Huons Co., Ltd.(320-26-95)

Issuing Office:

Center for Drug Evaluation and Research (CDER)

United States

Warning Letter 320-26-95

June 15, 2026

Dear Mr. Choo:

The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, Huons Co., Ltd., FEI 3007163376, located at 100 Bio Valley-ro, Jecheon, Chungcheongbuk, from November 12 to 21, 2025.

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 December 15, 2025, 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 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 laboratory records lacked complete and original data to support the analyses performed. For example:

A. During the inspection, we requested the testing worksheets from the (b)(4) studies you conducted on a compounding tank and its transfer line, which included endotoxin and bioburden tests. Initially, your firm provided only a portion of the data. The following day, your firm’s management informed our investigator of critical breaches in data integrity. The first (b)(4) run failed endotoxin limits, and the second (b)(4) run revealed significant bioburden levels. However, your team leader had instructed staff to discard the bioburden plates with significant growth and had manipulated camera timestamps to create backdated documentation. In addition, the endotoxin failure had not been documented or investigated.

B. During the walkthrough of your microbiology laboratories, we found 1,897 blank uncontrolled CGMP-related forms.

C. Pages were removed from your logbook and replaced with newly fabricated pages. Your microbiology team leader admitted to using a knife to remove completed pages from the logbook. Logbook pages were then manipulated to look like the originals, and the microbiology team leader instructed the analyst to backdate and omit testing information related to bioburden samples.

Your response indicates that multiple personnel involved in data manipulation are no longer employed at your firm, and you have established a data integrity team to help oversee microbiology laboratory data practices. We also acknowledge that you are using an independent third-party consultant to audit your operation and assist in meeting FDA requirements.

Your response is inadequate because it does not provide a corrective action and preventive action (CAPA) plan with sufficient actions to systemically implement management oversight and assure data integrity.

In your initial response to inspectional findings your firm contracted a third party to perform an assessment to adequately determine the extent of your firm’s data integrity issues. You initially committed to providing the interim and final reports of this assessment. However, you later informed the FDA that this document would be classified as an “internal audit”, and that reports would not be provided. The agency disagrees with your characterization of this assessment as an internal audit. This investigative assessment was initiated in response to FDA inspectional findings relayed by our investigators to your firm, and not part of a routine evaluation per a written quality assurance program. This assessment is part of the comprehensive investigation you initiated in response to FDA inspectional findings covered under 21 CFR parts 211.192 and 211.22 and therefore is subject to routine FDA review.

As part of this investigative assessment, your third party conducted interviews of staff regarding data integrity issues, and your firm provided these interviews as evidence in your initial response.

Furthermore, your correspondence indicates that data integrity issues extend beyond your microbiology laboratory and include recurring data integrity issues with total organic carbon testing (TOC) in the physical chemistry testing lab in the past. The agency expects full transparency throughout your remediation process. The events associated with these inspectional findings necessitate a comprehensive investigation and remediation process, including third-party assistance. All CGMP-related issues identified in the course of these retrospective assessments remain within the scope of quality unit’s investigation and are subject to review by the FDA.

Integrity of data is fundamentally compromised when there is a failure to record or maintain complete and accurate records of test results or conditions associated with testing. Furthermore, the lack of reliable data compromises the quality unit’s ability to exercise its function of ensuring compliance with applicable standards.

Your quality system did not adequately ensure the accuracy and integrity of data to support the safety, effectiveness, and quality of the drugs you manufacture. See FDA’s guidance document Data Integrity and Compliance With Drug CGMP for guidance on establishing and following CGMP compliant data integrity practices at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/data-integrity-and-compliance-drug-cgmp-questions-and-answers.

In response to this letter, provide:

• A comprehensive investigation into the extent of the inaccuracies and inconsistencies in data, records, and reporting. Your investigation should include:
  o A detailed investigation protocol and methodology; a summary of all laboratories, manufacturing operations, and systems to be covered by the assessment; and a justification for any part of your operation that you propose to exclude.
  o Interviews of current and former employees to identify the nature, scope, and root cause of data inconsistencies and inaccuracies. We recommend that these interviews be conducted by a qualified third party.
  o An assessment of the extent of data integrity deficiencies at your facility. Identify omissions, alterations, deletions, record destruction, non-contemporaneous record completion, and other deficiencies. Describe all parts of your facility’s operations in which you discovered data integrity deviations.
  o A comprehensive retrospective evaluation of the nature of the testing/manufacturing/other data integrity deficiencies. We recommend that a qualified third party with specific expertise in the area where potential breaches were identified should evaluate all occurrences of data integrity deviations.

• A current risk assessment of the potential effects of the observed failures on the quality of your drugs. Your assessment should include analyses of the risks to patients caused by the release of drugs affected by data integrity deviations and analyses of the risks posed by ongoing operations.

• A management strategy for your firm that includes the details of your global corrective action and preventive action plan. Your strategy should include:
  o A detailed corrective action plan that describes how you intend to ensure the reliability and completeness of all data, including analytical data, manufacturing records, and all data submitted to FDA.
  o A comprehensive description of the root causes of your data integrity deviations including evidence that the scope and depth of the current action plan is commensurate with the findings of the investigation and risk assessment. Indicate whether individuals responsible for data integrity deviations remain able to influence CGMP-related or drug application data at your firm.
  o Interim measures describing the actions you have taken or will take to protect patients and to ensure the quality of your drugs, such as notifying your customers, recalling product, conducting additional testing, adding lots to your stability programs to assure stability, drug application actions, and enhanced complaint monitoring.
  o Long-term measures describing any remediation efforts and enhancements to procedures, processes, methods, controls, systems, management oversight, and human resources (e.g., training, staffing improvements) designed to ensure the integrity of your company’s data.
  o A commitment to have a qualified consultant conduct extensive annual audits, for at least two years, to assist in evaluating CAPA effectiveness after you have executed your data integrity remediation protocol.
  o Contract with a third party to be physically present in the microbiology lab to oversee sampling and analysis of drug products for the U.S. Market. Ensure full implementation of photographic evidence using electronic controls (e.g., audit trails, preventing photo manipulation) to support all results obtained.
  o Inform FDA if you will be hiring a Chief Integrity Officer who is fully empowered to receive anonymous complaints from employees reporting data integrity concerns and with the authority to ensure any potential breach is promptly investigated (by independent quality assurance function, along with expertise from outside entities whenever needed.
  o A status report for any of the above activities already underway or completed.

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 open adequate investigations into out-of-specification (OOS) results.

For example, (b)(4) batch (b)(4) failed initial testing due to unknown impurities. Your firm opened an out-of-specification investigation that included performing hypothesis testing for contaminated glassware. To simulate your hypothesis, your firm prepared a second sample using glassware marked for disposal to mimic the original failed sample. This second sample met acceptance criteria. Your firm still used the passing hypothesis test results as justification to invalidate the original test result.

You also failed to adequately investigate other out-of-specification results, including the endotoxin failure discussed under the first violation in this warning letter.

In response you indicated that your firm is conducting a retrospective assessment of all OOS investigations for all U.S. drug products on the market, but you did not provide a specific timeline for completion. Your response is also inadequate because it fails to sufficiently address the need for improved quality unit (QU) oversight of investigations. In addition, the data integrity issues at your firm significantly compromise your QU’s ability to perform its obligation to assess laboratory data and evaluate OOS investigations.

For more information about handling failing, out-of-specification, out-of-trend, or other unexpected results and documentation of your investigations, see FDA’s guidance document Investigating Out-of- Specification (OOS) Test Results for Pharmaceutical Production at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/investigating-out-specification-oos-test-results-pharmaceutical-production-level-2-revision.

In response to this letter provide:

• A retrospective, independent review of all invalidated OOS (including in-process and release/stability testing) results for US products for the last three years from the initial date of inspection and a report summarizing the findings of the analysis, including the following for each OOS
  o Determine whether the scientific justification and evidence relating to the invalidated OOS result conclusively or inconclusively demonstrates causative laboratory error.
  o For investigations that conclusively establish laboratory root cause, provide rationale and ensure that all other laboratory methods vulnerable to the same or similar root cause are identified for remediation.
  o For all OOS results found by the retrospective review to have an inconclusive or no root cause identified in the laboratory, include a thorough review of production (e.g., batch manufacturing records, adequacy of the manufacturing steps, suitability of equipment/facilities, variability of raw materials, process capability, deviation history, complaint history, batch failure history). Provide a summary of potential manufacturing root causes for each investigation and any manufacturing operation improvements.

• 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.

3. Your firm failed to follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile and that include validation of all aseptic and sterilization processes (21 CFR 211.113(b)).

Smoke studies demonstrated a lack of unidirectional airflow in your ISO 5 aseptic processing operation. Multiple instances of turbulent airflow in critical areas of ampoule filling line (b)(4) were noted, including during the performance of interventions.

We also found severe hazards during interventions and (b)(4)RABS ((b)(4) Restricted Access Barrier System) (b)(4). Specifically, the operator’s head and upper body were fully inside the Grade A area and blocked first air over critical areas of operation. In addition, the (b)(4) on (b)(4)RABS line (b)(4) created an unacceptable and unnecessary disturbance of airflow when (b)(4).

In your response, you commit to repeating smoke studies with oversight from a third party. Your response is inadequate as you do not provide a timeline for addressing basic line deficiencies or providing suitable smoke studies. Your response also fails to indicate whether you are considering significant operational design changes, including enhanced process separation and minimization (or elimination) of frequent (b)(4) to access the aseptic processing line.

You also provide historical environmental and sterility data to justify your conclusion that these conditions represent a low risk to the quality of your drug products. This justification is inadequate given the operational deficiencies noted in the inspection as well as data integrity issues that raise concerns about the reliability of all microbiological data at your firm. Your firm acknowledges that due to these data integrity issues, “it may be premature to draw conclusions about product impact based on the sterility assurance data from sterility testing results and media fill results from the previous three years.”

In response to this letter provide:

• Comprehensive, independent risk assessment of all contamination hazards with respect to your aseptic processes, equipment, and facilities including, but not limited to:
  o All human interactions within the ISO 5 area (e.g., risk reduction or elimination of manual interventions wherever possible) Equipment suitability (e.g., reliability, capability, ergonomics, placement) and sufficient cleanroom space Air quality in the ISO 5 area and surrounding room including, but not limited to, air volume and flow Facility layout
  o Personnel Flows and Material Flows (movement throughout all rooms used to conduct and support sterile operations and all material transfers)
  o Specific CAPA recommendations that will comprehensively address the design and control hazards identified in the risk assessment

• A detailed remediation plan with timelines to address the findings of the contamination hazards risk assessment. Describe specific tangible improvements to be made to aseptic processing operation design and control at your facility and explain how this corrective action and preventative action (CAPA) will robustly remediate your deficient sterile manufacturing operations.

• Your plan to ensure appropriate aseptic practices and cleanroom behavior during production. Include steps to ensure routine and effective supervisory oversight for all production batches. Also describe the frequency of quality unit (QU) oversight (e.g., audit) during aseptic processing and its support operations.

• A thorough retrospective review and risk assessment that evaluates how poor aseptic technique and cleanroom behavior may have affected the quality and sterility of your drugs.

• Smoke studies under dynamic conditions, with thorough and complete evaluations of aseptic interventions and operator positioning within the critical filling areas. After you remediate your aseptic operation, provide smoke studies that visualize airflow and critically evaluate unidirectional airflow. Include a video of your dynamic smoke studies.

• A comprehensive summary of your remediated media fill program that ensures appropriate simulations of worst-case conditions in commercial manufacturing.

4. Your firm failed to establish an adequate system for maintaining equipment used to control the aseptic conditions (21 CFR 211.42(c)(10)(vi)).

You had inadequate procedures for monitoring of your (b)(4) gloves. Your procedures required sampling from (b)(4) glove on ampoule filling line (b)(4) at the conclusion of batch filling. In addition, your procedure lacked instructions that ensure all gloves are tested and specifying when they must be tested.

In addition, your firm lacked sufficient procedures on how to clean (b)(4) gloves, including but not limited to, provisions for adequate sporicidal disinfection frequency.

Your firm’s response to cleaning and disinfection deficiencies is inadequate because it lacks specific completion timelines for critical assessments and corrective actions. In your response your firm classifies the contamination risk from (b)(4) gloves as low. Your rationale for this is inadequate, as the product does not need to come into direct contact with the gloves for contamination to occur. You also do not address how you will ensure more frequent disinfection of (b)(4) gloves, including ad-hoc disinfection of gloves when needed during batch production.

Your response also cites environmental monitoring data as evidence of robust contamination prevention. However, the data integrity issues in the microbiology laboratory raise questions about the usefulness and validity of that data.

It is imperative that you establish an appropriate program for vigilantly maintaining (b)(4) gloves. In addition to appropriate robust disinfection and preventive maintenance, the environmental monitoring program should appropriately encompass all (b)(4) gloves.

A vigilant, ongoing personnel and environmental monitoring program is essential to detect and respond to potential product contamination hazards in your manufacturing environment in a timely manner. Loss of environmental control in an aseptic manufacturing facility can ultimately pose a serious hazard to patients.

In response to this letter provide the following:

• Your CAPA plan to implement routine, vigilant operations management oversight of facilities and equipment. This plan should ensure, among other things, prompt detection of equipment/facilities performance issues, effective execution of repairs, adherence to appropriate preventive maintenance schedules, timely technological upgrades to the equipment/facility infrastructure, and improved systems for ongoing management review.

• An independent, comprehensive review of your environmental monitoring (EM) program to ensure vigilant, timely detection and response to potential product contamination hazards in your manufacturing environment. This assessment should include, but not be limited to:
  o establishing appropriate limits
  o sampling methods
  o sampling locations and frequencies
  o trend analysis
  o appropriate investigation of deviations and adverse trends
  o and a comprehensive CAPA plan based on the findings of the assessment.

Additional Guidance on Aseptic Processing

See FDA’s guidance document Sterile Drug Products Produced by Aseptic Processing—Current Good Manufacturing Practice to help you meet the CGMP requirements when manufacturing sterile drugs using aseptic processing at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/sterile-drug-products-produced-aseptic-processing-current-good-manufacturing-practice.

Quality Systems

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 and production operations, we found your quality unit 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

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 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.

Drug Production Suspended

We acknowledge your commitment to suspend production of all drugs at this facility for the U.S. market.

On March 24, 2026, FDA held a teleconference with your firm, and recommended you initiate a voluntary recall of all batches of drug product manufactured at your facility that were in distribution and intended for the U.S. market that remain within expiry

On March 25, 2026, you committed to a voluntary recall of all drugs manufactured at your facility due to the significant CGMP violations.

In response to this letter, clarify whether you intend to resume manufacturing drugs for the U.S. market at this facility in the future.

If you plan to resume any manufacturing operations regulated under the FD&C Act, notify this office before resuming your drug manufacturing operations. You are responsible for resolving all deficiencies and systemic flaws to ensure your firm is capable of ongoing CGMP compliance. In your notification to the Agency, provide a summary of your remediations to demonstrate that you have appropriately completed all corrective actions and preventive actions (CAPA).

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 3, 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 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 Huons Co., Ltd. located at 100 Bio Valley-ro, Jecheon, Chungcheongbuk, 27159 Korea, (the Republic of) 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 days1. 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 3007163376 and ATTN: LeAnna Pearson.

Sincerely,
/S/

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

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.