Quality Assurance Workshop
The Quality Assurance Workshop continued with Karyn M. Campbell, director, Investigations Branch, US Food and Drug Administration’s Philadelphia District Office, who presented an update on FDA’s activities, including an overview of the agency’s reorganization—some of which had just been implemented days before. Campbell then provided information on recent warning letters, including the cyber letter issued to L’Oréal’s Lancôme brand.
“This is called a cyber letter because there is no inspection,” Campbell said, noting that FDA investigators do routine web searches for claims that cross over into the drug area.
Another warning letter presented by Campbell involved a foot scrub. But this went beyond claims issues; the products were adulterated and posed health issues for consumers, the document said.
According to the warning letter, an FDA sample of the foot scrub was found to have excessive microbiological levels. The letter, which was issued in 2012, was written following an inspection conducted in a US facility during which the agency found that the product was prepared, packed and held under unsanitary conditions.
“There are no GMPs for cosmetics,” Campbell told attendees. “When we don’t have GMP regulations established, we always have the Act,” she continued, referring to the Federal Food, Drug, and Cosmetic Act .
In its warning letter, FDA staff said it was compelled to state that the company did not follow GMPs, noted Campbell. Agency inspectors found filth and dust on manufacturing equipment, and said that raw materials were not routinely evaluated from a microbiological safety standpoint and finished products were also not being routinely tested.
“We are a very conservative agency, so we felt that these were very egregious,” she said.
A Serious Discussion About B. Cereus
Another hot topic on the docket was Bacillus cereus (b. cereus), which was addressed in the Cosmetic Microbiological Safety session. Dr. Michelle Callegan of the University of Oklahoma presented “Ocular Infections by Bacullus cereus and Other Organisms.”
Dr. Callegan told attendees that B. cereus is ubiquitous in nature.
“You can find it anywhere,” she told the audience, noting that it is even in such mundane places like black pepper.
According to Dr. Callegan the most common forms of B. cereus infection cases are typically gastrointestinal-related however there are non-GI infections—such as wounds or burns, respiratory (pneumonia) and ocular (endophthalmitis).
“Are non-GI B. cereus infections on the increase?” Dr. Callegan asked in her presentation. While only serious infections have been published in the literature and the majority of reported serious cases occurred in neonates, IV drug abusers and immunocompromised patients, a January 2011 alcohol swab recall by The Triad Group has led to increased concern from FDA —including those about B. cereus in cosmetics that are to be used around the eye area.
According to Dr. Callegan, infection with B. cereus usually results in blindness or loss of the eye itself within 24-48 hours, and despite treatment, 60-85% of all Bacillus cereus endophthalmitis cases result in significant vision loss. Also, 48-70% of all bacillus cereus endophthalmitis cases result in enucleation or evisceration of the eye.
Yet, according to Dr. Callegen, there has not been a lot of literature on B. cereus infections in the eye area, and those that have been published involved contact lens wear or eye injuries—such as using a pin to separate eye lashes after application of mascara, for example.
She said that it comes down to personal responsibility with products, and that when a consumer is taught to use them, they need to use that product in that manner. “You can do what you can, put inserts, little fine print—but when it gets to their home, it is out of your control.”
Dr. Callehan told the audience, “I don’t think you need to worry about B. cereus in cosmetics, and that is just my humble opinion.”
The B. cereous conversation continued in the afternoon with Steve Schnittger, vice president of global microbiology at Estée Lauder. His presentation was entitled “Microbiological Risk Assessment Review of B. Cereus.”
While FDA did not consider B. cereus a hazard five years ago, the agency appears to have changed that stance.
“We are here today to further support that B. cereus in our products is not a concern,” Schnittger noted.
In his talk, Schnittger presented a trio of case studies related to bascullus species. His goals were to show how in a preserved cosmetic matrix, these organisms should not be viewed as objectionable, and to focus on the importance of a risk assessment when determining potential risk of a cosmetic product.
The first study involved UK grain workers who were frequently found to be exposed to more than 1 million bacteria and fungi per m3 air. Levels of airborne endotoxin of over 10,000 EU/m3 were recorded and at all but one workplace visited and personal exposures reached over 600 EU/m3 at every workplace. In the study, there were no reported cases of traumatic eye infections even though the bacterial and fungal counts exceeded 1 x 109 c.f.u per gram and long-term exposure to high endotoxin, bacterial and particle levels, did not have an effect on lung function and did not appear to cause chronic lung damage.
The second case involved bacillus cereus in infant formula and came via “Final Assessment Report Bacillus Cereus Limits in Infant Formula Australian – New Zealand Food Standards (FSANZ).” As infant formula can be the sole source of nutrition for infants and frequency of consumption is very high, an infectious dose of b. cereus for infants is of concern because their immune system are not fully developed and are susceptible to bacterial infections.
The New Zealand Risk Assessment Study concluded that levels between 10 cfu – 100 cfu of Bacillus species was not a risk to infants when prepared and stored properly.
The Schnittger presentation also included a Survey of B. Cereus Contamination in Foods:
• 52% of 1546 food ingredients
While bacillus species is widespread in food products, according to the presentation by Schnittger, it is estimated that the rate of illness in the USA is 0.1 cases per 10,000,000 per year due to B. cereus.
The final case study presented by Schnittger was bit closer to home as it involvedimported cosmetics. A lipstick or a eye-shadow containing <10 CFU per gram of B. cereus would be delivering 0.01 – 0.05 grams of product per application. It would be delivering 10-2 cfu per gram of a bacteria per application of a preserved anhydrous product—the equivalent to 0.001 cfu per gram of product to an area of the body (the lips), which contains a very high bacterial load.
According to Schnittger, in Case 1 there was a high bacterial load in the eye area with no adverse reactions reported and no long-term adverse reactions observed. In Case 2, it was found to be acceptable that a productwas being given to an immune-compromised population and it contained levels of bacteria that could possibly range from <102 - <105 cfu per gram. And in the third case, there was a preserved or anhydrous hot pour product which is hostile to microbial growth containing levels of <10 cfu per gram of an organism(s) to an area of the body that may contain bacterial levels that could range from 10-1000 times higher than what is being delivered by the product.
In conclusion, Schnittger said data showed that in a non-cosmetic application, B. cereus is not to harmful even at levels 100 times higher than limits used for cosmetic products.
According to Schnittger, industry needs to be persistent with FDA about B. cereus, suggesting that the industry should be willing to take legal steps to defend the safety of its products.
Noting that today’s personal care products today aren’t just “water in oil emulsions being put on hair,” Schnittger said.“Products are more dynamic and the packaging is more dynamic. Risk assessment will help us determine if products are safe, what is the potential risk. And I think that I have shown today that the risks are minimal.”
During the Q&A portion of Schnittger’s presentation, Scott Sutton, a consultant with Microbiology Network (and an earlier speaker at the symposium), supported Schnittger’s stance by telling the audience, “If you are not willing to defend the safety of your products, you get what you get.”