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U.S. FDA’s Food Additive Program:

An Update on Resources and Challenges

18th Food Packaging Law Seminar

October 11, 2017

Arlington, VA

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Food Additives Program

Dennis Keefe, PhDDirector, Office of Food Additive Safety

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• Who We Are

• Our Resources

• How We Regulate

• Our Accomplishments

• U.S. FDA Regulation of Food Contact Substances

• FCN Program: Current Trends

• Challenges to the Program

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Our NumbersOFAS Human Capital: FTEs 1998-2017

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20

40

60

80

100

120

140

160

2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2017b

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How We RegulatePremarket Programs

Petition Process GRAS Notice Food Contact Notice Biotech Consultation

FAPs since 1958

CAPs since 1960

1997 to present 1997 to present 1992 to present

Mandatory Voluntary Mandatory Voluntary

Sponsor submits a petition asking FDA to issue a regulation

Sponsor informs FDA of their view that a use of a substance is GRAS

Sponsor submits a notification Sponsor informs FDA of their view that foods derived from the new plant variety are safe

FDA owns the safety decision Sponsor owns the safety decision; FDA evaluates their basis

FDA owns the safety decision but there is a 120-day “hammer”

Sponsor owns the safety decision; FDA evaluates their basis

FDA publishes a regulation FDA responds by letter (no questions, no basis, withdrawal)

FDA responds by letter (deficiency, effective, objection)

FDA responds by letter

No exclusivity No exclusivity By law, exclusive to manufacturer or supplier

Petition is available publicly through FOIA

GRAS Notice &FDA’s response are on FDA’s website

FDA maintains a database of effective notifications on its website

BNFs & FDA’s response are on FDA’s website

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Accomplishments by Fiscal YearIndustry Submissions

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50

100

150

200

250

2009 2010 2011 2012 2013 2014 2015 2016 2017

PNC

FCN

C/FAP

GRN

BNF

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How We Regulate Food Contact Substances

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Why We RegulateFederal Food Drug and Cosmetic Act

• Federal Food Drug and Cosmetic Act– Definitions

• Food Additive

• GRAS

• Color Additive

• Food Contact Substance

– Burden of Proof

– Safety Standard • Reasonable Certainty of no Harm

– Standard of Review• Fair Evaluation of the Data

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Why We RegulateFederal Food Drug and Cosmetic Act. Sec. 201(s) Food Additives

201(s) The term ‘‘food additive’’ means any substance the intended use of which results or may reasonably be expected to result, directly or indirectly, in its becoming a component or otherwise affecting the characteristics of any food (including any substance intended for use in producing, manufacturing, packing, processing, preparing, treating, packaging, transporting, or holding food; and including any source of radiation intended for any such use), if such substance is not generally recognized, among experts qualified by scientific training and experience to evaluate its safety, as having been adequately shown through scientific procedures (or, in the case of a substance used in food prior to January 1, 1958, through either scientific procedures or experience based on common use in food) to be safe under the conditions of its intended use; except that such term does not include—

(1) a pesticide chemical residue in or on a raw agricultural commodity or processed food; or

(2) a pesticide chemical; or

(3) a color additive; or

(4) any substance used in accordance with a sanction or approval granted prior to September 6, 1958, pursuant to this chapter, the Poultry Products Inspection Act [21 U.S.C. 451 et seq.] or the Meat Inspection Act of March 4, 1907, as amended and extended [21 U.S.C. 601 et seq.];

(5) a new animal drug; or

(6) an ingredient described in paragraph (ff) in, or intended for use in, a dietary supplement.

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Why We RegulateFFDCA Sec. 409(h) Food Contact Substance

(6) In this section, the term ‘‘food contact substance’’ means any substance intended for use as a component of materials used in manufacturing, packing, packaging, transporting, or holding food if such use is not intended to have any technical effect in such food.

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Why We RegulateFFDCA Sec. 409(h) Food Additives

(h) Notification relating to food contact substance(1) Subject to such regulations as may be promulgated under paragraph (3), a manufacturer or supplier of a food contact substance may, at least 120 days prior to the introduction or delivery for introduction into interstate commerce of the food contact substance, notify the Secretary of the identity and intended use of the food contact substance, and of the determination of the manufacturer or supplier that the intended use of such food contact substance is safe under the standard described in subsection (c)(3)(A) of this section. The notification shall contain the information that forms the basis of the determination and all information required to be submitted by regulations promulgated by the Secretary.(2)(A) A notification submitted under paragraph (1) shall become effective 120 days after the date of receipt by the Secretary and the food contact substance may be introduced or delivered for introduction into interstate commerce, unless the Secretary makes a determination within the 120-day period that, based on the data and information before the Secretary, such use of the food contact substance has not been shown to be safe under the standard described in subsection (c)(3)(A) of this section, and informs the manufacturer or supplier of such determination.

(B) A decision by the Secretary to object to a notification shall constitute final agency action subject to judicial review. (C) In this paragraph, the term ‘‘food contact substance’’ means the substance that is the subject of a notification submitted under paragraph (1), and does not include a similar or identical substance manufactured or prepared by a person other than the manufacturer identified in the notification.

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Why We RegulateFFDCA Sec. 409(h) Food Additives

(3)(A) The process in this subsection shall be utilized for authorizing the marketing of a food contact substance except where the Secretary determines that submission and review of a petition under subsection (b) of this section is necessary to provide adequate assurance of safety, or where the Secretary and any manufacturer or supplier agree that such manufacturer or supplier may submit a petition under subsection (b) of this section. (B) The Secretary is authorized to promulgate regulations to identify the circumstances in which a petition shall be filed under subsection (b) of this section, and shall consider criteria such as the probable consumption of such food contact substance and potential toxicity of the food contact substance in determining the circumstances in which a petition shall be filed under subsection (b) of this section.

(4) The Secretary shall keep confidential any information provided in a notification under paragraph (1) for 120 days after receipt by the Secretary of the notification. After the expiration of such 120 days, the information shall be available to any interested party except for any matter in the notification that is a trade secret or confidential commercial information.

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Why We RegulateFFDCA Sec. 409(c) Food Additives

(5) In determining, for the purposes of this section, whether a proposed use of a food additive is safe, the Secretary shall consider among other relevant factors—

(A) the probable consumption of the additive and of any substance formed in or on food because of the use of the additive;(B) the cumulative effect of such additive in the diet of man or animals, taking into account any chemically or pharmacologically related substance or substances in such diet; and(C) safety factors which in the opinion of experts qualified by scientific training and experience to evaluate the safety of food additives are generally recognized as appropriate for theuse of animal experimentation data.

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How We RegulateThreshold of Regulation (TOR) (21 CFR 170.39)

• A policy developed in the mid-1990’s in CFSAN using “notice and comment” rulemaking.

• Exempts from petition review, situations where the dietary exposure to an ingredient is below a “threshold level.” (EDI < 1.5 µg/p/d, 0.5 ppb dietary concentration)

• Applied to non-carcinogens but precludes non-negligible upper-bound carcinogenic risk

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How We RegulateFood Contact Notifications (21 CFR 170.100-106)

• Exposure ≤0.5 ppb (TOR)• No toxicology studies recommended• Comprehensive literature search

• Exposure >0.5 ppb and ≤50 ppb• As above plus genetic toxicity tests

• Exposure >50 ppb and ≤1 ppm• As above plus 2 subchronic oral studies (rodent and non-rodent)

• Exposure >1 ppm• Comprehensive tests including bioassays

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How We RegulateFood Contact Notifications (21 CFR 170.100-106)

Notification program with a “Hammer” due date

– 120-day timeline

– Effective notifications listed on FDA’s website (https://www.fda.gov/Food/IngredientsPackagingLabeling/PackagingFCS/Notifications/default.htm)

– Proprietary approval

– Not publicly available until review is complete

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Current Inventory as of May 4, 2017

FCNs Since inception

CY 2014 CY 2015 CY 2016 Jan – May 2017

Received 1797 118 116 118 36

Effective 1287 88 62 60 4

Withdrawn 443 30 54 48 10

Not Accepted 11 - - - 1

Objection 26 - - - -

Under review 30 - - 10 21

PNCs

Received 2012 180 221 176 52

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FCN Trends Since InceptionFCN Trends

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10

20

30

40

50

60

70

80

90

100

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016

Effective

Withdrawn

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Methodology for FCN AnalysisFCN Categorized by Year based on Date Received*

EffectiveNot

AcceptedObjection Withdrawn

Under Review

Was a Deficiency Letter or Request to Withdraw Issued?

Chemistry EnvironmentalAdministrative / Regulatory

MicrobiologyToxicology

NoYes

* Each FCN was individually analyzed for the information categorized20

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Observations

• In 2014 – 95 issued DL, 32 second DL (16 were single Environmental DL; 23 total 2nd Environmental DL)– Out of the withdrawn FCNs, 5 can be attributed solely to

Environmental deficiencies

• In 2016 – 107 issued DL/WL, 43 second DL/WL (12 were from single Environmental DL; 28 total 2nd Environmental DL)– Out of the withdrawn FCNs, 10 can be attributed solely to

Environmental deficiencies

• 2014 – 29 Antimicrobial Submissions

• 2016 – 38 Antimicrobial Submissions (↑ 30%)

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FCN Statistics 2014 (Red) vs. 2016 (Blue)

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107

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86

43

83

32

5

27

30

95

21

84

38

64

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1

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0 20 40 60 80 100 120

Withdrawn Submissions

DL or RWL

Phase 1 AL

Chemistry

Toxicology

Environmental

Administrative or Regulatory

Microbiology

Chem, Tox, & Env

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What’s the Secret to a Successful Food Contact Substance Notice?

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Other TrendsRecent Events of Note

• Citizen Petitions to initiate FDA rulemaking to amend existing food additive or color additive regulations (e.g., BPA, BHA, certified color additives) or to prohibit the use of a food ingredient (e.g., PHOs).

• Litigation to compel FDA to: respond to Citizen Petitions (e.g., BPA, PHOs, salt & sodium); finalize proposed rules (e.g., FSMA, GRAS Notification Program) or finalize food additive petitions (perchlorate).

• Food Additive or Color Additive Petitions (5) to repeal food additive regulations based on abandonment (e.g., BPA (2), 2 perfluoroalkyl compounds, perchlorate, styrene).

• Food Additive or Color Additive Petitions (6) to repeal food additive regulations based on safety (e.g., perfluoroalkyl ethyl compounds, perchlorate, 7 synthetic flavoring agents , 30 ortho-phthalates, lead acetate).

• “Active” packaging

• Novel protein sources (e.g., insect, microbial, GE-microbial, plant-based)

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Questions?

Contact The Office of Food Additive Safety

Tel: 202-402-1200 Email: premarkt@fda.hhs.gov

https://www.fda.gov/Food/IngredientsPackagingLabeling/default.htm

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