ATMP development and pre-GMP environment in academia: a safety net for early cell and gene therapy development and manufacturing

Silva, Daniel; Chrobok, Michael; Ahlén, Gustaf; Blomberg, Pontus; Sällberg, Matti; Pasetto, Anna

doi:10.1016/j.iotech.2022.100099

Cited by 8 publications

(10 citation statements)

References 13 publications

(14 reference statements)

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“…The required time and monetary investments are often disincentivized by high time-to-market pressures, costly clinical trials, and the complexity of the underlying biological mechanisms which are often not completely understood (Krishna et al, 2021;Silva et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

“…Automation and closing of manufacturing processes are seen as key drivers for making cell therapies affordable and accessible to large patient populations (Abraham et al, 2021; Heathman et al, 2015). The required time and monetary investments are often disincentivized by high time‐to‐market pressures, costly clinical trials, and the complexity of the underlying biological mechanisms which are often not completely understood (Krishna et al, 2021; Silva et al, 2022). Thus, there is a need for process development tools that are effective, efficient, and do not require extensive mechanistic knowledge of the underlying biological processes.…”

Section: Discussionmentioning

confidence: 99%

“…However, the wide range of cell types and therapeutic modalities that are involved essentially requires the development of a somewhat customized process for each of these therapies. This involves a significant amount of process development and optimization, which is often disincentivized by costly clinical trials and high time‐to‐market pressures (Kasemiire et al, 2021; Krishna et al, 2021; Silva et al, 2022). In the case of biopharmaceuticals, these challenges have partially been mitigated through in silico process development with digital twins, although these approaches have not been successful for cell therapies so far (Kroll et al, 2017; Zobel‐Roos et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

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Bayesian cell therapy process optimization

Claes,

Heck,

Coddens

et al. 2024

Biotech & Bioengineering

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Optimizing complex bioprocesses poses a significant challenge in several fields, particularly in cell therapy manufacturing. The development of customized, closed, and automated processes is crucial for their industrial translation and for addressing large patient populations at a sustainable price. Limited understanding of the underlying biological mechanisms, coupled with highly resource‐intensive experimentation, are two contributing factors that make the development of these next‐generation processes challenging. Bayesian optimization (BO) is an iterative experimental design methodology that addresses these challenges, but has not been extensively tested in situations that require parallel experimentation with significant experimental variability. In this study, we present an evaluation of noisy, parallel BO for increasing noise levels and parallel batch sizes on two in silico bioprocesses, and compare it to the industry state‐of‐the‐art. As an in vitro showcase, we apply the method to the optimization of a monocyte purification unit operation. The in silico results show that BO significantly outperforms the state‐of‐the‐art, requiring approximately 50% fewer experiments on average. This study highlights the potential of noisy, parallel BO as valuable tool for cell therapy process development and optimization.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Bayesian cell therapy process optimization

Claes,

Heck,

Coddens

et al. 2024

Biotech & Bioengineering

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“…Among all types of ATMPs, stem cell products are remarkably complex and varied in their manufacturing processes including methods for cell culture, induction of differentiation, cell storage and engraftment 23,24 . Generally it is difficult to assess whether prechange process and postchange process are analytically comparable, and nonclinical even clinical studies are needed in certain occasions 25 . Therefore, in‐depth analysis and discussions are needed to share regulatory considerations on CMC, nonclinical and clinical experience of comparability assessments and ultimately achieve convergence 26 …”

Section: Challenges and Perspectivesmentioning

confidence: 99%

“…23,24 Generally it is difficult to assess whether prechange process and postchange process are analytically comparable, and nonclinical even clinical studies are needed in certain occasions. 25 Therefore, in-depth analysis and discussions are needed to share regulatory considerations on CMC, nonclinical and clinical experience of comparability assessments and ultimately achieve convergence. 26 From the pre-clinical aspect, there is no scientific consensus on rational animal models to test cellular products.…”

Section: Challenges and Perspectivesmentioning

confidence: 99%

Advanced therapy medicinal products in China: Regulation and development

Lü

Wei

et al. 2023

MedComm

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Advanced therapy medicinal products (ATMPs) have shown dramatic efficacy in addressing serious diseases over the past decade. With the acceleration and deepening of China's drug regulatory reforms, the country sees a continuous introduction of policies that encourage drug innovation. The capacity and efficiency of the Center for Drug Evaluation (CDE), National Medical Products Administration have significantly improved, where substantial resources have been allocated to ATMPs with major innovations and outstanding clinical values that satisfy urgent clinical needs. These changes have greatly stimulated the research and development of biological products in China, ushering in a period of explosive growth in the number of investigational new drug (IND) applications of ATMPs. Here, we described China's ATMP regulatory framework and analyzed data on IND applications for ATMPs submitted to CDE. The data show that China's ATMP industry is expanding dramatically, but lagging behind in terms of the innovative targets and the coverage of indications. However, in recent years, the diversity of product types, targets, and indications is growing. We discussed challenges and opportunities in ATMP regulation. Risk‐based regulation and cross‐discipline collaborations are encouraged to promote more ATMPs toward market authorization in China.

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