Hatch-Waxman Revisited

1. Hatch-Waxman Revisited • Allows patent owners to recover time spent in clinical trials and FDA regulatory review • Specifically, pioneer companies are granted an extra half-day of patent life for every day spent in clinical trials and an extra day for every day spent in FDA review period • There are 2 restrictions: • effective life of drug patent cannot exceed 14 years • total time restored cannot exceed 5 years

2. However… • A patent term can only be extended once • Only one patent can be extended for a given regulatory review period • FDA authorization must be for first commercial use of active ingredient • Extensions are limited to what is covered by original FDA authorization

3. Hatch-Waxman & Generics • Generic share of prescription market has grown from 19% (1984) to 53% (2003) • This act permits generic manufacturers to cite safety and efficacy data from pioneer FDA applications • This relieves the burden of clinical trials (as long as bioequivalence is demonstrated) • Generic manufacturers are permitted to initial clinical tests (to demonstrate bioequivalence) before pioneer patents expire

4. Naming Drugs • Drugs have several types of names, each used for a different audience • Chemical and biological names are used to describe composition of small-molecule or biological drugs • Generic names are shared between branded and generic drugs to indicate common ingredients • Trade names of drugs are proprietary names used by different firms to brand their products

5. Chemical & Biological Names • Chemical or biological names provide scientific descriptions of drug composition • Chemical name for ibuprofen is 2-[4-(2-methylpropyl)phenyl] propanoic acid • Biological name for Amgen’s Epogen is recombinant erythropoietin

6. Generic Names • A generic name is created using specific nomenclature system and is used to identify generic versions of a branded drug • Generic name for Amgen’s Epogen is epoetin alfa • Ibuprofen is generic name for drugs marketed under Advil (Wyeth), Motrin (McNeil) and other trade names

7. Generic Names Table 8.4 Selected generic drug naming conventions

8. Trade Names • Trade names are used to uniquely brand an individual company’s version of the drug • A trade name must be approved by the FDA and cannot imply efficacy • Trade names are protected by trademark law, preventing generics from using them even after patent expires • This encourages pioneers to develop strong brand identity to expand market dominance past patent expiration

9. Other Naming Issues • Despite restriction that trade names cannot imply efficacy, drug makers often select names with connotations aligned with intended use • Examples: Vick’s Dayquil and Nyquil • Abbreviations may be used when appropriate (EPO common for epoetin alfa) • Drugs in development are referred to by their method of action (ex. ACE inhibitor) or internal code name (ex. MEDI-493 for Medimmune’s Synagis drug)

10. Recombinant DNA Advisory Committee (RAC) • Established October 7, 1974 by NIH in response to public concerns about safety of genetic manipulation • Main goal is to consider current state of knowledge and technology regarding recombinant DNA. Responsibilities include: • Review of human gene transfer trials • Assessment of ability of DNA recombinants to survive in nature • Potential for transfer of genetic material to other organisms

11. RAC • Also considers hypothetical hazards and methods for monitoring and minimizing risks • Committee members include scientists and non-scientists (representing public) • Guidelines include description of facilities and practices intended to prevent unauthorized release or inadvertent exposure to GMOs or rDNA • Compliance is mandatory for those receiving funding from NIH

12. US Department of Agriculture (USDA) • Regulates plant pests, plants, and veterinary biologics • Important to determine if plant is safe to grow outdoors • Several USDA agencies exist to regulate and monitor use of biotechnology in agriculture • Food Safety Inspection Service is responsible for monitoring safe use of engineered domestic livestock, poultry, and products derived from them

13. USDA - APHIS • Animal and Plant Health Inspection Service(APHIS) is responsible for protecting agriculture from pests and diseases • It regulates movement, importation, and field testing of GMOs through permits and notification procedures • APHIS also has Veterinary Biologics and Biotechnology Regulatory Services divisions • Other agencies include Foreign Agriculture Service & Economic Research Service

14. Environmental Protection Agency (EPA) • Regulates microbial and plant pesticides of chemical and biological origin, new uses of existing pesticides, and novel organisms that have industrial uses • BioPesticides and Pollution Prevention Division regulates distribution, sales, use, and testing of plants and microbes producing pesticidal substances

15. EPA • EPA sets tolerance limits for substances used on and in food and feed • EPA also sets tolerances for residues of herbicides used • Toxic Substances Control Act Biotechnology Program regulates microbes intended for commercial use that contain or express new combinations of traits • GE plants and organisms must conform with standards set by state and federal marketing statutes

16. Securities and Exchange Commission (SEC) • Mission is to protect investors, maintain fair, orderly, and efficient markets, and facilitate capital formation • SEC is responsible for ensuring that company public disclosures are accurate and complete • Challenge is that many biotech company disclosures are protected by FDA (not public information), so SEC usually does not usually have sufficient information • FDA has improved communications with SEC and began releasing carefully worded press releases to inform public of inconsistencies within a company