Applications Cell Therapies

The Competent Authorities are allowed a maximum of 60 days to review the data, or 90 days in the case of trials involving medicinal products for gene therapy, somatic cell therapy (including xenogeneic cell therapy), and all medicinal products containing genetically modified organisms. Such trials require written authorisation from the Competent Authority as distinct from other types of product where the authorities may just notify the sponsor of the acceptability (no-objection) of the application. If issues are raised, the sponsor may amend the application once, with a consequent extension to the allowed review period. 

Clinical Applicability. The regulatory conditions for cell therapy directly refer to the cells and the materials utilized during the cultivation. The use of cell lines, especially those of animal origin (e.g. stromal cell lines in cocultivation), and the use of animal serum should carefully be reconsidered, as this will make the seeking of clinical approval a difficult task. 

A number of other processes are in continuous development. Clinical applications of these therapies in the urogenital and cardiovascular systems, in peripheral and central nervous systems, pancreas, joint cartilage restoration, etc., are being studied. However, almost all procedures suffer from a common limitation the availability of donor cells. Cell therapies have to begin with a relatively high number of cells, and stem cells, irrespective of their origin, are always a minor subpopulation in tissues. 

Upon approval of the application and the comparability data, all products could be made available under the license. Some of the concepts addressed for umbilical cord hematopoietic stem cells may be important in future comparability demonstrations in hematopoietic and other cell therapies. 

Guidance for Reviewers Instructions and Template for Chemistry, Manufacturing, and Control (CMC) Reviewers of Human Somatic Cell Therapy Investigational New Drug Applications (INDs) (draft guidance) (August 2003)... 

Cell-based products present similarities as well as complex issues not encountered with traditional biologicals. Innovative uses of animal models have contributed to advances toward clinically applicable treatment options based on studies designed to answer specific questions. Novel models and experimental paradigms are best considered as a case-by-case approach applied to each specific product. Noninvasive imaging methods play a critical role in cell therapy by identifying how many cells reach the desired target and, if they survive, divide and differentiate to fulfill their intended function. 

Application of Current Statutory Authority to Human Somatic Cell Therapy Products and Gene Therapy Products. Federal Register 1993 58(197) 53248-51. 

The encapsulation of hepatocytes for a bioartificial liver, and cell therapy for the treatment of other hormone deficiencies or neurodegenerative diseases, such as Alzheimer s and Parkinson s, are also under investigation. Additional examples of cell encapsulation in polymer-polymer coacervates include non-autologous gene therapy,blood substitutes as well as the treatment of prostate cancer. Pharmaceutical applications of microcapsules encompass, in addition, trans-dermal drug delivery and protein delivery such as is required in anti-inflammatory therapy for arthritis. 

Member states have 60 days to consider a valid request from an applicant to conduct a clinical study, in the case of trials involving medicinal products for gene therapy or somatic cell therapy or medicinal products containing genetically modified organisms an extension of a maximum of 30 days may be allowed. If the request to conduct a study is refused by the competent national authority, the sponsor may on one occasion only modify or amend the protocol to take account of the objections raised. No further appeal mechanism is provided. 

ADSCs are a clinically applicable source for cell therapy. Tse et al. fabricated a PCL/PLA scaffold using the solvent-cast method, and the scaffolds were found to... 

Okada N. [Design and creation of cytomedicine for application to cell therapy], Yakugaku Zasshi 2005 Aug 125(8) 601-615. Japanese. 

Extension to the 60-day period is only permissible for trials of gene therapy or somatic cell therapy or medicinal products containing genetically modified organisms. In such a case an extension of 30 days is permitted with a further extension of 90 days in the event of local MS consultation with a group or committee also allowed for, bringing the total to 180 days. There is /jo time limit for xenogenic cell therapy applications. 

A common clinical trial application form will be used and will be accompanied by data on the Quality, Safety, and Efficacy of the IMP to the CA. The application process is an implicit approval within a maximum 60-day review period with one exception, for clinical trials with biotechnology IMPs, e.g., gene therapy, somatic cell therapy, and genetically modified organisms. In this case, written approval is mandatory and a 90-day review period will apply. 

Figure 11.2-3. Differentiation potential of embryonic stem cells. Illustration shows the possible application of ES cells for cell therapy.

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