Docket Management
Docket: 02D-0324 - Draft Guid.: Drugs, Biologics & Medical Devices Derived from Bioengineered Plants
Comment Number: EC -14

Accepted - Volume 9

Comment Record
Commentor Mr. David Miller Date/Time 2003-01-02 17:09:16
Organization Iowa Farm Bureau Federation
Category Association

Comments for FDA General
1. General Comments January 3, 2003 Dockets Management Branch (HFA-305) Food & Drug Administration 5600 Fishers Lane Room 1061 Rockville, MD 20852 Re: Docket No. 02D-0324: Guidance for Industry – Drugs, Biologics and Medical Devices Derives from Bioengineered Plants for Use in Humans and Animals Electronic delivery: The Iowa Farm Bureau Federation is the largest general farm organization in the state of Iowa with more than 150,000 member families representing more than 80,000 active farm families. We appreciate this opportunity to present comments regarding regulatory control of biotechnology-derived crops. We strongly support the use and application of biotechnology for crop production. We believe that scientific advancements in this arena hold great promise for increased crop production, improved disease and insect control, as well as nutrition and pharmaceutical applications. Iowa’s farmers have been early and rapid adopters of biotechnology for soybean and corn production. We believe that there are many significant economic and environmental benefits that accrue due to proper applications of this technology. We believe that it is important for USDA and FDA to coordinate their regulatory programs for plant materials modified through biotechnology that are intended for industrial and pharmaceutical uses. We believe that the identity-containment systems for field testing of these crops must be designed to achieve a very high probability of containment. Greater isolation through increased separation distances and stricter requirements on pollen movement control are appropriate requirements for such systems. We urge APHIS to provide more transparency with regards to the level of containment being targeted through the regulatory process. Unfortunately, any containment system for field-grown, pollen-shedding crops will be subject to some probability of system leakage. And, to date, there is no method for finding such system leaks, short of testing all of the non-regulated crops that are intended for food or feed. The lack of a visually-distinguishable characteristic for regulated plant materials that look identical to non-regulated materials shifts all of the risk of containment system failure to commodity crop producers, grain handlers and food or feed manufactures and marketers. The full federal regulatory program for pharmaceutical crops must take into account risks to the marketing system for fungible grains as well as risks that are associated with food safety and the environment. One way to solve this problem is to establish scientifically-sound, risk-based tolerances for adventitious presence of the regulated products in food and feed products. To facilitate this, FDA should categorize introduced proteins according to their risks to the food and/or feed systems. Minimal presence tolerances should be established for adventitious presence of low-risk proteins. In cases where adventitious presence of a pharmaceutical or industrial protein would pose significant health risk, USDA-APHIS or FDA should require some sort of visually-distinguishable characteristic for these products so that farmers, grain handlers, or others along the food and feed marketing chain can take appropriate steps to intervene if regulated pharmaceutical or industrial plant materials are observed in commodity grains. We recognize that inclusion of a visually-distinguishable characteristic does not assure the prevention of adventitious presence, nor does it guarantee that regulated and non-regulated grains will not become mixed, but it would create another tool for those in the food and feed marketing channels to take action to stop the further spread or contamination of additional grain supplies if such an event were to occur. Visual distinguishability would strengthen the ability of producers of food and feed crops to maintain integrity and quality of their crops and markets without reliance on extensive testing at each and every step of the marketing channel. This may become even more important if the level of field testing of pharmaceutical and industrial biotechnology crops becomes more prevalent in the major food production areas. From comments and guidance materials recently released by FDA, it appears that FDA’s approach to regulation of plant materials derived from biotechnology is one that is based on the principal that introduction of any regulated material into a food product is adulteration, and thus, strictly prohibited, regardless of the risk to human or animal health or the source of the introduction. On the other hand, it appears that both EPA and USDA-APHIS are taking a risk-based approach to regulation of the growing, handling and transport of such materials. This incongruity among the regulatory schemes leaves the door open for small, maybe even infinitesimally small, amounts of regulated materials to escape from the identity-contained production systems governing these products in the field, but these same infinitesimally small amounts could trigger product recalls and lead to significant market disruptions. The truly coordinated regulatory structure should have all parts of the regulatory process using scientifically-sound, risk-based criteria as the basis for the regulatory framework. Given that USDA-APHIS regulates the growing of regulated plant materials through a regulatory regime that could result in adventitious presence at very low levels in adjacent crops, it would seem to make sense that FDA, for purposes of determination of adulteration, should distinguish between overt introduction of an ingredient containing a regulated material versus simple adventitious presence at a very low level of a regulated material in crops that were not grown under USDA-APHIS control. At a minimum, we suggest that FDA consider establishment of risk classifications of introduced proteins and that USDA take these risk classifications into account when establishing the requirements for experimental field trial and production permits. 21 U.S.C. Section 342 says that, “A food shall be deemed to be adulterated: If it bears or contains any poisonous or deleterious substance which may render it injurious to health; but in case the substance is not an added substance such food shall not be considered adulterated under this clause if the quantity of such substance in such food does not ordinarily render it injurious to health.” We believe that under this policy FDA is not required to deem foods to be adulterated simply because miniscule amounts of a regulated material are found to be present in a food product. The regulated materials must be “added” materials, and it also requires that the added material be deemed to be deleterious or poisonous. FDA has set tolerances for pesticides and naturally occurring mycotoxins. FDA should also set tolerances for adventitious presence of regulated plant materials based on the risk of the introduced protein, especially if the introduced protein is one that is already in the food system, or could be determined to be GRAS (generally regarded as safe). We believe it is important for the regulatory agencies involved to develop field production protocols that will minimize any risk of out-movement of regulated materials into crops intended for food or feed. We would further suggest that USDA-APHIS provide more transparency with respect to the level or risk for out-movement that is being targeted by the production protocols. It would be appropriate for USDA to specify the level of risk of non-containment for regulated materials that identity-containment systems must achieve, and then require producers of regulated materials to justify how their identity containment system and field tests meets those requirements. We believe that it is possible to develop field testing protocols that use combinations of isolation and separation distances along with pollen movement control mechanisms such as male-steriles, mechanical de-tasselling, temporal offsets, etc., to achieve extremely low levels of risk of out-movement of pollen from regulated materials. We believe it would be consistent with a scientifically sound, risk-based regulatory system for FDA to regulate such materials in a similar risk-based manner if adventitious presence is detected at very low levels in food or feed products beyond the field space and buffer areas defined in the production permit. We believe that production protocols for biopharmaceutical crops, at a minimum, must take into account the following items: · physical containment (handling and storage) · physical separation from food and feed production (buffer zones) · temporal separation of pollination events (planting offsets) · biological degradation of plant residuals and volunteer seed · sequential separation from food and feed production (crop rotations) · the risk of the introduced protein (toxicity, allergenicity, etc.) · recordkeeping Physical Containment – We believe it is imperative that the production protocols for biopharmaceutical crops contain a plan for complete physical containment of the crop, its residues and any “volunteer” crop residues. We support the concept of use of dedicated equipment to minimize lack of containment. We believe a strong certification program (e.g. ISO 9000 or 9001) would be a valuable asset to those involved with production needing strong materials flow and control with auditable record systems. We believe that physical containment for biopharmaceuticals is more than identity preservation. It also means taking the steps to prevent out-movement of any regulated materials from the production, storage or handling systems. Physical Separation – Due to the nature of pollination movement, it is essential that adequate physical separation be established for any pollen-shedding crop with introduced proteins. We believe that USDA and FDA should set physical separation distances based on the risk of the introduced protein, the nature of the pollen shed of the carrier crop, and the level of containment being sought. Temporal Separation – We support the concept of temporal separation of the production of crops with introduced proteins. A 21-day separation should be adequate for most conditions. Biological Degradation – We urge USDA and FDA to consider the rate of biological degradation of dropped seed, volunteer crops, etc as they construct production protocol requirements. If a 100 seeds (an ear of corn) falls to the ground, and 90 percent of the kernels degrade in a year, then it is likely that there could be volunteer presence from this seed for three or four subsequent years. Sequential Separation – We believe that, as an additional safety measure, no food or feed crop (for harvest) be allowed to directly follow production of a biopharmaceutical crop. For a crop with a long degradation time for dropped seed, a multiple-year separation may be appropriate before any food or feed crop (for harvest) be allowed. We do not believe that forage or cover crops should be banned on such land, just that these crops not be allowed to be harvested for food or feed in the year following production of a biopharmaceutical crop. Risk of the Introduced Protein – We believe that FDA should classify all introduced proteins with regards to their health risks through either food or feed. Based upon that risk assessment, FDA and USDA should adjust the permit requirements for firld trials and production plots of biopharmaceutical crops. Low-risk crops, for example, may only have to meet a minimum set of production protocol standards, whereas high risk proteins may need to meet a higher set of containment and separation standards. Record Keeping – We support establishment of recordkeeping requirements for producers and handlers of any regulated crop materials. Such records should allow for a complete accounting for all regulated seed and the production and by-products from such seed. We support the inclusion of alternative uses (example: biomass energy production, co-firing of boilers, etc.) for unused seed, waste materials, residues or other by-products of biopharmaceutical production. However, all materials should be accounted for within the recordkeeping system. We appreciate the opportunity to provide these comments. We urge the federal government to take the necessary steps to fully coordinate a scientifically sound, risk-based regulatory process for plant materials modified through biotechnology. We believe there is much to be gained through applications of biotechnology through plants, but it is imperative that the development of this technology not disrupt, nor pose an undue threat, to our domestic food supply or international markets. Sincerely, David Miller Director, Commodity Services Iowa Farm Bureau

EC -14