The European Medicines Agency is on the verge of releasing revised guidance for advanced therapy medicinal products containing genetically modified cells, which includes chimeric antigen receptor (CAR)-T cell therapies.
The Guideline on quality, non-clinical and clinical aspects of medicinal products containing genetically modified cells was originally issued in 2012 but underwent revision and consultation from July 2018-July 2019. The revised version is expected to be adopted in October and published in November, according to Ana Hidalgo-Simon, MD, PhD, head of advanced therapies at EMA. She previewed the major changes at RAPS Convergence 2020.
There were an enormous number of comments on the document, Hidalgo-Simon said.The agency is also working on a Q&A document on principles of good manufacturing practices (GMP) for Advanced Therapy Medicinal Products (ATMP) starting material. There will likely be consultation on the document in 2021, she said. (RELATED: Regulation of advanced therapy medicinal products in the EU, Regulatory Focus, 16 July 2020.)
Major changesEMA chose to update the guidance to reflect the increase in clinical experience with these therapies, particularly chimeric antigen receptor-T (CAR-T) cells; to cover new categories of products, such as induced pluripotent stem (iPS) cells; and to allow for consideration of new tools for genetic modification of cells, such as genome editing technologies, she said.
The main quality updates are related to starting materials, the manufacturing process, and characterization and release. For example, the starting materials guidance will now include genome editing tools, while the manufacturing process includes a new section on comparability. The characterization and release portion of the guidance includes specific advice for CAR-T cells.
Additionally, the guidance calls for dose-finding studies to explore safety, toxicity, and anti-tumor activity at different dose levels, to define the threshold dose required for anti-tumor effect, and to define the recommended dose or range for Phase 2 studies. She said sponsors need to show a solid rationale for the criteria being used to find the dose.
The guidance also calls for Phase 3 confirmatory trials to follow a randomized controlled design, comparing the CAR-T cell therapy to a reference regimen, unless otherwise scientifically justified. Single-arm studies will continue to be allowed, but they will be the exception, Dr. Hidalgo-Simon said.
Be very careful with the design of the trials, she advised. The assumptions need to be really, very well backed.
When it comes to safety, the guidance calls for a 15-year follow period. While sponsors wont have all the answers at the time of submission, Hidalgo-Simon said they should have a plan that includes monitoring during the post-authorization period.
Hidalgo-Simon also advised sponsors to think beyond the approval process and consider what evidence will be needed to convince other stakeholders -- from patients to payers -- about the safety and efficacy of the therapy.
Avoiding development pitfallsRichard Dennett, PhD, the senior director of chemistry, manufacturing and controls regulatory affairs at PPD, also participated in the RAPS Convergence 2020 session on advanced therapies. He reviewed development points where companies can run into trouble with advanced therapies, particularly CAR-T cell products.Dennett recommended that product sponsors keep the end in mind when developing advanced therapies by focusing on the target product profile at the beginning of development. That profile includes the indication for which approval will be sought and the incidence of that indication; other considerations include mode of action, demographics, how much of the product needs to be produced, and market access and reimbursement considerations.
He also outlined several areas where developers should focus to create a watertight regulatory package, including sufficient product characterization, potency assay, impurities, formulation, stability, lack of sufficient development batches, and validation strategy.
Dennett urged developers to dive into the growing number of regulatory guidance documents for advanced therapies. In addition to the European guidance documents, developers should consultthe US Food and Drug Administrations Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs), which was released in January 2020. (RELATED: Advanced therapies: Trip hazards on the development pathway, Regulatory Focus, 02 August 2020)
Live and breathe the guidances that are out there, Dennett advised. They allow us to understand what expectations we need to meet.
The key to success in advancing CAR-T cell therapies is the mitigation of risk, Dennett said: The biggest risk is the one that you havent thought of.RAPS 2020 Convergence
Go here to see the original:
Convergence: EMA close to finalizing guidance for advanced therapies - Regulatory Focus
- Panasonic and Shinobi Therapeutics Partner to Develop Efficient and Cost-Effective iPS Cell Therapy Manufacturing ... - PR Newswire - April 24th, 2024
- SCG CELL THERAPY AND A*STAR LAUNCH JOINT LABS WITH COLLABORATION NEARING S$30 MILLION TO ... - PR Newswire - April 20th, 2024
- Detection of biomagnetic signals from induced pluripotent stem cell-derived cardiomyocytes using deep learning with ... - Nature.com - April 1st, 2024
- Researchers discover new microRNA-regulated pathway to boost iPS cell-derived platelet production - Phys.org - March 30th, 2024
- Standardized production of hPSC-derived cardiomyocyte aggregates in stirred spinner flasks - Nature.com - March 28th, 2024
- Synthetic Circuits Reveal the Key to Rewinding the Cellular Clock - The Scientist - March 13th, 2024
- synNotch-programmed iPSC-derived NK cells usurp TIGIT and CD73 activities for glioblastoma therapy - Nature.com - March 3rd, 2024
- Breaking through new research barriers with iPSC technology - News-Medical.Net - February 15th, 2024
- Abu Dhabi Stem Cells Centre partners with Rege Nephro and Kyoto University's Center for iPS Cell Research and ... - Abu Dhabi Media Office - January 12th, 2024
- Abu Dhabi Stem Cells Center partners with Japan-based Kyoto University and Rege Nephro - ZAWYA - January 12th, 2024
- Efficient and reproducible generation of human induced pluripotent stem cell-derived expandable liver organoids for ... - Nature.com - December 23rd, 2023
- Mechanisms, pathways and strategies for rejuvenation through epigenetic reprogramming - Nature.com - December 15th, 2023
- Shinobi Therapeutics Launches with Completion of $51M Series A to Advance Hypoimmune iPS-T Cell Therapy Platform - PR Newswire - December 13th, 2023
- CRISPRi gene modulation and all-optical electrophysiology in post-differentiated human iPSC-cardiomyocytes ... - Nature.com - December 7th, 2023
- World Hindu Congress 2023: Know all about the sessions and speakers - Organiser - November 23rd, 2023
- VCCT Inc., Leading the Field of Retinal Regeneration through iPS ... - Business Wire - November 21st, 2023
- Efficient protocol for the differentiation of kidney podocytes from ... - Nature.com - November 17th, 2023
- Vitamin B12 is a limiting factor for induced cellular plasticity and ... - Nature.com - November 17th, 2023
- Study reveals the critical role of microglia in human brain development - Medical Xpress - November 15th, 2023
- VCCT Inc., Leading the Field of Retinal Regeneration through iPS Cells, Raises 600 million Japanese yen (approximately $4 million USD) through... - November 15th, 2023
- Who are the leading innovators in iPSCs for the pharmaceutical ... - Pharmaceutical Technology - November 7th, 2023
- Using iPS Cells from I Peace, Heartseed Succeeds in Stable Production of High Purity Cardiomyocytes, A Major Step Forward in Advancing Autologous... - November 5th, 2023
- Systematic differences in discovery of genetic effects on gene ... - Nature.com - October 21st, 2023
- Pairwise biosynthesis of ion channels stabilizes excitability and ... - pnas.org - October 11th, 2023
- Scientists find multitude of genes associated with autism - The Statesman - October 9th, 2023
- Stem Cell Banking Market is Expected to Reach USD 16,474.30 ... - Digital Journal - October 7th, 2023
- Probing the individuality of cells and molecules - Open Access Government - October 5th, 2023
- Thymmune Therapeutics Receives $37M in Funding from the ... - Manchestertimes - October 3rd, 2023
- Thymmune Therapeutics Receives $37M in Funding from the ... - Business Wire - September 29th, 2023
- Less Funding to More Researchers Gets Nobel-level Results, Study ... - The Japan News - September 27th, 2023
- Brentuximab Vedotin Plus AVD Gets Positive CHMP Opinion for ... - OncLive - September 20th, 2023
- DKMS BMST Foundation India and Kokilaben Hospital unite to spread awareness about the Importance of Stem Cell Donation on World Marrow Donor Day - APN... - September 18th, 2023
- Vitamin B6 is governed by the local compartmentalization of ... - Science - September 14th, 2023
- Dolly the sheep creator Ian Wilmut dies aged 79 - BBC - September 14th, 2023
- Scientist who created Dolly the sheep dies aged 79: Professor Sir Ian Wilmut passes away five years after reve - Daily Mail - September 11th, 2023
- The global kits market is expected to grow at a CAGR of 7.4% from ... - Digital Journal - September 8th, 2023
- Eterna Therapeutics Announces Initiation of Development Activities ... - PipelineReview.com - September 8th, 2023
- Tokyo: 100 Years of Urban Regeneration / Tokyo's Nihonbashi Area ... - The Japan News - August 31st, 2023
- Transcriptome-based prediction of drugs, inhibiting ... - Nature.com - August 30th, 2023
- From the birds and the bees to IVG - The Gauntlet - August 26th, 2023
- Breakthrough creates stem cells without any memories - Freethink - August 26th, 2023
- Aging impairs the neurovascular interface in the heart - Science - August 26th, 2023
- For This Venture Capitalist, Research on Aging Is Personal; 'Bob ... - The Wall Street Journal - August 22nd, 2023
- Unleashing Potential: Illuminating the Future of Healthcare through Revolutionary Induced Pluripotent Stem Cel - openPR - August 18th, 2023
- A 'memory wipe' for stem cells may be the key to better therapies - The Conversation - August 16th, 2023
- Erasing epigenetic 'memory' to improve the quality of stem cells - FierceBiotech - August 16th, 2023
- HebeCell and Logomix Announce Collaboration for the ... - Business Wire - August 16th, 2023
- HebeCell and Logomix Announce Collaboration for the ... - Valdosta Daily Times - August 11th, 2023
- Advancing Clinical Trials with iPSC-Derived Liver Organoids - Microbioz India - August 11th, 2023
- Activation of cAMP (EPAC2) signaling pathway promotes hepatocyte ... - Nature.com - August 1st, 2023
- IPS HEART Announces Peer-Reviewed Publication in Cells of Aging Damage Reversal Showing GIVI-MPC Stem Cell Therapys Ability to Create New Skeletal... - July 30th, 2023
- Femtech in Japan: An Industry on the Rise - Femtech Insider - July 28th, 2023
- Association between enhanced carbonyl stress and decreased ... - Nature.com - July 28th, 2023
- Defects in early synaptic formation and neuronal function in Prader ... - Nature.com - July 27th, 2023
- IPS HEART Announces Peer-Reviewed Publication in Cells of ... - Business Wire - July 25th, 2023
- Cure to Autism and Alzheimer's May Be in Space, Says 1st Brazilian Scientist who Will Be on The ISS - Folha de S.Paulo - July 25th, 2023
- Futurama's Resurrection Ruins The Perfect Ending (& Shows Must ... - Looper - July 25th, 2023
- University Of Massachusetts Amherst's Team Bags Honour Of 2023 Armstrong Fund For Science Award - India Education Diary - July 20th, 2023
- Scientists working on IVG, a new reproductive method that can make human babies in labs - IndiaTimes - July 19th, 2023
- Co-transplantation of autologous Treg cells in a cell therapy for ... - Nature.com - July 13th, 2023
- Magic Valley and Biocellion Join Forces to Improve Bioreactor Tech ... - vegconomist - the vegan business magazine - July 13th, 2023
- IPS HEART Receives U.S. FDA Rare Pediatric Drug Designation for ... - Tullahoma News and Guardian - July 10th, 2023
- Hitachi : forms strategic research collaboration with Mass General Brigham in the field of regenerative medicine and GCT - Marketscreener.com - July 6th, 2023
- Cell therapy limitations with iPS-based multi-cell therapeutics - Drug Target Review - July 6th, 2023
- Remembering Dolly- The Clone Sheep On Her Birth Anniversary - Free Press Journal - July 4th, 2023
- Labs and Translational Research - UMass Medical School - June 28th, 2023
- Cellusion raises 2.83B series C round to progress iPS cell-derived ... - BioWorld Online - June 14th, 2023
- Japan-based Fujifilm introduces first-of-its-kind human iPSC-derived ... - BSA bureau - June 6th, 2023
- ALS: Parkinson's drug ropinirole may be an effective treatment - Medical News Today - June 4th, 2023
- Scientists predict lab-grown babies in five years - Kidspot - June 4th, 2023
- Lab-grown babies could become a reality within five years - Earth.com - May 26th, 2023
- Leading healthcare experts from MENA and beyond to explore the future of precision medicine in the region at PMES 23 this month - ZAWYA - May 24th, 2023
- Long-Awaited Ax-2 Mission Launches, Heads to Space Station - AmericaSpace - May 22nd, 2023
- Eterna Therapeutics and Factor Bioscience Announce New Data on ... - GlobeNewswire - May 17th, 2023
- Research Assistant job with UNITED ARAB EMIRATES ... - Times Higher Education - May 10th, 2023
- Regulation of synaptic connectivity in schizophrenia spectrum by ... - Nature.com - April 29th, 2023
- Researchers Discover Key Role of Glucose in Brain Activity - Laboratory Equipment - April 25th, 2023
- Structure of Huntington's Protein Revealed - Technology Networks - April 21st, 2023
- Study of brain immune cell infection may explain long COVID ... - NHK WORLD - April 19th, 2023
- The Mechanism That Regulates Activity of Memory Gene - Neuroscience News - April 19th, 2023
Recent Comments