WARNING LETTER

Genzyme Ireland Limited MARCS-CMS 728681 — June 22, 2026

Delivery Method:: Via UPS and EMAIL
Reference #:: CBER 26-728681
Product:: Biologics

Recipient:: Recipient Name

Mr. Cian O'Brien; Recipient Title

Site Head; Genzyme Ireland Limited; Unit 701 IDA Industrial Park
Old Kilmeaden Road
Co. Waterford
X91 TP27
Ireland; Cian.OBrien@sanofi.com

Issuing Office:: Center for Biologics Evaluation and Research (CBER); United States

WARNING LETTER

June 22, 2026

CBER 26-728681

Dear Mr. O'Brien:

The United States Food and Drug Administration (FDA) inspected your facility, located at the above address, between January 12, 2026, and January 20, 2026. During the inspection, FDA documented evidence of significant violations of current good manufacturing practice (CGMP) requirements, see 21 U.S.C. § 351(a)(2)(B) and 21 CFR parts 210 and 211, in the manufacture of your licensed biological products, Thymoglobulin (Anti-thymocyte Globulin [Rabbit]) and Altuviiio (antihemophilic factor [recombinant]) (collectively, “your products”). Because your methods, facilities, or controls for manufacturing, processing, packing, or holding drugs do not conform to CGMP, your 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). Your introduction of your products into interstate commerce is a prohibited act under section 301(a) of the FD&C Act, 21 U.S.C. § 331(a).

FDA’s inspection of your facility documented evidence of significant CGMP violations. At the conclusion of the inspection, FDA investigators issued a Form FDA-483, List of Inspectional Observations (Form FDA-483).

The CGMP violations applicable to your products include, but are not limited to, the following:

1. Your firm’s quality control unit failed to exercise its responsibility to ensure that drug products are manufactured in compliance with CGMP, and meet established specifications for identity, strength, quality, and purity, as required by 21 CFR 211.22.

Specifically, your quality unit failed to exercise its responsibility to ensure compliance with the following CGMP requirements:

a. Failure to ensure that laboratory records include complete data derived from all tests necessary to assure compliance with established specifications and standards, as required by 21 CFR 211.194(a). For example:

i. Multiple non-viable particulate excursions and repeated (b)(4) test failures across multiple batches present in instrument histories were not documented in laboratory records for review and investigation. (b)(4) testing was repeated up to 11 times without documentation.

ii. On multiple occasions, the number of active air monitoring samples documented in environmental monitoring records was not directly traceable to the instrument histories of the specific air samplers identified on those records. Additionally, logbooks documenting when environmental monitoring was performed were not always consistent with cleanroom entry and exit times for personnel performing the sampling. Consequently, these records could not be relied upon to accurately document environmental monitoring activities, as accurate records are critical to providing reliable evidence of environmental control.

iii. Your laboratory records were incomplete because quality control personnel used uncontrolled Review Checklists to unofficially document laboratory record reviews, which were subsequently discarded. Additionally, updates to your records were not always traceable or attributable to a specific person.

b. Failure to thoroughly investigate any unexplained discrepancy, or the failure of a batch or any of its components to meet any of its specifications whether or not the batch has already been distributed, as required by 21 CFR 211.192. For example, at the time of the inspection, your firm cancelled numerous deviations without investigating the root cause or assessing product impact.¹

These failures demonstrate a pattern in which your quality unit failed to exercise proper oversight, including oversight of your data integrity practices. Accurate and reliable data is necessary to ensure that your products meet established specifications for identity, strength, quality, and purity.²

Responses to the Form FDA-483

We have reviewed your responses, dated February 10, 2026, February 26, 2026, and April 8, 2026, to FDA’s Form FDA-483 in detail. While your responses indicate that your firm has implemented corrective actions to address each individual Form FDA-483 observation, you failed to address the underlying failure of the quality unit to ensure compliance with CGMP requirements. Moreover, your response lacks a comprehensive plan that addresses the root cause of your quality unit’s failure to fulfill its CGMP oversight responsibilities. In response to this letter, explain how your quality unit failed to detect and prevent the violations noted in this letter and describe what systemic corrective actions will ensure your quality unit can detect and prevent such violations in the future and ensure ongoing CGMP compliance.

We also note specific concerns regarding the adequacy of your response to the individual Form FDA-483 observations, as described below.

a. In response to observation 1 concerning data integrity failures, your firm has implemented corrective actions to address each specific failure and has also conducted data integrity training and engaged third-party experts to conduct a forensic independent assessment of your documentation, data management, and equipment usage practices. Your response states that your firm has “robust control and management of data” and that your controls “assure and maintain data integrity throughout the data life cycle.” The existence of the above-noted violations despite your described controls demonstrates that your data integrity program was not functioning as represented. Additionally, your response does not provide sufficient evidence to conclude that the data integrity failures are limited to the specific test instruments and records identified during the inspection. In response to this letter, provide a comprehensive assessment of the scope of data integrity deficiencies across your operations and perform any necessary product impact assessments based on your findings.

b. Regarding observation 2(e) concerning the cancellation of deviations, your conclusion that the cancelled deviations had no product impact is not adequately supported because deviations associated with failure to meet reject limits, failure to conduct secondary reviews, and other quality-related events were canceled without appropriate investigation. Although your retrospective review identified 36 deviations requiring further investigation, you did not provide sufficient justification for limiting the review to the selected timeframe nor did you assess whether additional canceled deviations may have existed for products outside the review period. To address our concerns, provide an expanded retrospective assessment of all canceled deviations, including those associated with deviations outside the selected review timeframe. Provide any associated investigations, including product impact assessments, and related corrective and preventive actions.

c. Regarding observations 4(a) and 4(b) concerning residue in filling (b)(4), your conclusion that (b)(4) conditions had no product impact is not adequately supported due to discrepancies within Deviation QE-1679805, which was approved and closed by your quality unit. Specifically, the (b)(4) analysis findings of an orange material for (b)(4) are inconsistently attributed across records within the deviation, and the investigation did not adequately address the identified orange material, including the reported (b)(4) as a contributing factor. To address our concerns, provide a revised investigation of Deviation QE-1679805 that resolves these discrepancies and includes a complete investigation of the orange material and (b)(4) as well as any related corrective and preventive actions.

Conclusion

Neither this letter nor the observations noted on the Form FDA-483, which were discussed with you at the conclusion of the inspection, are intended to be an all-inclusive list of deficiencies that may exist in connection with your products. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations. It is your responsibility to ensure full compliance with the FD&C Act, PHS Act, and all applicable regulations.

This letter notifies you of our concerns and provides you an opportunity to address them. Failure to adequately address these matters may result in action without further notice including, without limitation, seizure and/or injunction.

Please submit your response in writing within fifteen (15) working days from your receipt of this letter, outlining the specific steps you have taken or plan to take to address any violations and prevent their recurrence. Include any documentation necessary to show that the matters have been addressed. If you cannot address these matters within fifteen (15) working days, please explain the reason for your delay and the timeframe for completion. If you do not believe your products are in violation of the FD&C Act, PHS Act, or applicable regulations, include your reasoning and any supporting information for our consideration.

Send your electronic response and any questions regarding this letter to CBER’s Office of Compliance and Biologics Quality, Division of Case Management at CBERDCMRecommendations@fda.hhs.gov.

Sincerely,
/S/

Vincent Amatrudo
Acting Director
Office of Compliance and Biologics Quality
Center for Biologics Evaluation and Research

________________________

1 As part of your response to the Form FDA-483 (described below), your firm performed a retrospective review of the 74 cancelled deviations identified during the inspection and determined that 36 of these deviations required an investigation.

2 See FDA’s guidance document Data Integrity and Compliance With Drug CGMP: Questions and Answers available at https://www.fda.gov/media/119267/download.