Drug Development Process

“ The Biopharmaceutical Drug Development Process ” Clifford S. Mintz, Ph.D. www.bioinsights.com

Drug Development Process Discovery Development Clinical Testing Licensure Marketing & Sales Manufacturing

Drug Discovery
Target identification and validation
Production and/or synthesis of “drugs”
Interaction between drugs and targets characterized and validated in vitro
Tested for efficacy in animal models of disease
Technology transferred to development group

Drug Development
Process of production/synthesis of drug is validated and “scaled up” to produce larger quantities of the drug
Detection and analytical methods for the drug are created and validated
Toxicology and ADME experiments performed in animals
Investigational New Drug Application (IND) is prepared and submitted to the Food and Drug Administration (FDA)

Clinical Testing
IND is approved by FDA and drug is tested in human clinical trials
Phase I trials are conducted to assess drug safety; typically tested in healthy human subjects
Phase II trials are conducted to assess drug efficacy in patients suffering from the “target disease”; dosing is determined and numbers of patients in the trials are typically small
Phase III trials are conducted to assess overall therapeutic effect of drug in large numbers of ill patients

Licensure
Data from Phase I-III clinical trials tabulated and analyzed for overall safety and therapeutic efficacy
A New Drug Application (NDA) or Biological License Application (BLA) is prepared and submitted to the FDA for review
The NDA must contain:
All pre-clinical and clinical data
Documentation that describes the manufacture, formulation, validation and packaging/labeling of the drug
Production facility design and operation
Marketing Plan
If the application is approved, the company is granted a license to manufacture the product

Manufacturing
NDA or BLA is approved by the FDA; drug must be manufactured in commercial quantities to meet therapeutic demand
Drug is manufactured in protein production facility built and validated by the licensee or via a contract manufacturing organization (CMO)
This process is guided by cGMP regulations
Manufacturing facilities are initially inspected and then monitored from time to time by FDA

Scale Up and Production
Commonly referred to as “upstream processing”
Expression of recombinant proteins in animal cells, bacteria, yeast and other systems
Process is carefully controlled and tightly regulated; must be highly reproducible with as little variation as possible
Quality systems management is critical
Documentation, e.g. SOPs, validation, batch records, etc.
QC & QA
Facilities and environmental monitoring, equipment validation, cleaning control, etc.

Protein Purification and Recovery
Commonly referred to as “downstream processing”
Recombinant protein is isolated and purified via a variety of biochemical methods
Purified protein is analyzed and characterized by sophisticated analytical methods to insure identity
Like the upstream process, downstream processing is carefully controlled and tightly regulated; must be highly reproducible with as little variation as possible
Quality systems management is critical
Documentation, e. g, batch records, analytical reports, lot numbers are assigned
QC & QA
Facilities and environmental monitoring, equipment validation, cleaning control, etc.

Finished Product
Purified recombinant protein is placed into final container via a “sterile fill” process
Vial or package are given lot numbers and labeled according to licensing requirements
Finished product is shipped from manufacturer to drug distributors and then sold to public
Microbiological testing, QC, stability testing and other QA functions are critically important and vital to insure product quality and safety

Conclusions
The entire drug development process from discovery through licensing takes approximately 10-15 years
All aspects of development are very tightly controlled and highly regulated by cGMPs
cGMPs play a vital role in the production of safe and efficacious clinical materials and finished drug products
Mandatory adherence to cGMPs insures that product quality and safety is maintained through the lifecycle of an FDA-approved drug product

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Drug Development Process

by Clifford Mintz

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