Generic perspective and prospective 2
- 1. GENERIC DRUGS PERSPECTIVE AND PROSPECTIVE Gaurav M. Pharm (Pharmaceutics), Department of Pharmaceutics School of Pharmaceutical Education and Research, Jamia Hamdard 1 Krishnan S,Challenges to generic drug development, The Pharma Review (Published on february 2018)
- 2. Contents ■ Introduction ■ Types of Generics ■ History ■ Generics at present ■ Challenges faced by Generic ■ Future of Generics ■ References 2 Krishnan S,Challenges to generic drug development, The Pharma Review (Published on february 2018)
- 3. Generic drugs in simple terms are the copy of the branded ones having same ingredients, same dosage, same indications and exactly same pharmacological effects. Branded Generic ■ Cheaper: Manufacturer only spent on production. ■ Produced after the expiry of the patent period. ■ Supply by more then one company. ■ Studies: Equivalence and Bioequivalence. ■ Costly : because manufacturer spents a lot on research, developing & testing ■ Protected by patent laws from a specific period. ■ Supplied by only one company ■ Studies: Preclinical and clinical trials Have same API but may be different excipients and packaging 3 Krishnan S,Challenges to generic drug development, The Pharma Review (Published on february 2018)
- 4. Types of Generics Pure generics Branded generics Authorized generics When the formulation is sold by its original name. E.g. oral anti diabetic Metformin When the generic manufacturer giving a separate name to its product. E.g. Lipitor for Atorvastatin When the branded drugs covered as generics. Branded companies supply their drug to a generic firm, or to their own generic subsidiary, to market the product as a generic in return for royalties. This may create confusion, some times in the mind of4 Krishnan S,Challenges to generic drug development, The Pharma Review (Published on february 2018)
- 5. History 1906 Pure Food and drug act- Establishes regulation of food and drugs. 1938 Food, Drug and Cosmetic Act- Introduction safety standards. 1984 Hatch Waxman Act- Created an abbreviated mechanism from approval of generic copies of all drugs originally approved after 1962, by starting that preclinical and clinical testing does not have to be repeated for generics. 5 Krishnan S,Challenges to generic drug development, The Pharma Review (Published on february 2018)
- 6. Hatch- Waxman Act ■ The birth of modern generic drug industry can be traced back to the US legislation known as Hatch-Waxman Act Steps involves in development of potential generic drug: 6 Krishnan S,Challenges to generic drug development, The Pharma Review (Published on february 2018)
- 7. Objectives Reduce the cost associated with approval of generic For early experimental Motivating to generic manufacturers 7 Krishnan S,Challenges to generic drug development, The Pharma Review (Published on february 2018)
- 8. APPLICANT TRADE NAME GENERIC NAME DOSAGE APPROVAL Pfizer Lipitor Atrovastin calcium Tablet 1996 Pfizer TZ-3 Tioconazole Cream 1983 Pfizer Neurontin Gabapentin Tablet 1998 Pfizer Accupril Quinapril HCl Tablet 1991 Sunpharma Temozolomide Temozolomide Capsule 2014 Sunpharma Cequa Cyclosporin Ophthalmic 2018 Astrazeneca Plendil Felodipine Tab; extended release 1991 Astrazeneca Alvesco Ciclesonide Aerosol: inhalation 2008 Sandoz Amoxicillin & clavulanate potassium Amoxicillin & clavulanate potassium Suspension: oral 2002 Sandoz Betopic Betaxolol Ophthalmic 1985 8 Krishnan S,Challenges to generic drug development, The Pharma Review (Published on february 2018)
- 9. A rough comparison of generic and branded drugs 9 Krishnan S,Challenges to generic drug development, The Pharma Review (Published on february 2018)
- 10. RANK COMPANY COUNTRY TURN OVER 1 Teva Pharmaceuticals ISREAL 9.8 $ billion 2 Mylan US 9.4 $ billiom 3 Sandoz GERMANY 9.0 $ billion 4 Pfizer US 4.5 $ billion 5 Sun Pharmaceuticals INDIA 3.6 $ billion 6 Freseniow Kabi USA 2.8 $ billion 7 Endo International IRELAND 2.5 $ billion 8 Lupin INDIAN 2.5 $ billion 9 Sanofi FARNCE 2.0 $ billion 10 Krishnan S,Challenges to generic drug development, The Pharma Review (Published on february 2018)
- 11. U S FDA classifies generics as therapeutically equivalent to those of branded if it meets the following general criteria: (1)They are approved as safe and effective; (2)They are pharmaceutical equivalents in that they (a)Contain identical amounts of the same active drug ingredient in the same dosage form and route of administration, and (b)other applicable standards of strength, quality, purity, and identity; 11 Krishnan S,Challenges to generic drug development, The Pharma Review (Published on february 2018)
- 12. (3)They are bioequivalent in that a)They do not present a known or potential bioequivalence problem, and they meet an acceptable in vitro standard, or b)If they do present such a known or potential problem, they are shown to meet an appropriate bioequivalence standard; (4)They are adequately labelled; (5)They are manufactured in compliance with Current Good Manufacturing Practice regulations. 12 Krishnan S,Challenges to generic drug development, The Pharma Review (Published on february 2018)
- 13. Generics at present ■ With the rising healthcare costs, the interest in generic drugs has increased almost all over the world, whether it is a rich or a poor country. According to the report, the global generic drug market accounted for around USD 200.20 billion in 2015 ■ In India, a government study found that 39 million Indians were forced into poverty due to health problems and treatment costs. 13 Krishnan S,Challenges to generic drug development, The Pharma Review (Published on february 2018)
- 14. ■ It also found that drug prices increased 40% in the ten years between 2006 and 2016, with production of generics increasing only 15%, but at the same time branded drug prices rise 137 percent. ■ Prime Minister of India has planned to make a provision of free generic drugs through public health clinics and hospitals, beginning in October 2012, and which presently is practiced. 14 Krishnan S,Challenges to generic drug development, The Pharma Review (Published on february 2018)
- 15. 15 Krishnan S,Challenges to generic drug development, The Pharma Review (Published on february 2018)
- 16. Challenges faced by generics ■ Innovator patent extension : Major challenge faced by generics is the attempt by innovators to constantly extend the period of their exclusive by listing more and more patents in the orange book due to this generic developer constantly certify paragraph 3 or 4 either wait for newly listed patent to expire.(9) ■ Product Selection : Such product Selection is itself a challenge, based on a variety of factors such as innovator patent expiry, proposed revenue generation, market situation, patient population, number of other probable generic players, Active Pharmaceutical Ingredient (API) availability, complexity of the API/ formulation development and generic’s research and manufacturing capability. ■ FDA requirements for bioequivalence and high fees : The generic drug developers burden is the increasing fees prescribed by Generic Drug User Fee Act(GDUFA) for filling the ANDA and challenges to meet safety & efficacy requirement. Krishnan S,Challenges to generic drug development, The Pharma Review (Published on february 2018) 16
- 17. Price erosion: The concept of “generic” price erosion as compared to the branded drug pricing, In fact, there would be a cut-throat competition when various generic versions of the same drug are approved simultaneously. example : In 2003, Apotex was awarded 180-day exclusivity for Paroxetine (Paxil of Glaxo Smith Kline (GSK) and was expected to sell $ 575 Million during the 180-day period but sold ~200 Million as GSK introduced the authorized generics. 17 Krishnan S,Challenges to generic drug development, The Pharma Review (Published on february 2018)
- 18. Patient Perspective ■ Cost and compliance : Theoretically, generic medications should improve management and patient compliance because the obstacle of cost has been removed. ■ Inferiority complex : Another potential issue is that patients may be resistant to going on a generic medication because they perceive them as inferior to their branded counterpart. Generics are often considered second-rate medications due to perceived poor compliance with standard manufacturing practices, lack of patient knowledge about generics, and influence of the brand-name company Patient preference : We often need to consider our patient’s personality and past experience when deciding between generic and brand drugs as well. One important question to ask our patients is whether they have taken generics before and what the outcome was. If the patient had a poor experience, they may be baised towards branded medications and willing to pay the higher price. 18 Krishnan S,Challenges to generic drug development, The Pharma Review (Published on february 2018)
- 19. Future of Generics ■ The generics segment is experiencing dynamic growth in India and the Asia Pacific region. According to a 2016 study, the global generics market is expected to experience a 10.53 percent compounded annual growth rate (CAGR) from 2016-2020, with the value of drugs coming off expired patents equalling $150 billion by 2021 ■ And generic market expected to reach approx USD 380.60 billion by 2021. 19 Krishnan S,Challenges to generic drug development, The Pharma Review (Published on february 2018)
- 20. Upcoming off patent drug till 2021 BRAND GENERIC Acanya benzoyl peroxide/clindamycin Adcirca tadalafil Apidra insulin glulisine Astepro azelastine Atripla efavirenz/ emtricitabine/ tenofovir Fentora fentanyl Finacea azelaic acid Follistim follitropin beta Fortesta testosterone Levitra Vardenafil Tekturna aliskerin Tikosyn Dofetilide Treximet naproxen/sumatriptan Tyvaso treprostinil Vesicare solifenacin Lexiva fosamprenavir Lotronex alosetron Lyrica pregabalin Makena hydroxyprogesterone Namzaric memantine/donepezil Pradaxa dabigatran Promacta eltrombopag Remodulin Treprostinil Revlimid Lenalidomide Sensipar tablet cinacalcet Spiriva tiotripium Staxyn vardenafil Symbicort budesonide/ formotero Tekamlo aliskerin/amlodipine Xolair omalizumab In 2018, 30 Drugs Will offpatent 20 Krishnan S,Challenges to generic drug development, The Pharma Review (Published on february 2018)
- 21. BRAND GENERIC Afinitor everolimus Avastin bevacizumab Azasite azithromycin Eliquis apixiban Emend INJ fosaprepitant Exelon patch rivastigmine Exjade Deferasirox Factive gemifloxacin Firazyr icatibant Gilenya fingolimod Invega sustenna paliperidone Orencia abatacept Prezista darunavir Ranexa Ranolazine Rozerem ramelteon Tarceva Erlotinib Uloric Febuxostat BRAND GENERIC Atrovent HFA ipratropium hfa Byduredon exenatide Chantix varenicline Dexilant dexlansoprazole Inlyta axitinib Namenda XR memantine er Safyral drospirenone/ ethinyl estradiol/ levomefolate Saphris asenapine Silenor doxepin Sprycel dasatinib Tykerb lapatinib` Vigamox moxifloxacin BRAND GENERIC Bystolic nebivolol Crixivan indinavir Emtriva emtricitabine Hysingla ER hydrocodone er Perforomist formoterol Sutent sunitinib Veramyst fluticasone fuoroate Xarelto rivaroxaban Zomig ns zolmitriptan In 2019 In 2020 In 2021 21 Krishnan S,Challenges to generic drug development, The Pharma Review (Published on february 2018)
- 22. GBI Research’s survey examined the most promising emerging markets for generic drug manufacturers. The results of the survey are shown in the follow figure-1 22 Krishnan S,Challenges to generic drug development, The Pharma Review (Published on february 2018)
- 23. ■ Indian pharmaceutical companies are already well positioned in some of the generic pharmaceutical markets of developed nations. ■ This is due to product development skills through advanced technological capabilities, and low-cost manufacturing. Ranbaxy (now Sun Pharma) was the first Indian pharmaceutical company to recognize and take advantage of the generics market. After the acquisition by Sun Pharma, the company’s net worth in 2015 was around $4 billion. Other Indian companies that are also very active in the world’s generic drug industry are Dr. Reddy’s and Cipla. ■ According to a recent analysis, the Indian generics market is expected to exceed $27.9 billion by 2020, from the value of $13.1 billion in 2015, registering a CAGR of 16.3%. 23 Krishnan S,Challenges to generic drug development, The Pharma Review (Published on february 2018)
- 24. References 1. Ghate, S. R., Biskupiak, J. E., Ye, X., Hagan, M., Kwong, W. J., Fox, E. S., & Brixner, D. I. (2011). Hemorrhagic and Thrombotic Events Associated with Generic Substitution of Warfarin in Patients with Atrial Fibrillation: A Retrospective Analysis. Annals of Pharmacotherapy, 45(6), 701–712. doi:10.1345/aph.1p593 2. Toni Johnson : http://www.cfr.org/drugs/debate-over-generic-drug-trade/p18055 (Updated: August 3/11) 3. http://www.fda.gov/ucm/groups/fdagov-public/@fdagov-drugs- gen/documents/document/ucm071436.pdf (Accessed on 22-11-18) 4. http://professionals.epilepsy.com/page/hallway_generics.html (Accessed on 22-11-18) 5. http://medsdebate.com/lib/generics/ (Accessed on 22-11-18) 6. Editorial, GENERICS VS BRANDED DRUGS!, J MGIMS, September 2012, Vol 17, No (ii), i – iv 7. Chawla K, et. al. (2014). A Global Comparison Between Brand-Name and Generic Drugs. Indian Journal of Pharmacy Practice, Vol 7, Issue 3, Jul–Sep, 2014 8. Pharmalife article, The future of generic drugs and strategies for commercial success. (Published on 17/02/17 at 10:22am) 24 Krishnan S,Challenges to generic drug development, The Pharma Review (Published on february 2018)
- 25. 9. Krishnan S,Challenges to generic drug development, The Pharma Review (Published on february 2018) 10. Bera A, Mukherjee A(2012), The importance of generic drugs in India, International journal of pharmaceutical, chemical and biological science, IJPCBS 2012, 2(4), 575-587. 11. Pierini D, Anderson K,, How generic drug are made, US Pharm.2003;38(6)(generic drug review):26-31 12. https://www.pti-nps.com/nps/wp-content/uploads/2017/04/NPS_Drugs- Coming-Off-Patent-by-2022-Web.pdf 13. https://www.drugpatentwatch.com/p/applicant/Sandoz 25 Krishnan S,Challenges to generic drug development, The Pharma Review (Published on february 2018)
- 26. 26 Krishnan S,Challenges to generic drug development, The Pharma Review (Published on february 2018)