PHA 321 Drug Approval Process.pptx

Drug Development & Approval Process Wesley Sparkmon PHA 321 Agenda Compare and contrast drug substance and drug product. Describe the drug development and approval process from preclinical studies to post-marketing surveillance. Define IRB and describe the role that IRBs play in the drug approval pr...

Drug Development & Approval Process Wesley Sparkmon PHA 321 Agenda Compare and contrast drug substance and drug product. Describe the drug development and approval process from preclinical studies to post-marketing surveillance. Define IRB and describe the role that IRBs play in the drug approval process. Compare and contrast standard review and priority review of an NDA. Describe the process for approval of generic drugs. Distinguish the terms bioequivalents, pharmaceutical equivalents, therapeutic equivalents, pharmaceutical alternatives. Describe drug development costs and approval times. Emergency Use Authorizations The approval process for medical devices and biosimilars What is a Drug? According to the Food, Drug, and Cosmetic Act (FDCA, 1938), a drug (drug substance) can be defined as: A substance intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals. A substance (other than food) intended to affect the structure or any function of the body of man or other animals. Drug Product The finished dosage form, e.g., tablet, capsule, solution, that contains a drug substance (the active drug ingredient), generally, but not necessarily, in association with inactive ingredients. Drug Development Timeline 10 – 15 YEARS Target Identification CAUSE - Understand the disease Identify the underlying cause of the disease LOCATION - Choose a molecule to target with a drug Important to pick a target that is ‘drugable’ – one that can potentially interact with and be affected by a drug molecule. EFFECT - Test the target and confirm its role in the disease Show that the target is actually involved in the disease and can be acted upon by a drug. Drug Discovery Find a promising molecule, i.e. a ‘lead compound’ that could become a drug PRIORITIZE - Perform initial tests on promising compound Test Absorption, Distribution, Metabolism, Excretion, and Toxicology (ADMET) properties in living cells, animals, computational models Prioritize lead compounds OPTIMIZE - Alter the structure of lead candidates to improve properties At the end, the product is considered a “Candidate Drug” Preclinical Testing Involves laboratory and animal testing to ensure that the ‘drug candidate’ is safe for human testing The FDA requires thorough testing (in vitro and in vivo) before it approves drug candidates for human testing Examine techniques for large scale drug production Scale-up production from laboratory quantities to clinical testing quantity (and eventually scaled to market quantity) Roughly 1 in 1,000 compounds survive the pre-clinical phase and make it to the clinical phase Investigational New Drug (IND) IND Application - A request for FDA authorization to administer an investigational drug to humans (prior to clinical trials). The application includes: Animal Pharmacology and Toxicology Studies Manufacturing Information Clinical Protocols and Investigator Information Authorization must be secured prior to interstate shipment and administration of any new drug. Unless explicitly disapproved, INDs become effective 30 days after submission and clinical testing on humans may begin. Investigational New Drug (IND) Commercial IND – Sponsors who ultimately want to market the drug (e.g. pharmaceutical or biotech companies) Non-Commercial IND (Research IND) – Anyone who will not be marketing the drug (e.g., physician) Sponsor-Investigator IND: Submitted by physician who both initiates and conducts an investigation. Emergency Use IND: When experimental drug is needed for an urgent medical situation (life-threatening situations). Treatment IND: For use of promising experimental drugs in clinical testing for grave conditions. Allows drug to be available to patients in need before the drug is approved for marketing. Institutional Review Board (IRB) Purpose: To ensure the rights and welfare of clinical trials participants Participants must be fully informed and provide their written consent Approval: IRB applications must be filed at all clinical trial sites Hospital and academic research institutions Exploratory IND Study (Phase 0) Feasibility of candidates for further development assessed Recently approved and recommended by FDA Conducted early in phase I Involves very limited human exposure (