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  5. BioDiagnostic International - 554322 - 07/12/2018
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BioDiagnostic International MARCS-CMS 554322 —

Recipient Name
Dr. Satya Paul Anand, Ph.D
BioDiagnostic International

555 West Lambert Road, Suite C
Brea, CA 92821
United States

Issuing Office:
San Francisco District Office

United States



Black HHS-Blue FDA Logo



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


July 12, 2018
Dr. Satya Paul Anand, Ph.D.
BioDiagnostic International
555 West Lambert Road, Suite C
Brea, CA 92821
Dear Dr. Anand:
The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, BioDiagnostic International at 555 West Lambert Road, Suite C, Brea, California, from January 31 to February 27, 2018.
This warning letter summarizes significant violations of the Federal Food, Drug, and Cosmetic Act (FD&C Act) and current good manufacturing practice (CGMP) regulations for finished pharmaceuticals. See 21 CFR, parts 210 and 211.
Because your drug products were prepared, packed, or held under insanitary conditions, whereby they may have become contaminated with filth or rendered injurious to health, your drug products are adulterated within the meaning of section 501(a)(2)(A) of the FD&C Act, 21 U.S.C. 351(a)(2)(A).
In addition, 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).
We reviewed your March 13, 2018, response in detail and acknowledge your subsequent correspondence.
During our inspection, our investigator observed specific violations including, but not limited to, the following.
Insanitary Conditions Violations
You manufacture (b)(4), a drug product intended for vaginal use as a hemostatic solution to stop bleeding after cervical biopsies. During the inspection, our investigator observed filthy conditions in your facility, including dirty equipment and utensils covered with unknown residue. A large metal roll-up door at the entrance to your facility was open to the outdoors, while an open pot you use as a mixing vessel contained in-process material and was not covered. The insanitary conditions observed at your facility failed to protect drug products from contamination with filth.
CGMP Violations
1.    Your firm failed to have separate or defined areas or such other control systems necessary to prevent contamination or mix-ups (21 CFR 211.42(c)).
Our investigator documented that you have an employee food preparation area within your drug manufacturing area with no separation between open manufacturing equipment, cooking utensils, and personal-use items. The practices observed at your facility, which was observed open to the outdoors, increase the likelihood of your drug products becoming contaminated.
Your response is inadequate because it states that BioDiagnostic International is a “(b)(4)” and the facility has “(b)(4).”
We note your response also included a commitment to hire a professional cleaning crew. Increased cleaning, however, will not address the design flaws at your facility. In response to this letter, provide a protocol to comprehensively redesign your facility to be suitable for drug manufacturing, and related floor plans. Also commit to providing photographs of your facility remediation.
2.    Your firm failed to perform, 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, and for each batch of drug product required to be free of objectionable microorganisms, appropriate laboratory testing, as necessary (21 CFR 211.165(a) and (b)).
You routinely released your drug product, (b)(4), without testing for chemical or microbial quality. Without this basic testing you cannot determine whether each drug product batch meets specifications and is suitable for release.
It is essential that you test each drug product batch to ensure it meets all appropriate specifications. In addition to testing for chemical attributes including, but not limited to, identity and potency, each batch should also meet microbial specifications that are appropriate for the intended use of your drug product.
We acknowledge your response included a procedure for finished product acceptance criteria that said, “(b)(4).” Your response is inadequate because you could provide only drug product chemical testing results from 2009 for iron content. Notably, this testing from almost a decade ago included (b)(4) assay test results that fail the current USP specification. You provided no evidence that you have performed chemical and microbial testing on each batch you manufactured before making a batch disposition decision.
In response to this letter, provide:
  • a list of all batches of drug products produced at your facility that are within your labeled expiration date;
  • all chemical and microbial test methods and specifications used to analyze your drug products prior to a batch disposition decision;
  • a summary of test results obtained from testing retain samples of all drug product batches within expiry, if any, that may remain in distribution. These test results should include identity and strength of active ingredients and all other appropriate quality attributes. 
3.    Your firm failed to use equipment in the manufacture, processing, packing, or holding of drug products that is of appropriate design, adequate size, and suitably located to facilitate operations for its intended use and for its cleaning and maintenance (21 CFR 211.63). ­
You use kitchen cooking pots and household power tools to manufacture your drug product used for biopsy procedures. These include an (b)(4) and a (b)(4) to power an impeller shaft used to mix in-process solution. You also use (b)(4) to hold the in-process mix prior to filling the drug formulation into (b)(4) product vials.
CGMP requires that you use equipment that is qualified and suitable for its intended use in the manufacture of drug products.
Your response included a diagram of your (b)(4) mixing apparatus, however, your response is inadequate because it did not address the suitability of all your manufacturing equipment for its intended use, and provide a corrective and preventive action plan (CAPA) plan.
In response to this letter, conduct a comprehensive evaluation of the equipment used at your facility throughout drug product processing, and a CAPA plan that ensures use of only suitably designed and well-controlled equipment if you engage in future drug manufacture.
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 does not have a quality control unit. During the inspection, our investigator found that you do not have a functional quality system.
Your response is inadequate because you did not provide evidence that you have established appropriate written procedures for quality unit functions.
In response to this letter, provide a detailed description of the responsibilities of your quality unit and provide related written procedures.
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. 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 corrective actions and preventive actions 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 deficiencies and ensuring ongoing CGMP compliance.
Recall Initiated and Future Manufacturing Plans
We acknowledge that your firm initiated a recall of all (b)(4) drug product batches that were within expiration after multiple discussions with FDA. In response to this letter, clarify whether or not you intend to recommence manufacture of any drugs at this facility in the future.
Unapproved Drugs
Based on the evidence collected during the FDA inspection of your firm from January 31 to February 27, 2018, your firm is distributing the following unapproved prescription drug:
  • (b)(4) 
FDA Guidance for FDA Staff and Industry, Marketed Unapproved Drugs – Compliance Policy Guide (CPG) explains FDA policies aimed at ensuring that all drugs marketed in the United States have been shown to be safe and effective. See the guidance document at https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070290.pdf.
The CPG outlines FDA enforcement policies aimed at efficiently and rationally bringing all drugs requiring approved applications into the approval process without adversely affecting public health, imposing undue burdens on consumers, or unnecessarily disrupting the market. As described in the CPG, all drugs marketed without required applications are subject to enforcement action at any time, without additional notice.
For assistance in communicating with FDA on the application process for your unapproved drugs, contact FDA’s unapproved drugs coordinator, Dr. Sally Loewke, at 301-796-0710.
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.
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 response to:
CDR Steven E. Porter, Jr.
Director, Division of Pharmaceutical Quality Operations IV
United States Food and Drug Administration
19701 Fairchild Road
Irvine, CA 92612
Please reference unique identifier CMS 554322 on all correspondence.
If you have any questions about the content of this letter, please contact William V. Millar, Compliance Officer, at (510) 337-6896 or william.millar@fda.hhs.gov.
CDR Steven E. Porter, Jr.
Director, Division of Pharmaceutical Quality Operations IV
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