January 28, 2014 Memorandum To: Porcine Epidemic Diarrhea (PED) Emerging Issues Working Group From: Glen Gifford, DVM, MSc National Manager, Canadian Centre for Veterinary Biologics Canadian Food Inspection Agency Subject: Application for permit to import Porcine Epidemic Diarrhea Vaccine, RNA (trade name: iPED+) _______________________________________________________________________________ The Canadian Centre for Veterinary Biologics (CCVB) has received an application for a permit to import a PED vaccine from the United States. The vaccine is manufactured by Harrisvaccines Inc., Ames, Iowa, and is sold under the trade name iPED+. It is my understanding that the use of this vaccine in Canada (and other inactivated vaccines) would be acceptable to the CFIA colleagues in Programs, Operations, and Science Branches, as well as the Chief Veterinary Officers (CVOs), and other stakeholders in the Canadian swine industry. To confirm, I would like to consult with key stakeholders, e.g., CVOs, Canadian Pork Council (CPC), Canadian Association of Swine Veterinarians (CASV), and the Canadian Swine Health Board (CHSB) on the upcoming PED Emerging Issues conference call on January 29, 2014. I have, prepared this memo to serve as background for the conference call, so we can briefly discuss this proposal and solicit input from key stakeholders. The vaccine is intended for emergency use under veterinary supervision, as an aid in preventing porcine epidemic diarrhea (PED). The manufacturer recommends administering a 1 mL dose intramuscularly in healthy pigs 3 weeks of age or older, and repeating the vaccination approximately 3 weeks after administration of the first dose. The supervising veterinarian would provide herd-specific vaccination recommendations for immunization of various ages and classes of pigs. Pregnant gilts and sows could be vaccinated prior to farrowing, to stimulate production of colostrum antibodies for passive protection of piglets. The Harrisvaccines website has a news article where it is noted that, in previously infected herds, the iPED vaccine is being used at 7-21 days prefarrowing in previously infected sows to provide an immunity boost. http://www.harrisvaccines.com/index.cfm/18925/27312/actively_seeking_pedv_solution The initial import permit application is from a veterinarian who is animal health manager of a large multisite operation which has not yet been exposed to PED virus. The vaccine would be administered to pigs in sow barns, as a precautionary measure, to build resistance, in case the sites become exposed to PED virus in the future. Approximately 75,000 doses would be imported over 6 months for use in the company's herds (not for resale). The CFIA Canadian Centre for Veterinary Biologics (CCVB) is awaiting the manufacturer's test results for the batches that would be available for importation into Canada, and we intend to proceed as soon as possible with issuance of an initial import permit. We could issue similar permits to other veterinarians for emergency use of this vaccine in their clients' herds. We will restrict importations of this unlicensed vaccine to veterinarians, and will require that the veterinarians maintain records of the herds where the vaccine is used. If the iPED+ vaccine is fully licensed in the future, it would be distributed through a commercial importer. If other products are developed, the CCVB could also authorize their restricted use, under similar import permits, or a Permit To Release Veterinary Biologics for products manufactured in Canada. This vaccine cannot cause PED, however vaccinated pigs would develop antibodies to the PED virus spike protein, so they would test "positive" on surveillance tests that detect antibodies to this protein. -1– PED Vaccine Memo, continued January 28, 2014 The iPED+ vaccine is not yet licensed in the United States, or Canada. The USDA APHIS Center for Veterinary Biologics has authorized the manufacturer to produce the vaccine for emergency use, under veterinary prescription, based on demonstrated safety of the technology platform (the replicationdefective virus-like particle cannot cause PED) and reasonable expectation of efficacy (based on composition of the vaccine and preliminary immunogenicity studies in small numbers of vaccinated pigs which were shown to develop antibodies against the PED spike protein, which is believed to be an important target of PED virus neutralizing antibody. The iPED+ vaccine is based on a virus-like particle that is derived from genetically modified alphavirus Venezuelan Equine Encephalitis (VEE) virus, in which some essential structural genes have been deleted, and a segment of RNA coding for the antigens in the spike protein of PED virus has been inserted. The iPED+ vaccine is comprised of a segment of RNA coding for the PED virus spike protein, which is packaged within the structural proteins of an attenuated strain (TC-83) of VEE virus. The virus-like particles are capable of infecting cells within the tissues of the vaccinated animal, where they stimulate the infected cells to produce PED virus spike protein, but the virus-like particles cannot replicate, so the vaccine cannot cause VEE or PED. Since the virus-like particles lack the genetic information needed to produce their structural proteins, they cannot form complete viruses, and are, therefore, characterized as being replication-defective. This foreign antigen (PED virus spike protein) is expressed on the surfaces of infected cells, and is recognized by the animal's immune system, leading to protective immune responses against the spike protein of PED virus. Harrisvaccines has employed this virus-like particle technology to develop similar vaccines for other diseases, e.g., porcine reproductive and respiratory syndrome and swine influenza. As part of the review and approval process, the CCVB will be preparing an environmental assessment for the Harris Vaccines Porcine Epidemic Diarrhea Vaccine, RNA, which will be posted on the CCVB website at the following URL: http://www.inspection.gc.ca/animals/veterinary-biologics/licensedproducts/environmental-assessments/eng/1318464704520/1320704752007 Glen Gifford, DVM, MSc National Manager, Veterinary Biologics Animal Import/Export Division Animal Health Directorate Canadian Food Inspection Agency 59 Camelot Drive, Ottawa, Ontario Ottawa, Ontario, Canada K1A 0Y9 Telephone: (613) 773-7407 Facsimile: (613) 773-7570 Email: [email protected] -2-