International Stem Cell Banking Initiative (ISCBI) PSC 2019, June 30 th 2019, Los Angeles, CA. Opening P Panel el : Review a and Objectives es Chair: Stephen Lin (CIRM) Participants: Stephen Sullivan (GAiT), Glyn Stacey (ISCBI), Yoji Sato (Japan NIHS; HESI CT-TRACS), Ngaire Elwood (BMDI; ISCT)
Participants Stephen Lin Stephen Sullivan Yoji Sato Glyn Stacey Ngaire Elwood Senior Science Officer International Liaison Head of Division of Cell-Based Director Director, BMDI Cord Officer Therapeutic Products, NIHS Blood Bank ISCBI
4 th Annual Cell Therapy Conference – June 2018 Sessions 1. Learning from the current pluripotent space and the development of international standards 2. Bioanalytics and comparability 3. Tumorigenicity testing 4. Manufacture, Storage, and Shipment PSC 2019 Mtg, June 30th 2019, Los Angeles, CA. 3
Ses ession 1, n 1, Par art 1 1 – Learning g from om t the cu current pluripot otent s space ce PSC products covered in session: • ESC-derived Oligodendrocyte Progenitor Cells (allogeneic) • iPSC-derived Retinal Pigment Epithelial Cells (autologous) • iPSC-derived Neural Stem Cells (allogeneic) Takeaways: • Heterogeneity and stability of PSC products is highly variable • Understanding science behind cell therapy products is critical • Demonstrating equivalency of hCTPs is critical PSC 2019 Mtg, June 30th 2019, Los Angeles, CA. 4
Ses ession 1, n 1, Par art 2 2 – Develop opment of of i internation onal s standards Highlighted product characterization: • Genetic stability • Contamination • Feeder cells • Traceability of materials is important Takeaways: • There are no regulatory guidelines specific for PSCs and derivatives • Road map would be helpful PSC 2019 Mtg, June 30th 2019, Los Angeles, CA. 5
Sessi ssion 2 2 – Bioa oanalytics cs and c com omparability Takeaways: Perform the right level of product characterization to ensure product quality Critical quality attributes (CQA) must be controlled within critical process parameters (CPP) Manufacturing changes should be made prior to phase 3 clinical trials Genetic characterization is large topic. Two safety issues: a) potential for residual undifferentiated hPSCs b) Mutations in hPSCs that might lead to transformation of hPSCs or differentiated derivative into tumor cells PSC 2019 Mtg, June 30th 2019, Los Angeles, CA. 6
Sessi ssion 3 3 – tumor origenici city t testing Takeaways: Animal testing still standard • All animal models imperfect, but they do provide information on tumorigenic potential of cells • Incorporate 3Rs – reduce, refine, replace Genetic testing • Genetic testing. Regulatory agencies want it, but it is still informational • Recommend collection and curation of genomic data • Data processing (resources and expertise) and interpretation (relevance) remain a challenging issue for many. PSC 2019 Mtg, June 30th 2019, Los Angeles, CA. 7
Sessi ssion 4 4 – manufact cture, s stor orage, a and shipment Automated cell culture systems • Reduction of invasive process decisions • Non-invasive in-process analytics will be important • Providing high content specificity a highly desired goal of any closed system PSC 2019 Mtg, June 30th 2019, Los Angeles, CA. 8
Myopathy first condition be treated to get iPSC to the clinic Investors Politicians Regulators Ethicists Clinicians Hospitals SMEs Manufacturers Patients Academia
Language and coalescence of group vision for the manufacture cell therapies Cell therapy developers should: (i) support the growth of specialized language that comes with innovation and (ii) use the simplest possible common vocabulary to facilitate community-wide communication.
Beginning with the end in mind, what kind of PSC/iPSC do we want to use in therapies • Variation can be assessed (new statistical tools) • Optimally sourced and characterised primary tissue source • Optimal reprogramming • Optimally derived through automation, mechanisation in defined media and matrix conditions • Robust and consistent during scaling • Amenable to consistent assaying • Approved by Regulator for its intended purpose • Immune matched • Kill switch included for deviants? • Comparable lines
PSC/iPSC Comparability Initial steps towards PSC/iPSC line comparability: (i) selecting and periodically revising Critical Quality Attributes as a community, (ii) selecting what quality assays and what standards to use, and (iii) ensuring quality testing, conducted by different users across the community, is consistent and indicative.
Overview w from me m meeting • Key challenges remain in PSC manufacturing • Sharing experiences and data important • A mechanism/platform for sharing the data needs to be defined • Range of new standardisation groups emerging • More specific global regulatory guidance would be welcome PSC 2019 Mtg, June 30th 2019, Los Angeles, CA. 13
Output since ce 2018 m meeting • Report on IABS 4 TH International Conference Biologicals (2018) 56: 67–83 • Quality control guidelines for clinical grade PSCs Regen. Med. (2018) 13(7), 859-866 • Strategic Roadmap to filing a Biologics License Application for PSC products Biologicals (2019) 59: 68–71 • CT-TRACS/MEASURE position paper on tumorigenicity prepared: o “Tumorigenicity assessment of cell therapy products: The need for global consensus and points to consider”. (pre-submission stage) o Scoping of an International Multisite Study to further evaluate in vitro methods for tumorigenicity assessment, (initiative open to all interested participants, from the public and private sector.) • GAiT donor consent guidelines: www.gait.global/donor-consent PSC 2019 Mtg, June 30th 2019, Los Angeles, CA. 14
Sp Spect ctrum of of a act ctivi vities to m o make a PSC PSC therapy prod oduct ct Primary Donor Material iPSC generation Final Differentiated Product Autologous • • • No donor eligibility Traceability of reagents & Materials • determination materials Manufacturing process • • • Limited material testing Regulatory approval Regulatory approval • • Master Cell Bank Product stability • • Testing Safety Testing Allogeneic • • Reprogramming/Gene Efficacy Testing • • Donor Recruitment and Modification/Editing Storage Appropriate Donor Selection • Final formulation • Donor consent determination • Screening and testing required within 7 days of harvest PSC 2019 Mtg, June 30th 2019, Los Angeles, CA. 15
By building holistic understanding of complete translation process there will be less waste and confusion and will accelerate therapies to the clinic International Stem Cell Banking Initiative (ISCBI) PSC 2019 Mtg, June 30th 2019, Los Angeles, CA. 16
International Stem Cell Banking Initiative (ISCBI) PSC Manufacturing Expert Panels 2019 June 30 th 2019, Los Angeles, CA. Panel el 2: 2: Pluripot otent S Stem em C Cells a s as Manufac acturing C g Cell Substra rates - Chal allenges E es Encounter ered ed a and F For orec ecas ast Chair: Wen Bo Wang (Fate Therapeutics) Participants: Joseph Gold (US City of Hope) Yoji Sato (Japan Institute of Health Sciences ) Glyn Stacey (ISCBI)
Panel 2 - Participants Wen Bo Wang Joseph Gold Yoji Sato Glyn Stacey Sr. VP Technical Director of Manufacturing, Center Head of Division of Cell-Based Director, Operations for Biomedicine & Genetics Therapeutic Products UK Stem Cell Bank PSC Manufacturing Expert Panels 2019 - June 30th 2019, Los Angeles, CA. 18
Unique Advantages of Human iPSCs Isolation, Characterization & Selection of a Single iPSC Clone A Single Human Induced Pluripotent Stem Cell (iPSC) Unique starting material for cell therapy Unlimited Self- Potential to Differentiate Single iPSC Clone Renewal into 200+ Cell Types Precise Engineering Master Cell Banks Uniform in Extensive Composition Characterization Renewable Clonal Cell Line ---> Homogeneous Cell Products
Establishing a New Paradigm in Cellular Engineering Eliminating stochastic editing variability and heterogeneity associated with pool engineering
Panel 2: Pluripotent Stem Cells as Manufacturing Cell Substrates - Challenges Encountered and Forecast Stem Cell Processing, Process Monitoring, Quality Control and Cell Preservation: • Screening and Selection Methods • Culture Media/GMP Reagents Advances • Cell Expansion Equipment • Cell Expansion, Modification, and Differentiation Methods • Separation Techniques • Cell Culture Volume Reduction • Process Automation and Data Analytics • Monitoring and Feedback Control Technologies • Cell Attribute Testing and Measurement Technologies • Fill/Finish and Cryopreservation Technologies PSC Manufacturing Expert Panels 2019 21 June 30th 2019, Los Angeles, CA.
Panel 2: Pluripotent Stem Cells as Manufacturing Cell Substrates - Challenges Encountered and Forecast • 1) How to qualify the starting cells to reduce process variation? • 2) How to understand variation, understand allowable operating limits, and control variation? how much variation can a manufacturing process encompass before the method requires separate qualification/validation? • 3) How to demonstrate comparability for process changes? • 4) What is the biggest challenge for pluripotent stem cell derived therapies in your view? PSC Manufacturing Expert Panels 2019 22 June 30th 2019, Los Angeles, CA.
Recommend
More recommend
