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WARNING LETTER

bB BioChem Laboratories Inc. MARCS-CMS 552896 —


Recipient:
Recipient Name
Dr. Richard N. Nguyen
bB BioChem Laboratories Inc.

2098 South Grand Avenue, Suite G

Santa Ana, CA 92705
United States

Issuing Office:
Los Angeles District Office

United States


 

  

Black HHS-Blue FDA Logo

 

 

 
Division of Pharmaceutical Quality Operations IV
19701 Fairchild Road,
Irvine, CA 92612-2506
Telephone: 949-608-2900
Fax: 949-608-4417 

 

WARNING LETTER
 
 
VIA SIGNATURE CONFIRMED DELIVERY
 
 
 
July 3, 2018                                                                                                             
 
Dr. Richard N. Nguyen, CEO
bB BioChem Laboratories Inc.
2098 South Grand Avenue, Suite G
Santa Ana, CA 92705
 
Dear Dr. Nguyen:
 
The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, bB BioChem Laboratories Inc. at 2098 South Grand Avenue, Suite G, Santa Ana, California, from December 12 to 18, 2017.
 
This warning letter summarizes significant violations of current good manufacturing practice (CGMP) regulations for finished pharmaceuticals. See 21 Code of Federal Regulations (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).
 
In addition, the inspection revealed that your firm manufactures unapproved new drug products. Specifically, as formulated and labeled, Medicated Pain Relieving Oil Extra Strength and Medicated Pain Relieving Oil Sensitive Strength are unapproved new drugs in violation of section 505(a) of the FD&C Act, 21 U.S.C. 355(a).
 
We reviewed your January 9, 2018 response in detail, and acknowledge your subsequent correspondence. However, your response is inadequate because, while you committed to implement standard operating procedures, you did not provide specific details of corrective actions to bring your operations into CGMP compliance.
 
During our inspection, our investigators 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)).
 
You released your over-the-counter (OTC) drug products, Medicated Pain Relieving Oil Extra Strength and Medicated Pain Relieving Oil Sensitive Strength, without adequate quality control testing, including but not limited to identity and strength of active ingredients. Unless you test each batch, you do not know whether it conforms to finished product specifications and is suitable for release.
 
You also failed to establish specifications for your finished drug products.
 
In response to this letter, provide:
  • appropriate chemical and microbiological batch release specifications for each of your drug products; 
  • a commitment to test each batch to ensure conformance to finished product specifications prior to a final disposition decision; 
  • all chemical and microbial test methods used to analyze each of your drug products; and
  • a summary of test results obtained from testing retain samples of all drug products within expiry. You should test all appropriate quality attributes including, but not limited to, identity and strength of active ingredients and microbiological quality (total counts and identification of bioburden to detect any objectionable microbes). If your testing for any previously released batch yields an out-of-specification result, indicate the corrective actions you will take, including notifying customers and initiating recalls.
2.    Your firm failed to conduct at least one test to verify the identity of each component of a drug product. Your firm also failed to validate and establish the reliability of your component supplier’s test analyses at appropriate intervals (21 CFR 211.84(d)(1) and (2)).
 
You lacked testing of incoming raw materials, including active ingredients and components, for their identity, strength, and other appropriate quality attributes. Instead, your firm relied on certificates of analysis (COA) from unqualified suppliers. You also did not have written specifications for all incoming raw materials.
 
In response to this letter, provide:
  • the chemical and microbiological quality control specifications you use to approve release of each incoming lot of components 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 testing results on your supplier’s COA in lieu of testing each component lot for purity, strength, and quality, specify how you will first establish the reliability and consistency of your supplier’s test results for these attributes through initial validation (followed by 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 test results obtained from full testing of all components to evaluate the reliability of the COA from each component manufacturer. Include your standard operating procedure (SOP) that describes this COA validation program.
  • a summary of your procedures for qualifying and overseeing the adequacy of contract facilities that test the OTC drug products you manufacture.
  • a comprehensive, independent review of your material system to determine whether all containers, closures, and ingredients from each supplier are adequately qualified and assigned appropriate expiration or retest dates. Also determine whether your controls for incoming material lots are adequate to prevent use of unsuitable containers, closures, and components.
3.    Your firm failed to ensure that its drug product bore an expiration date that was supported by appropriate stability testing (21 CFR 211.137(a)).
 
You have not established a stability program, including written procedures. You alsodo not have stability data to support the three-year expiration dates for Medicated Pain Relieving Oil Extra Strength and Medicated Pain Relieving Oil Sensitive Strength drug products.
 
In response to this letter, provide your plan, with timelines, to develop and implement a complete drug stability program. This plan should also include an assessment of the stability of drug products currently on the U.S. market within expiry.
 
4.    Your firm failed to establish a quality control unit with the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging materials, labeling, and drug products (21 CFR 211.22(a)).
 
Your firm lacks a quality unit. You have not established written procedures that define the roles, responsibilities, and authorities of a quality unit. You lack a process for making an appropriate batch disposition decision. You also failed to establish systems and documentation for numerous basic drug manufacturing operations, including but not limited to, change control, complaints, supplier qualification, recalls, and annual product reviews. 
 
In response to this letter, provide a comprehensive assessment and a corrective action and preventive action (CAPA) plan to ensure that you establish an effective quality unit with appropriate authority, responsibilities and resources. Your response should also include a detailed procedure describing your remediated quality unit’s responsibilities. See FDA’s guidance document, Quality Systems Approach to Pharmaceutical CGMP Regulations, for help implementing quality systems and risk management approaches to meet the requirements of CGMP regulations (21 CFR, parts 210 and 211), at https://www.fda.gov/downloads/Drugs/.../Guidances/UCM070337.pdf
 
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 evaluate your operations and assist your firm in meeting CGMP requirements. We also recommend that the qualified consultant perform a comprehensive audit of your entire operation for CGMP compliance, and evaluate the completion and effectiveness of any CAPA you have implemented.
 
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 violations and ensuring ongoing CGMP compliance.
 
Unapproved New Drugs
 
Examples of claims observed on your product labels for Medicated Pain Relieving Oil Extra Strength and Medicated Pain Relieving Oil Sensitive Strength that establish the intended uses of the products include, but may not be limited to, the following:
 
“Uses…for temporary relief of minor aches & pains of muscles & joints associated with: o simple backache o arthritis o strains o bruises o sprains”
 
Based on the above claims, Medicated Pain Relieving Oil Extra Strength and Medicated Pain Relieving Oil Sensitive Strength are “drugs” as defined by section 201(g)(1)(B) of the FD&C Act, 21 U.S.C. 321(g)(1)(B), because they are intended for the diagnosis, cure, mitigation, treatment, or prevention of disease, and/or under section 201(g)(1)(C) of the FD&C Act, 21 U.S.C. 321(g)(1)(C), because they are intended to affect the structure or any function of the body. Specifically, these products are intended for use as external analgesics.
 
Drug products such as Medicated Pain Relieving Oil Extra Strength and Medicated Pain Relieving Oil Sensitive Strength that are intended for use as external analgesics, such as the temporary relief of minor aches and pains, are being evaluated as part of the OTC Drug Review. They have been proposed to be classified as generally recognized as safe and effective and not misbranded under the Tentative Final Monograph (TFM) for External Analgesic Drug Products for Over-the-Counter (OTC) Human Use (48 FR 5852, February 8, 1983) if they meet each condition in the TFM and each general condition in 21 CFR 330.1. Pending a final rule, FDA does not intend to pursue regulatory action against products marketed in conformance with the conditions proposed in the TFM and each general condition in 21 CFR 330.1. Such marketing, however, is subject to the risk that a final rule may require reformulation and/or relabeling or FDA approval through the “new drug” procedures of the FD&C Act (section 505). 
 
The labeling and formulation for Medicated Pain Relieving Oil Extra Strength and Medicated Pain Relieving Oil Sensitive Strength are not consistent with the TFM referenced above. Specifically, the labeled active ingredients include capsaicin, methyl salicylate, camphor, menthol, and eucalyptus oil. Eucalyptus oil is explicitly not permitted as an active ingredient in an OTC external analgesic drug product for counterirritant use without an FDA-approved new drug application (NDA) [see 21 CFR 310.545(a)(10)(ii)]. Such formulated and labeled products as Medicated Pain Relieving Oil Extra Strength and Medicated Pain Relieving Oil Sensitive Strength are not proposed under the TFM.
 
Thus, as formulated and labeled, Medicated Pain Relieving Oil Extra Strength and Medicated Pain Relieving Oil Sensitive Strength do not comply with the TFM described above. Additionally, we are not aware of similar OTC products as formulated and labeled that were available in the United States market on or before the inception of the OTC Drug Review.
 
Furthermore, we are not aware of sufficient evidence to show Medicated Pain Relieving Oil Extra Strength and Medicated Pain Relieving Oil Sensitive Strength, as formulated and labeled, are generally recognized as safe and effective. Therefore, these products are new drugs within the meaning of section 201(p) of the FD&C Act, 21 U.S.C. 321(p). As new drugs, Medicated Pain Relieving Oil Extra Strength and Medicated Pain Relieving Oil Sensitive Strength may not be legally marketed in the United States absent approval of an application filed in accordance with section 505 of the FD&C Act, 21 U.S.C. 355(a). Medicated Pain Relieving Oil Extra Strength and Medicated Pain Relieving Oil Sensitive Strength are not the subject of FDA-approved applications, and therefore, the current marketing of these products violate section 505(a) of the FD&C Act, 21 U.S.C. 355(a)). Introduction of such product into interstate commerce is prohibited under section 301(d) of the FD&C Act, 21 U.S.C. 331(d).
 
Conclusion
 
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. It is your responsibility to ensure that your firm complies with all requirements of federal law, including FDA regulations.
 
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.
 
Your written response should refer to the Warning Letter Number above (552896). Please address your reply to:
 
CDR Steven E. Porter, Jr.
Director, Division of Pharmaceutical Quality Operations IV
United States Food and Drug Administration
19701 Fairchild
Irvine, California 92612
 
 
If you have any questions about the content of this letter, please contact Jessica Mu, Compliance Officer, at 949-608-4477 and reference unique identifier CMS 552896 on all correspondence.
           

 
Sincerely,
/S/ 
CDR Steven E. Porter, Jr.
Director, Division of Pharmaceutical Quality Operations IV
 
  
 
Cc:     
David M. Mazzera, Ph.D.
California Department of Public Health
Food and Drug Branch
1500 Capitol Avenue, MS-7602
P.O. Box 997413
Sacramento, CA 95899-7413