1. The Lifecycle of Pharmaceutical products
Chapter-3.

2. Regulation of Pharms and Medical products in US
Drugs are regulated by the FDA
Center for Drug Evaluation and Research (CDER)
Biologics are regulated by The Center for Biologics Evaluation and Research (CBER)
Medical Devices are regulated by The Center for Devices and Radiological Health (CDRH)
All drugs made using GMPs or Good Manufacturing Practices (1963 regulations)
Have students review the history in the Introduction

3. Life Cycle of a Pharmaceutical Product
Cycle includes development, testing, approval, marketing and post marketing
10% of products are accepted for use
Drugs are developed by R & D
FDA now requires data from R & D concerning early research (preclinical)

4. Preclinical development
Product formulation & characterization
Product stability studies
Process development (processing+ purification)
Preclinical testing (Mutagenicity Pharmacokinetics (ADME)
IND( info :GLP, product/process develop, investigational plan

5. Testing If a compound shows promise toxicity testing is done
Toxicity of compound and metabolites are evaluated
Testing follows FDA guidelines, GLPs, Good Laboratory Practice regulations that govern animal studies
Later the drug is tested on human volunteers

6. Phases of Trials
Good Clinical Practices relate to the performance of clinical trials of drug safety and efficacy in human subjects
Phase-I clinical trials( toxicity/safety) are the first introduction of proposed drug (~100)
Phase-II clinical (efficacy/effectiveness) trials are performed on a small number of diseased patients to determine efficacy (~300)
Phase-III (confirmation and line extension) involves more patients

7. Biotech Products for Medical Use
Recombinant DNA Production of Pharmaceuticals
Begin with cultured yeast, insect, hybridoma or mammalian host cells modified so that they contain a genetic construct
Genetic construct includes the gene that codes for a protein of interest and the DNA sequences needed for the protein to work
Host cells express the gene and produce protein of interest (insulin)

8. Technical issues
Master cell band (MCB), is the key component in maintaining genetic stability
is the source of cells used for production
For bacterial cells, master cells are produced from original colony
Are frozen for later use after initial production
Working Cell band (WCB) produced by allowing the master cells to multiply after thawing
A history of the Cell banks is kept so that there is knowledge of the origin, etc.

9. Issues with cell cultures
Cultures must be stable
Use of a master cell bank helps maintain stability
Cultures must be free of contamination
Infectivity assays
Clearance studies
Contaminants include Viruses and bacterias, Pyrogens, Nucleic acids, proteins, residuals from processing, etc.
Infectivity assays involve growing cells along side test cells to see if they become infected.
Clearance studies intentionally add a contaminate to the productions system and study the ability of the process to remove it

10. Regulation of Food and agriculture
Food Safety
Contaminants
Food additives
FDA regulates these
Recombinant DNA methods
Safety- must be approved by FDA
Release of agents is also restricted.