1. Global impact of medicine shortages Lisa Hedman World Health Organization Department of Essential Medicines and Health Products Toronto, Canada 20-21 June 2013 Photos courtesy of Lisa Hedman unless otherwise noted.

2. Medicine shortages 2 |2 | Outline: Vulnerabilities in low- and middle-income countries Case study: anti-tuberculosis medicines Financing Trade trends in BRICS countries Unanswered issues

3. Shortage of essential medicines is a global problem…and there is insufficient information to determine the magnitude and specifics characteristics of the problem Photo: Dr Charles Senessie, Swissmedic Bulletin of the World Health Organization 2012;90:158- 158A. doi: 10.2471/BLT.11.101303

4. Medicine shortages 4 |4 | Access to public sector medicines Policy environment Market environment

5. Medicine shortages 5 |5 | Vulnerabilities in low- and middle-income countries AreaProblem leading to stock outs PolicyInconsistent policies lead to fragmentation of markets and limited demand RegulationWeak pharmacovigilance and surveillance FinancingDependency on donor financing can disrupt demand ManufacturingLack of production capacity that meet basic quality standards SupplyVulnerable forecasting and supply systems, open to influences of spurious, falsely labelled, falsified, counterfeit (SFFC) EmergenciesLack of purchasing power, locked out of international markets

6. Medicine shortages 6 |6 | WHO REPORT 2011 – GLOBAL TUBERCULOSIS CONTROL Case study: anti-tuberculosis medicines

7. Medicine shortages 7 |7 | 2009 daily dosing guidelines, based on 0.5 to 2 tablets per day Comparison to available PQS approved products (in mg) Individual tabletsCombination tablets Dispersible combination tablets Individual components Guideline Recommended dose Recommended format (in mg) T1T2CT1 CT 2CT3CT4 DT 1 DT 2 DT 3 Ethambutol 20mg/kg/day 100 or 50400 275 Isoniazid 10mg/kg/day 5030010015075 306030 Pyrazinamide35mg/kg/day 150400500 400 15060 Rifampicin 15mg/kg/day 75 150 60 Scale of current products is different and too complex to use within treatment guidelines Case study: anti-TB medicines and policy change

8. Medicine shortages 8 |8 | Case study: anti-TB medicines financing

9. Medicine shortages 9 |9 | Slide detail excepted from Clinton Health Access Initiative data, 2012 Cycloserine Case study: anti-TB medicines demand Demand estimated to drop below sustainable production levels when donor funding in India expires

10. Case study: anti-TB medicines quality study 10 Failure rate No sample suspected to be of spurious, falsely-labelled, falsified or counterfeit product Extreme deviation: API content of more than 20% from the declared content average dissolution of tested units lower than 25% below pharmacopoeia Q value

11. Medicine shortages 11 | The 17% of the world's population that live in low income countries accounted for only 1% of global pharmaceutical expenditure. Relative to GDP, low income countries spent more than 30% of total health budgets on medicines, compared with 17% in high income countries. Source: The World Medicines Situation, 2011. Higher costs as a cause

12. Medicine shortages 12 | Higher costs as a cause The World Medicine Situation 2011, Cameron et al, WHO

13. Medicine shortages 13 | Public sector prices paid for the lowest-priced generic medicines, range from 1.9 times to 3.7 times the international reference price (IRP) and from 5.3 times to 20.5 times for originator brands. Private sector prices of originator brand medicines were at least 10 times higher than the corresponding international reference prices, and were as much as 20 and 30 times higher in Africa. Higher costs as a cause The World Medicine Situation 2011, Cameron et al, WHO

14. Medicine shortages 14 | www.the.lancet.comwww.the.lancet.com, December 1, 2008, Medicine prices, availability, and affordability in 36 developing and middle-income countries: a secondary analysis; Cameron et al Example: Cost of Ciprofloxacin

15. Medicine shortages 15 | Example: Cost of Ciprofloxacin Median price ratios of public sector procurement prices for lowest-cost generics www.the.lancet.comwww.the.lancet.com, December 1, 2008, Medicine prices, availability, and affordability in 36 developing and middle-income countries: a secondary, analysis; Cameron et al 4.322.55

16. Medicine shortages 16 | Example: Availability of Cirpofloxacin www.the.lancet.comwww.the.lancet.com, December 1, 2008, Medicine prices, availability, and affordability in 36 developing and middle-income countries: a secondary, analysis; Cameron et al Average country-level mean percentage of availability by WHO region 49%24%

17. Medicine shortages 17 | Higher costs can be measured Challenges: lack of research and research approaches to determine the contribution of stock outs to the cost and burdens of: –Antimicrobial resistance (where alternative treatments can increase costs by 10-fold) –Irrational use –Contribution to increased mortality and morbidity Making the cost-benefit case

18. Medicine shortages 18 | Making the cost-benefit case: Supply Chain Costs It is clear that additional investment would improve stock outs caused by national or local supply chain failures Challenge: looking at the inverse, we do not know how much global shortages cost supply chains annually Challenge: stock out prevalence reports vary widely, but what is the cost in terms of under-treatment?

19. Medicine shortages 19 | Are the BRICS making a difference? Unpublished WHO report: Pharmaceutical Trade Expenditures in BRICS Countries, based on data from WTO 2012

20. Medicine shortages 20 | What is missing? –Quantification of the global problem –Evaluation of the effectiveness of reporting systems (e.g., SMS for life et al) –Evaluation of the effectiveness of legislation and financing in preventing stock outs –Agreed approaches to quantify costs and impact on disease burden e.g., antimicrobial resistance –Criteria for escalating problems –Logical framework for managing shortages

21. Medicine shortages 21 | Photo: Dr Charles Senessie, SwissmedIc Thank you to all