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WARNING LETTER

Jabones Y Productos Especializados SA de CV MARCS-CMS 558088 —


Recipient:
Recipient Name
Mr. Adrian Lopez Sepulveda
Jabones Y Productos Especializados SA de CV

Cernicalo 155, Col. La Aurora

44460 Guadalajara, Jalisco, C.P.,
Mexico

Issuing Office:
Center for Drug Evaluation and Research

United States


 

  

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10903 New Hampshire Avenue
Silver Spring, MD 20993 

 

Via UPS                                                                                 Warning Letter 320-18-74
Return Receipt Requested
 
September 5, 2018
           
 
Mr. Adrian Lopez Sepulveda
Chief Executive Officer
Jabones Y Productos Especializados SA de CV
Cernicalo 155, Col. La Aurora
Guadalajara, Jalisco, C.P. 44460
Mexico
 
Dear Mr. Sepulveda:
 
The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Jabones Y Productos Especializados SA de CV at Cernicalo 155, Col. La Aurora, Guadalajara, Jalisco, from March 20 to 23, 2018.
 
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 product is 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 April 9, 2018, response in detail.
 
During our inspection, our investigator 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)).
 
Your firm released your over-the-counter (OTC) drug product, (b)(4), without performing any final product testing, including but not limited to identity and strength of the active ingredient, (b)(4).  
 
In response to this letter, provide the following:
  • The actions you will take to determine the overall quality of your U.S. drug product batches within expiry which were previously released without adequate testing, including identity and strength of active ingredients.
  • Specifications established to determine that all batches of your product distributed to the U.S. market meet required chemical and microbial quality attributes.
  • Validation summary of all analytical methods you will use to test each batch of your U.S. drug product for identity, strength, quality, and purity. 
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 failed to test the incoming active pharmaceutical ingredient (API) and other raw materials you use in manufacturing your drug product to determine conformance to identity, purity, strength, and other appropriate specifications. Instead, your firm released API and other materials based on certificates of analysis (COA) from your supplier without establishing the reliability of the supplier’s analysis through appropriate validation and ensuring at least one specific identity test is conducted for each lot.
 
In response to this letter, provide the following:
  • Your procedure for incoming component testing. Include your corrective action and preventive action (CAPA) to ensure that you conduct at least one specific identity test for each incoming component lot (both active and inactive ingredients). Describe in detail how you plan to test each incoming component lot for conformity with all appropriate written specifications for purity, strength, and quality. If you accept your suppliers’ COA in lieu of testing each component lot for purity, strength, and quality, specify how you plan to establish the reliability of your suppliers’ test results for these attributes through periodic validation.
  • A comprehensive, independent review of your materials system to determine whether all containers, closures, and ingredients from each supplier are adequately qualified; drugs are assigned appropriate expiration or retest dates; and incoming material lot controls are adequate to prevent use of unsuitable containers, closures, and components.
  • A risk assessment for all drug products within expiry and distributed within the United States that were manufactured from components that were not tested. 
3.      Your firm failed to establish 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 lacks an adequate process validation program for your drug product. 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 to assure the quality of raw material inputs, in-process materials, and finished drugs. Process qualification studies determine whether an initial state of control has been established. Successful process qualification studies are necessary prior to 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/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070336. pdf.
 
In response to this letter, provide the following:
  • A detailed program for designing, validating, maintaining, controlling, and monitoring your manufacturing processes that includes vigilant monitoring of intra-batch and inter-batch variation to ensure an ongoing state of control.
  • Actions taken to determine the quality of your U.S. drug products which were released without a validated manufacturing process. 
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 lacked a quality unit. You have not established written procedures describing the roles, responsibilities, and authorities of the quality unit. Additionally, your firm lacked adequate systems and documentation for the following:
  • investigation of out-of-specification results;
  • complaint handling;
  • control of master batch records;
  • review of production records,
  • stability program; and
  • supplier qualification.
In response to this letter:
  • Obtain an independent, comprehensive assessment of your quality unit. Provide a thorough CAPA plan that establishes your quality unit. For example, one aspect of your remediation should include, but not be limited to, procedures that detail appropriate responsibilities and authorities (e.g., final review of all production and control records before a final batch disposition decision) of your quality unit.
  • 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 product currently on the U.S. market.
Overall Response
 
In your response, you acknowledged the significance of the CGMP observations. However, you provided limited corrective actions and did not provide sufficient detail and evidence to support that your proposed corrective actions will bring your operations and distributed drug products into compliance with CGMP. In your response, you also stated that you will stop manufacturing (b)(4) for the U.S. market.
 
CGMP Consultant Recommended
 
If your firm resumes manufacturing drugs for the U.S. market, we strongly recommend engaging a consultant qualified as set forth in 21 CFR 211.34 to assist your firm in meeting CGMP requirements. The consultant should comprehensively audit and assist with remediating your operations, including but not limited to incoming raw material testing, laboratory controls, quality unit authorities and resources, and all other elements of your quality system. Your CAPA should then be evaluated by the consultant to help ensure systemic remediation before you pursue resolution of your firm’s compliance status.
 
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.
 
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 in all your facilities.
 
FDA placed your firm on Import Alert 66-40 on August 1, 2018.
 
Until you correct all violations completely and we confirm your compliance with CGMP, FDA may withhold approval of any new applications or supplements listing your firm as a drug manufacturer.
 
Failure to correct these violations may also result in FDA continuing to refuse admission of articles manufactured at Jabones Y Productos Especializados SA de CV at Cernicalo 155, Col. La Aurora, Guadalajara, Jalisco into the United States under section 801(a)(3) of the FD&C Act, 21 U.S.C. 381(a)(3). Under the same authority, articles 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 deviations 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 electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov or mail your reply to:
Chhaya Shetty
Interdisciplinary Scientist
U.S. Food and Drug Administration
White Oak Building 51, Room 4359
10903 New Hampshire Avenue
Silver Spring, MD 20993
USA
 
Please identify your response with FEI 3007808836.
 
 
Sincerely,
/S/ 
Francis Godwin
Acting Director
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research