Food Additives Program

U.S. FDA s Food Additive Program: An Update on Resources and Challenges 18 th Food Packaging Law Seminar October 11, 2017 Arlington, VA 1 Food Additives Program Dennis Keefe, PhD Director, Office of Food Additive Safety 2 1

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 3 4 2

Our Numbers OFAS Human Capital: FTEs 1998-2017 160 140 120 100 80 60 40 20 0 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2017b 5 How We Regulate Premarket 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 6 3

250 Accomplishments by Fiscal Year Industry Submissions 200 150 100 50 PNC FCN C/FAP GRN BNF 0 2009 2010 2011 2012 2013 2014 2015 2016 2017 7 How We Regulate Food Contact Substances 8 4

Why We Regulate Federal 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 9 Why We Regulate Federal 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. 10 5

Why We Regulate FFDCA 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. 11 Why We Regulate FFDCA 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. 12 6

Why We Regulate FFDCA 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. 13 Why We Regulate FFDCA 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 the use of animal experimentation data. 14 7

How We Regulate Threshold 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 15 How We Regulate Food 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 16 8

How We Regulate Food 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 17 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 18 9

FCN Trends Since Inception FCN Trends 100 90 80 70 60 50 Effective Withdrawn 40 30 20 10 0 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 19 Methodology for FCN Analysis FCN Categorized by Year based on Date Received* Effective Under Review Not Accepted Objection Withdrawn Was a Deficiency Letter or Request to Withdraw Issued? Yes No Chemistry Toxicology Environmental Administrative / Regulatory Microbiology * Each FCN was individually analyzed for the information categorized 20 10

Observations In 2014 95 issued DL, 32 second DL (16 were single Environmental DL; 23 total 2 nd 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 2 nd Environmental DL) Out of the withdrawn FCNs, 10 can be attributed solely to Environmental deficiencies 2014 29 Antimicrobial Submissions 2016 38 Antimicrobial Submissions ( 30%) 21 FCN Statistics 2014 (Red) vs. 2016 (Blue) Chem, Tox, & Env 24 27 Microbiology 1 5 Administrative or Regulatory 9 32 Environmental 64 83 Toxicology 38 43 Chemistry 84 86 Phase 1 AL 9 21 DL or RWL 95 107 Withdrawn Submissions 30 48 0 20 40 60 80 100 120 22 11

What s the Secret to a Successful Food Contact Substance Notice? 23 Other Trends Recent 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) 24 12

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 25 13