Successful Completion Of Preclinical Phase

Drug product patent term expiration and the challenge begins Mittal Bhawana*A, Kaur GurpreetB, Kumar VikasB A- SD College, Barnala, Punjab, INDIA B- Deptt. of Pharmceutical Sciences, Punjabi University, Patiala Abstract:-Patent is used as a safe measure to prevent unlawful use/manufacturing of a product or process. While according to GATT provisions there is 20 years exclusivity for product patent in case of pharma products but every pharma MNC uses some “Defensive Strategies” to further extend their patent protection period. With molecules like rosiglitazone (Avandia,GSK), ramipril (Altace, Monarch), lansoprazole (Prevacid, Aboott/Takeda) going off-patent in 2009, the big phamra players are ready to use defensive strategies. Preclinical Phase

•Testing in animals •ADME of drug and metabolites •Metabolites Toxicity

Successful completion of Preclinical phase

File IND

Clinical Phase I

II

III

IV

Generic Drug approval

•IND tested on Human •20 to 80 Healthy volunteers •Acess Safety

•Several hundred patients •Both safety and efficacy accessed

•100 to 1000 subjects taken •Information used to create package inserts

•Post marketing phase •Continuous review process

File ANDA (Submit data showing bioequivalence with innovators product).

Milestone in generic drug approval process DESI review Paper NDA Hatch-Wxman act Para IV filling Under Hatch-Wxman act (1962) or 505 b(2) (1984) •Safety and Efficacy required in NDA •FDA announced 2 year grace period for manufacturers to supply eveidence of efficacy of drug products marketed before 1962.

•NDA can be filed for the generic version of drug based on published scientific literature.

•Title I includes provisions similar to ANDA process and Paper NDA. •Title II include patent term restoration rules.

Para IV filling by prospective generic manufacturer. Patent is invalid or not infringed by generic application. NDA holder starts patent infringement Suit. YES (Automatic 30 months stay and 180 day exclusivity)

NO (Generic applicant may enter)

Defensive strategies used by big pharma companies Defensive strategy

Evidence/Description

Example

Authorised generics (Branded generics)

Generic divisions established by big pharma; Pfizer.s Greenstone; Novartis Sandoz etc or Big pharma do financial settlements with generic manufacturers

Merck’s authorized generic version of Simvastatin (ZOCOR), Dr. Reddy's Laboratories launched authorized generic version of GlaxoSmithKline's Imitrex (sumatriptan succinate)

Pricing and aggressive marketing branded drugs

Big Pharmacy/ pharmacy benefit managers (PBMs), all branded drugs about to go off patent or already off-patented

At end of patent expiration this will hinders generics companies ability to compete

Citizen’s petitions (Blocking petitions)

Makers of branded drugs may question the safety of generic version

GSK’s questioned safety of Buproprion generics (Wellbutrin XL)

Settling lawsuits filed by generic compnies challenging blockbuster patents

Slows generic’s entry to market. Legal fights create uncertainty amoung generic manufacturers about rising the lauch of generics.

Schering-Ploough paid Upsher-Smith to delay bringing to market a generic version of potassium chloride (K-Dur), a blood pressure medication