1. Patent-Extender Drugs: Loop-holes in the Law Sandy H. Yoo 4/14/06

2. Patent-extender Drugs An increasingly widespread tactic used by pharmaceutical companies to extend the life of their drug patents by creating a slightly altered version of the original drug, which is then eligible under FDA rules for at least another few years of market monopoly. Novak V. Bristol-Myers Squibb lobbies for a patent loop-hole. Time Magazine. Nov 2001

3. Overview of FDA approval process Pre-Clinical testing on animals Investigational New Drug (IND) Application Clinical Studies Phase I Phase II Phase III New Drug Application (NDA) NDA review for approval or non-approval Division Director sign-off on new drug

4. Center for Drug Evaluation and Research (CDER) CDER is FDAs branch responsible for approving new prescription drugs and generic drugs They oversee approval of IND, NDA, and review and give final approval or disapproval of drugs

5. Pre-clinical Trials Manufacturers test their new drug on animals to ask: Is my drug safe to test in humans? Is there enough evidence of its pharmacological action to justify further clinical studies in humans? If the answers are YES, they submit an IND for approval to test in humans.

6. Clinical Studies: Phase I Initial introduction of new investigational drug into humans Determine drugs action, properties, and side-effects in humans Usually conducted in healthy human volunteers

7. Clinical Studies: Phase II Early controlled clinical studies to obtain effectiveness of the drug for a particular indication Usually well-controlled, closely monitored Conducted in a relatively small number of patients (several hundred people)

8. Clinical Studies: Phase III Expanded controlled and uncontrolled trials to evaluate risk-benefit ratio of drug Involves several hundred to thousands of people Gives basis for extrapolating data results to general population At any of the 3 phases, FDA can place a clinical hold

9. New Drug Application & Review Data from pre-clinical trials and Phases I, II, III studies become part of the NDA NDA undergoes formal review by CDER The drug can be legally marketed once division director signs-off on new drug

10. New Drug Development Process

11. Generic Drugs Approval Process Generics use abbreviated new drug application (ANDA) Do not have to include preclinical and clinical data to establish safety and effectiveness Instead must prove BIOEQUIVALENCE If all requirements are met, generic is approved

12. Hatch-Waxman Act 1984 Company can seek approval to market a generic before expiration of a brand- name patent Abbreviated new drug application (ANDA) 1 st company to submit ANDA gets 180- exclusivity Patent holder may file infringement suit This delays approval of ANDA for 30- months

13. NDAs Drug Classifications 1. New Molecular Entity 2. New Salt 3. New Formulation 4. New Combination of Two or More Drugs 5. Duplication of Product (i.e., new manufacturer) 6. New Indication (claim) (includes switch from prescription to OTC) 7. Already Marketed Drug Product - No Previously Approved NDA

14. To name a few…

15. References 1. US FDA Center for Drug Evaluation and Research. Available at: http://www.fda.gov/cder/ http://www.fda.gov/cder/ 2. Novak V. Bristol-Myers Squibb lobbies for a patent loophole. Time 2001, Nov 2. 3. Field A. Doctoring the Hatch-Waxman Act. Stanford Graduate School of Business Research Paper.