US Regulations

The commercial availability of ‘HoneySweet’ required regulatory approvals from the U.S. APHIS, and the U.S. Environmental Protection Agency (EPA). A voluntary submission to the U.S. Food and Drug Administration (FDA) is also typically a part of the regulatory process for GE food products.
A substantial body of research had been developed in the years between the initial development of ‘HoneySweet’ and data submission to the U.S. regulatory agencies which took place between 2003 and 2007. In addition to molecular characterization of the engineered plants, evaluation of resistance, and pomological studies, a series of risk assessment studies had been performed. These studies focused on the interaction of GE plums with PPV, aphid vectors, and with non-target insect species as well as gene flow. These investigations led to the findings that virus diversity was unaffected by PPV-CP transgenic plums; no virus recombinants were produced; there were no measurable effects on aphid populations or on other arthropods visiting the trees; no breakdown of PPV resistance in the presence of other Prunus viruses; and gene flow was quite low (http://www.aphis.usda.gov/brs/aphisdocs/04_26401p.pdf ).
Pre-submission consultations with U.S. regulatory agencies APHIS, FDA and EPA began in 2003. These consultations are not typical of many national regulatory systems but they are useful to applicants in preparing a submission that clearly addresses the regulatory requirements. APHIS has jurisdiction over the field testing of genetically engineered plants that contain plant pathogen genes or promoters. FDA has jurisdiction over GE plants used as food, and EPA regulates GE crop plantings of over ten acres for GE plants that produce molecules that protect plants against pests – protection against PPV in the case of ‘HoneySweet’. An application for determination of non-regulatory status was submitted to APHIS in September 20, 2004. A revised application was submitted on March 13, 2006 based on APHIS comments. In May, 2006, the petition submitted to APHIS was posted on the internet for 60 days of public comment. APHIS received 1,725 comments, 1,708 were not in support of deregulation. A large number of comments of non-support appeared to have been duplicated, cut and pasted, at the urging of a single anti-GMO website. APHIS addressed the comments and a determination of non-regulated status was made on June 27, 2007. The result of an Environmental Assessment undertaken by APHIS was a Finding of No Significant Impact (FONSI) (http://www.aphis.usda.gov/brs/aphisdocs2/04_26401p_com.pdf).
The dossier provided to the FDA consisted of information pertaining to the food uses of plum, compositional analyses of ‘HoneySweet’ compared to non engineered plum varieties, and in silico analyses of allergenicity and antinutrient potentials. Several databases and alignment approaches were used including the Allermatch allergen finder (www.allermatch.org), 7 and 8 amino acid word search using the same database, 80 amino acids sliding window alignment with the same database, and FASTA alignments done manually using the Codex Alimentarius guidelines which were used to create the Allermatch algorithms. The sequence was broken into 80 amino acid words and FASTA aligned with allergens (http://www.who.int/foodsafety/publications/biotech/en/ec_jan2001.pdf). The antinutrient potential of the insert sequences was evaluated using the NCBI antinutrient sequence data base. The submission to FDA was made on October 26, 2006 and was accepted on January 12, 2007. Following several requests for additional information or clarifications a communication was received from FDA on January 16, 2009 stating that, “Based on the safety and nutritional assessment USDA-ARS conducted, it is the understanding of FDA that USDA-ARS has concluded that plums derived from the new variety are not materially different in composition, safety, and other relevant parameters from plums currently on the market and that the genetically engineered plum line C5 does not raise issues that would require premarket review of, or approval by, FDA.” This letter indicated the completion of the FDA review.
A dossier was submitted to EPA in June, 2007. The initial EPA scientific review resulted in a request for additional information and/or clarifications and responses were submitted in July 2008. On October 29, 2008 EPA published in the Federal Register (73 FR 64325) a Notice of Receipt announcing an application to register a pesticide product containing a new active ingredient not included in any currently registered pesticide product (the PPV-CP gene). Four public comments were received during a 30 day comment period following the publication of the notice, all favorable.
EPA published a notice of filing of the petition in the Federal Register on November 14, 2008 (73 FR 67512) and the public was given a 30 day comment period. EPA received no comments on this notice. EPA required an independent laboratory validation (ILV) of the proposed method for detecting the transgene in ‘HoneySweet’ leaves. The leaf samples along with the detection method were sent out for third party validation. On April 1, 2010 the draft registration was published on the web (http://www.regulations.gov/#!docketDetail;D=EPA-HQ-OPP-2008-0742, accessed March 21, 2013) with a comment period ending on April 30, 2010. Sixty six comments were received sixty four were highly supportive of registration, including some questioning the need for registration and the classification of ‘HoneySweet plum as a biopesticide. These questions were raised with regard to the fact that the mechanism of resistance does not produce a plant incorporated protectant (PIP) since no CP is produced and DNA or nucleic acids have never been considered alone to be pesticidal substances. The labeling of trees as pesticidal was also brought into question. It was suggested that mandatory labeling of ‘HoneySweet’ trees and propagative material as pesticidal (fruit would not be labeled) would cause substantial damage to the market for ‘HoneySweet’ and sets a precedent for future transgenic virus resistant crops to be treated “in the same unscientific and irrational manner.” (for specific comments cited see http://www.regulations.gov/#!docketDetail;D=EPA-HQ-OPP-2008-0742, accessed March 21, 2013). EPA issued an unconditional Section 3 registration on August 8, 2011. At this point ‘HoneySweet’ had successfully completed the U.S. regulatory process, the first woody perennial tree fruit to have done so.