Animal Feed GRAS Notifications Geoffrey K. Wong, M.S. Division of Animal Feeds Center for Veterinary...
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Transcript of Animal Feed GRAS Notifications Geoffrey K. Wong, M.S. Division of Animal Feeds Center for Veterinary...
Animal Feed GRAS Animal Feed GRAS NotificationsNotifications
Geoffrey K. Wong, M.S.Geoffrey K. Wong, M.S.Division of Animal FeedsDivision of Animal Feeds
Center for Veterinary MedicineCenter for Veterinary Medicine
Pet Food Institute Pet Food Institute October 15, 2009October 15, 2009
PFI October 2009PFI October 2009 22
Ingredient Safety TeamIngredient Safety Team
Geoff Wong, MS (Team Leader) C. George Chang, DVM, PhD, DABT Tom Hendricks, PhD, MPH Marla Luther, PhD Becky Muir, PhD
PFI October 2009PFI October 2009 33
GRAS NotificationGRAS Notification
What is GRAS?!?What is GRAS?!?
PFI October 2009PFI October 2009 44
What is GRAS?What is GRAS? GRAS – Generally Recognized As SafeGRAS – Generally Recognized As Safe 1958 Food Additives Amendment to 1958 Food Additives Amendment to
Federal Food, Drug and Cosmetic ActFederal Food, Drug and Cosmetic Act Defined “food additive”Defined “food additive” Required premarket approval of food Required premarket approval of food
additivesadditives Established standards for safety and Established standards for safety and
reviewreview Created exemption to food additive Created exemption to food additive
definitiondefinition GRAS status for a specific use of substanceGRAS status for a specific use of substance
PFI October 2009PFI October 2009 55
GRAS ExemptionGRAS Exemption Any substance intentionally Any substance intentionally
added to an animal feed must added to an animal feed must be used in accordance with a be used in accordance with a food additive regulation for that food additive regulation for that use use unlessunless
the substance is GRAS among the substance is GRAS among experts qualified by scientific experts qualified by scientific training and experience to training and experience to evaluate its safety under the evaluate its safety under the conditions of its intended useconditions of its intended use
PFI October 2009PFI October 2009 66
GRAS Exemption GRAS Exemption (cont.)(cont.)
What does this mean in practical terms?What does this mean in practical terms? General recognition of safety is for a General recognition of safety is for a
substance for an substance for an intendedintended use use Two pointsTwo points
Substances are not GRAS, it is a particular use Substances are not GRAS, it is a particular use of a substance that is GRASof a substance that is GRAS
Feed use of substances varies with the animal Feed use of substances varies with the animal species, thusspecies, thus
Feed GRAS determinations must address Feed GRAS determinations must address intended use in the intended animal intended use in the intended animal speciesspecies
PFI October 2009PFI October 2009 77
Food Additive vs. GRASFood Additive vs. GRAS Food additives require FDA Food additives require FDA
premarket approval, a petition premarket approval, a petition processprocess 21 CFR 571.121 CFR 571.1
GRAS status is an exemption to food GRAS status is an exemption to food additive definitionadditive definition FDA involvement is not requiredFDA involvement is not required Firms can do their own determination Firms can do their own determination
for whether requirements for GRAS for whether requirements for GRAS status are metstatus are met
PFI October 2009PFI October 2009 88
What Uses can be GRAS?What Uses can be GRAS? Food additive definition is very Food additive definition is very
broad, but it does NOT include:broad, but it does NOT include: PesticidesPesticides Color additivesColor additives
Approved under another FDA premarket Approved under another FDA premarket processprocess
Drugs and new animal drugsDrugs and new animal drugs Some substances approved under Some substances approved under
specific laws administered by USDAspecific laws administered by USDA These substances cannot be GRASThese substances cannot be GRAS
PFI October 2009PFI October 2009 99
GRAS StatusGRAS Status There are two parts to establish that There are two parts to establish that
a use of a substance is GRASa use of a substance is GRAS Safety - Defined in 21 CFR 570.3(i)Safety - Defined in 21 CFR 570.3(i) General recognition - Addressed in 21 General recognition - Addressed in 21
CFR 570.30CFR 570.30 Fair evaluation of the data…Fair evaluation of the data…
Need to address all data and Need to address all data and informationinformation Cannot ignore the “inconvenient” or Cannot ignore the “inconvenient” or
contradictorycontradictory
PFI October 2009PFI October 2009 1010
GRAS Status GRAS Status (cont.)(cont.) Safety Safety – same as food additive– same as food additive
Reasonable certainty of no harmReasonable certainty of no harm 21 CFR 570.3(i) lists factors to be 21 CFR 570.3(i) lists factors to be
consideredconsidered ConsumptionConsumption Cumulative effect\exposureCumulative effect\exposure Appropriate safety factors Appropriate safety factors
For food animal species, need to For food animal species, need to consider possibility of tissue consider possibility of tissue residuesresidues
PFI October 2009PFI October 2009 1111
GRAS Status GRAS Status (cont.)(cont.)
General RecognitionGeneral Recognition Information needed for GRAS Information needed for GRAS
determinationdetermination Must be generally availableMust be generally available Must be generally accepted by Must be generally accepted by
qualified expertsqualified experts Information needed to establish Information needed to establish
GRAS status of an intended use of GRAS status of an intended use of substance cannot be confidentialsubstance cannot be confidential
PFI October 2009PFI October 2009 1212
InformationInformation Generally available data and Generally available data and
information information Usually means published studiesUsually means published studies Can include information in text booksCan include information in text books
Availability allows review by any Availability allows review by any experts qualified by scientific experts qualified by scientific experience and training to evaluate experience and training to evaluate the safety of substances added to foodthe safety of substances added to food
Consensus among experts about these Consensus among experts about these data and information establishes GRAS data and information establishes GRAS status of intended use of substancestatus of intended use of substance
PFI October 2009PFI October 2009 1313
Basis for GRAS Basis for GRAS DeterminationsDeterminations
Experts may base safety Experts may base safety conclusions on:conclusions on:
1)1) Experience based on common Experience based on common use in animal food before 1958use in animal food before 1958
Data and information must be Data and information must be generally availablegenerally available
Need to show Need to show commoncommon use use
OROR
PFI October 2009PFI October 2009 1414
Basis for GRAS Basis for GRAS (cont.)(cont.)
2)2) Scientific proceduresScientific procedures Most frequently usedMost frequently used Requires same quantity and quality of Requires same quantity and quality of
scientific evidence as required to obtain scientific evidence as required to obtain approval of a food additive regulationapproval of a food additive regulation
Scientific evidence must be generally availableScientific evidence must be generally available
GRAS status is GRAS status is more difficultmore difficult to to establish than a food additive establish than a food additive regulation due to requirement for regulation due to requirement for general recognitiongeneral recognition
PFI October 2009PFI October 2009 1515
Safety EvaluationsSafety Evaluations Addressing animal safety is complexAddressing animal safety is complex
Difficult to do cross-species comparisons Difficult to do cross-species comparisons of toxicity dataof toxicity data
Recent NRC report found insufficient data Recent NRC report found insufficient data to support extrapolation across species to support extrapolation across species
Animal safety studies in the individual Animal safety studies in the individual target species are often necessarytarget species are often necessary
Human food safety may also need to Human food safety may also need to be addressed, dependent on intended be addressed, dependent on intended useuse
PFI October 2009PFI October 2009 1616
GRAS NotificationGRAS Notification Proposed rule published in 1997Proposed rule published in 1997
Changing from petition to notification Changing from petition to notification processprocess
Publication date of final rule is unclearPublication date of final rule is unclear CVM implementing pilot programCVM implementing pilot program
Resources are still an issueResources are still an issue Will be announced in the Federal RegisterWill be announced in the Federal Register Anticipated start dateAnticipated start date
Late 2009Late 2009
PFI October 2009PFI October 2009 1717
GRAS Notification GRAS Notification (cont.)(cont.) Pilot program based on 1997 proposalPilot program based on 1997 proposal VoluntaryVoluntary
Firms can conduct a GRAS determination Firms can conduct a GRAS determination without notifying FDAwithout notifying FDA
Notice informs FDA of Notice informs FDA of notifier’s notifier’s determinationdeterminationthat a use of a substance is GRASthat a use of a substance is GRAS Notifier’s determination and responsibilityNotifier’s determination and responsibility Summary document, not raw data/complete Summary document, not raw data/complete
reportsreports FDA responds by letterFDA responds by letter
Notifier can withdraw notice at any time, Notifier can withdraw notice at any time, stops FDA reviewstops FDA review
PFI October 2009PFI October 2009 1818
Highlights of NoticeHighlights of Notice Talk to CVM as putting notice togetherTalk to CVM as putting notice together Summary of notifier’s determinationSummary of notifier’s determination GRAS notice should include:GRAS notice should include:
Statement of GRAS determinationStatement of GRAS determination Detailed information about identity of substanceDetailed information about identity of substance
Chemical identificationChemical identification Method of manufacture, exclude trade secret Method of manufacture, exclude trade secret
informationinformation Source of substanceSource of substance Characteristic propertiesCharacteristic properties SpecificationsSpecifications
Utility – Intended Uses, Levels, Target Animal Utility – Intended Uses, Levels, Target Animal SpeciesSpecies
PFI October 2009PFI October 2009 1919
Highlights of Notice Highlights of Notice (cont.)(cont.) Comprehensive discussion of basis for Comprehensive discussion of basis for
GRAS determinationGRAS determination Consideration of Food and Water ExposureConsideration of Food and Water Exposure Safety – reasonable certainty of no harmSafety – reasonable certainty of no harm Animal and, potentially human food, safetyAnimal and, potentially human food, safety
Favorable and unfavorable data/informationFavorable and unfavorable data/information Basis for GRAS status in light of both Basis for GRAS status in light of both
favorable and unfavorable informationfavorable and unfavorable information- fair evaluation- fair evaluation
Other administrative informationOther administrative information
PFI October 2009PFI October 2009 2020
Types of FDA ResponseTypes of FDA Response No questionsNo questions
Based on the information provided by Based on the information provided by [notifier], … the agency has no questions at [notifier], … the agency has no questions at this time regarding [notifier’s conclusion that this time regarding [notifier’s conclusion that [substance] is GRAS under the intended [substance] is GRAS under the intended conditions of use. The agency has not, conditions of use. The agency has not, however, made its own determination however, made its own determination regarding … GRAS statusregarding … GRAS status
No basisNo basis FDA has evaluated the information in [the FDA has evaluated the information in [the
GRAS Notice]…as well as other available GRAS Notice]…as well as other available data and information. Your notice does not data and information. Your notice does not provide a sufficient basis for a determination provide a sufficient basis for a determination that [substance] is GRAS under the that [substance] is GRAS under the conditions of its intended use.conditions of its intended use.
PFI October 2009PFI October 2009 2121
GRAS Notification GRAS Notification (cont.)(cont.) Inventory of GRAS notices and FDA Inventory of GRAS notices and FDA
responses on the Internetresponses on the Internet Notices available under Freedom of Notices available under Freedom of
Information Act (FOIA)Information Act (FOIA) May also be posted on InternetMay also be posted on Internet General recognition means information that General recognition means information that
establishes safety cannot be confidentialestablishes safety cannot be confidential CVM’s process will be similar to CFSAN’s CVM’s process will be similar to CFSAN’s
on-going pilot programon-going pilot program Information about CFSAN pilot program at Information about CFSAN pilot program at http://www.fda.gov/Food/FoodIngredientsPackaging/GenerallyRecognizedasSafeGRAS/default.htm
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