Memorandum 2011-02: Harmonized data requirements for live attenuated Newcastle Disease virus vaccine master seed viruses – Intracerebral pathogenicity index testing

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February 14, 2011

Canadian Manufacturers and Importers of Veterinary Biologics

This memorandum serves to notify regulated Canadian veterinary biologics manufacturers and importers of the requirement for filing intracerebral pathogenicity index (ICPI) test results for all master seed viruses that are used to produce live attenuated Newcastle Disease (ND) virus vaccines. These requirements have been implemented in order to conform with international ND vaccine safety assessment standards, which employ a standardized ICPI testing protocol to characterize the residual virulence of master seed viruses for modified live ND vaccines for use in poultry. This will also facilitate compliance with export certification requirements for Canadian hatching eggs, live poultry and poultry products destined for European markets.

Canadian importers and manufacturers of ND vaccines licensed prior to December 1, 2010, were contacted earlier in 2010 and required to submit ICPI test results for all master seed viruses used to produce licensed ND vaccines. Any live attenuated ND vaccines that derived from master seeds which do not conform with this documentation requirement have been removed from the respective Canadian Veterinary Biologics Product Licence or Import Permit.

All future live attenuated ND vaccine licensing applications must include ICPI test results for each ND master seed virus used to produce the vaccine. This ICPI testing must be conducted for each master seed virus, even if the master seed virus is derived from a known lentogenic ND virus strain. In the interest of reducing the use of animals for regulatory testing, the Canadian Centre for Veterinary Biologics (CCVB) will accept ICPI test results that were previously generated for another regulatory agency. In addition, the CCVB may consider alternative master seed test methods, as they become available and accepted internationally.

This ICPI testing requirement will apply to naturally derived attenuated master seed viruses, as well as genetically modified ND master seed viruses. The testing requirements for recombinant master seed viruses containing ND virus genes will be determined on a case-by-case basis.

Live attenuated ND vaccines for use in routine vaccination programs must be prepared from ND virus strains for which the master seed has been tested by a method which is consistent with European Commission requirements, and shown to have an ICPI of either of the following:

  1. less than 0.4 if not less than 107 EID50 (50% egg infectious dose) are administered to each bird in the ICPI test; or
  2. less than 0.5 if not less than 108 EID50 are administered to each bird, in the ICPI test.

The ICPI is calculated as shown in the following example. To conduct the test, 10 day-old chicks are tested by intracerebral inoculation of ND virus, and observed for eight days. The ICPI is calculated based on the cumulative scores in each category, multiplied by a weighting factor of 0, 1, or 2.

Example of ICPI Calculation using Number of Observations on Day 1-8 After Intracerebral Inoculation of Live Attenuated ND Vaccine Virus:

Clinical Signs12345678TotalScore
Number of birds – Normal 10 4 6 8 8 9 9 9 63 63 x 0 = 0
Number of birds – Sick 0 6 4 2 1 0 0 0 13 13 x 1 = 13
Number of birds – Dead 0 0 0 0 1 1 1 1 4 4 x 2 = 8

ICPI = (Total Score) 21 / 80 (Total Observations)

= 0.26

Manufacturers and importers are advised to consult with the CCVB regarding the specific documentation requirements for ND licensing submissions.

Glen Gifford, DVM, MSc
National Manager
Canadian Centre for Veterinary Biologics
Terrestrial Animal Health Division
Canadian Food Inspection Agency