WARNING LETTER
Natural Beauty Care Pty Ltd
MARCS-CMS 611974 —
June 09, 2021
Delivery Method:
VIA UPS
Product:
Drugs
Recipient:
Recipient Name
Mr. John Dwyer
Recipient Title
Chairman
Natural Beauty Care Pty Ltd
8 Teton Court
Highett
VIC
3190
Australia
Issuing Office:
Center for Drug Evaluation and Research | CDER
United States
Warning Letter 320-21-49
June 9, 2021
Dear Mr. Dwyer:
Your facility is registered with the United States Food and Drug Administration (FDA) as a manufacturer of over-the-counter (OTC) drug products. FDA has reviewed the records you submitted in response to our April 16, 2020, request for records and other information pursuant to section 704(a)(4) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) for your facility, Natural Beauty Care Pty Ltd; FEI 3010164028, at 8 Teton Court, Highett, 3190 Victoria, Australia.
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 FD&C Act (21 U.S.C. 351(a)(2)(B)).
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 listed OTC
(b)(4)
drug products with FDA. Your response to our request for records and other information under section 704(a)(4) indicated that you did not conduct adequate finished drug product testing on drug products shipped to the United States.
For example, we asked you to confirm whether analytical assay testing for active ingredient(s) is performed for each batch of your finished drug products, before release for distribution to the U.S. market. You replied that analytical assay testing for active ingredients is not currently performed for each batch of finished drug products.
Without adequate testing, there is no scientific evidence to support that your drug product batches conform to appropriate specifications before release.
Following our 704(a)(4) request, we note that you shipped several lots of
(b)(4)
products to the United States.
For all drug products imported to the United States before and after our 704(a)(4) request, provide the following in response to this letter:
• A list of chemical and microbial specifications, including test methods, used to analyze each lot of your drug products before a lot disposition decision.
• 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.
• 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.
2. 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)).
Based on the records and information you provided, you have not demonstrated that you are testing incoming lots of the active pharmaceutical ingredient (API) used to manufacture your OTC drug products to determine their identity.
For example, your response to our initial 704(a)(4) request for information on identity testing for each lot of component indicates that you check certificates of analysis (COA) of incoming material but do not perform identity tests. In addition, your January 28, 2021, email you confirmed that identity tests are not performed on incoming API before use.
You can rely on vendor COA for quality attributes, provided you conduct at least one test to verify the identity of each component lot before use in drug product manufacturing.
For all drug products imported to the United States before and after our 704(a)(4) request provide the following in response to this letter:
• A comprehensive independent review of your material system to determine whether all suppliers of components, containers, and closures are each qualified, and that 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 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 that describes this COA validation program.
• A summary of your program for qualifying and overseeing contract facilities that test the drug products you manufacture.
3. Your firm failed to establish and 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)).
You failed to provide adequate stability data to demonstrate that the chemical properties of your drug products remain acceptable throughout the assigned expiry period.
For example, the stability test report for
(b)(4)
drug product submitted in response to our 704(a)(4) request does not include testing for the active ingredient. In addition, you confirmed that you do not perform analytical assay testing for active ingredients for each batch of drug product on stability.
Without appropriate stability data, you cannot ensure your drug products meet established specifications and all pre-determined quality criteria throughout the drug product’s assigned shelf-life.
For all drug products imported to the United States before and after our 704(a)(4) request provide the following in response to this letter:
• A comprehensive, independent assessment and corrective and preventive action 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.
Process Controls
You acknowledged that you do not have process flow diagrams showing critical control points for each finished drug product manufactured at your facility. Without identifying critical process parameters and an ongoing program for monitoring process controls, you are unable to ensure stable manufacturing operations and consistent drug quality.
See FDA’s guidance document, Process Validation: General Principles and Practices, for general principles and elements of process validation at https://www.fda.gov/files/drugs/published/Process-Validation—General-Principles-and-Practices.pdf.
Quality Systems
Your firm’s quality systems are inadequate. See FDA’s guidance document,
Quality Systems Approach to Pharmaceutical CGMP Regulations
, for help implementing quality systems and risk https://www.fda.gov/media/71023/download.
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 if your firm intends to resume manufacturing drugs for the U.S. market. We also recommend that the qualified consultant perform a comprehensive audit of your entire operation for CGMP compliance and that the consultant evaluates 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.
Conclusion
The violations cited in this letter are not intended to be an all-inclusive list of violations associated with your drug products. You are responsible for investigating and determining the causes of these violations and for preventing their recurrence or the occurrence of other violations.
Note that FDA placed all drug products manufactured by your firm on Import Alert 66-40 on March 23, 2021, as the methods used in and the controls used for the manufacture, processing, packing, or holding of these drug products does not appear to conform to current good manufacturing practice within the meaning of section 501(a)(2)(B) of the FD&C Act. Drugs and drug products that appear to be adulterated or misbranded may be detained or refused admission without physical examination pursuant to section 801(a)(3) of the FD&C Act, 21 U.S.C. 381(a)(3).
All drugs and drug products manufactured by your firm may remain listed on this import alert until there is evidence establishing that the conditions that gave rise to the appearance of these violations have been resolved, and the Agency has confidence that future entries will be in compliance with the FD&C Act. This may include an inspection before the FDA considers the appearance of adulteration to be addressed.
Correct any violations promptly. FDA may withhold approval of any new drug 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.
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 correct your 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 3010164028 and ATTN: Ganesh Joshi.
Sincerely,
/S/
Francis Godwin
Director
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research
Content current as of:
08/24/2021
Regulated Product(s)
Drugs