Quality of venoms for use in antisera

1
Quality of venoms for use in antisera
Needs for Good Venom Production Practice
Guidelines?

• Global Issues in Clinical Toxinology-Melbourne
  2328 November 2008 Dr Harold de Pomyers

2
Introduction

• Background
• 25 years of expertise
• Based on experience of Pharma companies audits
  and Drug Agency Inspection
• Recommendations made to W.H.O. working group
• 4  must 
• Zoological accuracy
• Purity Hygiene of venoms
• Traceability Reproducibility
• Ethics Staff safety and species preservation

3
Zoological accuracy

• Accurate Taxonomy and Species Identification
• Exclusive use of latest agreed latine taxons
•  Saw-scaled viper  refers to 11 different
  species worldwide
•  Krait  refers to 17 different species from all
  Asia
• Lachesis muta is called 63 different local names
• What are Elaps corallinus, Naja tripudians,
  Cenchis contortrix ?
• Capacity to clearly identify the donor animals
  species
• Requires a long time practice
• Experts to be regularly consulted

• Knowledge of species distribution
• Antivenom from Indian Echis (carinatus)
  sochurecki does not protect against African Echis
  (carinatus) ocellatus.

4
Zoological accuracy

• Careful selection of relevant valences
• Medically Important Venoms
• From epidemiological studies in the target area
• Polyspecific or monospecific?
• Paraspecific activity
• May extend therapeutic claims if clearly
  demonstrated
• Intra-Species variations
• Venoms from various geographical origins of the
  target area
• Venoms from animal pools
• Origin guarantee
• Ability to do capture missions
• The most consistent proof
• The best fit to demand

5
Zoological accuracy

• Species certification
• Several analytical methods available
• Electrophoresis simple, easy to read, correct
  discriminating ability
• Mass spectrometry profile
• HPLC profile
• All methods request a reference venom
• Comparison with a known spectrum
• Needs for standards

6
Purity Hygiene of venoms

• Animal farming methods
• Zootechnical parameters
• Individual cage housing
• Periodic cage disinfection cleaning
• Animals separated in several rooms
• Veterinary parameters
• Quarantine at arrival of all new animals
• Prophylactic measures against worms and
  infectious agents
• Veterinary prescription only
• Periodic issuance of veterinary certificates
• Rodents
• Under veterinary control
• Kept separately and free from insects
• Feed free of Animal flours

7
Purity Hygiene of venoms

• Venom milking method
• Harmless animal handling methods
• Reasonable milking frequency
• Minimizing stress
• Avoiding injuries through gentle handling
• Avoid bacteria contamination
• Use of top filmed sterile vials for collection
• Tools disinfection after each milking
• Operator hands disinfection after each milking
• Keep venom unsoiled
• Reject venoms soiled by saliva
• Reject venoms soiled by blood
• Diluant or preservative free
• Crushed scorpion telsons is not pure venom

8
Purity Hygiene of venoms

• Venom handling and storing methods
• Avoid proteolytic degradation
• Immediate deep freezing (-80C)
• Lyophilisation and re-drying
• Refrigerated storage in waterproof vials
• Laboratory tools
• Clean and regularly disinfected
• Procedures avoiding any possible cross
  contamination
• Cold rooms Maintenance
• Permanent temperature recording
• Permanent distant temperature monitoring

9
Purity Hygiene of venoms

• Venoms from quarantined and diseased animals
• Venom from quarantined animals
• Rejected during all quarantine period
• Rejected if quarantine prolonged
• Venom from diseased animals
• Rejected as long as symptoms observed
• Use of veterinary drugs venom rejected during
  longest recommended withdrawal period
• Keep records of veterinary prescription and drug
  used

10
Traceability and reproducibility

• Milking procedure
• Make interspecies confusion impossible
• Group after group
• Geographical origin after geographical origin
• Species after species (or subspecies)
• Vials identification
• Before sampling
• Indelible
• Keep history records

11
Traceability and reproducibility

• At animal level
• Individual identification
• Individual cages
• Individual electronic identification
• Cages and animals allocated to room
• Individual animals allocated to permanent donors
  groups
• Capability to trace back to individual history
• Individual pathological history
• Individual therapeutic history
• Individual feeding history
• Individual weight curve
• Milking from wild animals?
• Absolutely contrary to any traceability
  standards. OK for sea snakes or scorpions under
  certain conditions.

12
Traceability and reproducibility

• Production batch management
• Clear batch definition
• Opening and closing dates
• Production dates
• Lyophilisation date
• Donor animals
• Batch clearance rules
• Clear specifications
• Control methods
• Compliance with specifications
• Precise rules for Batch number allocation
• Batch identification
• Rules
• Species and subspecies mention

13
Traceability and reproducibility

• Identification of storing containers
• Any container must be clearly identified
• Milking vial
• Lyophilisation vial
• Storage vial
• Mention of species, origin, batch, dates
• Indelible identification
• Storage
• Shelf Identification
• Computerized inventory management
• Temperature records and remote control

14
Safety, Regulation, Ethics

• Safety of staff
• Serpentarium
• Access restricted to trained staff
• Staff education about danger and risks
• Staff in-depth training
• Clear and rehearsed emergency procedures
• Appropriate tools and clothing
• Never alone when handling animals
• Multiplying hurdles to animal escape
• Remote video monitoring
• Maintenance of an antisera stock

15
Safety, Regulation, Ethics

• Species preservation
• CITES and IATA regulations compliance
• Knowledge and implementation of CITES rules
• Animal freight packing according to IATA
• Compliance with local regulations
• Reason shall prevail
• Capture only the strict necessary
• Discourage unofficial traders smuggling
• Ensure best possible shipping conditions
• Be ready for reception at arrival
• Scorpions milk them, do not crush telsons

16
Safety, Regulation, Ethics

• Authorizations to operate a  snake farm 
• Authorization to farm and milk venomous animals
• Given to the company
• Facilities and process to be approved
• Staff to be officially approved and certified
• Authorizations restricted to named species or
  families
• Authorizations periodically renewed

17
Conclusion

• Venom antisera are life-saving drugs
• Implying strict procedures and quality of
  materials used
• Production of quality venoms is not a hobby, it
  is a specialist job
• Antivenoms manufacturers should care for
  specialists and lasting suppliers
• Costs consecutive to the use of  bad  products
  are higher than costs of quality products
• Antivenoms should heal and not harm
• Same quality requirements should apply to all
• Avoid market distortions

18

• Thanks for attention