Recipient NameJin K. Song
- Beauty Manufacturing Solutions Corp.
1250 Freeport Parkway
Coppell, TX 75019-4410
- Issuing Office:
- Dallas District Office
January 12, 2018
CMS # 535116
UPS OVERNIGHT MAIL
Jin K. Song, Owner and CEO
Beauty Manufacturing Solutions Corp.
1250 Freeport Parkway
Coppell, Texas 75019-4410
The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Beauty Manufacturing Solutions Corp. at 1250 Freeport Parkway, Coppell, Texas (FEI 1610490), from June 19 to 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 firm’s July 24, 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 of its specifications, whether or not the batch has already been distributed (21 CFR 211.192).
Your firm failed to investigate test results showing that your water exceeds the allowable limit for microorganisms. Your tests on samples from your water system indicated that microorganism levels were too numerous to count (TNTC) on 25 out of 96 days. You use this water as a major component in manufacturing over-the-counter (OTC) drug products. Your failure to investigate violated your written procedures which require an investigation when results are above (b)(4) colony-forming units/milliliter (cfu/mL).
This system is fundamentally flawed as it is not capable of producing water that is suitable for use in pharmaceutical manufacture. In your response, you state that bulk product tests met drug product microbiological specifications. Your response is inadequate because quality control testing of a limited sample is insufficient to establish that a product is acceptable. Because microbiological contamination is not uniformly distributed and difficult to detect during testing, it is essential that stringent upstream controls be employed to assure the quality of a batch.
We note that you plan to eliminate dead legs in your water system. However, you did not commit to comprehensively redesign your system and create a new program for ongoing control, maintenance, and monitoring that ensures your firm consistently produces purified water that meets USP monograph specifications and appropriate microbial limits.
Your response is also inadequate because it did not address your failure to investigate the frequent, excessive levels of microorganisms in your water system. You did not explain how you will ensure adequate and effective investigation of out-of-limit test results moving forward.
In response to this letter, provide the following:
• A comprehensive evaluation of the water system design along with thorough corrective and preventive actions to be taken to install a suitable system.
• An effective program for ongoing control, maintenance, and monitoring that ensures the system consistently produces water that meets the purified water USP monograph specifications and appropriate microbial limits. Regarding the latter, it is important to note that total count limits that are significantly tighter than (b)(4) cfu/mL are appropriate for most topical products.
• A detailed risk assessment of the potential effects of the observed water system failures on the quality of each of your drug product lots within expiry, and notification to your customers of these significant deviations. This assessment should prioritize review of all lots made on a day that a water system sample was found to have TNTC levels. The assessment should not be restricted to products made with water solely from the sampling point that yielded excessive contamination, but also extend to other potentially-affected lots made with water from the system when it yielded this excessive contamination. Also, include other corrective actions and preventive actions (CAPA), including recall, if appropriate.
• A thorough assessment of your overall systems for investigating deviations, atypical events, out-of-specification (OOS) results, and failures. Your CAPA should include but not be limited to assuring that you promptly review various sources of variation in your operations that may cause errors, deviations or failures, and enhanced oversight and final approval of investigations by the quality unit.
2. Your firm failed to establish laboratory controls that include scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that components, drug product containers, closures, in-process materials, labeling, and drug products conform to appropriate standards of identity, strength, quality, and purity (21 CFR 211.160(b)).
Our investigator found that your microbiological test methods are not adequately verified. Specifically, you did not show that these methods can recover microorganisms in the presence of the antimicrobial agents that are present in your drug products.
In your response, you state that you “indirectly verified” your method suitability. You also state that you will be using (b)(4) in the future to “neutralize preservative systems.” Your response is inadequate because you did not provide any test results to demonstrate that your microbiological test methods are suitable for their intended use.
In response to this letter, provide supporting documentation demonstrating the suitability of your microbiological test methods for your drug products. If your review reveals that a method is deficient, provide your CAPA plan. In addition, provide a comprehensive assessment of your laboratory operations and specify all CAPA activities to be undertaken to ensure your laboratory operations are robust.
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.
Correct the violations cited in this letter promptly. Failure to promptly correct these violations may result in legal action without further notice including, without limitation, seizure and injunction. Unresolved violations in this warning letter may also prevent other Federal agencies from awarding contracts.
Until these violations are corrected, we may withhold approval of pending drug applications listing your facility. We may re-inspect to verify that you have completed your corrective actions. We may also refuse your requests for export certificates.
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. Reference CMS # 535116 within your response.
Send your written response to:
Mark W. Rivero
U.S. Food and Drug Administration
Office of Pharmaceutical Quality Operations, Division II, Compliance Branch
4040 North Central Expressway, Suite 300
Dallas, Texas 75204.
If you have questions regarding any issues in this letter, please contact Mr. Rivero at (504) 846-6103.
Monica R. Maxwell
Acting Program Division Director
Office of Pharmaceutical Quality Operations, Division II
Karen Tannert, R.Ph., MPH
Drugs and Medical Device Group Policy
8407 Wall Street
Austin, Texas 75754