NON-PATENT EXCLUSIVITIES

Dr. Bhaswat S. Chakraborty Sr. VP & Chair, R&D Core Committee

Cadila Pharmaceuticals Ltd.

Presented at the ASSOCHAM Conference on “IPR in Pharmaceuticals: Balancing Innovation &

Access”Pride Hotel, Ahmedabad, October 7, 2015

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DISCOVERY AND DEVELOPMENT OF NEW PHARMACEUTICALS Entail enormous intellectual and financial resources Thus, incentives and protections are required

Motivation Fair ROI Term of market exclusivity

NCE, NBE api/galenic products Internationally, 20 yr patent term from the date of filing Translates to ~8-12 years of exclusive sales rights

This exclusivity is balanced with a legitimate competition from the low cost generic drugs For development of generic drugs Other competitive aspects, e.g., para IV, compulsory

licensing 2

Chakraborty BS (2014). Pharma Bio World, June, 31-34

PATENT & NON-PATENT EXCLUSIVITIES FDA,EMA, CDSCO

Provide legal opportunities to extend the period free of competition Called non-patent exclusivity provisions

Both patents and exclusivity are similar concepts and both work in a similar fashion

Differences: Patents are granted by the patent office anywhere along the drug

development lifetime and can encompass a wide range of claims Exclusivity is exclusive marketing rights granted by the

regulatory agency upon approval of a drug and can run concurrently with a patent or not

Exclusivity is a statutory provision and is granted to an NDA applicant if statutory requirements are met Designed to promote a balance between new drug innovation and

generic competition 3

DATA EXCLUSIVITY Data exclusivity guarantees additional market

protection for originator Health authorities cannot accept applications for

generics during the period of exclusivity Patents can expire before or after drug approval, or

anywhere in between Exclusivity, however, is granted only upon approval

Some drugs have both patent and exclusivity protections while others have just one or none

Patents and exclusivity may or may not run concurrently and may or may not encompass the same claims

Exclusivity is not added to the patent life except paediatric exclusivity, which extends patent life for 6 mo.

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FIVE TYPES OF NON-PATENT EXCLUSIVITIES IN THE USA

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S. No. Exclusivity Term 1 Orphan Drug Entity (ODE) 7 years

2 New Chemical Entity (NCE) 5 years

3 "Other" Exclusivity (Mainly new clinical study exclusivity)

3 years

4 Pediatric Exclusivity (PED) – added to existing Patents/Exclusivity

6 months

5 Patent Challenge (PC ) – this exclusivity is for ANDAs only

180 days

ORPHAN DRUG ENTITY (ODE) Drugs for rare or unusual diseases (affecting 200,000

or fewer patients) are often treated as orphan drugs As drug companies are very reluctant to use resources for

such small, often obscure markets The US orphan drug act of 1983 was passed to address

this genuine but often neglected area of drug treatment Provides 7 yrs of market exclusivity period after its regulatory

approval ODE approved by FDA will not allow a generic or

another innovator product with same API labeled for same orphan indications However, a clinically superior or safer same orphan drug

for the same indications may be granted by the FDA6

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NEW CHEMICAL ENTITY (NCE)  An NCE is an active moiety for which no NDA was

previously filed to FDA The emphasis of exclusivity here is on the new active

moiety that is directly or indirectly responsible for the drug’s pharmacological action

The NCE exclusivity granted by the FDA is valid for 5 yrs During this period the FDA cannot approve a

competitor’s generic [505(J)] or follow on [505(b)(2)] application which is based on the same NCE

Like the case for ODE, the FDA can, however, accept or approve another NDA with evidence of adequate efficacy, safety, and quality based on the same NCE

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NEW CLINICAL STUDY EXCLUSIVITY  New clinical study exclusivity

Granted for reports of new clinical investigations (other than BA/BE studies) essential to the approval

E.g., formulations; salts; indications; dosing regimens; patient populations; OTC switches; or other label changes

Requirements include a) studies may not be BA/BE; b) studies must be conducted

or sponsored by applicant; c) the new results not rely on FDA reference files of previously submitted data; and d) studies must be essential to approval

 This type of exclusivity is granted for 3 years and during this period a competitor’s ANDA will not be approved by the FDA However, FDA can review an ANDA with the same drug

during this exclusivity period 9

PEDIATRIC EXCLUSIVITY (PED) Pediatric CTs

Children as patients may not metabolize/respond to a drug like the adults

Thus, appropriate & adequate CTs of the same drug on pediatric population to develop useful information of safety and efficacy

Generated pediatric efficacy and safety data need not be successful in statistical and conventional sense

Applicants receive an exclusivity of 6 months by FDA modernization act of 1997

When 6-mo pediatric exclusivity is granted Applies to all existing patents and exclusivity on all

applications held by the sponsor for that active moiety It does not stand alone PED is annotated in the exclusivity column and is linked to

exclusivity formerly granted. 10

ANDA FILINGS TO US FDA

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PATENT CHALLENGE (PC) Patent challenge or generic drug exclusivity came into

existence by virtue of Hatch-Waxman Act of 1984 This act provides for an exclusivity to the first ANDA

applicant containing a paragraph IV certification A para IV certification means that the applicant shall

provide the patent number and Certify, in its opinion and to the best of its knowledge, that

the patent is invalid, unenforceable, is not infringed by the manufacture, use, or sale of the drug product for which

the abbreviated application is submitted A substantially complete ANDA contains data that is sufficient to

permit a full review The length of patent challenge exclusivity is 180 days from the

day of marketing of the product 12

PATENT CHALLENGE (PC).. For approval process of paragraph IV, the generic

applicant must:1. Certify in its ANDA that the patent in question is

invalid or is not infringed by the generic product2. Notify the patent holder of the submission of the NDA

If an infringement suit is filed against generic applicant Within 45 days of ANDA notification Then, FDA approval to market the generic drug is

automatically postponed for 30 months unless, before that time, the patent expires or is judged

to be invalid or not infringed This 30-month postponement allows the patent

holder time to assert its patent rights in court 13

PARAGRAPH IV PATENT CHALLENGES

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EUROPE: SUPPLEMENTARY PROTECTION CERTIFICATES (SPCS) The process of obtaining a patent may reduce the

period to exclude others from practicing the patent The European patent law offers SPCs to compensate

patent holders for the regulatory delays of medicinal/plant products approval

An SPC extends the statutory 20-yr max by up to five years

Note that SPCs can be obtained only for products that have been authorized for the first time as medicinal products in the EU In Lithuania, however, an SPC may be obtained for any

approved patented product, provided the basic patent was filed after February 1st, 1994

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OTHER EXCLUSIVITIES IN EUROPE Under the data exclusivity directive, pharmaceutical

companies may receive up to 11 years to market their product without risk of competition 11 years of exclusivity are comprised of an “8+2+1” regime A drug company introducing its product to market in the EU

can enjoy 8 yrs of data exclusivity, 2 yrs of marketing exclusivity & 1 yr extension

During 8 yr period of data exclusivity, competitors cannot submit generic applications for MA

During this time, the innovator’s data is treated as a trade secret until the expiration of the 8 yr data exclusivity period

Within the data exclusivity period a new applicant must perform its own safety and tox studies & CTs, without dependence on innovator’s data

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OTHER EXCLUSIVITIES IN EUROPE..

 EU also has exclusivity for orphan drug medicines Rarity of condition (< 5 in 10,000) or insufficient return on investment Seriousness of condition (life threatening/chronically debilitating) Methods of diagnosis, prevention, or treatment exist in EU If a method does not exist, significant benefit should be assured

Once an orphan MA in centralized procedure or by all member states The community/member states will not accept another application for MA

for the same drug and indication for 10 yrs 6 months of PE patent extension plus

1 yr patent extension for products that have demonstrated a significant clinical pediatric benefit for an approved indication

2 yr of additional exclusivity for studies in PIP PUMA may provide 8 yrs of data exclusivity and 10 years marketing

exclusivity for products developed exclusively for use in the pediatric population

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EUROPEAN EXCLUSIVITIES

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THE INDIAN SCENARIO  Until 1994, India had relatively weak patent laws so that all

life-saving drugs could be provided to Indian citizens at low cost However, under TRIPs & GATT of 1994

Patent Amendment Act of 2005 is seeing Indian industry is in full compliance with TRIPs in all aspects

Both products and processes of all APIs and finished dosage forms are supposed to be non-infringing of existing relevant patents

In practice, no guaranteed data exclusivity in India Such non-exclusivity allows generic companies sometimes to

introduce competing products without doing their own safety and efficacy tests

Also, Indian Patents Amendment Act of 2005 excludes patentability for derivatives of known substances Unless efficacy is significantly greater than the original substance Also, DPCO has >350 essential drugs under price control thus not

encouraging non-patent exclusivity to the extent described above for US or EU.

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SUMMARY

CONCLUDING REMARKS It is fitting that pharmaceutical innovators would

like to enjoy a favorable return on their R&D investments since the investments often exceed the billion dollar mark these days

The non-patent market exclusivities along with the remaining patent term after approval provide for an optimal benefit to these stakeholders

When properly informed about these exclusivities, an innovator, NDDS sponsor or a generic manufacturer can develop their strategies for an appropriate short or long term, whatever is applicable in its case

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REFERENCES US Food and Drug Administration. (2011). How can I

better understand Patents and Exclusivity? http://www.fda.gov/ForIndustry/FDABasicsforIndustry/ucm238582.htm

Hathaway C., Manthei J., Scherer C. (2009) Exclusivity Strategies in the United States and European Union. FDLI Update, May/June issue, 34-39.

European Medicines Agency. (2013). Orphan designation. http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000029.jsp&mid=WC0b01ac05800240ce

European Medicines Agency. (2013). Medicines for children. http://www.ema.europa.eu/ema/index.jsp?curl=pages/special_topics/general/general_content_000302.jsp

Chakraborty B.S. (2011). Towards New Horizons in Pharma Research. Ingredients South Asia, October 16-31 issue, 34-36.

Janodia M.D., Chauhan A., Hakak S.M., Sreedhar D., Ligade V.S., Udupa N. (2008) Data Exclusivity Provisions in India: Impact on Public Health. Journal of Intellectual Property Rights, 13, 442-446. 22

ACKNOWLEDGEMENT: NILESH M SHAH

THANK YOU VERY MUCH

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