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  5. AN Co. Ltd. - 538516 - 12/13/2017
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AN Co. Ltd. MARCS-CMS 538516 —

Recipient Name
Park Soung Lul
AN Co. Ltd.

AN Bldg, 4th Floor, 35 Paldal-ro, 259-Beon-Gi
Jangan-Gu, Suwon-Si
North Korea

Issuing Office:
Center for Drug Evaluation and Research

United States



Black HHS-Blue FDA Logo



10903 New Hampshire Avenue
Silver Spring, MD 20993 


Via UPS                                                                                 Warning Letter 320-18-16
Return Receipt Requested
December 13, 2017           
Park Soung Lul
AN Co. Ltd
AN Bldg, 4th Floor
35 Paldal-ro, 259-Beon-Gi
Jangan-Gu, Suwon-Si
Gyeonggi-do, 16270
Dear Mr. Park:
The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, AN Co. Ltd at 1452-248 Yeongdong Hwanggan-ro Hwanggan-myeon, Yeongdong-gun Chungcheongbuk-do, from May 29–30, 2017.
This warning letter summarizes significant violations of current good manufacturing practice (CGMP) regulations for finished pharmaceuticals. See 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 June 19, 2017 response in detail.
During our inspection, our investigator observed specific violations including, but not limited to, the following.
1.    Your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any specifications, whether or not the batch has already been distributed (21 CFR 211.192).
You obtained an initial out-of-specification (OOS) viscosity test result for (b)(4) Cream lot (b)(4). The next two retest values were also OOS. You failed to conduct laboratory and manufacturing investigations into these OOS results, which included identifying a root cause and implementing corrective actions and preventive actions (CAPA). Instead, you rejected the batch without conducting an adequate investigation.
In your response, you stated that you re-trained personnel and that, in the future, your Research and Development department would investigate failing results and determine appropriate action plans. Your response was deficient as it did not specify how and when laboratory and manufacturing investigations would be conducted.
In response to this letter,
  • List all instances where a retest was conducted after obtaining an initial OOS or unexpected result, including final batch dispositions since January 1, 2015. Provide any associated investigations and CAPA for each instance.
  • Revise and provide detailed OOS procedures to ensure that investigations into OOS results are conducted adequately.
  • Provide a CAPA to improve overall quality oversight at your firm, including but not limited to improved procedures that ensure final quality unit approval of all investigations into deviations, atypical events, OOS results, and batch failures. 
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
2.    Your firm failed to 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)).
Our investigator observed that your firm stored all stability samples for your over-the-counter (OTC) drug product in (b)(4) mL (b)(4) containers. However, your products are distributed in different size (b)(4) containers, (b)(4) containers, and (b)(4) tubes.  
In your response, you stated that you have now begun to test products in their actual packaging configurations, and provided a stability testing worksheet. However, your stability testing worksheet indicated that you are not testing your drug products for assay of active ingredient.
In response to this letter,
  • Revise your stability protocol to include assay for active ingredient;
  • Provide data to support that your stability test methods are stability indicating and can detect   and quantify degradants; and
  • Conduct analyses on retain samples representative of all your OTC drug products currently within expiry and distributed to the U.S. for which you do not have adequate supporting stability data.  
3.    Your firm failed to establish and follow adequate control procedures to monitor the output and to validate the performance of those manufacturing processes that may be responsible for causing variability in the characteristics of in-process material and the drug product (21 CFR 211.110(a)).
You have not validated the processes used to manufacture your OTC drug products. You did not perform process performance qualification studies, and lacked an ongoing program for monitoring process control to ensure stable manufacturing operations and consistent drug quality.
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/downloads/drugs/guidances/ucm070336.pdf.
Your response stated that you rely on bulk and finished product testing to ensure products are consistent. Your response was inadequate as you did not commit to validating your manufacturing process prior to distribution of drug products.
In response to this letter, provide the following:
  • Timelines for process performance qualification for your OTC drug products, and a detailed process performance qualification protocol for each of your OTC drug products.
  • A data-driven and scientifically sound process validation program that appropriately identifies sources of variability, and ensures oversight of intra-batch and inter-batch variation on an ongoing basis throughout the product lifecycle. 
  • A risk assessment for distributed OTC drug products produced by an unvalidated process.  Your risk assessment should address products distributed to the U.S. and still within expiry.
CGMP Consultant Recommended
Based upon the nature of the violations we identified at your firm, we strongly recommend engaging a consultant, qualified as set forth in 21 CFR 211.34, to assist your firm in meeting CGMP requirements. Your use of a consultant does not relieve your firm’s obligation to comply with CGMP. Your firm’s executive management remains responsible for fully resolving all deficiencies and ensuring ongoing CGMP compliance.
Violations cited in this letter are not intended as an all-inclusive list. You are responsible for investigating these violations, for determining the causes, for preventing their recurrence, and for preventing other violations.
Until you correct all violations completely and we confirm your compliance with CGMP, FDA may withhold approval of any new applications or supplements listing your firm as a drug manufacturer.
Failure to correct these violations may also result in FDA refusing admission of articles manufactured at AN Co. Ltd at 1452-248 Yeongdong Hwanggan-ro Hwanggan-myeon, Yeongdong-gun Chungcheongbuk-do into the United States under section 801(a)(3) of the FD&C Act, 21 U.S.C. 381(a)(3). Under the same authority, articles may be subject to refusal of 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).
After you receive this letter, respond to this office in writing within 15 working days. Specify what you have done since our inspection to correct your violations and to prevent their recurrence. 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 or mail your reply to:
LT Loan Chin
U.S. Food and Drug Administration
White Oak Building 51, Room 4359
10903 New Hampshire Avenue
Silver Spring, MD 20993
Please identify your response with FEI 3003092574.
Francis Godwin
Acting Director
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research
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