Food and Drug Administration Drug Regulation BIT 120

FDA Regulatory body that governs testing and marketing of new therapeutic drugs, food, medical devices and procedures Establishes guidelines for how drugs should be tested in animal studies, as well as clinical trials Shares responsibility with clinicians and drug company

FDA FDA – federal science based law enforcement agency 9000 employees – scientists, MDs, inspectors, others $1.2 billion budget ($4/taxpayer)

FDA Mission Foods are safe, wholesome, sanitary and properly labeled Human and veterinary drugs are safe and effective Safety of devices intended for human use Public health and safety are protected from radiation Cosmetics safe and properly labeled

1906: Food and Drug Act regulates food, drugs and cosmetics ensure proper labeling and product unadulterated NOT DRUG SAFTEY 1927 Establish Food and Drug Administration 1933 FDA sought to revise laws to include safety eyelash dye- caused blindness cream- mercury poisoning weight loss drugs - death 1938: Revised Food, Drug and Cosmetic Act passed included drug safety (animal and clinical studies) and efficacy

Sulfanilamide Antibiotic Sold by Massengill Pill ‘solubilized’ in diethylene glycol ELIXIR 350 poisonings, 100 deaths Pulled from shelves because mislabeled - NOT an elixir Massengill not held responsible for poisoning

Issues Should drugs be available prior to completion of testing? HIV Needs of few vs many Cancer How Safe should drug be? Risk assessment Risk vs Reward Short term effects Long-term effects (withdrawal of a drug) Education of patient

Approval FDA reviews application 10-15% are denied FDA decides whether RAC needs to review RAC Recombinant DNA Advisory Committee reviews applications to use novel recombinant DNA procedures (ie Gene Therapy) part of NIH (National Institutes of Health) must publish meeting minutes for public view no release of GEO to environment (originally)

Where does FDA look for Safety? 1. During Pre-Clinical Studies lab and animal studies 2. Clinical Trials 3. During NDA review 4. Post-Marketing

Orphan Drug Act Orphan diseases affect <200,000 patients No cure or treatment Difficult to get patients for clinical trials Two incentives: 1) 7- year period of market exclusivity following approval of drug by FDA 2) 50% tax credit for clinical research expenses SEE HANDOUT

Early Regulations on rDNA Tech A Self-Imposed Moratorium On Recombinant DNA experiments until regulatory guidelines established recombinant microorganisms proliferate outside laboratory? Potential hazard to lab workers? B US National Institutes of Health 1. primary research grant agency for medical and health sciences 2. no legal status 3. issues guidelines containment of organisms (i.e., negative pressure rooms) (Later data shows that E coli K 12 strain unable to extensively live outside lab)

When recombinant version of approved protein is re-evaluated... Chymosin cheese making cows stomach hydrolyzes casien in milk Is rChymosin the same as naturally derived? Restriction mapping DNA hybridization DNA sequencing molecular weight biological activity Purification - remove E coli contaminants

Tryptophan Contaminated Batches caused by Enhanced bacterial strain Change in purification Caused EMS (eosinophilia-myalia syndrome) muscle pain respiratory arrest

Recombinant Bovine Somatotropin Arguments for 1. more milk/less cows 2. Levels of bST in milk no higher than control cows 3. bST no adverse reaction in humans Arguments against 1. Antibiotics given due to infection of milk glands causing allergic reaction 2. economic consequences little farmer put out of business

Release of GEO 1983 Submissions made to NIH-RAC 1. Submission announced to US Federal Register 2. Information disseminated 3. Reviewed by panel of experts 4. Public Meeting 5. Review by USDA (U.S. Dept of Agriculture) After lawsuit to block use of ice-minus bacteria… Responsibility of GEO release went to EPA (Environmental Protection Agency) USDA

References Biotechnology: Demystifying the Concepts Pages Pharmaceutical Research and Manufacturers of America- Publications ( Bio-link.org Molecular Biotechnology Glick and Pasternack