The draft guidance applies to GRAS notifications submitted to the FDA and self-affirmed GRAS conclusions, said the agency.
The best practices outlined by the FDA include:
1. How to identify GRAS panel members who have appropriate and balanced expertise;
2. How to reduce the risk that bias or the appearance of bias will affect the credibility of the GRAS panel’s report; and
3. How to limit the data and information provided to a GRAS panel to publicly available information.
The draft guidance is open to public comment on Regulations.gov until May 15, 2018 under docket FDA-2017-D-0085.
Potential conflicts of interest
The GRAS process has come under criticism in the past, with a 2013 paper published in JAMA Internal Medicine by Tom Neltner and colleagues from the Pew Health Group concluding that, “financial conflicts of interest were ubiquitous in determinations that an additive to food was GRAS”.
Neltner et al. found that 22.4% of the 451 GRAS notifications voluntarily submitted to the FDA between 1997 and 2012 were conducted by an employee of the manufacturer of the ingredient being scrutinized, while 13.3% were conducted by an employee of a consultancy selected by the manufacturer and 64.3% by an expert panel selected by a consultancy or the ingredient manufacturer.
Further analysis of the composition of the 290 expert panels involved in the 451 GRAS determinations studied showed that they draw on a very small pool of experts, 10 of which served on 27+ panels; one of which served on 128 panels and another on 225 panels, stated Neltner and his co-authors.
Similar concerns were raised by a 2010 report from the Government Accountability Office (GAO), which called on the FDA to improve its oversight of the GRAS process.
Dr Bob McQuate, chief regulatory officer / Sr VP of business development and co-founder of GRAS Associates, LLC, called the FDA’s draft guidance “needed”.
“While I have been closely involved in the “GRAS dialogue” on the challenges that surfaced with the GAO report and subsequent concerns expressed by Tom Neltner and consumer activists groups, I do find FDA’s clarification and guidance to generally be needed---particularly with parties that prepare independent/self-determined GRAS evaluations only occasionally.
“This becomes more important if such parties do not have a track record of successful notifications to FDA,” he added.
“This will have a significant impact”
Alexander Schauss, PhD, FACN, CFS, Senior Director of Research and CEO of AIBMR Life Sciences, Inc., told us that that he has been awaiting its release for some time and is pleased to see it finally published.
“The draft document will have a significant impact in defining further the parameters under which expert panel membership is selected, especially to avoid conflicts of interest when determining whether an ingredient is reasonably safe to be added to food for its intended use,” said Dr Schauss, who’s company has helped several firms prepare GRAS determinations for FDA review.
Dr Schauss added: “AIBMR takes seriously the responsibility empowered by the GRAS Final Rule to evaluate the safety of ingredients and their intended use when added to foods. As part of our best practices, we have consistently implemented a policy that each expert panel is chaired by individuals who are highly qualified to serve on the panel based by their training, experience and competency, to review the evidence supporting the safety of an ingredient seeking to obtain GRAS status.”
FDA or self-affirmation
The Food and Drug Administration (FDA) does not ‘approve’ food ingredients as GRAS, but does review their safety if a company submits a research dossier including the findings of an independent scientific panel. Following review, the FDA can issue a letter of no objection, leading to what is commonly referred to as “FDA GRAS”. However, the company remains responsible for ensuring the ingredient is safe and that it complies with all regulatory requirements.
Alternatively, a company can self-affirm GRAS after conducting all necessary research and forming an independent panel to determine its safety. To self-affirm, the company needs to be confident that it could defend the safety of its ingredient based on this process.
While the FDA does post information about GRAS notices filed since 1998 on its inventory of GRAS notices, this only applies to notifications submitted to the FDA. There is no official registry of self-affirmed GRAS ingredients. Seattle-based AIBMR has been running the GRAS Self-Determination Inventory Database (GSID) since 2012, but this is dependent on companies making self-affirmations public.
“Since its creation we have maintained the database and updated it on an ongoing basis whenever independent GRAS conclusions are made known to us,” said Dr Schauss.