Download SNBTS IVIgG Product Characteristics: Preparation

Safety of IVIgG
Elspeth McIntosh
SNBTS Medical Information and
Pharmacovigilance Manager
Plasma
• “Non-UK” Plasma - USA or Germany
• All suppliers audited by SNBTS and approved by
the MHRA
• Unpaid donors wherever possible
• Meet Red Book/EU Blood Directive and/or FDA
requirements
• Donor selection as per the UK
• Epidemiological data satisfactory
Plasma Testing
• Plasma tested for
– HBsAg
– Anti- HCV
– Anti-HIV
– ALT
– PCR for HCV,
HBV, HIV,
Parvovirus B19
• Plasma pools tested
for
– HBsAg
– Anti- HCV
– Anti-HIV
– PCR for HCV,
HBV, HIV,
Parvovirus B19
Product Safety
• Full Traceability From Donor To Final Product
• Notification System For Advising Of Post
Donation Infections
• Validated Virus Elimination Step(s)
• Control Of Process To Prevent Recontamination After Virus Elimination Step
• Clinical Trial Data
• Post Marketing Surveillance
Virus Inactivation and Removal
Devise methods that will selectively inactivate
and/or remove viruses without undue product
damage/loss.
Study relevant test viruses in scaled-down
process.
Ensure that method is capable of giving the
degree of virus inactivation/removal required.
Virus Inactivation and Removal
 Scale-up the process to ensure that the smallscale results can be fully reproduced at
production scale.
 Validate the production scale operation to
ensure that this has been achieved.
 Monitor and control the operations to prove that
the procedure has been accomplished correctly
on every occasion.
Pooled screened human p lasma
Cold ethanol fracti onation to yield
fraction II
Remove process ethanol
pH4/pep sin VI step
Product returned to a neutral pH
Sterilisa tion, aseptic dispe nsing
and freeze drying
SNBTS Intravenous Immunoglobulin
Virus Safety
• Cold ethanol fractionation
• pH4/pepsin virus inactivation
• effective against
– enveloped viruses e.g. HIV, Hep B and C
– and non-enveloped viruses e.g. Hep A
vCJD Precautions
• All PFC plasma imported from countries with no
vCJD cases and little or no BSE.
• Donors selection processes designed to
exclude those who may represent a risk.
• Decontamination of UK fractionation facilities
before processing of non-UK plasma in 1998.
vCJD Precautions
• Very low level of infectivity in plasma pool
should an infective donation be processed.
• Research work identifies the potential for prion
reduction during manufacturing.
• So
• Very low risk of vCJD being transmitted via PFC
products.
SNBTS IVIgG Clinical Use
• SNBTS IVIgG supplied since 1985
• 270kgs used every year
• Licensed for use in
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1o and 2o Hypogammaglobulinaemia
Children with HIV
Bone Marrow Transplant
Kawasaki Disease
ITP
Guillain Barre Syndrome
Antibody Profile
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Adenovirus
Chlamydia
CMV
Coxsackie B2
Epstein Barr
Herpes Simplex
Influenza A + B
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Measles
Mumps
Mycoplasma
Q fever
RSV
Rotavirus
Varicella Zoster
Serious ADRs
• Serious Reactions to IVIgG are rare but the
follwing are well described.
– Acute Renal Failure
– Anaphylaxis/Anaphylactoid Reactions
– Aseptic Meningitis
– Hypertension
– Haemolytic Reactions
Non Serious ADRs
• Idiosyncratic batch related reactions – One or more of the following symptoms:
pyrexia, rigors, backache, nausea/vomiting,
malaise, breathlessness, rash, hyper or
hypotension, headache.
IVIgG for Neonatal Use
• ~ 6000 patients, 32 studies.
• Cochrane Review - Prevention of infection in
pre-term/LBW infants
• Cochrane Review - Treatment of infection in
neonates.
• Cochrane Reviews - Isoimmune haemolytic
jaundice in neonates
Neonatal Use - SNBTS IVIgG
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Small trial early 1990s
Randomised to IVIgG or 5% Dextrose
Study to small to produce significant results
No product related adverse events
AND
No reports of neonatal reactions in routine use.
Neonatal ADRs
• Cochrane Reports
– No Serious Adverse Reactions.
– Non-serious Adverse Reactions transient,
included hypotension, tachycardia, and
haemolysis
– related to too rapid infusion of placebo or
immunoglobulins.
• One study - increase in respiratory rate
following the first infusion of IVIG
Causality
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Temporal relationship
Pharmacological plausibility
Recognised class effect
Dechallenge/rechallenge
Underlying illness and medications
Irreversible events
Transient/episodic events
Topics covered
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Plasma selection
Virus safety
vCJD
Clinical use of SNBTS IVIgG
Neonatal experience
Adverse reactions
Conclusion
• SNBTS IVIgG is a well established product.
• Steps in place to reduce risk of virus
transmission/vCJD.
• Low overall risk of adverse reactions.