WHO Guidelines on Transmissible Spongiform Encephalopathies in relation to Biological and Pharmaceutical Products (2003)

Key facts

• The consultation met at WHO headquarters in Geneva on 3 to 5 February 2003; the report is dated 16 September 2003, is 29 pages and was edited by WHO's Blood Safety and Clinical Technology Department.
• Its stated purpose was to update the 1997 WHO measures and to give regulators evidence for risk assessment, with a secondary aim of harmonising international regulation of TSE and medicinal products.
• The report names three reasons for policy concern: an unknown number of people may carry the BSE agent, misfolded prion protein is present in some peripheral tissues of vCJD patients, and blood from experimentally infected rodents, monkeys and sheep has transmitted disease.
• Tissues are grouped in three Annex tables: IA high infectivity (brain, spinal cord, retina and optic nerve, ganglia, pituitary, dura mater), IB lower infectivity (including lymphoreticular tissue, peripheral nerve, gut-associated tissue, cornea and blood) and IC no detected infectivity (including milk, skeletal muscle, semen and urine). The tables use only natural disease or primary oral infection in cattle, not laboratory-adapted strains.
• For animal derived starting materials the report says the ideal is to avoid bovine, ovine and caprine material, and otherwise to run a risk assessment covering source, cross contamination and the production process; sourcing from countries with absent or low BSE risk is preferred, and country geographic risk assessment is pointed to OIE and the EU Scientific Steering Committee, passed on to EFSA.
• On particular materials: milk and lactose from healthy cows are generally considered non-infectious; bovine serum should conservatively be assumed possibly infectious in small amounts; hide gelatin is lower risk than bone gelatin, with skull and spine best excluded and alkaline processing preferred; tallow derivatives made at high temperature under good manufacturing practice are considered highly unlikely to stay contaminated.
• For vaccines and recombinant products the report favours banked cells and seed lot systems on overall risk-benefit grounds, asks for carryover of potentially infectious seed material to be assessed, and recommends replacing working seeds of unknown provenance while allowing master seeds to stay.
• On blood, it found no credible transmission of CJD by human blood, components or plasma derivatives and none of vCJD by blood or plasma products at that date, noted infectivity in blood of sheep with natural scrapie, and said no screening test for donors existed.
• It kept the standing donor exclusions (human pituitary extract recipients, family history of CJD or similar TSE, human dura mater graft recipients), and advised recalling plasma derivative batches only when a donor is later recognised as having vCJD, not for classical CJD or risk-factor reports.
• It declined to recommend a single global blood policy, leaving each country to decide on precautionary measures with the effect on blood supply in view, and encouraged better methods to remove or inactivate agents and to develop antemortem tests for donor screening.
• The disease burden quoted was 313 iatrogenic CJD cases from past exposure (163 pituitary growth hormone, 136 dura mater, plus smaller groups) and, as of January 2003, 130 UK, 6 French and single Irish, Italian, US and Canadian vCJD cases.
• WHO's TSE hub page lists later related publications: a tissue infectivity guidelines document (16 September 2006) and WHO Tables on Tissue Infectivity Distribution (30 October 2010), and states that the 2003 consultation introduced a tissue infectivity category for risk assessment. The hub page does not list the 1999/2000 infection control guidelines.
• A separate WHO IRIS record, seen only as a search excerpt, describes "WHO infection control guidelines for transmissible spongiform encephalopathies" from a consultation of 23 to 26 March 1999, document WHO/CDS/CSR/APH/2000.3, 36 pages, dated 2000. Its content was not read. The 2006 tissue infectivity guidelines were confirmed only by their title page (2006, ISBN 978 92 4 154701 7).

Timeline

1. 1997WHO issues its earlier recommendations on medicinal products and TSEs (WHO/BLG/97.2), later updated by this report.
2. 1999WHO consultation in Geneva (23 to 26 March) that produced the infection control guidelines, published as document WHO/CDS/CSR/APH/2000.3 in 2000; seen only in a search excerpt.
3. 2001Joint WHO/FAO/OIE Technical Consultation on BSE, which the 2003 report cites as complementary work.
4. 2003Expert consultation held in Geneva, 3 to 5 February.
5. 2003Report published on 16 September 2003.
6. 2006WHO Guidelines on Tissue Infectivity Distribution in TSEs listed with date 16 September 2006.
7. 2010WHO Tables on Tissue Infectivity Distribution in TSEs listed with date 30 October 2010.