FDA’s Federal Register Notice on Reopening of the Comment Period on the Proposed Rule: Gluten-Free Labeling of Foods
Hopefully everyone has taken the time to read the Federal Register Notice. If not it is available at http://www.gpo.gov/fdsys/pkg/FR-2011-08-03/pdf/2011-19620.pdf. Here are a few things to consider:
- In 2007, the FDA released a proposed rule for labeling of foods as gluten free. The preamble to this rule listed two methods that could be used to establish a gluten threshold level—an analytical methods-based approach and a safety assessment-based approach.
- Under the analytical methods-based approach the gluten threshold would be based on the sensitivity of the validated tests used to assess foods for gluten content (the sensitivity of an assay refers to the level at which gluten can be accurately detected or quantified). Under the safety assessment-based approach the gluten threshold would be based on a daily intake of gluten considered “safe” for the vast majority of individuals with celiac disease.
- The safety assessment found the tolerable daily intake (TDI) for gluten to be 0.4 milligrams per day for adverse effects on the intestinal mucosa and 0.015 milligrams per day for adverse effects on clinical symptoms.
- If these TDI numbers are accurate it means that a person with celiac disease would have to limit themselves to less than a 1 ounce slice of bread containing 20 parts per million* of gluten each day to prevent intestinal damage; far less to prevent clinical effects.
*20 parts per million means 20 milligrams per kilogram of food
- Regarding use of the safety assessment-base approach, The Federal Register states the following, “FDA tentatively concludes that, based on the LOCs (level of concern)* identified in the safety assessment-based approach, the Agency should not use that approach in defining ‘‘gluten-free’’ because the estimation of risk to individuals with celiac disease associated with very low levels of gluten exposure may be conservative and highly uncertain.“
*For more information on LOCs, please see the Health Hazard Assessment for Gluten Exposure in Individuals with Celiac Disease available at: http://tinyurl.com/3b22eto
- In the Federal Register Notice the FDA tentative proposes to use an analytical methods-based approach to adopt a gluten threshold level of <20 parts per million as one of the criteria for labeling food gluten free.
- It is further stated in the Federal Register Notice that, “At the current time, FDA is not aware of any analytical methods that have been validated to reliably and consistently detect gluten below 20 ppm.”
You are not alone if you are confused by the disconnect between the findings of the safety assessment-based approach and the analytical methods-based approach. I have wondered how the FDA was going to reconcile the findings of the safety assessment with the level of gluten listed in the proposed rule (< 20 ppm) for the past three years—ever since I reviewed the safety assessment in 2008. If you would like to read blinded reviewer comments from the External Peer Review of the FDA/CFSAN the Draft Health Hazard Assessment for Gluten Exposure in Individuals with Celiac Disease, please see http://tinyurl.com/3g9exay. Reviewers include David Bellinger, PhD; Donald Kasarda, PhD; Michael Luster, PhD; Joseph Murray, MD; Tricia Thompson, MS, RD; Nga Tran, DrPH.
As I wrote in my review comments at that time, “Many of the TDI (tolerable daily intake) estimates are ridiculously low and do not make sense. The TDI for subchronic gluten exposure for morphological effects is listed as 0.4 mg/d. The TDI for acute, subchronic, and chronic clinical effects is listed as 0.015 mg/d. The FDA’s proposed rule on gluten-free labeling would allow a food to be labeled gluten free if contained less than 20 parts per million of gluten. Codex allows foods to be labeled gluten-free if they contain no more than 20 parts per million of gluten. If a person with CD ate just one ounce of a product containing 20 parts per million of gluten, they would be ingesting 0.57 mg of gluten (greater than the TDI values listed above). If these TDI values are disseminated to the public, persons with celiac disease will be afraid to eat.”
Minds much smarter than mine conducted the safety assessment. While I can point out issues that are confusing or do not make sense, I do not pretend to be an expert on safety assessment methodology. From my perspective, what would be most helpful is clarification from FDA on how they got from the findings of the safety assessment to what is written in the Federal Register notice.
For example, it would be helpful to know how FDA feels about the tolerable daily intake values in the safety assessment. Like the LOCs, do they also believe the TDI levels to be “conservative and highly uncertain?” If so, it would be very helpful for them to explain why to help calm fears among individuals with celiac disease.
If, on the other hand, FDA believes the tolerable daily intake values to be accurate, it would be helpful for them to explain why they are continuing to propose a threshold level of gluten of < 20 ppm. If they truly believe that gluten can not be reliably and consistently detected at levels below 20 ppm* then they should not allow certifying agencies to have lower standards of 10 ppm and 5 ppm.
*It is worth noting that when I discussed the level at which the R5 ELISA had been validated with Dr. Enrique Mendez (developer of the R5 ELISA) he referred me to the sensitivity levels. The sandwich R5 ELISA has a limit of detection for gluten of 3 ppm and a limit of quantification for gluten of 5 ppm.
If they believe lowering the standard to 15, 10, or 5 ppm will prevent industry from being able to manufacture gluten-free food, this belief appears to be unfounded. Based on testing done by Gluten Free Watchdog (www.glutenfreewatchdog.org), the majority of food is testing below 5 ppm gluten* and most of the products testing this low do not carry any specialty certification.
*As stated above, 5 ppm is the lower limit of quantification for gluten. 3 ppm is the lower limit of detection. There are no validated tests that test to zero.
It is the case that the methodology utilized in the safety assessment is generally used to assess the safety of substances that are toxic to all individuals not just certain individuals with a given medical condition. For example lead is toxic to all individuals; gluten is not. As stated in the Federal Register Notice, “FDA’s assessment of the adverse health effects of gluten exposure in individuals with celiac disease presented in the Gluten Report followed established hazard assessment components used within the Center for Food Safety and Applied Nutrition to determine TDIs for chemical and natural toxin contaminants in food.”
As a result, it may simply be the case that the safety assessment as currently conducted is not the best approach for determining safe levels of gluten for the approximately 1% of the US population with celiac disease.
Ideally, the upper limit of gluten allowed in foods labeled gluten free would be based on what is considered safe for the majority of individuals with celiac disease. However, one of the more important points to stress is just because a labeled gluten-free food is allowed to contain up to (but not including) 20 ppm gluten does not mean it contains that much.
What I would like to see
- It would be extremely helpful if the FDA would develop a Q & A or consumer/healthcare practitioner bulletin to address issues surrounding the safety assessment.
- It also would be helpful to have this available before the comment period is closed (or to perhaps extend the comment period).
The following is from http://tinyurl.com/3ok27gd
The FDA encourages members of the food industry, state and local governments, consumers, and other interested parties to offer comments and suggestions about gluten-free labeling in docket number FDA-2005-N-0404 at www.regulations.gov1. The docket will officially open for comments after noon on Aug 3, 2011 and will remain open for 60 days.
To submit your comments electronically to the docket go to www.regulations.gov2
1. Choose “Submit a Comment” from the top task bar
2. Enter the docket number FDA-2005-N-0404 in the “Keyword” space
3. Select “Search”
To submit your comments to the docket by mail, use the following address:
The Division of Dockets Management
Food and Drug Administration
5630 Fishers Lane, Room 1061
Rockville, MD 20852
Include docket number FDA-2005-N-0404 on each page of your written comments.