Inspections, Compliance, Enforcement, and Criminal Investigations

Wong Lap Kwong Medicine Company Limited 1/11/18



Black HHS-Blue FDA Logo



10903 New Hampshire Avenue
Silver Spring, MD 20993 


­­Via UPS                                                                                 Warning Letter 320-18-25
Return Receipt Requested
January 11, 2018
Ms. Amy Wing Mui Wong
Wong Lap Kwong Medicine Company Limited
Ground Floor, 93A Fuk Wa Street
Sham Shui Po, Kowloon
Hong Kong SAR
Dear Ms. Wong:
The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Wong Lap Kwong Medicine Company Limited at Flat B, 4/F, Wah Lung Industrial Building, 49-53 Wang Lung Street, Tseun Wan, New Territories from September 18 to 22, 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 product is 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 October 13, 2017 response in detail. Your response was inadequate because it did not adequately address the violations observed, and lacked detail and evidence to support your commitments.
During our inspection, our investigator observed specific violations including, but not limited to, the following.
1.      Your firm failed to establish adequate written responsibilities and procedures applicable to the quality control unit and to follow such written procedures (21 CFR 211.22(d)).
You lacked adequate written procedures for various functions, including, but not limited to:
  • customer complaints
  • recalls
  • annual product review
  • out-of-specification (OOS) or deviation investigations
  • change control
  • CGMP-related training
  • issuing batch records
  • documenting batch record review
  • cleaning
  • storage conditions
Your firm’s quality systems are inadequate. See FDA’s guidance document, Quality Systems Approach to Pharmaceutical CGMP Regulations, for help implementing modern quality systems and risk management approaches to meet the requirements of CGMP regulations (21 CFR, parts 210 and 211), at
In response to this letter, provide your comprehensive plan for establishing, supporting, and sustaining a robust quality system consistent with CGMP regulations. Include timelines in your plan.
2.      Your firm failed to ensure the identity of components, including your active ingredients and excipients from various suppliers (21 CFR 211.84(d)(1) and (2)).
You do not conduct an identity test for your active pharmaceutical ingredient, (b)(4), prior to use in the manufacture of your over-the-counter (OTC) drug product. Your firm also neglected to qualify suppliers before relying on their certificates of analysis.
In response to this letter, provide standard operating procedures (SOP) and describe in detail how you will qualify your suppliers and conduct identity tests on all incoming components. Additionally, provide a plan for retrospective testing and impact assessment of components used in drug products distributed to the United States.
3.      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, and your firm’s quality control unit did not review and approve those procedures, including any changes (21 CFR 211.100(a)).
You have not conducted process validation studies for your drug product to demonstrate that manufacturing processes can consistently produce drug products of acceptable quality by minimizing inter- and intra-batch variability.
Your response indicated that you will not conduct process validation studies until your new tanks for (b)(4) and (b)(4) are in place, which you estimate will occur in (b)(4). This is unacceptable as you have no data to support that your current manufacturing process can manufacture drug products in a state of control.
In response to this letter, describe your process validation program for ensuring an ongoing state of control throughout the process lifecycle. Include your process performance qualification protocol, a timeline for performing these studies, and how you will vigilantly monitor sources of variability in your operation throughout the drug lifecycle to mimimize batch variation and assure consistent product quality.    
4.      Your firm failed to routinely calibrate, inspect, or check according to a written program designed to assure proper performance of and to maintain written records of calibration checks and inspections of equipment used in the manufacture, processing, packing, and holding of a drug product (21 CFR 211.68(a)).
You have not calibrated your weighing scales, nor the (b)(4) and (b)(4) mechanisms in your (b)(4) tank and (b)(4) tank.
Your response indicated that you will only calibrate the tanks’ (b)(4) mechanisms after you obtain new tanks, which you estimate will occur in (b)(4). This is unacceptable as you did not provide a corrective action to assure your current equipment is functioning as intended.
In response to this letter, provide a comprehensive plan for qualifying and calibrating any existing or new equipment, and provide any associated SOP. During your remediation, if you find any uncalibrated equipment not functioning as intended, provide an impact and risk assessment for drug products still within your control, as well drug products within expiry distributed to the United States.
CGMP Consultant Recommended
Based upon the nature of the violations deviations 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.  The consultant should comprehensively assess manufacturing operations to ensure that all systems and processes, and ultimately, the products you manufacture, conform to FDA 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.
Labeling and Formulation Concerns
A review of labeling for your product (b)(4) reveals that some of your labeled inactive ingredients, such as “(b)(4),” are not included in FDA’s inactive ingredient database for approved drug products, nor are we aware of these ingredients being used as inactive ingredients in any OTC drug product.
We remind you that it is your responsibility to ensure that your product contains only suitable inactive ingredients that are safe in the amounts administered and do not interfere with the effectiveness of the preparation or with suitable tests or assays to determine if the product meets its professed standards of identity, strength, quality, and purity (21 CFR 330.1(e)).
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.
FDA placed your firm on Import Alert 66-40 on January 8, 2018.
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 continuing to refuse admission of articles manufactured at Flat B, 4/F, Wah Lung Industrial Building, 49-53 Wang Lung Street, Tseun Wan, New Territories 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 or mail your reply to:
LCDR Catherine Gould, Pharm.D.
Compliance Officer
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 3003338476.
Francis Godwin
Acting Director
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research


Page Last Updated: 01/23/2018
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