1 / 20

Challenges of Biosample Management in Advanced Therapies

This article explores the complications and regulatory developments in managing biosamples for advanced therapies, including unmet indications and testing complications. It also discusses options for certification and the importance of proper sample management.

eethridge
Download Presentation

Challenges of Biosample Management in Advanced Therapies

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Challenges of biosample management in Advanced TherapiesDrew Hope – Head of Advanced Therapy Quality

  2. 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

  3. Advanced Therapy Medicinal Products Guy’s and St Thomas’ NHS Foundation Trust and King’s College London’s Biomedical Research Centre

  4. 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

  5. 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

  6. Regulatory Framework Guy’s and St Thomas’ NHS Foundation Trust and King’s College London’s Biomedical Research Centre

  7. Raw materials Sample management Product intermediates Donor serology reconstitution Starting materials Certification Product administration Donation BioProcess procurement manufacture Drug Product finishing Guy’s and St Thomas’ NHS Foundation Trust and King’s College London’s Biomedical Research Centre

  8. 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

  9. 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

  10. 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

  11. Rapid microbiological methods • MycoSEQ • BacT/ALERT Guy’s and St Thomas’ NHS Foundation Trust and King’s College London’s Biomedical Research Centre

  12. Initial IPC - safety micro/rapid myco/rapid purity QC Dose/concentration viability Final (all QC) Micro – rapid/DI Myco – rapid/DI Endotoxin Phenotype Potency Certification – <4h short shelf life Guy’s and St Thomas’ NHS Foundation Trust and King’s College London’s Biomedical Research Centre

  13. One-stage Rapid tests Purity Identity Contaminants Potency Two-stage Initial IPC Rapid tests Safety critical Full – after use DI tests Non-safety Certification – Clinical need requires <14 d storage Guy’s and St Thomas’ NHS Foundation Trust and King’s College London’s Biomedical Research Centre

  14. 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. Parametric release Guy’s and St Thomas’ NHS Foundation Trust and King’s College London’s Biomedical Research Centre

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. Hierarchy of sampling QC – safety critical Special Drug Product Dose(s) certifiable within trial QC – non-safety retention compliant retention / reference reference Guy’s and St Thomas’ NHS Foundation Trust and King’s College London’s Biomedical Research Centre

More Related