- Delivery Method:
- VIA UPS
Recipient NameMr. Eduardo Acosta
Recipient TitleChief Executive Officer
- Nartex Laboratorios Homeopaticos S.A. de C.V.
Calzada Lazaro Cardenas # 708 – 770 Ote.
Col. Eduardo Guerra
27280 Torreon, Coah.
- Issuing Office:
- Center for Drug Evaluation and Research | CDER
Warning Letter 320-21-07
November 4, 2020
Dear Mr. Acosta:
The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Nartex Laboratorios Homeopaticos, S.A. de C.V., FEI 3009407408, at Calzada Lazaro Cardenas 708-770, Col. Eduardo Guerra, Torreon, Coahuila de Zaragoza, from February 24 to 28, 2020.
This warning letter summarizes significant violations of current good manufacturing practice (CGMP) regulations for finished pharmaceuticals, Title 21 Code of Federal Regulations (CFR) parts 210 and 211 (21 CFR parts 201 and 211).
Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your drugs 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 March 19, 2020, response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence.
During our inspection, our investigator observed specific violations and deviations 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)).
Your firm did not adequately validate the process and qualify the equipment used to manufacture your drug products. During the inspection, your firm provided our investigator a signed statement acknowledging that your firm had not performed any process validation or equipment validation for a variety of your homeopathic drug products distributed to the United States.
In your response, you provided validation documents for two drug products. You stated you would validate six additional drug products marketed to the United States. You further stated that you do not plan to initiate process validation for the remaining (b)(4) drug products due to lack of demand or discontinuing the drug product for the United States in 2020.
You response is inadequate. You did not perform a risk assessment for the drugs shipped to the United States without adequate process validation. Given that several of the drug products you produced for the U.S. market contains potentially toxic ingredients (e.g., (b)(4), (b)(4), and (b)(4)), failure to validate processes to identify and control sources of variation could place consumers at risk.
Process validation evaluates the soundness of design and state of control of a process throughout its lifecycle. Each significant stage of a manufacturing process must be designed appropriately and assure the quality of raw material inputs, in-process materials, and drug products. Process qualification studies determine whether an initial state of control has been established.
Successful process qualification studies are necessary before commercial distribution. Thereafter, ongoing vigilant oversight of process performance and product quality is necessary to ensure you maintain a stable manufacturing operation throughout the product lifecycle.
See FDA’s guidance document Process Validation: General Principles and Practices for general principles and approaches that FDA considers appropriate elements of process validation at https://www.fda.gov/media/71021/download.
In response to this letter, provide the following:
• A detailed summary of your validation program for ensuring a state of control throughout the product lifecycle, along with associated procedures. Describe your program for process performance qualification, and ongoing monitoring of both intra-batch and inter-batch variation to ensure a continuing state of control.
• A timeline for performing appropriate process performance qualification (PPQ) for each of your marketed drug products.
• Your process performance protocols, and written procedures for qualification of equipment and facilities.
• Risk assessment for product that remains on the market within expiry. Specify actions you will take in response to the risk assessment, such as customer notifications and product recalls.
2. Your firm failed to test samples of each component for conformity with all appropriate written specifications for purity, strength, and quality (21 CFR 211.84(d)(2)).
During the inspection, it was observed that you do not adequately test components prior to use in the manufacture of drug product destined for the United States. Although you conduct identity testing on incoming lots of components, you rely on supplier certificates of analysis (COA) for conformity with all other appropriate written specifications for purity, strength, and quality. You did not validate your supplier COA for appropriate written specifications for purity, strength, and quality.
In your response, you committed to revise your procedure to include “when verification of the Certificate of Analysis (COA) or certificate of Conformance (COC) for materials is used in our products for the US market that are received from our approved suppliers is necessary.”
Your response is inadequate in that it lacked sufficient detail for how each component will be tested for conformance with all appropriate written specifications for identity, strength, quality, and purity. Additionally, it is unclear if you plan to rely on your suppliers’ COA test results (with the exception of identity) in lieu of testing, as you did not provide detail about how you plan to establish the reliability of your supplier’s COA through appropriate validation of the supplier's test results at appropriate intervals.
In response to this letter, provide the following:
• 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 standard operating procedure (SOP) that describes this COA validation program.
The violations and deviation cited in this letter are not intended to be an all-inclusive list of violations that exist at your facility. You are responsible for investigating and determining the causes of violations and deviations and for preventing their recurrence or the occurrence of violations and deviations.
Until you correct all violations completely and we confirm your compliance with CGMP, FDA may withhold approval of any new drug applications or supplements listing your firm as a drug manufacturer.
Failure to correct these violations may also result in the FDA refusing admission of articles manufactured at Nartex Laboratorios Homeopaticos, S.A. de C.V., Mexico, into the United States under section 801(a)(3) of the FD&C Act, 21 U.S.C. 381(a)(3). Articles under this authority may be subject to refusal of admission, in that the methods and controls used in their manufacture do not appear to conform to CGMP within the meaning of section 501(a)(2)(B) of the FD&C Act, 21 U.S.C. 351(a)(2)(B).
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.
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.
Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov. Identify your response with FEI 3009407408 and ATTN: Rokhsana Safaai-Jazi.
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research