Mr. Byron Polanco
- Paramesh Banerji Life Sciences, LLC
220 North Center Drive
North Brunswick, NJ 08902
- Issuing Office:
- New Jersey District Office
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Division of Pharmaceutical Quality Operations I
10 Waterview Blvd, 3rd Floor
Parsippany, NJ 07054
Telephone: (973) 331-4900
FAX: (973) 331-4969
VIA UNITED PARCEL SERVICE
August 7, 2018
Mr. Byron Polanco
Quality Assurance Manager
Paramesh Banerji Life Sciences, LLC
220 North Center Drive
North Brunswick, NJ 08902
Dear Mr. Polanco:
The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Paramesh Banerji Life Sciences, LLC, at 220 North Center Drive, North Brunswick, New Jersey, from November 28 to December 7, 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 December 21, 2017 response in detail.
During our inspection, our investigator observed specific violations including, but not limited to, the following:
1. 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)).
You manufacture various drugs that are labeled as homeopathic from ingredients that pose potentially toxic effects. For example, labeling for some of your drugs indicates that they include the ingredient Belladonna, and others state that they include Nux vomica, which contains strychnine. Strychnine is a highly toxic, well-studied poison that is used as a rodenticide.
You released numerous lots of drugs that are labeled as homeopathic without validating your manufacturing process. This lack of process validation is an example of a failure to establish adequate written procedures. Before any batch is commercially distributed for use by consumers, a manufacturer should have gained a high degree of assurance in the performance of the manufacturing process such that it will consistently produce drug products meeting those attributes relating to identity, strength, quality, purity, and potency. Information and data should demonstrate that the commercial manufacturing process is capable of consistently producing acceptable quality products within commercial manufacturing conditions. Especially for drugs that contain ingredients with potentially toxic effects, failure to validate manufacturing processes could expose patients to unnecessary risks due to the lack of knowledge about and control over sources of variation.
In your response, you indicated that you will start producing products from their “crude substance[s]" at your New Jersey facility, and that you will establish written procedures to carry out tests for in-process and finished products. Your response cannot be fully evaluated; however, because you did not address your validation plan for your current process. Also, you did not provide your written procedures for your proposed manufacturing process and validation plan.
In response to this letter, provide your validation plans for both the current manufacturing processes and the proposed manufacturing processes for crude substances. Include your timeline for performing process performance qualification for your drug products, as well as your approach for monitoring batch-to-batch variations on an ongoing basis. In addition, provide a risk assessment for distributed drug products you manufactured using unvalidated processes.
2. Your firm failed to test samples of each component for identity and conformity with all appropriate written specifications for purity, strength, and quality. Your firm also failed to establish the reliability of component supplier analyses on which you rely in lieu of certain tests through appropriate validation of the supplier’s test results at appropriate intervals (21 CFR 211.84(d)(1) and (2)).
You did not test each component of your incoming raw materials before manufacturing your drug products to determine the components’ identity, purity, strength, and quality. Your firm relied on your supplier’s certificates of analysis (COAs) for strength testing of only one component, alcohol, without establishing the reliability of your supplier’s analysis through appropriate validation.
In your response, you stated that there are no known methods specified “in any documentation” for testing (b)(4) to verify identity, strength, quality and purity. You explained that, as a result, you have not performed any testing. You also stated in your response that you plan to bring all in process material manufacturing (b)(4) to your facility and that you will carry out testing on in process material where “applicable”.
Your response was inadequate. While bringing raw material manufacturing operations to your facility may help you better control the quality of these materials, you will still need to test your raw materials for identity prior to use, in accordance with 21 CFR 211.84(d)(1), as well as conduct in process testing in accordance with 21 CFR 211.110. You are responsible for establishing appropriate specifications to ensure that raw and in process materials conform to appropriate standards of identity, purity, strength, and quality, in accordance with 21 CFR 211.160(b). You did not specify if each component will be fully and appropriately tested for identity and strength prior to use in manufacturing and whether other attributes will also be tested.
In response to this letter, provide:
- Your procedure for testing each incoming active pharmaceutical ingredient.
- Your plan to test each component for conformity with all appropriate written specifications for identity, purity, strength and quality.
- Your plan for performing at least one identity test for all incoming components used in your drug products labeled as homeopathic.
- Your description, in detail, of how you plan to establish the reliability of your supplier’s test results through periodic validation, if you accept your supplier’s COA in lieu of testing components for purity, strength, or quality.
- A risk assessment for any drug products manufactured using components which were not adequately tested and controlled.
3. Your firm failed to establish an adequate 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, and your firm failed to establish written procedures applicable to the quality control unit (21 CFR 211.22(a) and (d)).
Your firm lacked an adequate quality control unit.
Your Quality Policy Manual and your procedures did not adequately cover all operations on the site. For example, the manual only contained a high-level description for monitoring components of your in-coming materials, and you failed to establish adequate written procedures to verify that your incoming components and in-process materials conform to appropriate specifications.
See FDA’s guidance document, Quality Systems Approach to Pharmaceutical CGMP Regulations
, for help implementing modern 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
In your response, you indicated you planned to revise and update the Quality Policy Manual and your procedures within the first quarter of 2018. Your response cannot be fully evaluated because you did not provide updated copies of the quality manual and procedures, and you did not state when these items would be implemented.
In response to this letter, provide:
- Your plan to establish an adequate quality control unit with appropriate authority and sufficient resources to carry out its responsibilities and consistently ensure drug quality.
- Your updated procedures, covering all aspects of your facility and operations that may affect the identity, strength, quality, and purity of your drug product.
- Your corrective action plan to ensure that you create and maintain documentation to demonstrate acceptability of all operations.
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 fully resolving all deficiencies and ensuring ongoing CGMP compliance.
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 believe that your products are not in violation of the FD&C Act, include your reasoning and any supporting information for our consideration. If you cannot complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion.
Your written notification should refer to the Warning Letter Number above (CMS# 545140). Please address your reply to:
Maya M. Davis
US Food & Drug Administration
One Montvale Avenue, 4th Floor
Stoneham, MA 02180
If you have questions regarding the contents of this letter, telephone Maya Davis, Compliance Officer, by telephone at 860-240-4289 x25, or by email Maya.Davis@fda.hhs.gov
. Please identify your response with FEI 3011020725.
Diana Amador Toro
Division Director/OPQO Division 1
New Jersey District Office