Generic entries of new chemical entities: challenges for controlling promotion and ensuring safety.

Transcription

1 Generic entries of new chemical entities: challenges for controlling promotion and ensuring safety. Prof Rohini Fernandopulle MBBS,PhD Professor in clinical pharmacology, Faculty of Medicine Univesity of Colombo Sri Lanka

2 Sri Lanka Population: 20,450 (2009) Area: 25,332 square miles (65,610 sq km) State provides free health and education Infant mortality: 10 /1000 LB Average Life expectancy at birth: 74y Adult literacy 92% Population below US $ 2 a day ( ) : 41.6 % Total state health budget 2009 = LKR 71.4 billion (1.5 per cent of GDP). 7.5 billion on pharmaceuticals

3 Control Substance Unit Office of MT&S Director Deputy Director Law Enforcement Unit Pharmacovigilance Unit Post Marketing Unit GMP Unit Registration & Licensing Unit Administration Unit No of Pharmacist attached to NRA 11 Pharmacologists, scientists Permanent Nil University academics provide advice as a voluntary service

4 Need for generic versions of NCEs in Sri Lanka? Ensure timely access to possibly life saving medications at a price affordable to the government and consumer

5 NCE generics in Sri Lanka Country of origin 100% from India In India the unrestrained generic proliferation that follows the introduction of a new molecule is a phenomenon without parallel elsewhere in the world 1. Annual rate of approval of new drugs in India is comparable with US FDA (median, 24 v. 27; mean [SD] 26.4 [9.52] v [6.73]). EMEA =24 1

6 India 1,2 Ensure timely access 1 Clopidogrel, approved in February 2001, spawned at least 16 generics within a year of approval, presently 62 Gatifloxacin, approved in October 2001, had at least 20 generics by 2002 Valdecoxib, cleared only in August 2002, had at least 10 generics by end of Rosiglitazone to date has approximately 32 generics Enoxaparin 13 biosimilars

7 Sri Lanka Ensure timely access 2 Indian manufacturers seek registration in Sri Lanka Past 5 years 70 new molecular entities registered Do they meet the WHO criteria for a generic medicine? Most are pharmaceutically similar" may not necessarily be therapeutically equivalent Rofecoxib (Vioxx) licensed in USA, European Union Countries and Australia in In Sri Lanka two years later (June 2001) By November 2004, 25 branded generics registered

8 Ensure affordability 1 Yes, only silver lining, competition forces lowering of prices Most innovators are not available in Sri Lanka after introduction of generic NCEs Why? unable to compete with lower price of generic NCEs Avandia not registered in SL after 2006

9 Ensure affordability 2 Enoxaparin both innovator and generic available Cost difference between innovator and generic is 3USD (1 USD = LKR112) Annual requirement difference is USD30,000

10 Safety and rational use? What is the problem Despite rapid proliferation of NCEs it is an acknowledged fact that real therapeutic advances are relatively rare From 1995, 21 drugs in U.S.A removed from the market for safety reasons 50% involved heart complications on the market from 11 months to 30 years average time to recall was 8 years

11 Challenges unique to resource limited settings 1 Ensuring safety, quality and rational use Inability to monitor promotional activities though ethical code for promotion is available MT&S has regulations but committee reviews printed and broadcast promotion of OTC medicines only Many pharmaceutical delegates verbally promoting generic NCEs Roughead et al 3, analysed meetings between PD and GPs omission of risk information was common, and that adverse reactions and interactions were mentioned only in statements that minimised the risk of the product being detailed.

12 Challenges unique to resource limited settings 2 Innovator not in market no obligation to inform safety concerns issued from stringent authorities Innovator should act as reference product to each generic regulator could make it an obligation to the generic manufacturer to update any change happening with originator such as new safety concerns, new indications/more precise indications etc. High cost of internet and maintenance of web site Doctors prescribe NCEs, without a balanced judgment of their risks and benefits in a given situation

13 Case study of Avandia

14 Approved Indications for Avandia Treatment of type 2 diabetes mellitus: as monotherapy in adults (particularly overweight adults) inadequately controlled by diet and exercise. as dual oral therapy in combination with metformin, in adults (particularly overweight adults) with insufficient glycaemic control despite maximal tolerated dose of monotherapy with metformin a sulphonylurea, only in adults who show intolerance to metformin or for whom metformin is contraindicated, with insufficient glycaemic control despite monotherapy with a sulphonylurea as triple oral therapy in combination with metformin and a sulphonylurea, in adults (particularly overweight adults) with insufficient glycaemic control despite dual oral therapy

15 Rosiglitazone Sri Lankan scenario Medicine Registration in US, FDA Registration in Sri Lanka Country of Manufacture Avandia In USA May 25, 1999 October 2002 USA / Spain Generic 1 February 2003 India Generic 2 November 2003 India Generic 3 January 2004 India Generic 4 March 04 India Generic 5 December 04 India Generic 6 January 05 India Generic 7 November 06 India Generic 8 March 07 India

16 Avandia Avandia case is instructive, as it follows the wellworn path of so many drugs, hailed as miracles at their inception, advertised widely led to more generics, both reap huge revenues, before their dangerous, poorly understood characteristics are exposed No continuous update from innovator not reregistered since 2006 EMEA decision communicated through WHO

17 Risk Management strategy for NCEs

18 REMS Risk evaluation and minimization strategy The Food and Drug Administration Amendments Act of 2007 (FDAAA) granted the FDA the authority to require the submission and implementation of a REMS if the FDA determines a REMS is necessary to ensure that a drug s benefits outweigh its risks.

19 REMS for Avandamet by US FDA A. Medication Guide The goal of the REMS is to communicate the risks of AVANDAMET. A Medication Guide will be dispensed with each AVANDAMET prescription. B. Communication Plan The REMS for AVANDAMET does not include a Communication Plan. C. Elements to Assure Safe Use The REMS for AVANDAMET does not include elements to assure safe use. D. Implementation System Because the REMS for AVANDAMET does not include elements to assure safe use, an implementation system is not required.

20 Medicines promotion in Risk Mitigation Not mentioned in the REMS guidance document WHO definition of medicines promotion All informational and persuasive activities by manufacturers and distributors, the effect of which is to induce the prescription, supply, purchase and/or use of medicinal drugs. By definition the aim of promotion is to stimulate product sales. At present, even the United States does not have the capacity to adequately control promotion of the products on its own.

21 Medicines promotion in Risk Mitigation 2 REMS proposed by manufacturer to the regulator How about Promotion Regulation for Risk Mitigation (PRORMS) by regulator to the manufacturer at the time of approval with monitoring for compliance till safety is well established

22 PRORMS Promotion to whom? to all doctors, pharmacist / only specialists till effectiveness and safety is established Submission of all promotional material of NCEs (including generics) for regulatory approval studies suggest that the guidelines and regulations for self control by industry are not effective 4. NRA could appoint a team of popular specialists to monitor the activities of PD

23 References 1. Ghosh A, Hazra A, Mandal SC. New drugs in India over the past 15 years: Analysis of trends. Natl Med J India 2004;17: Med India on mobilhttp:// price/index accessed on November 6 th Roughead EE. The pharmaceutical representative and medical practitioner encounter: implications for quality use of medicines accessed on November 6 th Norris P, Herxheimer A, Lexchin J. Drug promotion what we know, what we have yet to learn. Reviews of materials in the WHO/HAI database on drug promotion

24 Thank You