Sante Manufacturing Inc.(320-26-94)

Issuing Office:

Center for Drug Evaluation and Research (CDER)

United States

Warning Letter 320-26-94

June 5, 2026

Dear Mr. Kirby:

Your facility is registered with the United States Food and Drug Administration (FDA) as a manufacturer of over-the-counter (OTC) drug products. FDA has reviewed the records you submitted in response to our July 7, 2025, request and subsequent correspondence for records and other information pursuant to section 704(a)(4) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) for your facility, Sante Manufacturing Inc., FEI 3021535057, at 516 John Street N 11A & 11B Aylmer, Ontario, Canada.

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

Because your methods, facilities, or controls for manufacturing, processing, packing, or holding of drugs as described in your response to our 704(a)(4) request 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)).

Following review of records and other information provided pursuant to section 704(a)(4) of the FD&C Act, significant violations were observed including, but not limited to, the following:

1. 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)).

Your firm manufactures OTC drug products such as (b)(4). Based on the records and information you provided, you did not demonstrate that you adequately tested each shipment of each lot of incoming (b)(4), a component at high risk for (b)(4) contamination, prior to its use in manufacturing. This includes testing of (b)(4) used in manufacturing drug products to determine its appropriate identity. Your firm also relied on the supplier’s certificate of analysis (COA) and accepted the (b)(4) component based on your supplier’s COA without establishing the reliability of your supplier’s test analyses at appropriate intervals.

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

Without adequate testing and confirmation of reliability of supplier test results, you lack scientific evidence that the components or drug products conform to appropriate specifications prior to use in the drug products you manufacture.

In response to this letter, provide:

• A commitment to provide (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).

• A full risk assessment for drug products that are within expiry which contain any ingredient at risk for (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), including customer notifications and product recalls for any contaminated lots. Identify additional appropriate corrective actions and preventive actions (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.

• 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 revalidation. In addition, include a commitment to always conduct at least one specific identity test for each incoming component lot. In the case of (b)(4), and certain additional high-risk components we note that this includes the performance of parts (b)(4) of the United States Pharmacopeia (USP) monograph.

• The chemical quality control specifications you use to test each incoming lot of high-risk drug components to determine acceptability for use in manufacturing.

• 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.

2. Your firm failed to establish adequate written procedures for production and process control designed to assure that the drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess (21 CFR 211.100(a)).

Based on the records and information you provided, you did not demonstrate that you have adequately qualified your (b)(4) system. Additionally, you did not demonstrate that you adequately monitor your (b)(4) system. Because you use (b)(4) from this system as a component in your drug products, you should ensure that it meets, at a minimum, the USP (b)(4) monograph testing requirements and appropriate microbial limits in light of its intended use. Further, you did not demonstrate that you have an appropriate process validation program.

Process validation evaluates the soundness of design and state of control of a process throughout its lifecycle. Each significant stage of a manufacturing process must be designed appropriately and assure the quality of raw material inputs, in-process materials, and finished drugs. Process qualification studies include intensive monitoring and testing throughout each significant process stage to characterize intra-batch variation and evaluate batches to determine whether an initial state of control has been established.

Successful process qualification studies are necessary before commercial distribution. Thereafter, ongoing vigilant oversight of process performance and product quality is necessary to ensure you maintain a stable manufacturing operation throughout the product lifecycle.

See FDA’s guidance document Process Validation: General Principles and Practices for general principles and approaches that FDA considers appropriate elements of process validation at https://www.fda.gov/media/71021/download.

In response to this letter, provide:

• A detailed summary of your validation program for ensuring a state of control throughout the product lifecycle along with associated procedures. Describe your program for process performance qualification (PPQ) and ongoing vigilant monitoring of both intra-batch and inter-batch variation to ensure a continuing state of control. Also, describe your equipment and facility qualification program.

• A timeline for performing appropriate PPQ for each of your marketed drug products. Also provide a risk assessment and any follow-up actions to be taken for the distributed drug products produced without performing any process validation studies.

• Process performance protocol(s), and written procedures for qualification of equipment and facilities.

• A procedure for your (b)(4) system monitoring that specifies routine microbial testing of (b)(4) to ensure its acceptability for use in each batch of drug products produced by your firm.

• The current action/alert limits for total counts and objectionable organisms used for your (b)(4) system. Ensure that the total count limits for your (b)(4) are appropriately stringent in view of the intended use of each of the products produced by your firm.

• A procedure governing your program for ongoing control, maintenance, and monitoring that ensures the system consistently produces (b)(4) that meets (b)(4) USP monograph specifications and appropriate microbial limits.

3. 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).

Based on the records and the information you provided, you did not demonstrate that your quality unit (QU) adequately exercises its authority and responsibilities including, but not limited to, implementing effective procedures and conducting adequate oversight of the drug products you manufacture. For example, your QU failed to ensure:

• Establishment of an appropriate written testing program designed to assess the stability characteristics of drug products and to use results of stability testing to determine appropriate storage conditions and expiration dates (21 CFR 211.166(a)).

• Appropriate validation of your analytical methods (21CFR 211.160(b)).

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 production 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. For guidance on establishing and maintaining CGMP-compliant quality systems, see FDA guidance documents: Q8(R2) Pharmaceutical Development at https://www.fda.gov/media/71535/download, Q9(R1) Quality Risk Management at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/q9r1-quality-risk-management and Q10 Pharmaceutical Quality System at https://www.fda.gov/media/71553/download.

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.

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

FDA placed all drugs and drug products offered for import into the United States from your firm on Import Alert 66-40 on April 27, 2026.

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 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 Sante Manufacturing Inc., at 516 John Street N 11A & 11B, Aylmer, Ontario, Canada, 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 3021535057 and ATTN: LaKeesha M. Sifontes.

Sincerely,
/S/

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