Dockets Management Branch (HFA-305)
Food and Drug Administration
5630 Fishers Lane, Room 1061
Rockville, Maryland 20852

Re:     Proposed Pre-Market Notification Regulation for Bioengineered Foods; Docket No. 00N-1396

Dear Sir or Madam,

The Food Marketing Institute (FMI) is pleased to respond to the Food and Drug Administration's (FDA's) request for comments on the Agency's proposal to require the submission of data and information regarding plant-derived bioengineered foods to FDA before the foods are brought to market. 66 Fed. Reg. 4706 (Jan. 18, 2001); 66 Fed. Reg. 17517 (Apr. 2, 2001).

As discussed more fully below, FMI supports FDA's proposed pre-market notification rule. The proposal represents an immediate and sound exercise of the Agency's authority consistent with the scope of its jurisdiction under the Federal Food, Drug, and Cosmetic Act (the FD&C Act). Once promulgated, the new regulation will increase the regulatory oversight of foods developed through biotechnology, as well as the transparency of the oversight process. We hope and expect that the heightened oversight and transparency provided by the final rule will encourage continued consumer confidence in FDA and the safety of the food supply.

     I.     Executive Summary

FMI is a non-profit association that conducts programs in research, education, industry relations and public affairs on behalf of its 1,500 members and their subsidiaries. Our membership includes food retailers and wholesalers, as well as their customers, in the United States and around the world. FMI's domestic member companies operate approximately 21,000 retail food stores with a combined annual sales volume of $300 billion, which accounts for more than three-quarters of all grocery sales in the United States. FMI's retail membership is composed of large multi-store chains, small regional firms, and independent supermarkets.

FMI and its members have a longstanding commitment to ensuring that consumers are offered high quality food and have confidence in the safety of the food that they purchase. We value the opportunity to work closely with FDA on important food safety programs, such as the Partnership for Food Safety Education and the consumer brochure on irradiation.

With respect to biotechnology, FMI's Board of Directors adopted a policy statement on bioengineered food on October 16, 1999. (copy enclosed) Among other elements, our policy statement urges FDA to institute a mandatory pre-market evaluation program for foods produced through biotechnology. A copy of the statement, which was also adopted by the Grocery Manufacturers of America, was sent to FDA in advance of the Agency's December 1999 hearings.

FMI also developed a brochure for grocery stores to distribute to consumers to provide objective information on bioengineered foods. (copy enclosed) In light of FDA's leadership role on this issue, our brochure cites the Agency's website as a good source of information for consumers. We also responded to FDA's request for comments on the Agency's current policy, joined in a petition with other food industry trade associations asking FDA to develop food biotechnology labeling guidance, and provided comments on the Agency's proposed labeling guidance.

Given the support for a mandatory pre-market evaluation program expressed in our policy statement, FMI applauds the Agency's proposal. Combining a formalized consultation procedure with a mandatory pre-market notification requirement will enhance FDA's ability to ensure that manufacturers are properly executing their duties to market foods that are safe and meet all applicable legal requirements.

    II.     Legal Background

     A.     Statutory Authority

The FD&C Act broadly prohibits the adulteration of food. Food will be considered adulterated under the FD&C Act if it contains an added poisonous or deleterious substance that may render the food injurious to health. 21 USC §342. Additionally, any food that contains a substance that meets the statutory "food additive"definition will be considered adulterated, unless the substance is used in compliance with an applicable food additive regulation. 21 USC §§402, 409.

In relevant part, the FD&C Act defines a "food additive"as a substance that is reasonably expected to become a component of food under the intended conditions of its use. 21 USC §321(s). Substances that are "generally recognized, among experts qualified by scientific training and experience to evaluate [the food's] safety, as having been adequately shown through scientific procedures . . . to be safe under the conditions of its intended use"(or "GRAS") are expressly excluded from the food additive definition and, therefore, from FDA's pre-market review authority over food additives. 21 USC §321(s).

The FD&C Act thus imposes a clear legal duty on those who introduce food into the market place --including foods produced through biotechnology --to ensure that the food satisfies all of the applicable statutory requirements, including those related to the safety of the food. The legal duty imposed on manufacturers is buttressed by the enforcement tools set forth in the FD&C Act. In this regard, FDA may seize foods that violate the statute or seek an injunction against or criminally prosecute those responsible for introducing such foods into commerce. See 21 USC §§332, 333, 334.

In 1992, FDA issued a formal interpretation of the FD&C Act¡¦s general requirements with respect to the oversight and labeling of foods produced through biotechnology in a document entitled, "Statement of Policy: Foods Derived from New Plant Varieties"(hereinafter "FDA Policy Statement"). 57 Fed. Reg. 22984 (May 29, 1992). The FDA Policy Statement recommended procedures for manufacturers to use in evaluating new food products. Manufacturers have been encouraged to follow those procedures and then to follow the Agency's voluntary "consultation" process to discuss with FDA the legal and scientific significance of the data obtained. According to FDA, the voluntary consultation process has worked well and the Agency believes that all of the products of food biotechnology that are currently marketed have been evaluated through the current consultation process.

     B.     Proposed Pre-Market Notification System

FDA's proposed pre-market notification program for bioengineered foods formalizes the current voluntary consultation process and imposes a requirement to submit a premarket biotechnology notice (PBN) to the Agency at least 120 days before the bioengineered food is marketed. Proposed Part 192.

The purpose of the presubmission consultation is to "discuss with [FDA] safety, nutritional, or other issues that may be associated with the bioengineered food." Proposed 21 CFR §192.10(b). To initiate a consultation, FDA recommends that the prospective notifier, often the manufacturer, submit a synopsis of the requested consultation that provides information on the bioengineered food, its manufacturing process, its intended technical effect, and its intended applications. Id. §192.10(f). FDA will establish an administrative file for the consultation and will discuss the materials with the submitter if requested to do so. Id. at §192.10(i).

At least 120 days "before the bioengineered food is marketed," FDA requires the submission of a PBN, which must include the following elements:

      

.     Attestation that the bioengineered food is as safe as comparable food, that the PBN is a balanced submission, and that the notifier will make additional data available to FDA upon request;

      
.     A synopsis of the PBN;

      
.     Information on the status of the food at other federal agencies and any foreign governments;

      
.     Data regarding the method of development, including characterization of the parent plant, construction of the vector used in the transformation of the parent plant, and character of the introduced genetic material;

      
.     Discussion of any newly inserted genes that encode resistance to an antibiotic;

      

.     Information on the identity of and dietary exposure to substances introduced into or modified in the food; and

      

.     Support for the notifier¡¦s claim that the bioengineered food is as safe as a comparable food.

Proposed 21 CFR, Part 192. Within 15 days of receipt, FDA will conduct a preliminary review of the PBN to ensure that it is complete. If all of the necessary information has been included, FDA will "file" the PBN and begin the substantive evaluation.

FDA expects to complete its substantive evaluation of the PBN within 120 days of the filing date. The Agency specifically reserves the right, however, to extend the evaluation period by an additional 120 days, during which time, FDA "expects that the bioengineered food will not be marketed." Proposed 192.30(d)(1). Following completion of its review, the Agency will advise the notifier either (1) that FDA currently has no further questions regarding the notifier's conclusion of the bioengineered food's safety or (2) that the PBN does not provide a sufficient basis for the notifier's conclusion that the bioengineered food is as safe as comparable food. In the latter case, the response will state the Agency's expectation that the bioengineered food will not be marketed. Proposed 192.30(d)(2), (3).

The proposed rule includes specific provisions regarding the public availability of documents related to both the pre-submission consultation and the PBN. Specifically, with respect to the pre-submission consultation, the fact of a company's consultation with FDA, along with the data and other information in the administrative file that FDA establishes would be disclosable to the public under the Freedom of Information Act (FOIA), unless the person requesting the pre-submission consultation claimed that the information was confidential and FDA agreed. Proposed Section 192.10(c).

With respect to PBN's, FDA intends to make a list of filed, pending PBN's readily available to the public based on the information provided in the PBN's synopsis. Proposed Section 192. 40(a), (b). The contents of filed, pending PBN's would be available to the public through FDA's electronic reading room or by request. Id. at §192.40(d). Once the Agency has completed its evaluation, the text of FDA's response and the Agency's reviewing memorandum would also be made available to the public by placing the information on the Internet or in a paper or electronic file that is available at FDA for public review and copying. Id. at §192.40(e).

    III.     Comments on Proposed Pre-Market Notification Regulations

             A.     FMI Supports Increased Regulatory Oversight, Transparency, and Agency Coordination

FDA's proposed pre-market notification rule represents a significant regulatory improvement in many respects. Once finalized, the rule will increase FDA's ability to oversee biotech foods before and after they reach the marketplace. Although FDA officials have stated their belief that the Agency has reviewed all biotech foods that are currently on the market, the pre-market notification regulation will provide greater assurance in this regard. Moreover, although the determinations of a new food's safety and regulatory status are generally the manufacturer's responsibility under the system set forth in the FD&C Act and discussed briefly above, FDA involvement in the decisionmaking process and in the efforts to determine the appropriate tests and procedures to establish the safety of the food can only increase the overall efficiency and effectiveness of the food safety system.

Equally as important, the new regulations include provisions that will affirmatively enhance the transparency of the process, which should increase consumer confidence. As discussed more fully above, a list of filed, pending PBN's will be posted publicly, along with each PBN synopsis. Following completion of its evaluation, the Agency's analytical memorandum and response letter for each PBN will also be posted. Other materials, such as documents relating to pre-submission consultations and the portions of the PBN beyond the synopsis will continue to be available to the public under the Freedom of Information Act. The ready availability of information on the substances that FDA is considering, as well as the Agency's safety conclusions regarding the substances, should serve to increase consumer confidence in FDA's oversight activities.

Another benefit of the proposed rule is the increased coordination among the federal agencies that it will foster. The PBN must include information on the status of the subject substance at other federal agencies. See Proposed Section 192.25(c). We hope this requirement will heighten awareness of the agencies as to their fellow agencies'activities and, ultimately, improve coordination and cooperation among the federal agencies charged with overseeing the safety of the food supply.

             B.     Scope

As discussed above, the proposed regulations require FDA to be notified about "any bioengineered food . . . that will be introduced into interstate commerce for consumption in any form by humans or other animals."1   Proposed 21 CFR §192.5(a). "Bioengineered food,"however, is limited to food derived from a plant that is developed using a transformation event. Proposed 21 CFR §192.1(a).

The scope of the proposed regulation reflects the scope of the 1992 FDA Policy Statement, which is, essentially, the predecessor to the proposed regulation. However, we are concerned that new products may be under development or on the horizon that would not be covered by the proposed rule. For example, we understand that biotechnology producers are currently developing foods involving non-plant species, including animals such as fish, and that at least one such product is currently being monitored by FDA's Center for Veterinary Medicine (CVM) in the animal drug construct. See, e.g., FDA, "A New Kind of Fish Story: The Coming of Biotech Animals"in FDA Consumer (Jan.-Feb. 2001); Kaufman, "'Frankenfish'or Tomorrow's Dinner?" in The Washington Post at A01 (Oct. 17, 2000).

Although CVM may be working on a separate policy regarding transgenic animals, we believe consumer confidence would be strengthened by a unified FDA policy covering all foods produced through biotechnology. Recognizing that a policy of this nature probably will not be available in the near term, we recommend that FDA at least include a clear statement regarding the comprehensive nature of the Agency's oversight of all bioengineered foods, not just those derived from plant sources, in the preamble accompanying the final rule.

             C.     Timing

   1.     Submission Time

Proposed Section 192.5(c) requires notifiers to submit PBN's at least 120 days before the bioengineered food is "marketed." The proposed regulations do not define the term "marketed," nor does the preamble explain the term. The absence of explanation renders the submission requirement somewhat vague.

The proposed regulations do define the term "commercial distribution," which is the "introduction, or delivery for introduction, into interstate commerce for sale or exchange for consumption in any form by humans or other animals." Proposed 21 CFR §192.1(b). However, "marketing" might refer to a process such as advertising of a product that precedes the food's actual introduction or delivery for introduction into commerce. Accordingly, we recommend that FDA clarify the required submission timing and add any necessary definitions to the final rules.

                2.     FDA Response Time

The proposed rule states that FDA will issue its evaluation of the PBN within 120 days of the date on which the Agency files the PBN. Proposed 21 CFR §192.30(c). FDA chose the 120-day limit because (1) "it is consistent with contemporary expectations of the Congress for another notification program"and (2) FDA believes that "it can, in most circumstances complete its evaluation of a PBN within 120 days." 66 Fed. Reg. at 4713. Although we urge the Agency to review PBN's carefully and expeditiously, we are concerned that the 120-day standard may be difficult for FDA to meet.

First, the other notification system to which the Agency refers is the notification program for food-contact substances, which are, generally, materials used in food packaging or food processing equipment. 21 USC §348(h); see, also, 65 Fed. Reg. 43269 (July 13, 2000) (proposed regulations for food-contact notification program). As substances that are not directly added to food, but might become incidental elements of food, the potential dietary exposure to food-contact substances is minuscule. Indeed, many food-contact substances are now considered under the Agency¡¦s Threshold of Regulation policy, which exempts food-contact substances from regulation as food additives if the substances will not enter the diet at more than vanishingly small levels, i.e., 0.5 parts per billion (ppb). 21 CFR §170.39. Given the tiny dietary exposure, the commensurate risks are small and the data required to establish the safety of the intended conditions of use are generally less extensive. To assume that the Agency can review and evaluate the substantial safety information that will presumably be necessary to satisfy the potentially broad dietary exposure to bioengineered foods in the same amount of time that the Agency can review a food-contact notification seems optimistic.

The second basis for FDA¡¦s belief that it can complete its evaluation of a PBN within 120 days is the Agency's recommendation that prospective notifiers use the presubmission consultation program. 66 Fed. Reg. at 4713. Along these lines, FDA notes that the "median time for FDA's response to a final consultation was approximately 155 days and the average time was approximately 175 days." Id. at note 10. Despite FDA's recommendations, however, notifiers are not required to utilize the presubmission consultation program. Although FDA has allowed itself the option of extending the evaluation period for at least an additional 120 days, the extra four months may not compensate for the notifier's failure to utilize the presubmission consultation system, a process that will generally entail substantially more than 120 days. Moreover, the fact that the median and average times for responding to a final consultation (presumably the equivalent of a PBN) now exceed 120 days further suggests that the Agency may have difficulty meeting the 120-day standard.

Although we recognize that FDA is in the best position to evaluate its capabilities, we are concerned that the Agency may be setting itself up for failure or at least difficulty, a result that will not enhance and may harm consumer confidence. Accordingly, we respectfully request that the Agency reconsider and reconfirm its ability to meet the regulatory standard that has been proposed.

            

D.     Regulations Should Be Amended To Include Specific Reference to Toxicity Data

Proposed Section 192.25 sets forth the information that must be included in a PBN. Part VI of the PBN must include the health and safety data relevant to the substances introduced or modified in the food, such as the following: the chemical identities, levels, and dietary exposures to the substances; data on the substances'allergenicity; and "a discussion of data or other information relevant to other safety issues that may be associated with the substances introduced into, or modified in, the food." Proposed 21 CFR §192.25(f).   The latter phrase is the closest reference we could find to toxicity data. Although we recognize that traditional "Redbook"2 principles on the toxicological feeding studies appropriate for establishing safety would be difficult to apply in the biotechnology context3 and that, in most cases, appropriate safety data will need to be determined on an individual basis, we recommend that the Agency provide some further guidance on toxicity data in the regulations, if only to allay concerns of consumers who have been told that FDA does not require any safety testing on bioengineered foods.

             E.     Mandatory Nature of Pre-Market Notification Process

Section 701(a) of the FD&C Act authorizes the promulgation of regulations for the efficient enforcement of the Act. 21 USC §371(a). FDA relies on this provision as the specific basis for proposing the pre-market notification regulations. See, e.g., 66 Fed. Reg. at 4712, cols 1, 2. FDA further states that the pre-market notification system must be mandatory to ensure that the Agency is aware of all bioengineered foods entering commercial distribution that are subject to FDA¡¦s jurisdiction and to help ensure that all market entry decisions by the industry are made consistently and in full compliance with the law. Id. Although FDA sets forth a compelling argument for why the regulations should be mandatory, the strength of the associated enforcement mechanism will serve as the measure of whether the system is actually mandatory.

In the preamble, FDA fully explains the range of legal resources and sanctions that will be brought to bear on bioengineered foods that are introduced into commerce despite the fact that they are adulterated, misbranded, or otherwise not in full compliance with the FD&C Act. 66 Fed. Reg. at 4722. For example, seizure of the food, as well as potential injunctive relief and criminal penalties would clearly apply if a manufacturer of a bioengineered food that met the FD&C Act's "food additive" definition introduced the food into commerce, despite the fact that the Agency responded to the PBN by stating that the PBN did not provide a sufficient basis for establishing the legal status of the food. However, FDA is less clear with respect to the penalties that would apply for failure to file a PBN on a bioengineered food that otherwise complied with the FD&C Act, e.g., the product was properly considered GRAS and no special labeling was warranted. If FDA intends to apply any enforcement tools in this situation, we recommend that the final rules be clarified in this regard.

            

F.     FDA Should Monitor the Pre-Market Notification System for Sufficiency To Ensure Safety of Food Supply and Consumer Confidence

Finally, the type of system proposed by the Agency deserves comment. Specifically, FDA has proposed a pre-market notification rather than pre-market approval program. Indeed, FDA unequivocally states in the preamble that the proposed system is not a mandatory "premarket approval"program. 66 Fed. Reg. at 4711 ("FDA is neither proposing to require premarket approval for all foods developed using rDNA technology nor is the agency proposing an across-the-board requirement that all such foods bear special labeling."). FDA's understanding of the extent of the program is further reflected in the responses that the Agency intends to provide following the conclusion of the evaluation period. For example, if FDA decides to extend the evaluation period or if the Agency concludes that the PBN is insufficient to support a suitable regulatory status, the response letter in either circumstance states that FDA "expects that the bioengineered food will not be marketed." Proposed 21 CFR §192.30(d)(1), (3) (emphasis added).

Although a stronger system might eventually be necessary, we believe the system proposed by the agency will immediately improve the Agency's oversight of bioengineered foods in a manner that is consistent with FDA's current statutory authority.4 Given the Agency's dedication to ensuring a safe food supply and sufficient oversight of foods produced through biotechnology, we expect that FDA will periodically appraise the efficacy of the pre-market notification system to ensure that it fully serves the needs of ensuring the safety of the food supply and maintaining high consumer confidence in the food supply.


*          *          *


We appreciate your consideration of our comments. If we may provide further information on this issue or if we may be of assistance in any other way, please do not hesitate to let us know.

Sincerely,

Tim Hammonds
President and CEO

Enclosures

1   The proposal exempts from the pre-market notification requirement those bioengineered foods that, essentially, have been the subject of a previous FDA evaluation. Proposed Section 192.5(a)(1)-(3).

2   FDA, Toxicological Principles for the Safety of Food Ingredients (2000).


3   The problems with traditional toxicological feeding studies in the context of bioengineered foods include the practical difficulties inherent in exposing the test animals to sufficient quantities of the test substance, which is present at very low levels in the food, without disturbing the nutritional balance of the diet in a manner that would compromise the validity of the test results.

4   Indeed, to attempt to subject all bioengineered foods to the pre-market approval jurisdiction granted to the agency for food additives and from which several categories of foods are explicitly excluded (e.g., GRAS) might place the rule in legal jeopardy.