WARNING LETTER IS RECEIVED FOR REPEAT VIOLATIONS AND OBJECTIONABLE (SPECIFIED) MICROORGANISMS
COMMENT
Miramar Cosmetics of Doral, Florida received a Warning Letter for repeat violations from 2007, the presence of objectionable (“specified”) microorganisms, responding after 15 business days after the Form FDA 483 was issued and the manufacturing of drugs without an approved application.
We acknowledge your firm’s written response, received April 13, 2011; however, because this response was received more than 15 business days after the Form FDA 483 was issued, it has not been considered1. We plan to evaluate this response along with any other written material provided, as a direct response to this Warning Letter.
Specific violations observed during the inspection include, but are not limited to, the following:
CGMP Violations:
1. Your firm has not established appropriate written procedures to prevent objectionable microorganisms in drug products not required to be sterile [21 C.F.R § 211.113(a)].
For example, your firm failed to establish appropriate written procedures for monitoring the microbiological quality of the water used to manufacture drug products.
COMMENT
Drug products should have the microbiological quality of water monitored to assure that it is in compliance and permits the manufacture of non-sterile drugs that meet cGMP. Typically, Purified Water would be used to manufacture non-sterile product and have a specification of 100 Colony Forming Units (CFU) per gram. Final non-sterile product would have a specification of 100 CFU per gram for bacteria and 10 CFU per gram for yeast/mold (see USP<1111>). The FDA has begun to not tolerate repeat Observations that it (FDA) considers important (see below).
This is a repeat observation from the 2007 inspection.
2. Your firm has not established specifications, test procedures, and laboratory control mechanisms [21 C.F.R § 211.160(a)].
For example, your firm has not established the effectiveness of the preservative Isothiazolinone at (b)(4) % used in the “Sport Cream formulation,” a pain relief topical drug product.
This is a repeat observation from the 2007 inspection.
COMMENT
Products that are manufactured as non-sterile and contain preservatives, e.g., Isothiazolinone, should be tested as per USP<51> Antimicrobial Effectiveness Testing to ascertain its effectiveness. Not establishing this specification not only violates the USP monograph, but also §211.160(a). Please note that this Observation is also one that the FDA found in 2007.
3. Your firm has failed to perform appropriate laboratory testing, as necessary, of each batch of drug product required to be free of objectionable microorganisms [21 C.F.R § 211.165(b)].
For example, your firm failed to conduct microbiological testing for 32 batches of topical drug products (Sport Cream, Hongotrim Spray and Hongotrim Soap) prior to release.
This is a repeat observation from the 2007 inspection.
COMMENT
Microbial testing should be an integral part of any specifications for non-sterile products that may permit the growth of microorganisms. To not perform microbiological testing of 32 lots prior to release suggests that the product may be contaminated/adulterated and not suitable for release. For this to be a repeat violation is considered to be a major FDA issue.
4. Your firm has failed to prepare batch production and control records with complete information relating to the production and control of each batch of drug product [21 C.F.R. § 211.188].
For example, your firm failed to prepare batch records with complete manufacturing instructions. Specifically, the batch records for Hongotrim Spray (lot 100913-1) failed to include: (1) instructions for the addition of ingredients; (2) a statement of actual yield and percentage of theoretical yield at the appropriate phase of processing, and; (3) a record of filling, packaging, and labeling operations.
This is a repeat observation from the 2007 inspection.
Repeat observations from prior inspections indicate that your quality control unit is not exercising its responsibilities or may not have the appropriate authority to carry out its responsibilities. Due to continuing CGMP issues at your firm, we recommend you engage a third party consultant having appropriate CGMP expertise to assess your firm’s facility, procedures, processes, and systems to ensure that your drug products have their appropriate identity, strength, quality, and purity. You are responsible for ensuring that your firm’s drug manufacturing operations comply with applicable requirements, including the CGMP regulations and the Act.
COMMENT
A lack of complete manufacturing batch records has been an on-going issue within this Company and again represents a repeat Observation. The FDA’s suggestion of “engaging a third party consultant having appropriate CGMP expertise” is often an area that the FDA encourages when a Client receives a Consent Decree. While there exists no hint of this from the FDA, the lack of knowledge and understanding suggests to the FDA that additional outside assistance be provided.
Your firm claims that you are “not manufacturing OTC drugs” at this time. However, we note that you continue to have drugs on the market and still produce products with drug claims. In addition, your firm makes cosmetics, which are also subject to CGMP.
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