Inspections, Compliance, Enforcement, and Criminal Investigations

McCallum Manufacturing Ltd 4/9/18

 

  

Black HHS-Blue FDA Logo

 

 

 
10903 New Hampshire Avenue
Silver Spring, MD 20993 

 

Via UPS                                                                                Warning Letter 320-18-45
Return Receipt Requested
 
 
April 9, 2018
           
 
Mr. Iain McCallum
Owner
McCallum Manufacturing Ltd.
6A-D, Redbrook Business Park
Withorpe Road
Barnsley, South Yorkshire, S75 1JN
United Kingdom
 
Dear Mr. McCallum:
 
The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, McCallum Manufacturing Ltd., at 6A-D, Redbrook Business Park, Withorpe Road, Barnsley, South Yorkshire, from July 24 to 26, 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 August 15, 2017, response in detail.
 
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 product, (b)(4), without adequate testing for conformance to specifications, including identity and strength. You lacked testing procedures, specifications, and analytical data to support the release of your drug product.
 
In your response, you stated that you now have written standard operating procedures (SOPs) for, among other things, “testing finished products,” but you did not provide copies of any of these SOPs or the specifications you or your contract testing laboratories are using to release your drugs.
 
In response to this letter, describe your corrective action plan and testing procedures to ensure that all drug product batches are tested for identity and strength prior to release for distribution to the United States. Your written procedures should describe your testing requirements for your products, as well as validated test methods with appropriate acceptance criteria.
 
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) & (2)).
 
You failed to test the incoming raw materials you use to manufacture your (b)(4) drug products to determine their identity, purity, strength, and other appropriate specifications.
 
Instead, your firm used results from your suppliers’ certificates of analysis (COA) without establishing the reliability of your suppliers’ analyses through appropriate validation, and without conducting at least one specific identity test. You may not rely on your suppliers’ COA to verify the identity of your components.
 
In your response, you said that you identified all incoming materials used in the manufacture of the (b)(4) products against known standards. Your response was inadequate because you did not provide procedures for testing incoming materials or results from any testing. In addition, you did not provide any information on how you will establish the reliability of your suppliers’ test results.
 
In response to this letter, provide your procedure to test incoming components. Also, provide a detailed description of how you plan to test each component for conformity with all appropriate written specifications for identity, purity, strength, and quality. Explain how you intend to perform at least one identity test for all incoming components used in your drug products. If you accept your suppliers’ COA in lieu of testing components for purity, strength, and quality, specify how you plan to establish the reliability of your suppliers’ test results through periodic validation.
 
3.      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 control unit. You lacked written procedures for many quality unit operations, such as CGMP training, change control, annual product reviews, complaint handling, and oversight of various other basic drug manufacturing and testing operations.
 
In your response, you indicated that your firm is a small company and does not have the resources for a quality unit. You stated that you are responsible for reviewing and approving all quality related documents. Your response was inadequate. Regardless of the size of your company, as a drug manufacturer, you must have a quality unit that is responsible for and authorized to perform certain operations.
 
In response to this letter, explain how you will establish defined roles and responsibilities for personnel performing the duties of your quality unit. These individuals should have appropriate authority and sufficient resources to carry out their responsibilities to ensure consistent drug quality.
 
4.      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 lacked process validation for your OTC (b)(4) product, including an ongoing program for monitoring process control to ensure stable manufacturing operations and consistent drug quality.
 
See FDA’s guidance document, Process Validation: General Principles and Practices, for information on approaches that FDA considers appropriate elements of process validation, at https://www.fda.gov/downloads/drugs/guidances/ucm070336.pdf.
 
You did not address your process validation plan in your response.
 
In response to this letter, provide your validation plan. 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.
 
5.      Your firm failed to prepare batch production and control records with complete information relating to the production and control of each batch of drug product produced (21 CFR 211.188).
 
Your production and control records did not define and document process parameters to ensure that in-process materials and your finished drug products meet quality requirements. For instance, your batch records did not include information such as identity of the equipment, actual (b)(4) time, temperature, filling and packaging operation steps, and yield percentage specifications.
 
In your response, you stated the batch records were amended to include this information. Your response was inadequate because you did not provide a copy of any of these batch records.
 
In response to this letter, provide your master production and control records for your drug products to demonstrate that they fully document each significant and validated manufacturing step. Also, submit one executed batch production and control record for your (b)(4) drug product.
 
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.
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.
 
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 refusing admission of articles manufactured at McCallum Manufacturing Ltd., 6A-D, Redbrook Business Park, Withorpe Road, Barnsley, South Yorkshire, 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 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:
 
Mr. Lixin (Leo) Xu
Compliance Officer
U.S. Food and Drug Administration
White Oak Building 51, Room 4212
10903 New Hampshire Avenue
Silver Spring, MD 20993
USA
  
Please identify your response with FEI 3004464535.
 
Sincerely,
/S/ 
Francis Godwin
Acting Director
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research

Page Last Updated: 04/16/2018
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