Inspections, Compliance, Enforcement, and Criminal Investigations

CMI Cosmetic Manufacturers Inc. 4/25/13


Department of Health and Human Services logoDepartment of Health and Human Services

Public Health Service
Food and Drug Administration
 Silver Spring, MD  20993 


Warning Letter
CERTIFIED MAIL                                                                                    
WL: 320-13-13
April 25, 2013

Ms. Valerie Dicianna
CMI Cosmetic Manufacturers Inc.
90 Moyal Court
Concord, Ontario
Canada L4K 4R8
Dear Ms. Dicianna:
During our October 22, 2012 through October 24, 2012, inspection of your pharmaceutical manufacturing facility, CMI Cosmetic Manufacturers Inc., located at 90 Moyal Court, Concord, Ontario, Canada, an investigator from the U.S. Food and Drug Administration (FDA) identified significant violations of current good manufacturing practice (CGMP) regulations for finished pharmaceuticals, Title 21, Code of Federal Regulations, Parts 210 and 211. These violations cause your drug product(s) to be adulterated within the meaning of Section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. 351(a)(2)(B), in that the methods used in, or the facilities or controls used for, their manufacture, processing, packing, or holding do not conform to, or are not operated or administered in conformity with, CGMP. 
Our inspection also revealed that your firm failed to fulfill its registration obligations under Section 510(i)(1) of the Act and its listing obligations under Sections 510(i)(2) and 510(j). 21 U.S.C. 360(i)(1) and (2), 360(j).
We have conducted a detailed review of your firm’s response dated November 6, 2012, and note that it lacks sufficient corrective actions. 
Our investigator(s) observed specific violations during the inspection, including, but not limited to, the following:
1.    Your firm failed to withhold from use each lot of components, drug product containers, and closures until the lot had been sampled, tested, or examined, as appropriate, and released for use by the quality control unit (21 CFR 211.84(a)).

For example,
a.    Your firm failed to conduct identity tests of incoming raw materials, such as (b)(4), (b)(4) and (b)(4), yet used these components in the manufacture of your drug products, (b)(4), (b)(4) and (b)(4).  

b.    Your firm accepts and relies upon the suppliers’ Certificates of Analysis (CoAs) for drug components without conducting adequate vendor qualification.

In your firm’s response, you indicated that you will arrange for an outside contractor to conduct testing of the raw materials.  However, you failed to identify the type of testing the contractor will perform for each of the drug products you manufacture (i.e. CoA testing, identity testing). 
Without establishing the reliability of the vendors’ analyses, through appropriate validation of its test results at appropriate intervals, your firm has no assurance that drug product components meet all appropriate written specifications for purity, strength, and quality. In your response to this letter, include a detailed plan to ensure that you do not use unverified components in your drug products. Include commitment to rely on a supplier’s CoA only if your firm both conducts a specific identity test on every incoming batch of component and has established the reliability of that supplier’s analyses through initial validation of its test results (as reported on CoAs) followed by verification at appropriate intervals. Please include a timeline for the validation of your analytical methods that are intended to test the identity of the components used in the manufacture of your finished drug products. 
2.    Your firm failed to establish and follow adequate written procedures for cleaning and maintenance of equipment (21 CFR 211.67(b)).
For example, your firm has failed to evaluate the effectiveness of your cleaning procedures. You do not have data to show that your equipment cleaning procedure is adequate to prevent cross-contamination.  Specifically, your firm has not conducted cleaning validation, cleaning verification, or swab recovery studies for multi-use equipment used in the production of your OTC drug products. 
In your response, you committed to having a company “test the validity of [your] Standard Operating Procedures, Sanitization and Cleaning of Equipment and amend if necessary.”  Your response is inadequate because you failed to commit to conducting cleaning validation studies. In your response to this letter, please include an action plan for the completion of the cleaning validation and the protocol that will be used to execute the cleaning validation studies. 

3.    Your firm failed to establish and follow adequate written procedures for the preparation of master production and control records designed to assure uniformity from batch to batch (21 CFR 211.186(a). 

For example, the master production records for your (b)(4) and (b)(4) do not include either the batch size or the weight or measure of each component. Your response to this observation indicates that you will revise the master production records; however, you have not identified what changes will be included in the revised master batch records. In your response, provide copies of your revised master production and control records. If the changes made to your master production records require revalidation, please include an action plan for completing the validation as well as a copy of the validation protocol. 
We are concerned about your firm’s failure to comply with fundamental CGMP requirements such as documenting changes to your manufacturing process and ensuring that drug products meet proper quality and purity standards. Please refer to the CGMP regulations at 21 CFR Parts 210 and 211, which can be accessed at We also recommend that you seek the advice of a third party consultant for assistance with a complete evaluation to determine the improvements needed at your facility to conform to the CGMP requirements. 
As noted above, your firm failed to fulfill its registration obligations under Section 510(i)(1) of the Act and its listing obligations under Sections 510(i)(2) and 510(j). 21 U.S.C. 360(i)(1) and (2), 360(j).   For example, in 2011 and 2012, drugs that you manufactured or otherwise processed at the above-referenced establishment were offered for import into the United States. During this same time period, however, your firm did not maintain a current establishment registration and complete and accurate drug product listing with the FDA.
Please note that a drug offered for import into the United States may be refused admission under section 801(a)(3) of the Act (21 U.S.C. § 381(a)(3)), if the drug appears to be adulterated or misbranded. Under section 502(o) of the Act (21 U.S.C. § 352(o)), the failure to register an establishment as required by section 510 or to list a drug as required under section 510(j) renders a drug misbranded.  In addition, a drug offered for import into the United States may be refused admission under Section 801(o) of the Act if the importer, owner, or consignee is not able to provide a statement of the registration of the establishment that manufactured it. Information on how to register and list is available at the following internet website: If you continue to produce drugs that are offered for import into the United States, you must complete the required registration and listing.   You should provide evidence that you have fulfilled these requirements in your response to this letter.
The violations 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 the violations identified above and for preventing their recurrence and the occurrence of other violations.  
Until all corrections have been completed and FDA has confirmed corrections of the violations and your firm’s compliance with CGMP, FDA may withhold approval of any new applications or supplements listing your firm as a drug product manufacturer. In addition, your failure to correct these violations may result in FDA refusing admission of articles manufactured at CMI Cosmetic Manufacturers Inc. into the United States under Section 801(a)(3) of the Act, 21 U.S.C. 381(a)(3). The articles are subject to refusal of admission pursuant to Section 801(a)(3) of the Act, 21 U.S.C. 381(a)(3), 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 Act, 21 U.S.C. 351(a)(2)(B). 
Within fifteen working days of receipt of this letter, please notify this office in writing of the specific steps that you have taken to correct and prevent the recurrence of violations, and provide copies of supporting documentation. If you cannot complete corrective actions within fifteen working days, state the reason for the delay and the date by which you will have completed the corrections. Additionally, if you no longer manufacture or distribute the drug products at issue, provide the date(s) and reason(s) you ceased production.  Please identify your response with FEI # 3003420009.
Please send your reply to the following address: 
Merideth Rose
Consumer Safety Officer
U.S. Food and Drug Administration
Center for Drug Evaluation and Research
Office of Manufacturing and Product Quality
Division of International Drug Quality
White Oak, Building 51
10903 New Hampshire Ave
Silver Spring, MD 20993
Tel: (301) 796-1287
Fax: (301) 847-8741
Michael D. Smedley
Acting Director
Office of Manufacturing and Product Quality
Office of Compliance
Center for Drug Evaluation and Research

Page Last Updated: 05/06/2013
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