# Presentation: 181574

## Slide 1

**Notes:**
Good Afternoon, My name is Anna P. Shanklin from the US Food and Drug Administration--FDA
FDA’s mission---pure and simple---is to promote and protect the public health by helping safe and effective products reach the marketplace and monitoring those substances while they are still on the market.
 Today we will discuss a very important aspect of our agency’s mission---

## Safety Assessment of Food Additives

- Anna P. Shanklin, Ph.D.
- Department of Health and Human Services
- U.S. Food and Drug Administration
- Center for Food Safety and Applied Nutrition

- Food Advisory Committee
- Additives and Ingredients Subcommittee
- LATEX ALLERGY
- August 26-28, 2003

- How FDA Regulates Food Additives?

**Notes:**
Food Additives---- in today’s presentation  Safety Assessment of Food Additives---CLICK---How FDA regulates Food Additives. 

Additives provide a variety of useful functions in foods such as helping to keep foods wholesome and appealing in transport.  Additives also helps improve foods taste, texture, consistency, color and even nutritional value.  

## OVERVIEW

- Introduction
- Food & Drug Law
- Evaluation of Safety
- Natural Rubber Latex (NRL)
- Latex Allergy and Food Safety
- Conclusion

**Notes:**
In this presentation we will review aspects of [READ SLIDE]

We will review the Food and Drug Law to learn about the legal framework in place for food additive approvals.

In covering these aspects, we will review intimately the food additive review process outlined in the law and gain more understanding of the safety evaluation of food additives and how we should apply the provisions in the law to evaluate Natural Rubber Latex (NRL) a food additive and its implications in food mediated latex allergic reactions.

## CFSAN’s Mission

- To promote and protect the public health by ensuring that:
- The food supply is safe and wholesome and cosmetics are safe
- Food and cosmetic products are honestly and accurately labeled

- OFAS --- Food Ingredients

**Notes:**
CFSAN’s mission is to fulfill FDA’s mission by [READ SLIDE]

CLICK--- The Office of Food Additive Safety within CFSAN has the task of ensuring that the use of food ingredients is safe.

## OFAS’s “Food Ingredients” Universe

_**Direct Food Ingredients**_
_**Color Additives**_
_**GRAS Ingredients**_
_**Foods/Ingredients produced using modern biotechnology**_

_**Processing Aids**_
_**Food Irradiation Equipment**_
_**Food Packaging/Food Contact Substances**_

- Sweeteners; Preservatives; Fat;
- Nutrients; Texturizers (thickeners,
- Emulsifiers, etc.); Flavors

- To process food
- To inspect food

- In food, animal feed, drugs,
- cosmetics,medical devices(i.e. sutures
- and contact lenses)

- Antimicrobials(meat and poultry
- Processing); Defoamers; Ion exchange
- resins

- Enzymes; Fiber; Proteins;
- Lipids; Sugars; MSG; Antimicrobials;
- Phytosterols/stanols; Flavors;
- Infant formula ingredients

-  Plants w/herbicide resistance or insect
-  resistance, delayed ripening, etc.;
-  often use GRAS concept

-    Coatings (paper, metal, etc);
-    New/recycled plastics including both
-    polymers and monomers; Paper;
-   Adhesives; Ingredients in Pkgs.(i.e.
-   colorants, antimicrobials, antixoxidants,
-   etc.);Packaging material for use  during
-   food irradiation,; Food packaging
-   “formulations”

**Notes:**
Note: May replace slide with OLD VERSION for better graphics

Let’s look at OFAS’s vast universe of Food Ingredients.  Food ingredients include:  READ SLIDE----

Foods and Food Ingredients and --

## Food and Drug Law

**Federal, Food, Drug, and Cosmetic Act**
**	****	****	****	****     ****FFDCA**

**Notes:**
Substances and items for use in, on, or in contact with food ----CLICK---fall under the jurisdiction of the Federal, Food, Drug, and Cosmetic Act. Often referred to as the Act or the FFDCA.  It is the basic food and drug law of the United States.

## FDA Authority

- FFDCA

- “The LAW”

**Notes:**
The FDA is the Federal agency responsible for administering the main part of the FFDCA.  The law gives FDA authority over food and food ingredients and  is intended to assure the consumer that foods are pure and wholesome, safe to eat, and produced under sanitary conditions.

## OFAS & FFDCA

**Food Additive Provisions**
**Sec. 409 **

- Federal Food, Drug,
- And Cosmetic Act

**409**

**Notes:**
The Office of Food Additive Safety is mainly responsible for administering the food additive provisions of the Act found in section 409. 

 Our administration of sec 409 focuses on the evaluation of proposed uses and safety information for new food additives and once a safety determination has been made, writing regulations stipulating safe conditions of use for the new food additive. 

## Regulations

- LAW

**NOT**

****

- Food Additive

- FFDCA

- 21 CFR

**Notes:**
Regulations are not law—A regulation is a standard or requirement of conduct based on [or defined by] the law. However, a regulation has the full force of law.  

US Federal regulations are compiled in the Code of Federal Regulations (CFR).  Specifically, FDA regulations are in part 21.

Although--CLICK---our food additive regulations are not law they are intended to be written such that noncompliance with such a regulation would violate some section of the Law, specifically—CLICK—The FFDCA

The law provides a framework for assuring the safe use of these additives or chemicals on or in food.

## “PRE-MARKET” APPROVAL

**1958 Food Additives Amendment **
**of FFDCA**
**Sec. 409**

**Notes:**
Under this framework, the agency(FDA) must approve new food additives before they can be used in a manner in whereby they may become components of foods which is in accordance with the Food Additives Amendment to the Act (sec. 409) passed in 1958 which requires FDA approval of new food additives prior to their inclusion in food thus the term—pre-market approval.

## What is a Food Additive?

- 		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;_....
- 		if such substance is _not_ Generally Recognized As Safe,

_***Sec. 201(s) FFDCA: Definition***_

_***21 CFR 170.3(e)(1)***_

**Notes:**
What is a food additive---- Legally, the definition can be found in sec 201(s) of the FFDCA Act and in 21 CFR 170.3(e)(1).
						READ Definition

Yes, even food contact articles and Food packaging are considered Food additives if they are expected to migrate to food.

The definition excludes substances that are generally recognized as safe---GRAS--- by qualified experts such as----salt, sugar, and sodium carbonate,---among others

## Any substance, that is reasonably expected to become a component of food as a result of its intended use,

If such use in not Generally Recognized As Safe (GRAS)

_***Sec. 201(s) FFDCA: Definition***_

- Any substance, that is reasonably expected to become a component of food as a result of its intended use,
- If such use in not Generally Recognized As Safe (GRAS)

_**IN SHORT**_

**Notes:**
In the broadest sense, a food additive is any substance used in a manner whereby it may become a component of food, if such use is not Generally recognized as safe.

## Food and Drug Law

_**Sec. 409 Unsafe Food Additives**_: the use of a food additive is unsafe, unless that use conforms to a regulation, notification, or exemption issued by FDA under Sec. 409.
_**Sec. 402 Adulterated Food**_: a food is adulterated...if it is, or if it contains any food additive that is unsafe.
_**Sec. 301 Prohibited Acts**_: the introduction or delivery into interstate commerce of any food that is *adulterated or misbranded.*

- FFDCA

**Notes:**
In addition to the definition of a food additive in sec 201(s), other important provisions are provided in the Law relating to how we regulate food additives. READ SLIDE.
Together, these provisions provide a mechanism for FDA to ENFORCE the LAW.  For example---

## Food and Drug Law

**MOM’S ****Apple Pies**

**Sweetner **
**Unapproved **
**Food Additive**

- Adulterated Food

- Interstate Commerce

- FDA
- Enforcement

**Maryland  ********   Virginia**

**Food and Drug Law**

**Notes:**
For example---the presence of an unsafe food additive renders a food adulterated, and when that food moves into interstate commerce, a violation of the FFDCA occurs.  FDA can then proceed with an enforcement action against the person introducing the adulterated food into interstate commerce.

The same applies for food packaging----for example---

## Food and Drug Law

**New antioxidant **
**“****Unapproved”**

**Antioxidant migrates**
**Adulterated Food**

**[A]**

**[A]**

**Interstate Commerce**

**FDA **
**Enforcement**

**Food and Drug Law**

**Notes:**
Candy Wrapper----Antioxidant Example

## Why are food additives regulated?

- FDA has
- authority to
-  prevent adulteration of Food
- (FFDCA)

- Unsafe Food Additive = Adulterated Food
- Unapproved Food Additive = Unsafe Food Additive
- Unapproved Food Additive = Adulterated Food

**Notes:**
Again, food additives are regulated because the FFDCA prohibits the interstate distribution in the US or importation, of food and articles that are adulterated.
Click---Points to remember----Click---READ bottom of slide

## Food Drug & Cosmetic Act 

*(As amended, 1958)*

- Defines “food additive” w/GRAS exemption
- Requires premarket approval of new uses of food additives
- Establishes the standard of review
- Establishes the standard of safety
- Establishes formal rulemaking procedures

**Sec. 409 FFDCA**

**Notes:**
The 1958 amendment to the Act in addition to defining a food additive and establishing pre-market review of food additives also established

2 Key Concepts of the food additive approval process.

## Food Drug & Cosmetic Act 

*(As amended, 1958)*

- Defines “food additive” w/GRAS exemption
- Requires premarket approval of new uses of food additives
- Establishes the standard of review
- Establishes the standard of safety
- Establishes formal rulemaking procedures

**Sec. 409 FFDCA**

**Notes:**
The standard of review and

## Food Drug & Cosmetic Act 

*(As amended, 1958)*

- Defines “food additive” w/GRAS exemption
- Requires premarket approval of new uses of food additives
- Establishes the standard of review
- Establishes the standard of safety
- Establishes formal rulemaking procedures

**Sec. 409 FFDCA**

**Notes:**
The standard of safety for food additive approvals. 

The amendment also established formal rule making procedures. 

Under the general safety standard of the Act, a food additive cannot be approved for a particular use unless a fair evaluation of the data available to FDA establishes that the additive is safe for that use.

## Standard of Review

- “Fair evaluation of the data ...”

**Notes:**
Thus the standard of review criterion requires a fair evaluation of the data and not infiltration of personal attitudes or preferences of administrative officials--

## From the Senate Report on the“Food Additives Amendment of 1958”

- From the Senate Report on the***“Food Additives Amendment of 1958”***

- “The committee has endeavored to prescribe a new statutory criterion requiring that a high standard of fairness be observed in administrative rule-making under this bill.  _Personal attitudes or preferences_ of administrative officials could not prevail on the basis of being supported by substantial evidence picked from the record without regard to other evidence of probative value in the record.”

**Notes:**
The 1958 Senate report states [READ SOME OF SLIDE]

## House of Representatives, Report No. 2284,“Food Additives Amendment of 1958”

*Committee on Interstate & Foreign Commerce, 85**th** Congress, 2**nd** Session, July 28, 1958*
- 	“The committee feels that the Secretary’s findings of fact and orders should not be based on isolated evidence in the record, which evidence in and of itself  may be considered substantial without taking account of the contradictory evidence of equal or even greater substance...”

**Notes:**
Futhermore, Read some of slide---
Fair Evaluation of the data

## Standard of Safety

- “Reasonable certainty of no harm”

**Notes:**
The standard of safety relies on the concept of reasonable certainty of no harm----

## Standard of Safety

- “Reasonable certainty of no harm”

**Notes:**
Reasonable

## Standard of Safety

- “Reasonable certainty of no harm”

**Notes:**
Certainty

## Standard of Safety

- “Reasonable certainty of no harm”

## Standard of Safety

- “Reasonable certainty of no harm”

## Standard of Safety

- “Reasonable certainty of no harm”

**Notes:**
Harm----CLICK
Equal emphasis on each word---Commissioner David Kessler

## Standard of Safety

- “Reasonable certainty of no harm”

- 21 CFR 170.3(i)

- "SAFE"

**Notes:**
SAFE------The regulation 21 CFR 170.3(I) defines “safe” as a reasonable certainty in the minds of competent scientist that the substance is not harmful under its intended conditions of use---this is the standard

## Standard of Safety

- “Reasonable certainty of no _Harm_”

**Notes:**
Harm!! CLICK
What is Harm?

## Standard of Safety

- “Reasonable certainty of no _Harm_”

- What is Harm?

**- ****Harm refers to Health**

- Man or Animal

**Notes:**
Harm refers to Health

## Standard of Safety

- “Reasonable certainty of no _Harm_”

- What is Harm?

- - Harm refers to Health

**Man or Animal**

**Notes:**
Of Man or Animal

## Standard of Safety

- Petitioner burden to demonstrate a “reasonable certainty of no harm”
- FDA Assessment

**Notes:**
The standard of safety set forth by the law requires the petitioner to demonstrate a reasonable certainty of no harm from the intended use of the additive.  

FDA will assess whether it has received adequate documentation to appropriate questions regarding the safety of the proposed use of the additive.

## REASONABLE CERTAINTY OF NO HARMLegislative History of the FFDCA

- _REASONABLE CERTAINTY OF NO HARM_*Legislative History of the FFDCA*

- The concept of safety used in this legislation involves the question of whether a substance is hazardous to the health of man or animal. Safety requires proof of a _reasonable certainty that no_ _harm will result_ from the proposed use of an additive.
- It does not—and cannot—require proof beyond any possible doubt that no harm will result under any conceivable circumstance.

- H.R. Report, No. 2284, 85th Congress (1958)

**Notes:**
It is very clear in the legislative history of the FFDCA [READ SLIDE]. 

## REASONABLE CERTAINTY OF NO HARMLegislative History of the FFDCA

- _REASONABLE CERTAINTY OF NO HARM_*Legislative History of the FFDCA*

- The concept of safety used in this legislation involves the question of whether a substance is hazardous to the health of man or animal. Safety requires proof of a _reasonable certainty that no_ _harm will result_ from the proposed use of an additive.
- It does not—and cannot—require proof beyond any possible doubt that no harm will result under any conceivable circumstance.

- H.R. Report, No. 2284, 85th Congress (1958)

**Notes:**
Furthermore, the standard as described in the 1958 Congressional report, does not and it cannot require proof beyond any possible doubt—READ rest of SLIDE.

In prescribing these standards, Congress recognized that absolute safety of any substance can never be proven,  and in the report it indicates that the concept of safety as outlined in the legislative history does not and it cannot require proof beyond----- READ rest of SLIDE.

## Section 409

**Notes:**
The law provides the legal framework for regulating the safe use of food additives.  [PAUSE] Let’s review this legal framework.

## Section 409 Requirements

- Any person may petition to establish safety

- "Food Additive Petition Process"

**Notes:**
Under Section 409 anyone may petition FDA to issue a regulation prescribing safe conditions of use of an additive more formally known as the Food Additive Petition Process. 
Keeping in mind our standard of review (fair evaluation of the data) and standard of safety(reasonable certainty of no harm)---let’s clarify(or examine) the petition process more intimately---

## Food Additive Petition ReviewThe Safety Decision

- _Food Additive Petition Review_***The Safety Decision***

**It is NOT intended to ensure, nor is it possible to ensure, safety with absolute certainty: **
***	******(“Reasonable Certainty of No Harm rather than ***
***	******“******Certainty of No Theoretical Possibility of Harm”)***
**Does NOT weigh risks and benefits**
**It is NOT intended to enforce or limit consumer choices. **

_**What the evaluation is NOT**_**:**

**Notes:**
READ SLIDE
Solely a safety decision,

Benefits not to be considered in safety decision/ We do not consider if another additive or alternative is good and can get the job done

Necessity is not a criterion we can use

## Food Additive Petition ReviewThe Safety Decision

- _Food Additive Petition Review_***The Safety Decision***

**It ****DOES****, in fact, ensure safety**
**It ****IS**** a consensus decision made under uncertainty that provides a fair evaluation of all the data of record...**
**	****	****-That must protect the public health**
**	****	****-That will withstand scientific, procedural, and legal ****	****	**** challenge from all sides**

**Notes:**
READ SLIDE!!

## Safety Standard 

- Approvals are Safety Based Only
- Reasonable Certainty of No Harm
- Harm refers to Health of Man or Animal
- Fair Evaluation of the Entire Record
- Benefits not weighed in Safety Decision

**Highlights**

**Notes:**
In review, the approval of a food additive is:
Solely based on safety, READ SLIDE

Let’s review the process and key players in the safety decision-

## Key Players

**Consumer Safety Officer (CSO)**
**C****hemistry**
**T****oxicology**
**E****nvironmental**

**E**

**Notes:**
The safe use of a substance is determined through a series of reviews of the relevant scientific data and information submitted by the petitioner.

A typical submission will go through chemistry, toxicology, and environmental science reviews and the review is managed and coordinated by a Consumer Safety Officer.

## Data Requirements

- Identity
- Conditions of proposed use
- Intended technical effect
- Method for determining “quantity”
- Full reports of safety studies (data)
- Manufacturing methods
- Environmental information (NEPA)

**Sec. 409 FFDCA**

**Notes:**
In order for FDA’s key players to evaluate the safety of a substance for its proposed use, certain scientific information is needed: READ SLIDE

## Safety Evaluation

- A “full blown” exhaustive
- safety evaluation of all
- appropriate studies, with agency ownership of safety decision.

- Standard of Review

**Notes:**
We want to emphasize that a full-blown exhaustive safety evaluation of all appropriate studies is done with agency ownership of safety decision.

## Safety Evaluation

- Estimation of Exposure
- Proposed Conditions of Use
- Concentration (safe)
**Level with no adverse effects observed toxicologically**

- “ The dose makes the poison”

**Notes:**
We also want to emphasize that in the safety evaluation of a substance an important requirement is the estimation of the food additive’s probable human exposure  under its proposed conditions of use to determine whether its use or presence in food at a given concentration is safe.  

The key determinant in the evaluation of a substance in or added to the diet  is the relation of it probable human exposure to a level at which adverse effects are observed in toxicological studies or as a popular coined phrase states---

Click--the dose makes the poison.

## Technical Review

- FDA scientist review data and evaluate petitioner’s safety argument
- FDA communicates with petitioner to resolve any questions and/or additional data needs
- FDA review, documentation
- FDA reaches a scientific conclusion and makes a recommendation

_**Key Players**_

**Notes:**
The technical review process is very thorough----READ SLIDE

## FDA’s Action on the Petition

- Complete the review
- Establish a Regulation
- Deny the Petition

_**Section 409 Requirements**_

**Notes:**
Section 409 also stipulates required actions on a food additive petition after it has been submitted.

FDA must---read slide

## Other Legal Requirements

- Objections and Public Hearings
- Judicial Review
- Amendment or Repeal of Regulations

_**Section 409 Requirements**_

**Notes:**
The FFDCA legal framework in Section 409 also outlines other provisions pertaining to the response of actions on petitions

FDA must allow for objections to the actions to be filed by any person and honor request for a public hearing
The Act also allows for judicial review of objections filed

The requirement we want to focus on is---Amendment and Repeal of Regulations

## Amendment or Repeal

- IN
- Regulation

- OUT
- Regulation

- =

- Food Additives

- FDA Responsibility

**Notes:**
In amending or repealing a regulation, it is essential to understand that it is a process equivalent to the process for approvals

In the process for approvals---there is issuance of a regulation and  in the process for Amendment/Repeal there is issuance of a regulation

Simply put, if it comes in as a regulation ---- it goes out as a regulation.
FDA responsibility under the LAW.

## Legal Aspects of Food Additive Approvals

- Food Additives unsafe until FDA decision
- Regulations stipulate an identity, specifications and conditions of safe use
- Regulations do not provide specific product approvals
- Direct additives or Food-contact substance

**Notes:**
For review, the legal framework for food additive approvals provides---READ SLIDE

Regulations state an identity, specifications and conditions of safe use and the detailed specifications may include the types of food in which the additive is permitted, the manner of use, and any special labeling required.

This process for review of additives is for those added directly to food as well as food-contact substances such as packaging.

## Food Additive Regulations21 CFR Parts 170-189

- General Provisions					170 & 171
- Direct Food Additive Regulations			172 & 173
**Indirect Food Additive Regulations****	****174-178**
- Irradiation of Foods				179
- Substances permitted on interim basis		180
- Prior Sanctioned Substances			181
- GRAS Ingredients					182-186
- Prohibited Substances				189

- Title 21 CFR 177.2600 *Rubber articles intended for repeat use*

**Notes:**
Specifically the food additive regulations are arranged—[READ SLIDE] with parts 174-178 listing the indirect food additive or food contact materials or food contact substance regulations

## Food Drug & Cosmetic Act 

*(As amended, 1958, 1997)*

- Defines “food additive” w/GRAS exemption
- Requires premarket approval of new uses of food additives
- Establishes the standard of review
- Establishes the standard of safety
- Establishes formal rulemaking procedures
-      -----**As amended 1997**(**FDAMA**)-----
- Defines “food contact substance”(FCS)
- Establishes a premarket notification program for FCSs

- Sec. 409(h) of FFDCA

**Notes:**
We want to touch briefly on the fact that--- In 1997 the Food and Drug Administration Modernization Act (FDAMA) amended the Act ---

## Food Drug & Cosmetic Act 

*(As amended, 1958, 1997)*

- Defines “food additive” w/GRAS exemption
- Requires premarket approval of new uses of food additives
- Establishes the standard of review
- Establishes the standard of safety
- Establishes formal rulemaking procedures
-      -----**As amended 1997**(**FDAMA**)-----
- Defines “food contact substance”(FCS)
- Establishes a premarket notification program for FCSs

- Sec. 409(h) of FFDCA

**Notes:**
To establish a food contact notification process as the primary method by which the FDA regulates food additives that are food contact substances.
FCN process contained in section 409(h) of the Act.

## Food Drug & Cosmetic Act 

*(As amended, 1958, 1997)*

- Defines “food additive” w/GRAS exemption
- Requires premarket approval of new uses of food additives
- Establishes the standard of review
- Establishes the standard of safety
- Establishes formal rulemaking procedures
-      -----**As amended 1997**(**FDAMA**)-----
- Defines “food contact substance”(FCS)
- Establishes a premarket notification program for FCSs

- Sec. 409(h) of FFDCA

**Notes:**
Also gave us the statutory definition of a Food Contact Substance.

## What is a Food Contact Substance?

_***(Section 409(h)(6) of the FFDCA***_***)***
- 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 food.

**FCS**

- Indirect Food Additives

**Notes:**
What is a Food Contact Substance?

## Food Contact Notifications

**Food Additive that is subject of an effective notification **
****
**Safe food additive**

**Notes:**
Thus for our purpose it is important to emphasize that under the legal framework established by the Act-----READ SLIDE

## Brief SummaryFood Additive Approvals

- _Mechanism_: FFDCA---Sec. 409---Necessary Tools
- _Process_: Safety Evaluation---Scientific review team
- _Result_: Regulations, notifications, and exemptions

**Notes:**
Food Additive approvals in brief.

Sec. 409 gives FDA all the necessary tools for assuring safe use of food additives.

Again, regardless of whether the FDA is petitioned or Notified, the safe use of a substance is determined through a series of reviews of the relevant scientific data and information submitted. We review the safety of each substance under its proposed conditions of use.  Review carried out by qualified and competent scientist.

The safety assessment of the food additive is concluded by writing regulations, allowing notifications to become effective or by granting exemptions.

## Brief SummaryFood Additive Approvals

- Petitioner is responsible for demonstrating safety
- FDA is responsible for
- Conducting a full and fair evaluation of the data and information
- Issuing a regulation if FDA scientists conclude the requested use is “SAFE”

**FDA**

**Petitioner**

**Notes:**
In reviewing roles and responsibilities-----

The petitioner’s responsibility----
AND
FDA’s responsibility-----

## Food Additive Regulations21 CFR Parts 170-189

- General Provisions					170 & 171
- Direct Food Additive Regulations			172 & 173
**Indirect Food Additive Regulations****	****174-178**
- Irradiation of Foods					179
- Substances permitted on interim basis			180
- Prior Sanctioned Substances				181
- GRAS Ingredients					182-186
- Prohibited Substances					189

- Title 21 CFR 177.2600 *Rubber articles intended for repeat use*

**Notes:**
TRANSITION SLIDE
Now that we are well versed on how FDA evaluates the safety of food additives and the regulatory process for food additive approvals----

Let‘s examine a specific food additive----an indirect food additive---food contact material--- Natural rubber.

Let’s review it based on the FFDCA law, section 409 and the standards of review and safety previously discussed---

## Natural Rubber Latex“NRL”

- § 172.615	***Chewing gum base***
- § 175.105	***Adhesives***
- § 175.125	***Pressure-sensitive adhesives***
- § 175.300	***Resinous and polymeric coatings***

- Regulations

**Notes:**
Natural rubber is listed, along with conditions of safe use in Title 21 CFR 177.2600 issued in 1963, therefore, it is an acceptable indirect food additive.

It is used in the production of latex food service gloves (food contact substance)

FDA’s current position is that provided the compositional requirements, limitations and specifications of the regulation are met, the use of natural rubber as a component of food service gloves is in compliance with 21 CFR 177.2600 and is not an unsafe food additive.

## Natural Rubber Latex“NRL”

**§**** 177.1010**	***Acrylic and modified acrylic ******	******	******	******	******plastics, semirigid and rigid***
**§**** 177.1200**	***Cellophane***
**§**** 177.1210**	***Closures with sealing gaskets for ******	******	******	******	******food containers***
**§**** 177.2600**	***Rubber articles intended for ******	******	******	******	******repeated use***

- Regulations

**Notes:**
Natural rubber is listed, along with conditions of safe use in Title 21 CFR 177.2600 issued in 1963, therefore, it is an acceptable indirect food additive.

It is used in the production of latex food service gloves (food contact substance)

FDA’s current position is that provided the compositional requirements, limitations and specifications of the regulation are met, the use of natural rubber as a component of food service gloves is in compliance with 21 CFR 177.2600 and is not an unsafe food additive.

## Natural Rubber Latex“NRL”

**21 CFR 177.2600 (Feb. 1, 1963)**
**Manufacture of Latex Food Service Gloves**
- Acceptable “indirect” food additive---FCS
**FDA Position**
- NRL currently “safe” food additive

**Notes:**
Natural rubber is listed, along with conditions of safe use in Title 21 CFR 177.2600 issued in 1963, therefore, it is an acceptable indirect food additive.

It is used in the production of latex food service gloves (food contact substance)

FDA’s current position is that provided the compositional requirements, limitations and specifications of the regulation are met, the use of natural rubber as a component of food service gloves is in compliance with 21 CFR 177.2600 and is not an unsafe food additive.

## Natural Rubber Latex“NRL”

- Exposure ---- Response
- Allergic Reactions
- Latex Proteins

_**The Issues**_

**Notes:**
The Issues with NRL 

As previously discussed, exposure to NRL has been shown to elicit a range of responses in sensitized people.

Of specific concerns are various allergic responses to the natural rubber latex usually as result of prolonged cumulative exposure to NRL.

These allergic reactions have been linked to latex proteins.

## Latex Allergyand Food Safety

**Problem: Food Mediated Latex Allergic Reactions**

**Notes:**
FDA has received reports of latex allergenic individuals (those already sensitive to latex---hypersensitive) displaying allergic reactions to foods believed to have been handled by workers wearing NRL food service gloves.

CLICK----Thus the problem becomes food mediated latex alllergic reactions

(CFSAN) has been gathering information relating to food mediated latex allergy in an effort to determine if there are data to support the claim that latex proteins are transferred to food as a result of the use of latex food service gloves, and if such food may trigger an allergic response in hypersensitive consumers. And if there is sufficient evidence to propose a regulatory action---such as an amendment/repeal of the current regulation in 177.2600.

First let’s take a look at the glove--

## The Glove

- Barrier to Infectious Agents
- Food Contact Material
- Subject to the Law (FFDCA)
- Approval
- 		Intended Use
- 		Fair Evaluation
- 		Reasonable Certainty of No Harm

- Latex Allergy and Food Safety

**Notes:**
Latex Food Service Gloves are used by the food service industry as a barrier to infectious agents that may be present on the hands of food workers.

Gloves are considered a Food contact material.

Therefore, they are subject to the LAW.

The approval 

## Latex Allergenic Proteins

- Indicated in Food Mediated Allergic reactions
- Constituents of an Indirect Food Additive
- FFDCA (Sec. 409)---Food & Drug Law
- Evaluation---General Safety Standard

- Latex Allergy and Food Safety

**Notes:**
It has been suggested that latex food service gloves are responsible for introducing natural rubber allergens to food, thus rendering the food adulterated.

The proteins are components of food contact articles that may migrate to food as a result of their intended use in food service gloves, thus constituents of food additives.

As such they are subject to the safety requirements in the Law and their assessment of safety should be based on section 409 of the Act under the general safety standard.

Finally, evaluation and any regulatory actions on the use of NRL in food contact articles should be based on the general safety standard---?

## Standard of Safety

- “Reasonable certainty of no harm”

**Notes:**
Reasonable certainty of no harm.   

Our actions regarding the use of of natural rubber latex in contact with food has to be focused on this standard.

We cannot operate outside the confines of the law.

## Latex Allergyand Food Safety

- Food Mediated Latex Allergic Reactions
- How do we address the Problem

**Notes:**
So Food Mediated Latex Allergic Reactions----How do we address the problem!!

## Latex Allergy and Food Safety

- Safety First
- FDA must operate under the Law (FFDCA)
- Approval  --- Issuance of a Regulation
- Approvals are “safety” based only
- No explicit balancing of risks/benefits
- Amendment or Repeal --- Issuance of a Regulation

**Addressing the Problem**

- Use of additive = Unsafe food?

**Notes:**
In addressing the problem of food mediated latex allergic reactions we must consider..........

Safety is our first priority----- Before we act we must consider ---CLICK--- if the use of the additive would result in the production of unsafe food

FDA must operate under the confines of the Law--- BOUND BY LAW

We must consider that Food Additive approvals result in the issuance of a regulation/ [notification(?) should I mention?]  There is a legal framework in place.

Food additive regulations are issued based solely on data relating to the safety of the additive itself

Food additive provisions do not provide a mechanism for FDA to consider risk/benefits analysis relative to other options when reviewing the safe use of a substance

The same legal framework for approvals is applied to amendments or repeals----

 FDA responsibility to uphold the law and to operate within its provisions.

Therefore---

## SUMMARY

- Sec. 409 FFDCA---Food Additive Provisions
- Review Process
- Fair Evaluation of the Data --- “Review”
- Reasonable Certainty of No Harm --- “Safety”
- NRL---21 CFR 177.2600

**Notes:**
For review, What did we learn regarding how FDA regulates Food Additives?

There is a legal framework established and provisions in sec. 409 of the FFDCA.

It provides for a solid review process conducted by competent scientist.

Foundation: Fair Evaluation of Data

Safety Standard: Reasonable Certainty of No Harm

We have also discussed a specific indirect food additive regulation and have determined that any regulatory action regarding NRL should be based on our assessment with fair evaluation of the data.

And that currently NRL is a safe food additive under section 177.2600 provided it is in compliance with the regulation.

## CONCLUSIONS

- Evaluation of Safety

- Food and Drug Law

- Latex Allergy and Food Safety

**Notes:**
Finally, we have reviewed the legal framework in place for food additive approvals. And we have reviewed the review process and safety evaluation of food additives as outlined in the law.

We have also reviewed the issue of food mediated latex allergic reaction and hopefully have gained a greater understanding of how to address the problem from a public health standpoint, understanding FDA’s responsibility to operate within the confines of the law.

## Slide 71

**Notes:**
Good Afternoon, My name is Anna P. Shanklin from the US Food and Drug Administration--FDA
FDA’s mission---pure and simple---is to promote and protect the public health by helping safe and effective products reach the marketplace and monitoring those substances while they are still on the market.
 Today we will discuss a very important aspect of our agency’s mission---

## Slide 72

**Notes:**
QUESTIONS!!