On FDA’s Proposed Rule on Intentional Adulteration

FDA released its proposed rule on intentional adulteration of food in a December 24 Federal Register notice. The proposed rule, Focused Mitigation Strategies To Protect Food Against Intentional AdulterationFocused Mitigation Strategies To Protect Food Against Intentional Adulteration, would apply to both domestic and foreign facilities that are required to register with the agency and would require those companies to develop and implement a food defense plan.

The proposal introduces some terminology that may initially cause confusion among stakeholders. For example, the term ‘‘actionable process step,’’ is the food defense counterpart of the familiar term ‘‘critical control point’’ (CCP) used in Hazard Analysis and Critical Control Point (HACCP) plans. HACCP per se does not appear in the language of FSMA, which instead allows hazard analysis and preventive controls to be achieved by any means that can be shown to be effective. For the purposes of food defense, we will need to become familiar with the term ‘‘actionable process step,’’ which is a step identified during a vulnerability assessment. A vulnerability assessment, meanwhile, is similar to the hazard analysis conducted in developing a HACCP plan.

Yet another key term, “significant vulnerability,” is the food defense version of the term “reasonably likely to occur” which is used in the preventive controls proposed rules.

In many situations it may be difficult to say what constitutes a significant vulnerability. This is also an issue in the preventive controls rules, where what may or may not be “reasonably likely to occur” is a challenge for the regulators to sharply define. The agency defines a “significant vulnerability” as a vulnerability for which “a prudent person knowledgeable about food defense would employ food defense measures because of the potential for serious adverse health consequences or death and the degree of accessibility to that point in the food process.”

The agency has identified four key activity types as being especially vulnerable to intentional adulteration: bulk liquid receiving and loading; liquid storage and handling; secondary ingredient handling; and mixing and similar activities. But the agency is open to ideas about what other types of products and facilities may be vulnerable. Judging by the number of questions asked in the proposal, it is clear that even some fundamental elements of the proposal may be open to change before a final rule takes shape.

As proposed, the rule includes numerous exemptions. For example, it would apply to food in liquid storage tanks, but not to the holding of food in general. It would not apply to the packing, re-packing, labeling, or re-labeling of food where the container that directly contacts the food remains intact, the agency says. It would not apply to activities of a facility that are subject to produce safety standards. With some exceptions, it would not apply to alcoholic beverages at a facility that meets certain conditions. And it would not apply to the manufacturing, processing, packing, or holding of food for animals.

The proposed rule would not apply to a “qualified” facility. Qualified facilities would include very small businesses, with less than $10 million in annual sales of food. But some companies could be deemed “qualified” if during the preceding 3-year period the average annual value of the food manufactured, processed, packed or held at the facility sold directly to qualified end-users exceeded the average annual monetary value of the food sold by such facility to all other purchasers, and if the average annual monetary value of all food sold during the preceding 3-year period was less than $500,000.

The agency is seeking comments by March 31, 2014 on the proposed exclusions – and, of course, on all other elements of the proposed rule.

FDA’s Proposed Rule on Antibacterial Soaps

In 2010 the Natural Resources Defense Council (NRDC) sued FDA to force the agency to issue a final rule on antibacterial soaps. As part of a settlement signed last month, the agency issued a proposed rule Dec. 16, 2013 and committed to taking final action by 2016. Well before this lawsuit, however, FDA was investigating this area and considering action on this topic.

FDA’s focus centers on triclosan, an antibacterial agent that’s long been under agency scrutiny. More than 30 years ago, FDA reviewed evidence and concluded that triclosan wasn’t proven either safe or effective (category III), although years later toothpaste containing triclosan was approved. Nonetheless, antibacterial products have been widely marketed for years. Widespread use of these products and related public health and environmental concerns provided a backdrop for the NRDC lawsuit that was the ultimate catalyst for FDA’s regulatory action. As Janet Woodcock, director of FDA’s Center for Drug Evaluation and Research, stated: “Due to consumers’ extensive exposure to the ingredients in antibacterial soaps, we believe there should be a clearly demonstrated benefit from using antibacterial soap to balance any potential risk.”

FDA Action and Rationale

On Dec. 16, 2013 the FDA released a proposed regulation to ban certain ingredients in anti-bacterial soaps if manufacturers cannot prove that these products are safe to use and more effective than plain soap and water for preventing the spread of infections. Such a move could potentially force makers of antibacterial products to reformulate all bar soaps, liquid soaps, body washes, and dishwashing liquids labeled as “anti-bacterial” and “antimicrobial” to keep them on store shelves.

According to Colleen Rogers, a lead microbiologist at FDA, “there’s currently no evi­dence that OTC antibacterial soap products are more effective at preventing illness than washing with plain soap and water”. Moreover, antibacterial soap prod­ucts contain ingredients, such as triclosan and triclocarban, which according to FDA, may pose risks associated with long-term, daily use that may outweigh the benefits. Active ingredients in these soaps may contribute to bacte­rial resistance to antibiotics, and may also have unanticipated hormonal effects that are an FDA concern based on animal study data.

Because of these concerns, FDA’s proposed rule requires manufac­turers to provide more substantial data to demonstrate the safety and effectiveness of antibacterial soaps. The proposed rule covers only consumer antibacterial soaps and body washes that are used with water. It doesn’t apply to hand sanitizers, hand wipes or antibacterial soaps that are used in health care settings such as hospitals.

Most soaps labeled “antibacterial” or “antimicrobial” contain at least one of the antibacterial ingredients that FDA has targeted in this proposed rule. Certain household cleaning products and some toothpastes may also contain them.

Laboratory tests that have historically been used to evaluate the effectiveness of anti­bacterial soaps don’t directly test the effect of a product on infection rates. That would change with FDA’s cur­rent proposal, which would require studies that directly test the ability of an antibacterial soap to provide a clinical benefit over washing with non-antibacterial soap and water.

Environmental concerns also brought the Environmental Protection Agency (EPA) into the picture and the two agencies have been collaborating on scientific and regulatory issues regarding triclosan. EPA is updating its assessment of triclosan’s use in pesticides and its overall environmental impact, while FDA has focused on the antimicrobial’s widespread use by consumers in soaps and body washes. In sharing information, the two agencies are assessing exposure risks.

Next Steps

FDA’s proposed rule doesn’t require the antibacterial soap products to be removed from the market at this time. When the proposed rule is finalized, either companies will have provided adequate data to support an antibacterial claim, or if not, they must reformulate to remove the active ingredients or relabel to remove the antibacterial claim from the product’s labeling in order to continue marketing these products. The proposed rule is available for public comment for 180 days, with a concurrent one year period for companies to submit new data and information, followed by a 60 day rebuttal comment period.

Manufacturers of antibacterial soap and body wash products and trade associations are sure to respond with comments. Two industry trade groups, the Personal Care Products Council and the American Cleaning Institute, already cited a review of two dozen studies they say showed washing hands with antimicrobial soaps produces “statistically greater reductions in bacteria on the skin” than plain soap.” They may also offer legal arguments about the absence of serious adverse event data resulting from antibacterial soap use as well as study data and scientific literature support. Results of animal studies will likely be submitted as well as clinical studies using standardized microbe doses to try to satisfy the agency’s data requirements. However, it’s not likely that manufacturers would incur the enormous cost of full scale clinical trials to obtain prospective human data.

Industry groups intend to file comments reaffirming that use of antibacterial soap products does not contribute to antibiotic resistance. However, the question is whether they can provide sufficient efficacy and safety data to convince FDA that the benefits outweigh the risks. The assessment of published scientific literature alone won’t persuade FDA, since they’ve already concluded that existing scientific data aren’t adequate to support safe and effective product use.

If FDA determines an antibacterial claim is not supported, companies must reformulate to remove or replace a category III ingredient or relabel their products. How one would relabel such a marketed antibacterial soap product is a big unknown. Would FDA permit a disclaimer stating an ingredient like triclosan lacks evidence of safety and efficacy and allow such products to remain on the market? Would consumers continue to use these products without an antibacterial claim? We suspect it will be a while before these issues are resolved.