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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 • • • • 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 • • • • 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 • • • • • • 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 • • • • • • 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 • • • • • 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