December 6th, 2011
FDA Public Meeting on Cosmetic Microbiology Safety – Nov. 30, 2011
Scott Sutton, Ph.D.
On Wednesday, November 30th of 2011 I had the pleasure of attending the USFDA CSFAN meeting on “Cosmetic Microbiology Safety Issues”.
This meeting had been announced in the November 1, 2011 Federal Register (vol. 76, no. 211 pp. 67461-3) with a stated purpose to:
“provide stakeholders an opportunity to present information regarding cosmetic safety and to suggest areas for the possible development of FDA guidance documents. FDA is seeking information regarding microbiological testing of cosmetics; types of preservative systems and how to test their efficacy; the identity and prevalence of microorganisms, including antibiotic-resistant strains, that pose specific health risks in finished products; routes of exposure to microorganisms and the corresponding infective doses; product and packaging characteristics that affect microbial growth and risk of infection; particular subpopulations that may be at greater risk of infection when using different cosmetic products; the occurrence of adverse events associated with microbial contamination of cosmetics; and any other issues relevant to the microbiological safety of cosmetics.”
It was with great anticipation then that I went, hoping to learn what was behind some confusing recent actions in the cosmetic realm of microbiology. One of the most disruptive of these is the de facto (albeit unwritten) requirement for absence of Bacillus cereus from cosmetics, especially cosmetics for the eye.
The meeting opened with a welcome from Dr. Linda Katz who reviewed the responsibility of FDA in the cosmetics arena, and how FDA interacts with industry. There was also a brief discussion in this presentation of how FDA gathers information. Dr. Katz concluded by reminding the audience that this was primarily a “listening session” for FDA.
The following speaker, Dr. Patricia Hansen, presented on FDA’s perspective in cosmetics, focusing on the need for safety. She pointed out that ISO had developed a GMP (ISO 22716), an antimicrobial efficacy test (ISO/DIS 11930) was discussing the possibility of an international standard for identifying objectionable organisms and setting microbial limits standards for cosmetics. Dr. Hansen went on to discuss the need to update FDA guidance, eliminating inconsistencies and harmonizing with international standards. She stated specific needs for input on preservation and microbial quality, on Microbiological Risk Assessment, and on adverse events. An interesting point was made during this presentation was that the agency feels antibiotic resistant strains of bacteria are objectionable. This is a debatable point. As antibiotic resistance is frequently conferred by promiscuous plasmids, the mere trait of “antibiotic resistance” may be a transient state and one that many commensal organisms can share (Mathur, S and R Singh. 2005. Intl J Food Microbiol 105(3):281-295, Macovei, L and L Zurek. Appl. Environ. Microbiol. 2006, 72(6):4028-4035, Smith, D L et al. 2002. PNAS 99:6434–6439).
The first public comments were from the Environmental Working Group (http://www.ewg.org/). Their website states that their “team of scientists, engineers, policy experts, lawyers and computer programmers pores over government data, legal documents, scientific studies and our own laboratory tests to expose threats to your health and the environment, and to find solutions. Our research brings to light unsettling facts that you have a right to know.” The speaker, Etan Yeshua, urged FDA to protect the microbiological safety of cosmetics, prevent the use of toxic preservatives and require accurate labeling of preservatives (including expiry dating). He asserted that their organization’s database listed 948 aqueous-based cosmetic products that had no recognizable preservatives (an obvious problem), and that their data show approximately 3500 products were preserved with one or more of 22 toxic preservatives. Among these preservatives was parabens, problematic, in the opinion of EWG, for its links to cancer and reproductive issues. He concluded with several specific recommendations:
- Conduct a comparative analysis of foreign and domestic formulations. Mr. Yeshua stated that Europe has more stringent limits on hazardous chemicals than does the US, and that many companies will market one formulation in the US and a different one in Europe as a result. If the product can be made to meet European standards, why should theUS be provided a more toxic formulation, he asked.
- Improve product labeling to include all ingredients and expiry dating
- Evaluate the disparity in preservative concentrations among products. This disparity can be very wide, and FDA should develop guidelines for the safe formulation of preservative products.
The second public speaker was Jay Ansell, Ph.D. Vice President, Cosmetics Programs, Personal Care Products Council (PCPC) (http://www.ctfa.org/). Their website states that “the Council’s more than 600 member companies manufacture, distribute, and supply the vast majority of finished personal care products marketed in the U.S. As the makers of a diverse range of products millions of consumers rely on everyday, from sunscreens, toothpaste and shampoo to moisturizer, lipstick and fragrance, personal care products companies are global leaders committed to product safety, quality and innovation.” He presented an overview of the safety, Quality Assurance program and controls that PCPC member companies have in place through a system of voluntary standards. In addition to the “built-in quality” of the cosmetic manufacturers, there is currently post-market surveillance for the industry. As a result, Dr. Ansell noted that the FDA discontinued its Product Experience Report program in 1996. There is an adverse events reporting system in place, which shows (at least from 2004-2011) that these events are rare, with infections from cosmetics extremely rare. The ISO, he notes, has an “objectionable organism” standard under development with which they are participating. He concluded with a pledge to continue PCPC use of quality techniques, risk assessment, regulatory compliance based on science and to assist and participate in FDA initiatives.
The next presentation was from Phil Geis, Ph.D. of Geis Microbiological Quality (an independent consulting company affiliated with Advanced testing Lab). Dr. Geis, having worked at P&G for 30 years, is a long-standing member of the PCPC Microbiology committee and reviewed several of the projects that the PCPC Microbiology Committee has completed or are developing in terms of product quality and patient safety. He discussed Quality product design from R&D, and the need for controls on raw materials, preservation, packaging, reasonable consumer use and risk assessment. Quality is preserved on the manufacturing side by controls on the facility, raw materials, environmental monitoring and finished product testing ensure safe products. This testing was assisted by the use of modern microbiological techniques that gave rapid answers to the level of one CFU/g. The last aspect of safe products, as described by Dr. Geis, was the need for safe use by the consumer. Dr. Geis apparently addressed industry concerns that B. cereus would be identified as an objectionable by emphasizing that cosmetic, though typically including no detectable microorganisms, are not and need not be sterile and that innovation and consumer choice would suffer if sterility was required. He concluded with the assertion that the US Consumer Industry is the leader in safety, and that industry’s development of appropriate risk assessment tools will continue to ensure that state. “The cosmetic industry has an excellent record of microbiological quality and safety as accomplished with appropriate use of a small number of safe and effective preservatives. These products are not sterile nor should they be.”
It was after this presentation that the first questions from the floor were raised (although the opportunity had been provided after every presentation). This author asked the first, noting that the day was more than half over and little had been said about the situation with B. cereus, and none of that definitive. Dr. Katz replied that FDA needs industry input on what should be considered “objectionable” in a cosmetic formulation. In addition, there needed to be further definition of products marketed to specific locations (hospitals, assisted care living, etc). Another question dealt with the use of rapid methods in the cosmetic industry, and how this could be done to the level of 1 CFU (enhancement of numbers by preliminary incubation in recovery broth was the answer). Dr. Geis, in reply to further questions, repeated an earlier statement that preservatives (parabens and the so-called formaldehyde releasing agents) were safe for use in cosmetics and if forbidden would make cosmetics very difficult to preserve.
The next public comment was presented by Mr. David Steinberg (Principal of Steinberg & Associates, an independent consulting firm – http://www.steinbergconsult.com). Mr. Steinberg is Executive Director of the Cosmetic Preservative Council (an organization he founded in 2006). He presented a review of current cosmetic regulation and the concern over “pathogens”. Mr. Steinberg then discussed the actual use of preservatives in cosmetics as determined by a voluntary registration program administered by FDA. According to these data (see Cosmet Toilet Oct. 2008 for article http://www.cosmeticsandtoiletries.com/magazine/pastissues/2008/31010244.html) there are only about 20 preservatives in significant use. Of these, perhaps a total of eight are responsible for the majority of cosmetic systems on the market. These preservatives are reviewed for safety by the independent Cosmetic Ingredient Review (CIR). The problems seen with preservatives in cosmetics, Mr. Steinberg asserted, were due to excessive preservative concentrations in the formulation and this has led to the marketing claim of “preservative-free” being seen as desirable. This has, in turn, led to a number of dubious “-free” claims. Mr. Steinberg pointed out the Canadian response to this was to regulate the claim with specific requirements to safeguard the consumer. He also noted that it is very unlikely that new preservatives will be developed soon. Mr. Steinberg presented some of the basic economics of the problem, based on increases in expectations for safety and efficacy testing. In the 1960’s the cost to develop a preservative was about $2,000 (USD). In the 1980’s this had increased to about $100,000 and the last preservative approved for general use in the US took 5 years of development at a cost in the 7-figure range. He concluded with a pledge to support the FDA in ensuring the continued safety of cosmetics.
Richard Whiting, Ph.D. next presented on a project to develop a risk assessment model undertaken at the behest of PCPC. Dr. Whiting is Senior Managing Scientist of Exponent (an engineering and scientific consultancy – http://www.exponent.com). He presented on the mechanisms of risk analysis, focusing on the development of a risk assessment tool to quantify the risk to the consumer of pathogenic organisms in cosmetics. This presentation emphasized the need for data in determination of risk to the consumer.
There were several questions posed after Dr. Whiting’s presentation. The first was about risk assessment proper – that this was not really a new topic. Dr. Whiting agreed, but stated that the quantitative aspect of this effort was new to the industry. This author then posed a question, noting that investigations into OOS or excursions were expected to follow a particular logic, that a problem was identified, the root cause of that problem determined, a solution to the root cause was proposed and then the efficacy of the solution to correcting the problem was established through data collection. The first act in this is always to identify the problem. What was the problem in Cosmetic Microbiological Safety that FDA was attempting to correct with changes in regulatory positions? An FDA representative answered that this effort was preventative in nature.
After this question and answer period Dr. Linda Katz presented a summary of the conference. She thanked everyone and reminded the audience that the deadline for submission of written comments to FDA (Docket No. FDA-2011-N-0770) was January 30, 2012. At this point the meeting concluded.
As I left the meeting I have to admit to experiencing some disappointment. It is not that FDA was unclear about the purpose of the meeting (to listen to stakeholder comments) or that industry is to be criticized for failing to press points of interest (this probably was not the forum for a “frank and candid” discussion). However, I did feel the sense of an opportunity missed. The US faces some significant challenges in terms of product safety – not only in the personal care side but also in pharma, biotech, OTC and medical devices. However, most of the microbiological safety issues I see evidence of as a consultant and as a fairly well-read observer of the regulated industries (at least that portion related to microbiology and biological contamination control) is the result of either willful or ignorant violations of basic GMP. In other words, it really does not seem to me that at this time we need new regulation to ensure product Quality and consumer/patient safety. Instead, at least in my opinion, we need to encourage continued vigorous enforcement activity to remove those manufacturers willing to conduct manufacturing under slovenly conditions and those willing to decrease overhead costs by sacrificing the “Quality” function. FDA is to be commended for the Agency’s clear increase in enforcement activity, not only against the primary companies but also, as appropriate, the contract manufacturing and contract testing facilities.
However, this meeting did not seem focused on addressing specific problems but rather on a general desire to revise guidance which has, admittedly, been on the books a number of years. However, spending significant effort on trying to prevent undefined problems does not seem productive and may be distracting. I wish that the reasons for the Agency’s concern in Cosmetic Microbiological Safety could have been communicated clearly so that everyone could focus on finding solutions to well-defined problems not addressed by current guidance, if these problems exist.