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Response to FDA Questions on Premarket Biotechnology Notice (PBN) Proposal
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May 3, 2001
Dockets Management Branch (HFA-305)
Food and Drug Administration
5630 Fishers Lane, Room 1061
Rockville, MD 20852
- Re: Premarket Notice Concerning Bioengineered Foods
Docket No. 00N-1396
Dear Sir/Madam:
The Biotechnology Industry Organization (BIO) is the not-for-profit trade organization which represents over 950 biotechnology companies, academic institutions, state biotechnology centers and related organizations in all 50 U.S. states and 33 other nations. BIO members are involved in the research and development of agricultural, health care, industrial and environmental biotechnology products. A significant number of BIO members are using biotechnology to improve the agronomic, nutritional and other properties of many tree, fruit, vegetable and field crops.
BIO strongly endorses a mandatory premarket notification process that will ensure review by the Food and Drug Administration (FDA or agency) under the Federal Food, Drug, and Cosmetic Act (FFDCA or act) of all food and feed products produced using biotechnology and enhance consumer access to product information and agency determinations. FDA's proposed rule would strengthen the current consultation process that has worked well since 1992 by providing for mandatory notification, mandatory data submission, mandatory review and mandatory disclosure. BIO member companies have consulted with FDA on all products that are on the market today and fully support a rigorous FDA review process.
Response to FDA Questions on the Premarket Biotechnology Notice (PBN) Proposal
The following numbered paragraphs respond to specific questions and requests for comments raised by FDA regarding the proposed rule.
1. Should a final rule encompass crops developed by wide crosses or other conventional breeding methods?
The final rule will work most effectively if the PBN process and FDA's resources are focused on biotechnology-derived food, as defined in the proposal. BIO supports the position set forth in the FDA's 1992 Policy regarding the circumstances under which
foods derived from new plant varieties, including wide crosses, may be subject to the food additive requirements of the FFDCA. The PBN proposal is being issued by FDA because of the public's interest in biotechnology-derived foods and in order to ensure that FDA has the maximum amount of information about foods from biotechnology-derived plants and the ability to administer the FFDCA's various provisions in the most efficient manner possible with respect to those foods. The agency has made it clear that the scientific and legal underpinnings of the 1992 Policy remain in effect. The scope of the proposed rule is also consistent with the scope of existing premarket regulatory programs at EPA and USDA.
2. Is the scope of premarket notification and exclusion from notification appropriate?
The proposed scope of premarket notification and exclusion from notification is appropriate. The definition of "transformation event" would be more accurate and consistent with the FDA's intent (as described in the preamble to the proposed rule) if it referred to the introduction of genetic material "into the genome of an organism".
BIO agrees with FDA's conclusion that a PBN should not be required for a biotechnology-derived food for which both the applicable transformation and the use or application of the biotechnology-derived food have been addressed satisfactorily in a completed consultation under the 1992 Policy. 66 Fed. Reg. 4713. Proposed section 192.5(a)(3) already reflects FDA's position by specifically including letters issued by FDA between May 1, 1994, and the effective date of the rule. However, the wording of the preceding two numbered paragraphs in proposed section 192.5(a) could be read to require that the transformation event and use or application of the biotechnology-derived food have been addressed in a previous PBN submission. This language should be revised to make it clear that it is sufficient for these issues to have been addressed either in a previous PBN submission or a consultation that results in a letter issued between May 1, 1994, and the effective date of the final PBN rule.
3. How should FDA administer submissions under the current premarket consultation process pending as of the date the final rule takes effect?
Under appropriate circumstances, a notifier that has a premarket consultation pending at the time the final rule takes effect should be given the option of completing the consultation process or converting to a PBN. In order to avoid any potential for abuse of this option, only those companies that have initiated a consultation more than 45 days before the effective date of the final rule would be eligible to complete the consultation process. Parties initiating a consultation within 45 days of the rule's effective date would be required to submit a PBN. While most companies are likely to convert their consultation to a PBN, this flexibility will ensure that FDA has an opportunity to properly review the biotechnology-derived food and, at the same time, recognize the nature of the agricultural cycle in which planting seasons are of critical importance to seed companies and growers. Where delay inherent in converting a particular consultation to a PBN would result in the loss of a planting season, a company might decide to exercise its option to complete the consultation process instead.
4. Is it appropriate for FDA to require that the data or information submitted relate to a plant line whose derivation can be traced to the transformation event that is the subject of the notice and that contains the genetic material introduced via the transformation event?
BIO agrees that it is appropriate to require that the data or information submitted relate to a plant line whose derivation can be traced to the transformation event that is the subject of the notice and that contains the genetic material introduced via the transformation event. Of course, FDA would be expected to continue the current practice, widely adopted by regulatory agencies in the U.S. and elsewhere, of accepting certain studies that are appropriately conducted using pure protein, identical or substantially similar to the protein expressed in the plant.
5. Is it appropriate for FDA to require an electronic disclosure copy of a PBN and to provide a notifier with an opportunity to request a waiver from this requirement?
BIO supports enhanced public access to information concerning PBNs, including information made available in electronic form over the Internet. Notifier preparation of a disclosure copy of a PBN will help expedite the availability of this information and, if properly administered, will also help prevent the inadvertent disclosure of any trade secret and confidential commercial information contained in the PBN that is entitled to protection from competitors under federal law. BIO encourages the agency to provide notifiers with the opportunity to request a waiver from the requirement for submission of an electronic disclosure copy.
6. What technological advances in rDNA technology are likely to result in commercial products that would not be addressed by the proposed submission requirements?
The Coordinated Framework issued by the Executive Branch in 1986 anticipates a dynamic regulatory process in which refinements may be necessary and desirable to keep pace with the technology and continue to provide for the safety of the food supply. In keeping with that approach, the PBN proposal builds on knowledge gained by FDA since issuance of the 1992 Policy. The definitions in the proposal are sufficiently broad to cover the range of biotechnology-derived plants currently under development. The preamble to the proposed rule correctly notes that as rDNA technology continues to evolve it may not be possible for the agency to anticipate every new scientific and regulatory issue that may arise. BIO will work with the FDA to consider appropriate future modifications to its policies, procedures, guidelines and rules in order to ensure consumer confidence in the safety of biotechnology-derived foods.
7. Is it appropriate/adequate for FDA to require that a PBN include data or information about the identity and function of substances introduced into, or modified in, the food, the level of these substances in the biotechnology-derived food, dietary exposure to these substances, the potential that a protein introduced into the food will be an allergen, and a discussion of other safety issues that may be associated with these substances?
In keeping with the scope and type of data currently being submitted to FDA as part of the consultation process, BIO agrees that it is both appropriate and adequate for the agency to require that a PBN include data or information about the identity and function of substances introduced into, or modified in, the food, the level of these substances in the biotechnology-derived food, dietary exposure to these substances as expressed in the food, the potential that a protein introduced into the food will be an allergen, and a discussion of other safety issues that may be associated with these substances.
8. Should the rule also include a requirement that a premarket notice for a biotechnology-derived food include methods by which the food could be detected? In particular, under what circumstances should such methods be required? Under what rationale (e.g., the modification to the crop makes the food acceptable for animal feed but unacceptable for human food)? Should any such required methods be only for raw agricultural commodities, representative finished foods likely to contain the modified food, or both? Should any such required methods contain sufficient information, such as primer sequences, to enable technically-proficient non-government laboratories to use them? What other criteria, if any, should there be for required methods (e.g., cost)?
BIO supports a process that will ensure that validated test methods for detection of protein in raw grain are in place and accessible prior to market entry. In most cases, the appropriate test methods would be provided to the Grain Inspection, Packers and Stockyards Administration (GIPSA) within USDA in accordance with current industry practice. In those few instances where the biotechnology-derived food was not comparable to a conventional food, then a validated test method for the appropriate component of the food would be provided to FDA as part of the PBN or other appropriate regulatory process. Under longstanding agency policy, the labeling of food must disclose all facts that are material in light of representations made in the labeling or in light of consequences that may result from the use of the food (e.g., enhanced nutritional content, allergenicity). If, consistent with this policy, FDA or the producer should determine that labeling was required for a finished food, then a validated test method for the appropriate component of the finished food should be provided to FDA. Some of the factors to be considered by the agency in addressing test methods for representative finished foods include technical feasibility, variation in food matrices and cost.
9. FDA requests comment on the public disclosure and confidentiality provisions of the proposed rule and on the adequacy of the information that FDA is proposing to provide to notifiers regarding the relevant FOIA procedures and criteria.
BIO supports enhanced consumer access to product information consistent with protections afforded to trade secret and confidential business information under federal law and applicable FDA regulations (21 C.F.R. pt. 20). Consumer acceptance is of critical importance to the biotechnology industry and access to relevant product information is a key element in assuring that acceptance. At the same time, appropriate safeguards must be in place to protect the financial investments made in the development of biotechnology products and the many thousands of jobs that are tied to the biotechnology industry. Without adequate research and development funding and a talented labor pool the many benefits of biotechnology will not be realized. The proposed rule strikes an appropriate balance between these two objectives.
The rule would make a PBN public on the date it is filed by the agency. Proposed § 192.40(a)(1). However, the FDA would have up to 15 working days after filing the PBN to send a letter informing the notifier of the date on which the FDA filed the PBN. Proposed § 192.30(b). In many cases, this would likely result in members of the public making inquiries of the notifier prior to the notifier realizing that FDA had filed the PBN. In order to allow the notifier to better respond to public inquiries, the rule should provide that, at the notifier's request, FDA would be required to alert the notifier of the filing of the PBN either by telephone, facsimile or electronic mail.
Additional Comments
1. Consistent and Accurate Terminology. The proposed rule requires submission of a "premarket biotechnology notice," but uses the term "bioengineered food" to describe the category of foods subject to the PBN requirement. In addition to the inconsistency in terminology, "bioengineered food" incorrectly suggests that in all or even most cases a significant difference would exist between the biotechnology-derived food and its conventionally-derived counterpart. In a companion notice published for comment on the same day, the agency made available a draft guidance for industry on voluntary labeling. As that guidance suggests, the terminology most readily understood by the public relies on the concept of products developed using biotechnology. The PBN rule should consistently use the term "biotechnology" rather than "bioengineered" and should use such phrases as "produced by biotechnology," "developed using biotechnology" and "biotechnology-derived" when describing the category of foods subject to FDA premarket review.
2. Attestation Requirements. The proposal would require the notifier to attest to several very broad and conclusory statements, but provides little or no justification for these requirements. Proposed § 192.25(a)(1)(i), (ii) and (5). Because of the rather novel nature of these proposed requirements, FDA needs to carefully consider the various legal and practical implications prior to promulgation of a final rule. Further review by FDA is particularly warranted with regard to the proposal that each PBN include a statement of compliance with the requirements of the FFDCA. Proposed § 192.25(a)(1)(ii). Assuming such a requirement can be justified, any such statement should be expressly limited to the intended use of the biotechnology-derived food as described in the PBN. Consistent with proposed section 192.25(a)(5), any attestation ultimately required by FDA should begin with the clause "[t]o the best of your knowledge."
3. Information on Regulatory Status. The proposal would require the notifier to describe the status of the biotechnology-derived food at other federal agencies and foreign governments. BIO supports enhanced coordination amongst regulatory agencies involved in the review of products of biotechnology. Operating under the Coordinated Framework, each of the three lead agencies -- FDA, EPA and USDA -- would be expected to be able to readily determine the status of submissions at the other two agencies. If FDA decides that this type of information is needed independently from the notifier, it should be limited to food or feed use of the biotechnology product. This appears to be the intent of the proposal, as reflected in the reference to EPA review of plant pesticide residues in proposed section 192.25(c)(2). The requirement to provide status information should also be limited to submissions that would authorize or otherwise clear the biotechnology product for commercialization (e.g., a petition for nonregulated status at USDA or for a tolerance exemption at EPA). Information required for activities outside the U.S. should be limited to whether a submission for a particular food or feed use has been approved or denied.
4. Relationship to PIPs. BIO agrees that, for foods that have been engineered to express a pesticidal substance, there should be a process to ensure coordination between the reviews conducted by the two responsible agencies -- FDA and EPA -- as related to issues of food safety. As currently worded, however, the rule could be interpreted to suggest that if any regulatory process related to the biotechnology product is pending at EPA at the time that FDA completes its review of the PBN, the FDA will not consider the PBN to have satisfied the premarket notice requirement. Proposed § 192.30(e)(2). Given the nature of the pesticide regulatory process, this would be an entirely unjustified interpretation that could unnecessarily delay the completion of PBN reviews that fully satisfied all applicable requirements of the Act. For example, registrants of previously approved pesticides routinely submit applications to amend their registrations under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). The vast majority of these FIFRA amendments would have no relevance to the issues associated with FDA's review under the FFDCA. Any coordination required under the rule should be limited to issues related to tolerances or tolerance exemptions that fall within EPA's jurisdiction under section 408 of the FFDCA. This would appear to be consistent with FDA's intent as expressed in section VIII.C. of the preamble to the PBN proposal. 66 Fed. Reg. 4718.
5. FDA Review Period. As proposed, the rule could be interpreted to permit FDA to extend the review period for PBNs indefinitely through repeated extensions of 120 days. Proposed § 192.30(d)(1). An efficient premarket notification process needs to provide all stakeholders with a greater degree of certainty regarding the length of the review period. BIO recognizes that FDA should be able to stop the clock "for cause" when it is waiting for additional information to be supplied by a notifier and the final rule should provide the agency with the flexibility to do so within the first 60 days of the review period. After that date, however, no further extensions should be necessary or appropriate. BIO recognizes that, under the proposed rule, FDA always has the ability to find that a PBN is not adequately supported and that the product should not be marketed. Proposed § 192.30(d)(2).
6. FDA Response to PBN. Under the proposed rule, the notifier would be required to attest that the biotechnology-derived food is as safe as comparable food and that the intended use of the food is in compliance with all applicable requirements of the FFDCA. The rule is designed to provide FDA with adequate time and information to evaluate the statements made in the PBN. For notifiers that do not satisfactorily complete the PBN review process, the proposal indicates that FDA will have the option to "inform a notifier that the premarket notice does not provide a basis for the notifier's view that the bioengineered food is as safe as comparable food or is otherwise lawful." 66 Fed. Reg. 4722; proposed § 192.30(d)(2). Yet for notifiers that satisfactorily complete the PBN process, proposed section 192.30(d)(3) would provide a rather perfunctory letter noting only that the agency has no questions, at this time, regarding the notifier's views on safety and compliance. In those situations in which the PBN review is successfully concluded, a definitive statement that more accurately reflects the regulatory status of the food would help to ensure that accurate information is provided to potential customers in the U.S. and internationally. Such a statement should logically be the converse of the statement that FDA would make regarding a PBN that does not provide a sufficient basis for the notifier's views.
For these reasons, BIO recommends that the letter provided to a notifier that has successfully completed the PBN process contain the following statement: "The FDA finds that the data and information submitted as part of the PBN, or otherwise available to the agency, provide a sufficient basis for the notifier's view that the biotechnology-derived food is as safe as comparable food and is otherwise in compliance with all applicable requirements of the Federal Food, Drug, and Cosmetic Act, and the agency has no questions regarding these determinations at this time. The biotechnology-derived food is cleared for commercial distribution pending any necessary regulatory action by USDA and/or EPA."
Response to Specific Information Collection Questions
1. Is the proposed collection of information necessary for the proper performance of FDA's functions? Will the information have practical utility? Is FDA's estimate of the burden of the proposed collection of information accurate, including the validity of the methodology and assumptions used? How could the quality, utility, and clarity of the information to be collected be improved? How could the burden of the collection of information on respondents be minimized, including through the use of automated collection techniques, when appropriate, and other forms of information technology?
Consistent with the data which BIO members have submitted to FDA since 1992, the rule would require submission of extensive data and information concerning the safety and nutrition of the biotechnology-derived food and its method of development. The notifier would be required to attest that the submission is balanced, including both favorable and unfavorable information. In addition, the notifier would be required to make relevant data or information that are not included in the PBN available to FDA upon request while the PBN is pending or after the biotechnology-derived food enters commerce for cause. Proposed § 192.25(a)(3).
BIO supports the proposed requirements for submission of relevant health and safety data, but makes specific recommendations elsewhere in this comment letter for instances in which the proposal requests information that is unnecessary or excessive. BIO also has questioned the justification for the various proposed attestation requirements. Concerning the requirement for postmarket submission of data, BIO suggests that the intent be clarified as being limited to data already in the possession or control of the notifier (i.e., FDA is not imposing a postmarket requirement that would obligate the notifier to generate original data or to obtain data from third-parties). With regard to estimated recordkeeping burden, the agency's discussion under the Paperwork Reduction Act states that the notifier would maintain a record of relevant data and information that are not included in the PBN. 66 Fed. Reg. 4725. This suggests that it was FDA's intent to limit the postmarket requirement to data in the possession or control of the notifier.
Thank you for the opportunity to comment on the premarket notification proposal.
Sincerely,
Michael J. Phillips, Ph.D.
Executive Director for Food and Agriculture
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