- Delivery Method:
- VIA UPS
Recipient NameMs. Leanne Preston
Recipient TitleChief Executive Officer
- Wild Child WA Pty Ltd.
2 Action Road
Malaga WA 6090
- Issuing Office:
- Center for Drug Evaluation and Research | CDER
10903 New Hampshire Avenue
Silver Spring, MD 20993
December 6, 2019
Warning Letter 320-20-11
Dear Ms. Preston:
The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Wild Child WA Pty Ltd., FEI 3006210769, at 2 Action Road, Malaga, Western Australia, from May 27 to 31, 2019.
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 response to our Form FDA 483, received on June 12, 2019, in detail and acknowledge receipt of your subsequent correspondence.
During our inspection, our investigator observed specific violations including, but not limited to, the following.
1. 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 released finished over-the-counter (OTC) drug products, (b)(4), to the U.S. market without adequately testing the identity and strength of the active ingredient, (b)(4). For example, your firm uses an analytical method (residue on ignition) for assay that is inferior to the method established in the United States Pharmacopeia (USP) monograph for (b)(4). In addition, your firm does not perform the minimum fill test, a test specified in the USP monograph.
Appropriate testing of each batch before release is one of many essential elements necessary to ensure that the drug products you manufacture meet appropriate specifications.
In your response, you stated that quantitative chemical tests were not performed because your Australian GMP license allows you to perform physical testing only. Your response included a commitment to revise specifications to include the quantitative titration method for (b)(4) content and minimum fill testing.
Your response is inadequate because the corrective actions only apply to future batches and do not include a commitment to evaluate or test retain samples for batches already distributed to the U.S. market. Drug products distributed to the U.S. market must be manufactured in accordance with U.S. drug regulations.
In response to this letter, provide:
• A comprehensive, independent assessment of your laboratory practices, procedures, methods, equipment, documentation, and analyst competencies. Provide your plan to assess laboratory system effectiveness and a subsequent detailed CAPA that ensures full remediation.
• 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 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.
• An evaluation of all test methods used for the analysis of drug products distributed to the United States. State whether each method used is the USP method. If you use an alternate method, provide your studies showing equivalence or superiority to the compendial method.
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)).
Your firm does not have an adequate ongoing program for monitoring process control to ensure stable manufacturing operations and consistent drug quality. Specifically, you did not provide documentation to show that the manufacturing processes for OTC (b)(4) drug products have been validated.
Our inspection also found instances where batches of (b)(4) were manufactured using significantly different (b)(4) parameters.
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/media/71021/download.
In your response, you provided an action plan to perform validation on (b)(4) formulations for various (b)(4) tanks, which will include (b)(4) sample points after (b)(4) times. You stated that samples would be quantitatively analyzed for (b)(4) content.
Your response is inadequate because it lacked sufficient information on your planned validation activities, including timelines for completion and draft protocols.
In response to this letter, provide:
• An assessment of each drug product process to ensure that there is a data-driven and scientifically sound program that identifies and controls all sources of variability, such that your production processes will consistently meet appropriate specifications and manufacturing standards. This includes, but is not limited to, evaluating suitability of equipment for its intended use, sufficiency of detectability in your monitoring and testing systems, quality of input materials, and reliability of each manufacturing process step and control.
• 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, and ongoing monitoring of both intra-batch and inter-batch variation to ensure a continuing state of control. Also include your program for qualification of your equipment and facility.
• A timeline for performing appropriate process performance qualification (PPQ) for each of your marketed drug products.
• Your process performance qualification protocol(s).
3. Your firm failed to conduct at least one test to verify the identity of each component of a drug product (21 CFR 211.84(d)(1)).
Your firm failed to test your incoming components for identity, including (b)(4), used to manufacture drug products.
In your response, you stated that individual testing of excipient components is not mandated in Australia for (b)(4), and inactive ingredients are accepted based on the supplier's certificate of analysis (COA). You indicated that a Fourier Transform Infrared (FTIR) instrument would be purchased to implement identification testing for each ingredient.
Your response is inadequate because no documentation or timeline was provided to indicate when identity testing of components used in U.S. drug products would begin.
In response to this letter, provide:
• 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.
• Documentation of test results obtained for all lots of (b)(4) active ingredient used to manufacture OTC (b)(4) drug products for the U.S. market showing identification testing performed. Specify the test method used for identification testing and provide the method. If the method used is not the method listed in the USP monograph, provide evidence to show that the method used is equivalent or better than the compendial method.
• 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 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 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 SOP describing this COA validation program.
• A summary of your program for qualifying and overseeing contract facilities that test the drug products you manufacture.
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 resolving all deficiencies and systemic flaws to ensure ongoing COMP compliance.
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 these violations and for preventing their recurrence or the occurrence of other violations.
Until you correct all violations completely and we confirm your compliance with CGMP, FDA may withhold approval of any new drug applications or supplements listing your firm as a drug manufacturer.
Failure to correct these violations may also result in the FDA refusing admission of articles manufactured at Wild Child WA Pty Ltd., 2 Action Road, Malaga, 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 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 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-OMO-Communications@fda.hhs.gov or mail your reply to:
Carrie Ann Plucinski
U.S. Food and Drug Administration
White Oak Building 51 , Room 4235
10903 New Hampshire A venue
Silver Spring, MD 20993
Please identify your response with FEI 30062 10769.
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research