Challenges for Cell-Based Medicinal Products From a Pharmaceutical Product Perspective

A comprehensive report of long-term stability data for a range ATMPs: A need to develop guidelines for safe and harmonized stability studies

“…Another aspect of stability testing is the need to guarantee the sterility of the ATMPs throughout their shelf life, and therefore their safety [63,64]. Microbiologic controls should be part of stability study plans, in consideration of the fact that containers may lose their seal during time [29,65,66]. We show here that different DPs cryopreserved in different excipients in freezing bags with overwrap bags, or in cryovials, always maintained sterility for up to 13,5 years.…”

GMP-Grade Manufacturing and Quality Control of a Non-Virally Engineered Advanced Therapy Medicinal Product for Personalized Treatment of Age-Related Macular Degeneration

“…Here, the validation of the manufacture process and QC for batch release of the new ATMP tIPE has been described. The specific challenges included the following: setting the GMP requirements, standardization, assessment of its biological nature, short production times, potential alterations of the ATMP ex vivo (e.g., cell death), small sized autologous products whose amount is limited to clinical dose, irreversible cell labelling preventing cell characterization or purification, and the maintenance of a closed, GMP-compliant circuit from starting material collection to production, transport, and transplantation [ 9 , 34 ].…”

“…Advanced therapies offer promise for millions of patients but manufacture of GMP-compliant ATMPs is challenging [ 9 , 13 , 40 ] often requiring the development of novel methodologies to simplify the workflow in closed and automated systems. For the validation of tIPE, the protocol comprises an in vivo ValRun that is feasible for any novel cell therapy displaying strong constraints in cell number and production time.…”

“…Gene therapy, cell therapy, and tissue engineering, known as ”advanced therapies” are the new frontiers for personalized treatments for currently untreatable diseases [ 1 , 2 , 3 , 4 , 5 , 6 ]. Respective Advanced Therapy Medicinal Products (ATMPs) are biopharmaceuticals, whose development is associated with novel challenges for production, quality control (QC), transport, storage and application [ 7 , 8 , 9 ]. Even when ATMPs are often produced for one patient [ 7 , 8 , 10 ], they must be produced and controlled under Good Manufacturing Practice (GMP) compliant practices and pharmaceutical conditions [ 11 ], which comprises standardized and validated manufacture and QC performed by qualified personnel using qualified devices, under rigorous hygienic conditions.…”

Approach of resource expenditure estimation toward mechanization in the manufacturing of cell-based products

“…Regenerative medicine, or therapy using cell-based products, has begun to cure many patients through growing commercialization of products made from autologous or allogeneic cells or tissue [ [1] , [2] , [3] ]. Recent advances in the research and development of pluripotent stem cell-based products using human embryonic stem cells (ESC) or induced pluripotent stem cells (iPSC) have resulted in the commencement of clinical trials [ [4] , [5] , [6] ].…”