Questions often arise regarding when is a microorganism “specified” vs. “objectionable”? USP<62> lists a total of seven individual and groups of microorganisms to include Ps. aeruginosa that are considered “specified”. However, in a broader category they are also considered as “objectionable”. A recent Warning Letter discusses the microbiological results from a manufacturer of both gels and shampoos.
The U.S. Food and Drug Administration (FDA) conducted an inspection of Gilchrist & Soames, Inc., cosmetic manufacturing facility, Plainfield, Indiana, from September 22 to October 5, 2015 to determine their compliance with the Federal Food, Drug, and Cosmetic Act (the Act). The firm manufactures and distributes hotel amenity products, including shower gels, shampoos, lotions, and conditioners, to retail and charitable organizations. These products are intended to be applied to the human body for cleansing, beautifying, promoting attractiveness, or altering the appearance, and as such, are cosmetic products within the meaning of section 201(i) of the Act [21 U.S.C. §321(i)].
The FDA collected a sample of their “Gilchrist & Soames Spa Therapy Conditioning Shampoo” product during the inspection, and “(b)(4) Shower Gel,” “Pelican Hill Shower Gel,” and “Essential Elements Shampoo” products post-inspection. Their analysis of these products, manufactured at their facility, found significant microbial contamination. The microbial contamination of the “Gilchrist & Soames Spa Therapy Conditioning Shampoo,” “(b)(4) Shower Gel,” “Pelican Hill Shower Gel,” and “Essential Elements Shampoo” products causes these products to be adulterated.
- FDA analysis of your “Gilchrist & Soames Spa Therapy Conditioning Shampoo” and “(b)(4)Shower Gel” products determined that of the five subsamples analyzed for each product, all contained the pathogen Pseudomonas aeruginosa. P. aeruginosa is opportunistically pathogenic to humans and highly resistant to antibacterial agents such as quaternary ammonium compounds, penicillin, and many broad-spectrum antibiotics. It is among the most virulent opportunistic pathogens and can cause severe and life-threatening infections (especially in immunocompromised patients, burn patients, patients suffering from respiratory disease, cancer, chemotherapy patients, etc.). P. aeruginosa can survive in topical and eye-area cosmetics and has been implicated in significant eye infections which may lead to corneal ulcers and blindness.
Cosmetic products are not expected to be aseptic; however, they must be free of high-virulence microbial pathogens and the total number of aerobic microorganisms per gram must be low.
USP Chapters that one should review include USP<1111> and USP<62> which discuss the numbers of microorganisms recommended within non-sterile products as well as ‘objectionable” microorganisms. Within USP<62> P. aeruginosa is viewed as both “specified” and “objectionable”.
- FDA analysis of your “Gilchrist & Soames Spa Therapy Conditioning Shampoo,” “(b)(4) Shower Gel,” “Pelican Hill Shower Gel,” and “Essential Elements Shampoo” products determined that the subsamples of the products contained an excessive level of microorganisms as evidenced by high Aerobic Plate Counts (APC), which may render them injurious to users because the presence of such microorganisms in these finished products can increase the users’ risk of infection. APC measures the level of microorganisms in a product and can indicate the quality of the product. FDA’s guideline is that the APC should not be greater than 500 CFU/g for eye area cosmetics and 1,000 CFU/g for all other products. These guidelines can be found in the BAM (Click Here). Specifically, your products contained APC of up to 210,000,000 CFU/gm. Of particular concern, the high counts of Enterobacter gergoviae. Enterobacter gergoviae are part of the normal intestinal flora and may be considered an opportunistic pathogen. Individuals with weakened immune systems, who suffer from a serious pre-existing condition, who have been treated surgically or belong to another sensitive group of persons are at particular risk of infection.
Microbial counts as high as 2.1 x 108 per gram can be hazardous to one’s health (if healthy) and particularly hazardous with individuals who have weakened immune systems. The high aerobic plate counts also illustrate how readily bacteria may thrive within conditioning shampoos and shower gels.
The FDA further found that:
Their investigators also observed the following insanitary practices that could cause their products to be adulterated under section 601(c) of the Act in that these practices may lead to insanitary conditions and may cause the products manufactured in their facility to become contaminated with filth or rendered injurious to health. Specifically, the FDA observed that:
- The microbiological safety of starting materials and/or raw ingredients is not routinely evaluated by your firm. Materials are not sampled and tested for conformance with specifications and to ensure the absence of filth, microorganisms, and other adulterants prior to processing or usage. Your firm does not perform any microbial testing on any incoming raw materials, nor have you validated your suppliers’ quality testing through independent verification.
No mention of preservatives was noted as being present within the raw materials, in-process materials or finished product. I find this somewhat surprising since almost all shampoos, conditioners and gels commercially available contain one or more preservatives. Perhaps because the products are provided for hotel guests and are assumed to be “single use only”, the manufacturers believe the products to not require any preservative systems.
We acknowledge receipt of your firm’s October 14, 2015, October 27, 2015, December 8, 2015, December 21, 2015, and January 19, 2016, letters sent in response to the FDA 483 issued to your firm at the close of the inspection. In your letters you stated that you are currently evaluating raw material inventory and determining which raw materials are micro-sensitive. We also note that you state that you send micro-sensitive raw materials to be tested for microbiological content at an external laboratory. We cannot evaluate the adequacy of your corrective actions without the supporting documentation.
- The equipment used to manufacture your products is not maintained in a clean and orderly condition, or sanitized at appropriate times. Your firm was also unable to document clean out procedures for (b)(4)gallon bulk raw material tanks and (b)(4) gallon tank (b)(4) water tank use for manufacturing and equipment cleaning. As suggested in FDA’s Draft Guidance for Industry: Cosmetic Good Manufacturing Practice (Click Here), FDA expects cosmetic firms to document equipment cleaning and procedures and assure that the processes are adequate to prevent adulteration.
In your firm’s response letters you provided a date of February 29, 2016, for your cleaning validation studies to be completed. We also note that you state water samples are being collected and analyzed by your third-party lab. We cannot evaluate the adequacy of these corrective actions without the supporting documentation.
- Raw materials, in-process samples and finished products should be tested or examined to verify their identity and determine their compliance with specifications for physical and chemical properties, microbial contamination, and hazardous or other unwanted chemical contaminants. However, your products continue to be contaminated with microorganisms. Specifically, P. aeruginosa was isolated by FDA from a sample of 1.5 oz bottles of “Thymes naia Body Wash” lot 1308, collected by an FDA investigator on December 17, 2014. The analytical results for this sample were sent to you on March 6, 2015. Yet, P. aeruginosa was isolated from FDA samples of “Gilchrist & Soames Spa Therapy Conditioning Shampoo,” packaged in June, 2015, and ” (b)(4)Shower Gel,” “Pelican Hill Shower Gel,” and “Essential Elements Shampoo,” all packaged in September, 2015.
Where was the microbiologist? I remain quite surprised that the FDA did not strongly suggest to this vendor that they should have a microbiologist on the staff that would be examining raw materials, in-process materials and finished products to assure the absence of both “objectionable” and “specified” microorganisms. While the FDA expects cosmetic firms to document equipment cleaning and procedures and assure that the processes are adequate to prevent adulteration, they also expect that all tankage be evaluated for microbial content.