Expanding Choice

If you produce a food that uses an ingredient that is derived from a major food allergen, but does not cause an allergic response that poses a risk to human health, you can get an exemption from the Food Allergen Labeling and Consumer Protection Act (FALCPA) allergen-labeling requirement … but it’s not easy.

Under FALCPA, manufacturers who want to obtain an exemption from the allergen-labeling requirement for a specific ingredient can:

• Submit a petition that provides scientific information demonstrating that an ingredient derived from a major food allergen; or
• Submit a notification providing scientific information demonstrating that the ingredient “does not contain allergenic protein” (or providing information that there has been a previous determination through a premarket approval process under section 409 of the FD&C Act that the ingredient does not cause an allergic response that poses a risk to human health).
   

Manufacturers that are able to demonstrate to FDA that an ingredient qualifies for a labeling exemption do not need to place an allergen declaration on the food label for that ingredient.

In June, FDA issued the final guidance document, “Food Allergen Labeling Exemption Petitions and Notifications,” to help food manufacturers provide adequate data to support the request for such exemptions. But why was this guidance issued now? And what does it take to get such an exemption?
 

FDA Guidance.

To gain FDA’s perspective on the new guidance, QA asked the following questions of the agency’s Strategic Communications and Public Engagement Staff, Office of Foods and Veterinary Medicine, Marianna Naum:
 

QA. The FALCPA Rule on allergen derivatives is not new; why did FDA elect to create/publish this Guidance at this time?

FDA. FALPCA requires labeling of foods containing ingredients derived from any of the major food allergens (milk, eggs, fish, crustacean shellfish, tree nuts, wheat, peanuts, and soybeans). Because an ingredient derived from a major food allergen may be modified enough to no longer present a risk to food allergic consumers, FALPCA created two processes through which a manufacturer can obtain an exemption from the labeling requirement for a specific ingredient. The FDA is issuing this guidance to enhance the quality of submissions received by FDA and help expedite the FDA’s review of such submissions.
 

QA. Understanding that it is guidance not regulation, is it simply to provide manufacturers with information or does it change any previous guidance?

FDA. This guidance provides more detailed information to industry about the data the agency needs when evaluating submissions that seek exemptions from the labeling requirements for ingredients derived from major food allergens.
 

QA. There seems to be a fairly strong focus on consumption levels/consumer exposure. How does this impact the potential reaction of a food-allergic person?

FDA. Reaction risk for food allergic individuals is a function of multiple factors. In food allergen risk assessment, one of the most important factors is the amount of exposure to an allergen consumed from a single eating occasion. Factors such as age, consumption of multiple foods, and other consumer eating habits may all play a role in augmenting or decreasing this amount of exposure. There is enormous variability within the allergic population in reaction risk to allergen dose exposures, and not all allergic individuals react at the same allergen dose or concentration in a food. However, as allergen dose exposures increase, there is a greater chance that individuals in a population of allergic consumers may react or be at risk for reaction when exposed to that dose. Estimated consumption levels can vary from product to product and provides important exposure information on how much allergen would or could be consumed by the population of allergic individuals in worse case eating-occasion scenarios. This information helps inform the potential risk for reaction in a population of consumers.
 

QA. Pre-submission consultation with FDA is recommended if risk assessment-based or safety assessment-based approaches are used. Why is this needed and what would be the key focus of this consultation?

FDA. Pre-submission consultation is not required, but is encouraged in the case of all submissions received under FALCPA. In the case of submissions based on risk assessment and safety assessment approaches specifically, consulting with the agency provides an opportunity to discuss the submission and the likely complex scientific arguments with a submitter prior to actually receiving the submission.
 

QA. What will the review process include?

FDA. The review process at the agency is a thorough pre-marked evaluation of the material provided by a review team. Our reviewers work to analyze the information provided and make recommendations regarding the response to the submission.

QA. How long should a submitter expect review and approval, denial, or questions to take?

FDA. It is difficult to estimate the amount of review time we will require. The amount of time is largely dependent on the complexity as well as the overall quality of the submission.  As such, it is anticipated that the review time and time to a response will be variable.
 

QA. If denied, will the submitter be provided with an explanation so as to allow for further refinement of the ingredient or submission?

FDA. Yes. Denial letters issued in the past have explained the deficiencies and this will continue.
 

Industry Perspective.

Since 2005, only 11 companies have submitted petitions or notifications for exemptions. Of these, only two have been approved. The low number of submissions and even lower number of approvals may likely be due, at least in part, to the amount of information needed to “demonstrate to FDA that the ingredient qualifies for a labeling exemption.” This is easily shown by the 55-page petition submitted for exemption of a soy lecithin product used as a processing aid, and the 173-page notification for an ice structuring protein preparation requesting a fish-labeling exemption—two that were approved. (The documents are available for viewing/download at http://1.usa.gov/1f3H8vu and http://1.usa.gov/1L9KlYi.)

Putting forth the time, effort, and expense to jump over all the hurdles needed to declare a food ingredient to be allergen-free can be a very complex undertaking for a company, said Thomas Grace, CEO of Elution Technologies, Bia Diagnostics. “The hurdles for a company to overcome to provide all the statistical data to show the ingredient has been processed [to not cause an allergic response] seems to be very high,” he said. “I would think you would have to have clinical studies showing the allergen is no longer active, or you might be able to use mass spectrometry data, to show the protein(s) are now broken down to single peptides. But even then, I would think you would still have to prove the amount of hydrolyzed or modified protein does not cause a response.

“It’s very difficult for a company to show that there is no immunological effect to any individual,” Grace said. “So it’s how to do that study that is a major hurdle.”

Grace cited FDA’s guidance recommendation for ELISA testing, but noted that secondary methods also should be used. As stated in the guidance: “Enzyme-linked immunosorbent assay (ELISA)-based methods are the most widely used methods for detecting or measuring food allergens. However, given the limitations of ELISA-based methods, submitters should consider using additional analytical methods, such as using polymerase chain reaction (PCR) or mass spectrometry, to supplement data obtained using ELISA assays.”

But, Grace said, “I don’t think there’s a lot of data on these.”

An additional complexity is testing in the matrices of the final product(s) in which the ingredient may be used. “Proteins that are modified may still be immunologically active or ‘hidden’ and difficult to detect in a complex matrices such as baked, heated, extruded, boiled or deep-fried foods,” Grace said. In fact, the proteins could be made even more immunologically active by heating or processing. Another thing to consider is the variation in the foods themselves, and that testing of one product—say, a blueberry muffin—may not necessarily be representative of all blueberry muffins because of how it is baked and the specific ingredients used.

Additionally, he said, the hurdle may be different for people with different allergies, and the standard consumer consumption of a food must be taken into consideration. If testing was conducted at a level different than that consumed, could there be enough difference to cause a response in an individual? Such dose response information is a critical aspect of the exemption petition/notification (as discussed in the FDA response to the third question, above.)
 

The positives.

Because of the complexity and requirements of exemption submissions, Emport LLC President Emily Kaufman noted that a company needs to ensure that the benefits will be worth the commitment needed to demonstrate that the derived ingredient no longer contains the allergenic protein. “The exemption process is geared toward large-scale companies that can dedicate staff to getting this done,” she said.

But it can be done if one follows the process and is able to answer FDA’s questions and respond to any objections. “Anyone who is thinking about starting the process should read the submissions on FDA’s website to see what has been approved and where FDA made objections,” she said.

Though difficult and complex, Kaufman sees the in-depth requirements and resulting exemptions as positive and exciting. Not only will ingredient exemptions allow more choice for those who deal with food allergies, but also, she said, “Because of the way FDA regulations are structured, companies and consumers can feel safe in the knowledge that if a food or ingredient is granted an exemption to FALCPA labeling, it has gone through a laborious process to ensure safety.”

But even more, Kaufman said, “It’s really exciting to see the possibilities that exist, and will exist, to harvest functional parts of food and make them available to a wider group.” As an example, she cited USDA’s funding of research on a treatment of peanuts with protein-breaking enzymes that would reduce their allergens by 98% to 100%. “If the USDA is able to continue along with their research and prove that they can modify peanuts so that the allergenic proteins are destroyed, those peanuts would be a major game-changer for the industry,” she said. “I’d imagine any approved allergen-free peanuts are still a few years away, but it’s fun to think about.”

Applying for exemption approval may be time- and money-consuming, but she said, “It’s exciting to read documents like these and realize how serious the agencies are about ensuring food safety. It’s reassuring.”

The author is Editor of QA magazine. She can be reached at llupo@gie.net.