and cracked (b)(4) were recorded as 0 CFU and discarded without secondary analyst review. The practice of non-reporting of TNTC (b)(4) results, and the investigator's direct observation of a colony on a plate recorded as 0 CFU illustrates the unreliability of your data, and further demonstrates that lack of secondary verification is unacceptable.

In your response, you state that analyst interviews and a retrospective review of laboratory data revealed inconsistent reporting practices dating back to February 2025. You acknowledge that some analysts were selectively recording test results, documenting only pour plate results when (b)(4) results were TNTC (out of specification), and only documenting (b)(4) results when they were within specification. You commit to revising your procedures, training analysts, and periodically auditing plate readings.

Your response is inadequate. You do not address whether the selective omission TNTC (b)(4) results during this period affected the accuracy of certificates of analysis issued to customers, or whether any customers received incomplete or potentially inaccurate microbiological data. Although you updated your reporting procedure to require secondary review, you provided no evidence to verify the completeness and accuracy of the historical data reviewed.

Reliability of data is compromised when there is a failure to maintain complete records of the conditions and data associated with all tests. Furthermore, the lack of complete data compromises the quality unit’s (QU) ability to exercise its function of ensuring compliance to applicable standards.

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 comprehensive assessment of documentation systems used throughout your manufacturing and laboratory operations to determine where documentation practices are insufficient. Include a detailed corrective action and preventive action (CAPA) plan that comprehensively remediates your firm’s documentation practices to ensure you retain attributable, legible, complete, original, accurate, contemporaneous records throughout your operation.

2. 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 investigate aberrant media conditions (e.g., cracked or desiccated (b)(4) plates) used for testing raw material and drug product samples in your microbiological laboratory.

In your response, you state that you opened an investigation to determine the scope of affected samples and adequacy of results and transferred microbial samples into an alternative incubator as an interim measure. Based on analyst interviews and a limited records review, you concluded that the results are valid. We acknowledge your plan to retest affected samples as a means of confirming your initial test results.

Your response is inadequate. Without photographic evidence of plate conditions at the time of reading, there is no basis to retroactively confirm any result. Your conclusions rely solely on analyst interviews and data records that you acknowledged are unreliable. Furthermore, you did not commit to discontinuing the use of damaged plates for microbiological testing.

Data integrity depends on complete and accurate documentation of test results and conditions. Failure to maintain such records undermines the reliability of your data. The use of deficient media similarly compromises the validity of microbiological test results and raises questions about the suitability and robustness of your methods.

In response to this letter, provide:

• A comprehensive, independent assessment of your overall system for investigating deviations, discrepancies, complaints, out-of-specification results, out-of-limit 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, QU oversight, and written procedures. Address how your firm will ensure all phases of investigations are appropriately conducted.
• A comprehensive CAPA plan, overseen by a qualified consultant, for handling microbiological sampling media to ensure robust and reliable data. Establish a system that ensures uninterrupted custody and full reconciliation of all microbiological samples, including but not limited to:
  o Unique labeling of each sample
  o Signatures of all staff who handle the sample
  o Complete tracking of sample integrity and custody
  o Date and time of each activity (e.g., sample collection, delivery, incubation, removal from incubator)
  o Digital time-stamped photos of all plates at the time of reading. Ensure full implementation of photographic evidence to support all results obtained.
  o Signatures of personnel performing reading of microbial counts
  o Provisions for verifications and routine quality assurance oversight.

3. Your firm’s quality 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 QU lacked adequate oversight and control over your laboratory operations to ensure a state of control and adherence to applicable quality standards.

Significant findings in this letter demonstrate that your firm does not operate an effective quality system in accord with CGMP. In addition to the lack of effective management oversight of your laboratory operations, we found your QU is not enabled to exercise proper authority and/or has insufficiently implemented its responsibilities. Executive management should immediately and comprehensively assess your company’s global manufacturing operations to ensure that your systems, processes, and products conform to FDA requirements.

Your firm’s quality systems are inadequate. See FDA’s guidance documents ICH Q10 Pharmaceutical Quality System and 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/71553/download and https://www.fda.gov/media/71023/download, respectively.

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:

• A determination of whether procedures used by your firm are robust and appropriate
• Provisions for QU oversight throughout your operations to evaluate adherence to appropriate practices
• A complete and final review of each batch and its related information before the QU disposition decision
• Oversight and approval of investigations and discharging of all other QU duties to ensure identity, strength, quality, and purity of all products
• Also describe how top management supports quality assurance and reliable operations including, but not limited to, timely provision of resources to proactively address emerging manufacturing/quality issues and to assure a continuing state of control.

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. 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 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

You are responsible for investigating and determining the root causes of any violations and implementing corrective and preventative measures to ensure future and sustained compliance so that these violations and any others do not occur.

Unresolved violations may 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.

Send your written response to [email protected] within 15 business days of receipt of this letter.¹ Identify your written response with FEI 3014704316 and ATTN: Christopher Keating in the subject line of the email.

If you have information that you believe demonstrates that your products are not in violation of the FD&C Act and FDA regulations, include that information for our consideration.

FDA posts warning letters to www.FDA.gov.

Sincerely,
/S/

Francis Godwin
Director
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research
U.S. Food and Drug Administration

Cc: Ms. Amanda Berd, Site Leader
(b)(4)

______________________

1 Under program enhancements for the Generic Drug User Fee Amendments (GDUFA) reauthorization for fiscal years (FYs) 2023-2027, also known as the GDUFA III Commitment Letter, your facility may be eligible for a Post-Warning Letter Meeting to obtain preliminary feedback from FDA on the adequacy and completeness of your corrective action plans.