PTC on the manufacture and quality control of human somatic cell therapy medicinal products.
Points to consider on xenogeneic cell therapy medicinal products (June 2004)
Safety and Quality Control of Medicinal Product and Medical Devices using Cell and Tissue (1999)
Guidance for reviewers. Instructions and template for chemistry, Manufacturing, and Control (CMC) reviewers of human somatic cell therapy investigational new drug applications(INDs) (2003)
Guidance for human somatic cell therapy and gene therapy. FDA (1998)
A proposed approach to the regulation of cellular and tissue based products. FDA (1997)
Guidance on application for products comprised of living autologous cells manipulated ex vivo and intended for structural repair and reconstitution. FDA (1996)
Application of current statutory authorities to human somatic cell therapy products and gene therapy products. FDA (1993)
Regulations on Clinical Study and Marketing Approval for Gene Therapy Product (KFDA Notification No2000-61, 2000. 12)
Regulations on Marketing Approval for Biological Product (KFDA Notification No2003-26, 2003. 5)
Regulations on Review of Specification and Test Methods for Medicinal Product (KFDA Notification No2003-60, 2003. 12)
IND(Investigational New Drug) Application
After completing preclinical testing, the company files an IND with FDA to begin to test the drug in people. The IND becomes effective if FDA does not disapprove it within 30 days. The IND shows results of previous experiments, how, where and by whom the new studies will be conducted; the chemical structure of the compound; how it is thought to work in the body; any toxic effects found in the animal studies; and how the compound is manufactured. In addition, the IND must be reviewed and approved by the Institutional Review Board where the studies will be conducted, and progress reports on clinical trials must be
New Drug Application (NDA)
Following the completion of all three phases of clinical trials, the company analyzes all of the data and files an NDA with FDA if the data successfully demonstrate safety and effectiveness. The NDA must contain all of the scientific information that the company has gathered. NDAs typically run 100,000 pages or more. By law, FDA is allowed six months to review an NDA. In almost all cases, the period between the first submission of an NDA and final FDA approval exceeds that limit; the average NDA review time for new molecular entities approved in 1992 was 29.9 months.
Once FDA approves the NDA, the new medicine becomes available for physicians to prescribe. The company must continue to submit periodic reports to FDA, including any cases of adverse reactions and appropriate quality-control records. For some medicines, FDA requires additional studies (Phase IV) to evaluate long-term effects.
Preclinical Application department conducts laboratory and animal studies to show biological activity of the compound against the targeted disease, and the compound is evaluated for safety.
These tests take approximately three and one half years.
+ Application, analysis and evaluation of pre-clinical safety
+ Application, analysis and evaluation of pre-clinical efficacy
+ Application, analysis and evaluation of pre-clinical stability
+ Application, analysis and evaluation of application and dosage
+ Application, analysis and evaluation of physicochemical and biological
Safety and Efficacy
+ Manufacturing and Control
+ Pharmaceutical and Biological information
Physicochemical, Biological Characteristics
+ Pharmacological data
+ Toxicological data
+ Stability data
Chemistry, Manufacturing and Control
+ Safety and Quality Control of Medicinal Product and Medical Devices using Cell and Tissue (1999)
Characterization of cell population for administration
Collection of cells
Cell culture procedures
Cell banking system
Materials used during manufacturing
+ Cell collection and culture
+ Cell banking
+ Product Manufacturing Process
+ Product Testing
Preclinical Animal Application
+ Pharmacology Studies Supporting Effects
+ General Pharmacology Studies if possible
+ ADME Studies if possible
+ Change of Product Characteristics
+ Effect of Products on Normal Cells and Tissues
+ Undesirable Immune-response by Products or by Factors Secreted from Products
Clinical Application Department
Analysis and Evaluation of clinical data and clinical Application, if needed
+ Application, analysis and evaluation of clinical safety
+ Application, analysis and evaluation of clinical efficacy
+ Application, analysis and evaluation of application
20 to 80 people test a new treatment simply to see if it's safe in humans.
Here healthy people can participate. They often make up Phase I safety trials, and they test
vaccines or preventive care.
100-300 patients take experimental treatments to test safety further and seek
the first hints of whether it works
Phase 3 studies enroll several thousand patients to confirm effectiveness and monitor side effects. In Phase 3 studies, and sometimes Phase 2, patients are randomly assigned to either the experimental treatment, a placebo or standard care.
Studies also may be double blind meaning neither the patient nor the researcher knows who is getting the treatment or the placebo until the study ends.
Information of clinical studies
+ Summary of Clinical Experience
+ Information Regarding Target Disease
+ Justification of the clinical use of the product
+ Selection of Subjects
+ Informed Consent
+ Treatment Procedure
+ Primary and Secondary Endpoints Including Infection
+ Plans for Analyses
+ Records of Investigational Products
+ Records of Subjects