Shantou S.E.Z. Baojie Industry Co., Ltd. - 703439 - 04/15/2025

---

---

---

Warning Letter 320-25-66

April 15, 2025

Dear Mr. Wu:

The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Shantou S.E.Z. Baojie Industry Co., Ltd., FEI 3016787260, at Sihuang Road Lugang Town, Chaonan District, Shantou, Guangdong, China, from August 26 to 30, 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, 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 September 11, 2024 response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence.

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

1. Your firm failed to test samples of each component for identity and conformity with all appropriate written specifications for purity, strength, and quality. 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 over-the-counter (OTC) (b)(4) drug products without adequate assurance of the quality of components used in their manufacture. For example, you failed to adequately test your incoming components, including identity testing for each shipment of each component lot used in the manufacture of your OTC drug products. Instead, you relied on your suppliers’ certificate of analysis (COA) without establishing the reliability of your component suppliers’ test analyses at appropriate intervals. Additionally, your firm failed to test a representative sample from each shipment of each lot of high-risk components used in your drug products.

Of note, after FDA sent an electronic request for records and other information pursuant to section 704(a)(4) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 374(a)(4), on October 2, 2023, you committed to performing identity testing on every lot of high-risk components and every batch of finished products. However, during the inspection, and despite previous commitments, you failed to adequately test your incoming high-risk components for contamination.

In your response to the Form FDA 483 issued to your firm after the August 2024 inspection, you state that you would contact your third-party laboratory to retest (b)(4) and (b)(4), and include identity testing of your raw materials, including (b)(4). Your response is inadequate. You failed to provide sufficient details on how you will ensure adequate identity testing of a representative sample from each lot of (b)(4). Further, you do not address potential impact on drug products in the U.S. market within expiry. FDA is also concerned that you had committed to corrections previously but did not implement them.

Without adequate testing, you do not have scientific evidence that the 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 ensure adequate quality.

The use of ingredients contaminated with (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) contamination at (b)(4).

In response to this letter, provide:

• The chemical and microbiological quality control specifications you use to test and release each incoming lot of component for use in manufacturing.
• 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 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.
• A summary of your program for qualifying and overseeing contract facilities that test the drug products you manufacture.
• 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 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.
• 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 A, B, and C of the United States Pharmacopeia (USP) monograph.

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)).

You use (b)(4) as a component in your drug products and for cleaning production equipment. However, you have not established that the (b)(4) system is adequately designed, maintained, and monitored to ensure that it consistently produces (b)(4) suitable for its intended use. You also lacked appropriate testing of your (b)(4) system, and your sampling frequency is not representative of actual use.

In your response, you state that you would re-evaluate the qualification of your (b)(4) system. Your response is inadequate. You failed to provide an assessment of the impact your (b)(4) system has on your drug products in the U.S. market within expiry.

The lack of data regarding the state of control of your (b)(4) system poses a potential risk for objectionable microbiological contamination into your drug products. (b)(4) must be suitable for its intended use and routinely tested to ensure ongoing conformance with appropriate chemical and microbiological attributes.

In response to this letter, provide:

• A comprehensive remediation plan for the design, control, and maintenance of the (b)(4) system, including a robust monitoring program.
• A (b)(4) system validation report, along with a summary of any improvements made to the system design and the ongoing control and maintenance program.
• Your total microbial count limits to monitor whether this system is producing (b)(4) suitable for the intended uses for each of your products.
• 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.

3. Your firm failed to establish and follow an adequate 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)).

You did not have adequate stability data to demonstrate that the quality attributes of your drug product remain acceptable throughout the labeled expiry period. For example, your stability testing procedure only requires an organoleptic assessment (odor, color, appearance) and lacks chemical and microbial analysis. Without appropriate stability studies, there is no scientific evidence to support that your drug products retain their quality attributes through the labeled (b)(4) expiry.

In your response, you state that you plan to revise your firm’s procedure to clarify that the stability test time for finished products will be 30 days, and for new products, it will be 6 months. Your response is inadequate. You failed to provide an assessment on the potential impact of your drug products in the U.S. market within expiry, a scientific rationale for the proposed revisions to your stability testing procedure to support the labeled expiry, and a commitment for ongoing stability studies.

In response to this letter, provide:

• A comprehensive, independent assessment and CAPA plan to ensure the adequacy of your stability program. Your remediated program should include, but not be limited to:
  o Stability indicating methods.
  o Stability studies for each drug product in its marketed container-closure system before distribution is permitted.
  o An ongoing program in which representative batches of each product are added each year to the program to determine if the shelf-life claim remains valid.
  o Detailed definition of the specific attributes to be tested at each station (timepoint).
• All procedures that describe these and other elements of your remediated stability program.

4. 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) did not provide adequate oversight for the manufacture of your OTC drug products. For example, your QU failed to ensure the following:

• Adequate testing of your incoming components for identity, purity, strength, and other appropriate quality attributes (21 CFR 211.84(d)(1) and 211.84(d)(2)).
• Establishment of written procedures for production and process controls (21 CFR 211.100(a)).
• Establishment of an adequate, ongoing stability program (21 CFR 211.166(a)).
• Establishment of a procedure and for the performance of appropriate product reviews (21 CFR 211.180(e)(1)).
• Verification of testing methods to ensure accurate, precise, and reliable results (21 CFR 211.194(a)(2)).

As part of your response, you state that you are “unfamiliar with FDA standards”, even though you have a history of distributing drugs to the United States. 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.

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 each batch and its related information before the QU disposition decision.
  o 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 if your firm intends to resume manufacturing drugs for the U.S. market. 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 CAPA 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.

Cosmetics Manufactured for Distribution in the United States

In addition, some of the products you manufacture may be regulated as cosmetics, as defined in section 201(i) of the FD&C Act [21 U.S.C. 321(i)]. Any cosmetics you manufacture must comply with applicable statutory and regulatory requirements, including the FD&C Act. We note that under section 301(a) of the FD&C Act [21 U.S.C. 331(a)], it is a prohibited act to introduce or deliver for introduction into interstate commerce a cosmetic that is adulterated or misbranded.

We also note that the Modernization of Cosmetics Regulation Act of 2022 (MoCRA) provides new requirements with which facilities that manufacture cosmetic products must comply. You may find the FD&C Act, MoCRA, and FDA’s regulations through links on FDA’s website at www.fda.gov.

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 products offered for import into the United States from your firm on Import Alert 66-40 on April 9, 2025.

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 re-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 Shantou S.E.Z. Baojie Industry Co., Ltd., Sihuang Road Lugang Town, Chaonan District, Shantou, Guangdong, China, 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 [or misbranded] 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 3016787260 and ATTN: Kevin Maguire.

Sincerely,
/S/

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

Cc:
Registered U.S. Agent:
Panatural USA, Inc.
Sol Great Labs
3705 W. Pico Blvd.
Suite 1766
Los Angeles, CA 90019-3451
peter@panaturalusa.com
russ@thesourcingsolution.com