“The Biopharmaceutical Drug

Development Process”

Clifford S. Mintz, Ph.D.

www.bioinsights.com

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Drug Development Process

Discovery

Developmen
t
Clinical Testing

Licensure

Manufacturin
g
Marketing &
Sales
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 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

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 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)

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 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

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 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

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 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

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 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.

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 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.
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 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

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 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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