The Lifecycle of Pharmaceutical products Chapter-3.

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

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)

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

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

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

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)

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.

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

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.