Process Change Evaluation Framework for Allogeneic Cell Therapies: Impact on Drug Development and Commercialization

Hassan, Sally; Huang, Hsini; Warren, Kim; Mahdavi, Behzad; Smith, David; Jong, Simcha; Farid, Suzanne S.

doi:10.2217/rme-2015-0034

Cited by 21 publications

(34 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Due to the relatively low cell numbers and the fact that only one dose is required per donor, the culture medium volumes used are low in comparison with allogeneic therapies, aimed at a scale economy. In an allogeneic process, the media costs are generally the most relevant cost contributor per dose [29,50] and the impact of the price of the supplement would be probably more relevant. In future work, the impact of hPL versus FBS as a supplement for allogeneic mesenchymal stem/stromal cell therapies should be the object of analysis.…”

Section: Multipassage Harvesting Density Is the Key Cost Driver For Xmentioning

confidence: 99%

“…Decisions concerning manufacture process should be taken relatively early on the development of a cell-based therapy, preferable before a Phase III clinical trial, as effects on changes in cell potency and safety with process specificity may be a concern [50]. Therefore, in addition to cost, the decision of the manufacturing process to be selected should also consider the therapeutic action of the obtained cells.…”

Section: Considerations For Model-driven Cost-effective Process Transfermentioning

confidence: 99%

See 1 more Smart Citation

Modeling Biological and Economic Uncertainty on Cell Therapy Manufacturing: the Choice of Culture Media Supplementation

2018

View full text Add to dashboard Cite

To evaluate the cost-effectiveness of autologous cell therapy manufacturing in xeno-free conditions. Materials & methods: Published data on the isolation and expansion of mesenchymal stem/stromal cells introduced donor, multipassage and culture media variability on cell yields and process times on adherent culture flasks to drive cost simulation of a scale-out campaign of 1000 doses of 75 million cells each in a 400 square meter Good Manufacturing Practices facility. Results & conclusion: Passage numbers in the expansion step are strongly associated with isolation cell yield and drive cost increases per donor of $1970 and 2802 for fetal bovine serum and human platelet lysate. Human platelet lysate decreases passage numbers and process costs in 94.5 and 97% of donors through lower facility and labor costs. Cost savings are maintained with full equipment depreciation and higher numbers of cells per dose, highlighting the number of cells per passage step as the key cost driver.

show abstract

Section: Multipassage Harvesting Density Is the Key Cost Driver For Xmentioning

confidence: 99%

Section: Considerations For Model-driven Cost-effective Process Transfermentioning

confidence: 99%

Modeling Biological and Economic Uncertainty on Cell Therapy Manufacturing: the Choice of Culture Media Supplementation

2018

View full text Add to dashboard Cite

show abstract

“…Overcoming regulatory hurdles for the use of these therapies is often challenging, as boundaries are set to ensure high quality, efficacy, and safety, while maintaining low costs. 19 Specifically, the Food and Drug Administration provides strict regulations on the use of such therapies, and thus there are few, if any, widely used stem cell products regularly available, despite numerous clinical trials. These hurdles may prevent the implementation of such therapies in everyday practice.…”

Section: Discussionmentioning

confidence: 99%

An MRI Evaluation of Patients Who Underwent Treatment with a Cell-Mediated Gene Therapy for Degenerative Knee Arthritis: A Phase IIa Clinical Trial

et al. 2016

View full text Add to dashboard Cite

Multiple therapies have been developed to slow down the progression of knee osteoarthritis (OA), with the aim of avoiding or delaying TKA. One such potential method is cell-mediated gene therapy, which utilizes allogeneic human chondrocytes modified to express transforming growth factor-β1. Using magnetic resonance imaging (MRI), we evaluated patients who underwent treatment with this injection in a Phase II study and assessed structural changes in: (1) bone marrow edema lesions, (2) cartilage defect depth and surface area, (3) articular bone surface and osteophytes, and (4) meniscus structure and signal, as well as changes in (5) joint fluid, (6) periarticular inflammation, and (7) synovial inflammation. Twenty-seven patients (6 men and 21 women) who had late-stage OA were randomized 1:1 to receive a 3:1 mixture of nontransduced chondrocytes and genetically engineered chondrocytes, at doses of 6 × 10 cells (group 1) or 1.8 × 10 cells (group 2). MRI was performed at baseline (preinjection), and at 6 and 12 months postinjection. The whole-organ MRI score system was used to assess the aforementioned changes. Treatment was considered to be successful if patients experienced an improvement in or no change in their scores, indicating that the disease had not progressed. All patients in both cohorts individually demonstrated an improvement or no change in one or more of the assessment parameters. At 6 months, the low-dose cohort demonstrated worsening in mean scores in one parameter (bone surface and osteophytes), while the high-dose cohort demonstrated no worsening in mean scores. At 12 months, the low-dose cohort had worsening in the mean score in a subset of one parameter (cartilage signal intensity), and the high-dose cohort demonstrated worsening in mean scores in two parameters (bone surface osteophytes and periarticular inflammation). This is the first study to evaluate MRI changes in patients treated with this injection. These findings provide an impetus for further research on this topic, as well as a starting point for Phase III testing.

show abstract

“…The Lang factor approach was used to estimate the FCI for each facility. 32,33 The indirect cost associated with running the facility is calculated as an annual cost. Direct and indirect costs per batch are calculated by spreading their annual values evenly among the batches performed in a single campaign.…”

Section: Model Inputsmentioning

confidence: 99%

Benchmarking biopharmaceutical process development and manufacturing cost contributions to R&D

Farid

Baron

Stamatis

et al. 2020

mAbs

View full text Add to dashboard Cite

This study aims to benchmark and analyze the process development and manufacturing costs across the biopharmaceutical drug development cycle and their contribution to overall research and development (R&D) costs. This was achieved with a biopharmaceutical drug development lifecycle cost model that captured the costs, durations, risks and interdependencies of the clinical, process development and manufacturing activities. The budgets needed for process development and manufacturing at each phase of development to ensure a market success each year were estimated. The impact of different clinical success rate profiles on the process development and manufacturing costs at each stage was investigated, with a particular focus on monoclonal antibodies. To ensure a market success each year with an overall clinical success rate (Phase I to approval) of 12%, the model predicted that a biopharmaceutical company needs to allocate process development and manufacturing budgets in the order of~$60 M for pre-clinical to Phase II material preparation and~$70 M for Phase III to regulatory review material preparation. For lower overall clinical success rates of~4%, which are more indicative of diseases such as Alzheimer's, these values increase to~$190 M for early-phase and~$140 Mfor late-phase material preparation; hence, the costs increase 2.5 fold. The costs for process development and manufacturing per market success were predicted to represent 13-17% of the R&D budget from pre-clinical trials to approval. The results of this quantitative structured cost study can be used to aid decision-making during portfolio management and budget planning procedures in biopharmaceutical development.

show abstract

Process Change Evaluation Framework for Allogeneic Cell Therapies: Impact on Drug Development and Commercialization

Abstract: The framework can facilitate early decision-making during process development.

Cited by 21 publications

References 21 publications

Modeling Biological and Economic Uncertainty on Cell Therapy Manufacturing: the Choice of Culture Media Supplementation

Modeling Biological and Economic Uncertainty on Cell Therapy Manufacturing: the Choice of Culture Media Supplementation

An MRI Evaluation of Patients Who Underwent Treatment with a Cell-Mediated Gene Therapy for Degenerative Knee Arthritis: A Phase IIa Clinical Trial

Benchmarking biopharmaceutical process development and manufacturing cost contributions to R&D

Contact Info

Product

Resources

About