Drug Product Substitution: Orange Book Outline PDF

Drug product substitution “Orange Book” Learning objectives FDA legislation Brand name vs. Generic products – Therapeutic equivalency – Bioequivalence – Pharmaceutical equivalency Drug product substitution – Why generic prescription substitution? – FDA’s approval processes (NDA and ANDA) – Orange Bo...

Drug product substitution “Orange Book” Learning objectives FDA legislation Brand name vs. Generic products – Therapeutic equivalency – Bioequivalence – Pharmaceutical equivalency Drug product substitution – Why generic prescription substitution? – FDA’s approval processes (NDA and ANDA) – Orange Book Therapeutic vs. generic substitution FDA legislations 1906: Pure Food and Drug Act (established FDA) 1938 Federal Food, Drug and Cosmetic Act products must be safe and pure; required to submit NDA 1962 Kefauver-Harris Amendments products must be safe and effective; required to conduct clinical trials 1984 Hatch-Waxman Act Drug Price Competition and Patent Term Restoration Act 2009 Biologics Price Competition and Innovation Act Generic drug products Generics are drug products that are identical (or comparable) to brand name product, in terms of: – drug substance – dosage form – strength – route of administration – quality – performance characteristics – intended use Brand vs Generic Generic medicines work the same as brand-name medicines. Generic drugs must meet high standards to receive FDA approval. Approved generic medicines are generally only sold after patents and exclusivities protecting the brandname version end. Generic medicines cost less than brand-name medicines. Myths about generic drugs Generics – – – – are not as safe are not as potent take longer to act in the body are made in sub-standard manufacturing facilities Brand and generic product development Phase 3 Phase 2 Phase 1 Brand product Generic product Generic substitution Cost-saving therapeutic alternatives – reduce costs, increase drug use and prevent drug shortages – social and economical justification Generic substitution may not be appropriate for all drugs: – Hormones – Drugs with Critical Dose (CD) and Narrow Therapeutic Ratio (NTR) State laws Varies, check the state laws where you practice Iowa: 510B.6 Dispensing of substitute prescription drug for prescribed drug – pharmacy may request the substitution of a lower priced generic and therapeutically equivalent drug for a higher priced prescribed drug. – pharmacy shall obtain the approval of the prescribing practitioner prior to requesting any substitution under this section. – pharmacy shall not substitute an equivalent prescription drug contrary to a prescription drug order that prohibits a substitution. Regulatory Process for Generics To gain FDA approval, a generic product must: – meet the same requirements for identity, strength, purity, and quality – be manufactured under the same strict standards of FDA's good manufacturing practice regulations required for innovator products http://www.fda.gov/cder /ogd/ Therapeutic equivalence Therapeutic equivalence (TE) – Pharmaceutical equivalence (PE) ü same drug ü same dosage form ü same route of administration ü same strength – Bioequivalence (BE) ü Cmax (tmax) and AUC ü FDA’s bioequivalence range: 80 – 125% FDA’s Orange Book list approved drug products with TE evaluations – approved based on safety and efficacy helps to identify multisource products – products that are available in more than one TE products helps to determine products that are therapeutically equivalent (TE) to each other – TE codes assists generic company in identifying reference products – “RLD” and “RS” AB code If test product and RLD/RS are TE (PE + BE), then they – Get an “AB” code – “A_” There are TE products – “AB” Bioequivalence test Assumption: – TE products are equally safe and effective AB1, AB2. … codes Multisource drug products with two or more reference listed drugs FDA Waivers Products in conventional dosage forms not presenting bioequivalence problems Injectable aqueous solutions and, in certain instances, intravenous non-aqueous Injectable oil solutions – type of oil used as a vehicle should be identical Solutions and powders for aerosolization Topical products “B” Codes Drug products that FDA, at this time, considers not to be therapeutically equivalent to other pharmaceutically equivalent products – Approved drug products – Drug products are under regulatory review – Rate and extent of absorption may not be same – FDA has an insufficient basis to determine therapeutic equivalence – Comparison may not have been made B_ Codes BC: Extended release (oral, injectable) products ü If bioequivalence data are available (they will be coded as AB) BD: Drugs with documented BE problems BE: Delayed release oral products BN: Products in aerosol-nebulizer drug delivery systems BP: Potential BE problems (e.g., parenteral suspensions) BR: Rectal dosage forms for systemic delivery BT: Topical products with bioequivalence issues (almost all dosage forms other than solution) BX: Insufficient data submitted BS: Products having drug standard deficiencies Practice problem open the orange book website practice the TE-codes with the drug “tretinoin” http://www.accessdata.fda.gov/scripts/cder/ob/default.cfm Summary: product substitution Scientific: – FDA guidance; OB Legal: – State Provider: – Insurance; formularies Economics: – Cost Professional judgment!