BioAsia Worldwide Sdn Bhd - 700093 - 03/25/2025

---

---

---

Warning Letter 320-25-57

March 25, 2025

Dear Mr. Ho:

The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, BioAsia Worldwide Sdn Bhd, FEI 3015509166, located at U-11, Lumut Port Industrial Park, Mukim Lumut, Sitiawan, Perak from October 14 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, 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 November 4, 2024 response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence. Your response is inadequate because you failed to provide supportive documentation for evaluation or adequate evidence of corrective actions taken to bring your operations into compliance with CGMP.

During our inspection, our investigator observed specific violations 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 21 CFR 211.84 (d)(2)).

Your firm contract manufactures over-the-counter (OTC) (b)(4) drug products, including (b)(4) and (b)(4). You failed to perform adequate identity testing of each component lot used in the manufacture of these drug products. You also relied on your suppliers’ certificate of analysis (COA) without establishing the reliability of your component suppliers’ test analyses at appropriate intervals. Furthermore, you failed to demonstrate that the component (b)(4), used to manufacture your drug product (b)(4), meets United States Pharmacopoeia (USP) specifications.

In your response, you state identity testing and verification of the supplier’s COA will be performed. Your response is inadequate because you did not provide adequate details of your supplier qualification program and how you will ensure appropriate incoming testing will be performed for each component. Additionally, you did not propose testing retain samples or otherwise conduct an analysis of previously used drug product components to ensure all quality attributes were met.

Without adequate testing, you do not have scientific evidence that the components conform to appropriate specifications before use in the manufacture of your drug products. You have a responsibility to sample, test, and examine drug components before use in production to ensure acceptable quality parameters are met.

In response to this letter, provide:

• A comprehensive 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.
• The chemical and microbiological quality control specifications you use to test and release each incoming lot of component for use in manufacturing.
• 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 COAs 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 re-validation. In addition, include a commitment to always conduct at least one specific identity test for each incoming component lot.
• 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 (SOP) that describes this COA validation program.

2. Your firm failed to have, for each batch of drug product, appropriate laboratory determination of satisfactory conformance to final specifications for the drug product, including the identity and strength of each active ingredient, prior to release (21 CFR 211.165(a)).

Your firm failed to perform appropriate testing on your drug products prior to release for distribution. For example, you rely on physical and organoleptic testing, such as appearance and odor. Furthermore, you failed to perform adequate testing on (b)(4) and (b)(4) to demonstrate appropriate strength for (b)(4) and (b)(4), respectively, prior to release.

In your response, you state that each batch of finished (b)(4) will be tested for assay. Your response is inadequate because you did not provide sufficient details regarding the analytical methods that will be used. Additionally, you failed to provide a plan to test retain samples of finished drug products to ensure all quality attributes were met.

Furthermore, in your response, you commit to performing microbiological testing of your drug products. Your response is inadequate because you did not propose to perform method validation nor state whether you intend to follow USP test methods. You did not provide sufficient information to demonstrate that your methods are equivalent to or better than the applicable USP compendial methods and suitable for their intended use.

Drug product batches must be tested for identity, strength, quality, and purity prior to release. Testing is essential to ensure that the drug products you manufacture conform to all pre-determined quality attributes appropriate for their intended use, including microbiological specifications. Without adequate testing, you lack scientific data to support that each drug product batch conforms to appropriate specifications before release.

In response to this letter, provide:

• A list of chemical and microbial specifications, including test methods, used to analyze each lot of your drug products before a lot disposition decision.
  o An action plan and timelines for conducting full chemical and microbiological testing of retain samples to determine the quality of all batches of drug product distributed to the United States that are within expiry as of the date of this letter.
  o A summary of all results obtained from testing retain samples from each batch. If such testing reveals substandard quality drug products, take rapid corrective actions, such as notifying customers and product recalls.
• 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.

3. Your firm failed to establish 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)).

Your firm failed to conduct adequate stability studies on the OTC drug products, (b)(4) and (b)(4). For example, your stability program did not include full shelf-life studies evaluating the OTC drug products for the entire length of your established expiry dates. In addition, your accelerated stability study did not include testing for strength at any time point. Furthermore, no scientific data was provided to support that a 90-day accelerated study can justify a (b)(4) expiration for the (b)(4).

In your response, you state that you will begin stability studies. Your response is inadequate because it lacks sufficient detail describing your stability program procedures and protocols.

Without an adequate stability program, you cannot confirm that your drug products will meet established specifications and all pre-determined quality criteria throughout their shelf life.

In response to this letter, provide:

• A comprehensive assessment and corrective action and preventive action (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 failed to establish 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)).

Your firm failed to validate your manufacturing processes for your OTC drug products. Your firm also failed to qualify equipment and validate your cleaning processes for non-dedicated equipment used to manufacture your OTC drug products.

In your response, you state that your firm is working on creating a master validation plan, qualification plan, and a cleaning validation document. Your response is inadequate because you have not provided details on performing process validation studies for each OTC drug product or your equipment qualification plans. You also did not provide a protocol driven cleaning validation study.

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 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 that you maintain a stable manufacturing operation throughout the product lifecycle.

Without adequate process validation, incorporating all manufacturing inputs and parameters that can affect product quality, your firm lacks basic assurance that you can reproducibly deliver products that meet specifications. See FDA's guidance for industry, Process Validation: General Principles and Practices for general principles and approaches that the 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 monitoring of both intra-batch and inter-batch variation to ensure a continuing state of control.
• A timeline for performing appropriate PPQ for each of your marketed drug products.
• Process performance protocol(s), and written procedures for qualification of equipment and facilities.
• A detailed program for designing, validating, maintaining, controlling, and monitoring each of your manufacturing processes that includes vigilant monitoring of intra-batch and inter-batch variation to ensure an ongoing state of control. Also, include your program for qualification of your equipment and facility.
• Appropriate improvements to your cleaning validation program, with special emphasis on incorporating conditions identified as worst-case in your drug manufacturing operation. This should include, but not be limited to, identification and evaluation of all worst-case:
  o Drugs with higher toxicities
  o Drugs with higher drug potencies
  o Drugs of lower solubility in their cleaning solvents
  o Drugs with characteristics that make them difficult to clean
  o Swabbing locations for areas that are most difficult to clean
  o Maximum hold times before cleaning
  In addition, describe the steps that must be taken in your change management system before introduction of new manufacturing equipment or a new product.
• A summary of updated SOPs that ensure an appropriate program is in place for verification and validation of cleaning procedures for products, processes, and equipment.

5. 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) failed to perform adequate oversight for the manufacture of your OTC drug products. For example, your QU failed to ensure the following:

• Establishment of an adequate training program (21 CFR 211.25(a))
• Performance of appropriate product reviews (21 CFR 211.180(e))

In your response, you state that your employees will be trained in 21 CFR 210 and 211 (b)(4). Your response is inadequate because you do not provide sufficient details on how your staff will be trained in 21 CFR 210 and 211 regulations. Additionally, you did not address completing product reviews retrospectively.

An adequate QU overseeing all CGMP operations is necessary to ensure consistent drug quality. 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.

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 audit¹ 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.

Cosmetics Manufactured for Distribution in the United States

In addition, we note that 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. 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.

Further, your facility may be subject to requirements of the Modernization of Cosmetics Regulation Act of 2022 (MoCRA). Information on MoCRA requirements may be found at https://www.fda.gov/cosmetics/cosmetics-laws-regulations/modernization-cosmetics-regulation-act-2022-mocra.

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 February 20, 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 BioAsia Worldwide Sdn Bhd, U-11, Lumut Port Industrial Park, Mukim Lumut, Sitiawan, Perak 32000, Malaysia, 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 3015509166 and ATTN: Barbara Wilimczyk-Macri.

Sincerely,
/S/

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

______________________

1 i.e., Quality System, Facilities & Equipment System, Materials System, Production System, Packaging & Labeling System, and Laboratory Control System per FDA’s guidance document Quality Systems Approach to Pharmaceutical CGMP Regulations.