New GRAS Guidance (Generally Recognized as Safe)

Final ruling on Substances Generally Recognized as Safe (GRAS) guidance to be published in the Federal Register – Aug 17th  

“… detailing the criteria for concluding that the use of a substance in human or animal food is [GRAS] … The rule addresses the types of scientific evidence that can be used to demonstrate safety as well as the role of publications in evaluating whether the scientific evidence of safety is ‘generally available and accepted.’


Much of the GRAS guidance covers mechanics for submitting and making a GRAS determination. A great deal is spent discussing how private information would be handled and used, for GRAS determination.


No matter the source of the information used to make a determination, its clear the FDA wants “scientific evidence” and that is “generally accepted” to be true (see summary of changes). These appear to be significant hurdles. We will have to see how these are applied in new GRAS submissions.


Examples Using new Guidance


With this GRAS guidance the preamble includes two examples, Partially Hydrogenated Oils (PHO) and Caffeine, that the FDA considers NO LONGER safe.


Partially Hydrogenated Oils:

“Although we had not listed the most commonly used PHOs in either part 182 or part 184, they had been used in food for many years … In a [prior] notice [we] … described new scientific evidence …on our tentative determination that PHOs are not GRAS for any use in food based on current scientific evidence establishing the health risks associated with the consumption of trans fat. In the Federal Register of June 17, 2015 (80 FR 34650), we issued a declaratory order announcing our final determination that there is no longer a consensus among qualified experts that PHOs are GRAS for any use in human food.”



“The GRAS list…includes the use of caffeine in cola-type beverages at a maximum level of 0.02 percent (§ 182.1180)…we issued four warning letters regarding the use of caffeine under markedly different conditions of use…i.e., the use of caffeine as an added ingredient in alcoholic beverages…The companies subsequently ceased distribution of these products.” Further the “FDA has engaged with the National Academies of Science…[to conduct] a systematic review on the health effects associated with the consumption of caffeine”


Summary of Changes


Proposed Rule Final Rule
Would not define,any terms Defines the terms “amendment,” “GRAS,” “GRAS notice,” “notified substance,” “notifier,” “qualified expert,” “supplement,” “we, our, and us,” and “you and your.”
Referred to a “GRAS,determination” Refers to a “GRAS conclusion” or “conclusion of GRAS,status”
Referred to the statutory GRAS provision as an,“exemption” Refers to the statutory GRAS provision
as an,“exclusion”
Would not use “Plain Language” techniques as outlined in a Presidential Memorandum dated June 1, 1998 (Ref.,21) and in “Improving Electronic Dockets on and the Federal Docket Management System:
Best Practices for Federal
Agencies” (Ref. 22).
Uses “Plain Language” techniques such as pronouns
and,short regulatory sections
Was silent,on whether you could incorporate into your GRAS notice specifically identified data,and information previously submitted to CFSAN or CVM Expressly provides for,you to incorporate into your GRAS,notice specifically identified data,and information previously submitted to CFSAN or CVM
Would not specify individual parts,of a GRAS notice Specifies the seven parts of a GRAS notice
Would require,three paper,copies of a GRAS notice Provides that you may submit,a GRAS notice,either in electronic format that,is accessible for our evaluation or on paper.,If you send your GRAS,notice on paper,,a single,paper copy is sufficient.
Referred to dated and signed,statements in a GRAS,notice as a “claim” Refers to dated,and signed statements in a GRAS notice,as “signed statements”
Assumed that a notice will,not contain any information that,is protected from,public disclosure under the FOIA Specifies that you must not include,any information that is trade secret or confidential commercial information in certain sections of the signed,statements in your GRAS notice, but does not otherwise prohibit the submission of information that is protected from public,disclosure under,the FOIA.
Would require that you inform,us of the “common or usual,name” of the notified substance Requires that you provide,an “appropriately descriptive term” for the notified substance
Would not require that,you state your view,as to whether any data,and information in your GRAS notice are exempt from,disclosure under the FOIA Requires that you state your,view as to,whether any of the data and information in your GRAS notice,are exempt,from disclosure under,the FOIA (e.g.,,as trade secret,or as commercial or financial information that is privileged or confidential)
Would not expressly require a signed,certification regarding the representative and balanced nature of the GRAS notice Expressly requires a signed certification that to the best of your knowledge, your,GRAS notice is a complete, representative, and balanced submission that includes unfavorable information, as well as favorable information, known to you and pertinent to the evaluation of the safety and GRAS,status of the use of the substance
For a notified substance of natural,biological origin, would,require source information such as genus,and species For a notified substance of natural,biological origin, requires source information that includes applicable data and information at the sub-species level (e.g., variety, strain),in addition to genus and species
Would require the method of manufacture (excluding any trade secrets) Requires a description of the method of manufacture of the notified substance in sufficient detail to evaluate the safety of the notified substance as manufactured; you may include trade secret,information
Would not expressly require relevant data and information bearing on the physical or other,technical effect,the notified substance is intended to produce When necessary to demonstrate safety, expressly requires relevant data and information bearing,on the physical or other,technical effect the notified substance is intended to produce, including the quantity of the notified substance required to produce such effect
Would require,consideration of dietary,exposure as part of a comprehensive discussion of the data and information that,you rely on to establish safety, using,the statutory language of section 409(c)(5)(A) and (B),of the FD&C Act Separates,the statutory language of section 409(c)(5)(A) and (B) of the FD&C Act into,two distinct parts of the GRAS,notice: (1) Part 3, which addresses how much,of the notified substance consumers would eat as part,of the total diet (including exposure from,its intended use and all sources in the diet),,as well as how,much consumers would,eat of other substances (e.g., contaminants or by- products); and (2),Part 6, which requires,that you address, in your narrative, the safety of the notified substance, considering all dietary sources and taking,into account,any chemically or pharmacologically related substances in such,diet
Would require a “comprehensive discussion” of, and citations to, generally available and accepted scientific data, information, methods, or principles that you rely,on to establish safety Requires a narrative (Part 6 of a GRAS notice) and,a list of supporting data and information (Part,7 of a GRAS notice)
Would not require,consideration of dietary,exposure as part of a comprehensive discussion of the data,and information that you rely on to establish safety,for a conclusion of GRAS status through experience based on common use in food Expressly requires consideration of dietary exposure, regardless,of whether your conclusion of GRAS status is through,scientific procedures or through,experience based on common,use in food
Would require a comprehensive discussion of any reports of investigations or other information that may appear to be inconsistent with the GRAS determination Requires that you either:,(1) Identify, discuss, and place in context, data and information that are, or may appear to be, inconsistent with your conclusion of GRAS status; or (2) state that you have reviewed the available data and information and are not aware,of any data and information that are, or may appear to be, inconsistent with,your conclusion of GRAS,status
Would not require that you identify data and information that,you view as exempt from,disclosure under,the FOIA If you view any of the data and information in your notice,as exempt from disclosure under the FOIA, requires that you identify the specific data,and information.
Would not require that you explain how there could be a basis for a conclusion of GRAS status if qualified experts generally do not have access,to non-public, safety-related data and information Requires that you explain how there,could be a basis,for a conclusion of GRAS status if qualified experts generally do not have access to non-public, safety- related data,and information
Would require that the comprehensive discussion include,the basis for concluding that there,is consensus,among qualified experts that there is reasonable certainty that the,substance is not harmful under,the intended conditions of use Uses the term “generally recognized” rather,than the term “consensus”
Was silent on whether you could submit an amendment to a GRAS,notice Expressly provides for you to submit,a timely “amendment” to a GRAS notice,before we respond,to your,GRAS notice or cease,to evaluate your GRAS notice
Considered,that it was implicit that you could ask,us to cease to evaluate a GRAS,notice Expressly provides that you may,ask us to cease to evaluate your GRAS notice, and expressly provides that we will inform,you of our decision regarding your request
We would acknowledge receipt of a GRAS notice,within 30 days of receipt We will conduct,an initial evaluation of your submission to determine,whether to file it as a GRAS,notice for evaluation of your view,that the notified substance is GRAS under the conditions of its intended use. If we,file your submission as a GRAS notice,,we will send you a letter that informs you of the date,of filing. If we do not file,your submission as a GRAS,notice, we will,send you a letter,that informs you of that,fact and provides our reasons,for not filing,the submission as a GRAS,notice.
We would respond to,you in writing,within 90 days of receipt of the notice Within 180 days of filing,,we will respond to,you by letter based,on our evaluation of your notice. We may extend the 180 day timeframe by 90 days,on an as needed,basis. If we extend,the timeframe, we will inform you of the extension as soon as practicable but no later than within 180 days of filing.
Was silent on procedures that apply,when the intended conditions of use of a notified substance include,use in a product or products subject,to regulation by USDA’s FSIS Specifies procedures that apply when the,intended conditions of use of a notified substance in human,food include,use in a product or products subject to regulation by USDA’s,FSIS.
We noted that, although the decision to submit,a GRAS notice,would be voluntary, the provisions governing the GRAS notification procedure, including the information to be submitted, would be mandatory The regulatory text of the final rule specifies that the data and information in a GRAS,notice are considered a mandatory, rather,than voluntary, submission for purposes of its status,under the FOIA and our public information requirements in part 20
Was silent on whether you could submit additional information to a GRAS notice,after we respond to it Expressly provides for you to submit,a “supplement” to,a GRAS,notice after we respond,to your GRAS,notice or cease to evaluate it
Would presumptively convert,any filed, pending GRAS affirmation petition to a notice on the effective date of the rule.,If we did not receive an amendment from the petitioner within 90 days,of the effective date of the rule, with information and statements analogous to those in the proposed “GRAS exemption claim,” we would consider the converted petition to be inadequate as a notice,and would send the petitioner a letter to that effect. On the effective date,of the rule, we,will close the docket for any,GRAS affirmation petition that is still pending. Any person who submitted a GRAS affirmation petition that is closed may submit,a GRAS notice,and request that,we incorporate the GRAS affirmation petition.

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