Download Biomedical Research Centre

Challenges of biosample
management in Advanced
Therapies
Drew Hope – Head of Advanced Therapy Quality
Overview
ATMPs
Complications for testing
Samples
Regulatory developments
Options for certification
Guy’s and St Thomas’ NHS Foundation Trust and King’s College London’s
Biomedical Research Centre
Advanced Therapy Medicinal Products
Guy’s and St Thomas’ NHS Foundation Trust and King’s College London’s
Biomedical Research Centre
Unmet indications
RegenMed – Stroke / myocardial infarction / neurodegenerative
diseases / AMD / chondrocytes / CLI
Guy’s and St Thomas’ NHS Foundation Trust and King’s College London’s
Biomedical Research Centre
Unmet indications
Immunotherapy – Cancer / IBD / diabetes / Organ Transplants
Guy’s and St Thomas’ NHS Foundation Trust and King’s College London’s
Biomedical Research Centre
Regulatory Framework
Guy’s and St Thomas’ NHS Foundation Trust and King’s College London’s
Biomedical Research Centre
Sample management
Raw materials
Product intermediates
reconstitution
Donation
Starting materials
Certification
BioProcess
procurement manufacture
Drug Product finishing
Guy’s and St Thomas’ NHS Foundation Trust and King’s College London’s
Biomedical Research Centre
Product
administration
Donor serology
Test complications
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Inhibitory effects – e.g. turbidity
Potency understanding
Phenotype assays
Safety-critical testing for certification
Guy’s and St Thomas’ NHS Foundation Trust and King’s College London’s
Biomedical Research Centre
GMP Annex 2 revision
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In operation 31 Jan 2013
Short shelf life (<14 d)
Certification prior to test completion
‘Continuous assessment of the
effectiveness of the quality assurance
system must be in place’
Guy’s and St Thomas’ NHS Foundation Trust and King’s College London’s
Biomedical Research Centre
In process testing
• Assurance for safety critical testing
– Bacteria, mycoplasma, endotoxin, potency,
purity
• Each intervention = opportunity
• Closed-system sampling
Guy’s and St Thomas’ NHS Foundation Trust and King’s College London’s
Biomedical Research Centre
Rapid microbiological methods
• MycoSEQ
• BacT/ALERT
Guy’s and St Thomas’ NHS Foundation Trust and King’s College London’s
Biomedical Research Centre
Certification – <4h short shelf life
• Initial
• IPC - safety
– micro/rapid
– myco/rapid
– purity
• QC
– Dose/concentration
– viability
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Final (all QC)
Micro – rapid/DI
Myco – rapid/DI
Endotoxin
Phenotype
Potency
Guy’s and St Thomas’ NHS Foundation Trust and King’s College London’s
Biomedical Research Centre
Certification – Clinical need
requires <14 d storage
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One-stage
Rapid tests
Purity
Identity
Contaminants
Potency
• Two-stage
• Initial
– IPC
– Rapid tests
– Safety critical
• Full – after use
– DI tests
– Non-safety
Guy’s and St Thomas’ NHS Foundation Trust and King’s College London’s
Biomedical Research Centre
Parametric release
• Full certification by IPC only. Annex 17
• Impossible for ATMPs:
– 3.4 Parametric release can only be approved for
products terminally sterilized in their final container.
Guy’s and St Thomas’ NHS Foundation Trust and King’s College London’s
Biomedical Research Centre
Sample complications
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Donor blood tests
Retention for imputability - allogeneic
Sample short shelf-life
Autologous products & small batches
Reference / retention
Guy’s and St Thomas’ NHS Foundation Trust and King’s College London’s
Biomedical Research Centre
Donor samples
• EUTCD: HIV 1/2, HBsAg, HBc, HCV,
syphilis, [HTLV I/II]
• Donation and >6 months [NAT]
• ART – own use = no sampling
• hES cell lines incompatible
Guy’s and St Thomas’ NHS Foundation Trust and King’s College London’s
Biomedical Research Centre
Imputability samples
• Allogeneic donor retest
• Serum, blood or cells samples
• Retain before use/expiry/disposal of
ATMP
• Not a requirement of EU Directives
Guy’s and St Thomas’ NHS Foundation Trust and King’s College London’s
Biomedical Research Centre
Short shelf life
• Samples retained become useless
• Add preservative to store – alters
characteristics
• Undertake much of QC at the time of
formulation – resource issues
Guy’s and St Thomas’ NHS Foundation Trust and King’s College London’s
Biomedical Research Centre
Autologous – small batches
• Retention samples to repeat QC 2×
– Annex 19 – in its finished primary packaging
– 4× Required for PIC/S guide for retesting
• Allogeneic: QC and retains more than
required for the trial
• Autologous frequently a batch of 1
• Make many samples from small residue
• Diluted product - meaningless
Guy’s and St Thomas’ NHS Foundation Trust and King’s College London’s
Biomedical Research Centre
Hierarchy of sampling
QC – safety critical
Drug Product Dose(s)
QC – non-safety
retention
retention / reference
reference
Guy’s and St Thomas’ NHS Foundation Trust and King’s College London’s
Biomedical Research Centre