Meg O’Brien, Ph.D. Director, Global Access to Pain Relief Initiative Procurement & Manufacture of IR Oral Morphine: Uganda experience 1

2 Ensure that government policy makers are familiar with the issues and prepared to take a lead role in improving access to pain relief Mindset Consult key stakeholders and partners and identify key barriers to access to pain relief and solutions to address them Organize Review national quotas from the International Narcotics Control Board as well as national importation, storage, and prescribing regulations to ensure that they are up to date or identify needed changes Regulations Establish budget for medication purchase, storage, and distribution. Estimate quantities by product and formulation, identify suppliers, secure product registrations, develop tenders, place and pay for orders, receive and distribute to regional medical stores Procurement Organize awareness-raising activities, in-service training, and continuing medical education; develop reference materials and guidelines; and sensitize health workers and administrators Health workers Establish pain treatment by trained clinicians, usually at large clinical centers or specialized clinical units (for example in cancer centers) Initiation Scale-up by integrating pain treatment into service delivery at regional and district hospitals and ensuring adequate geographical coverage to make pain relief accessible to all who need it in the country. Nationalization Create a sustainable stakeholder base in a country Empowerment O’Brien et al, Lancet Oncology (in press)

Background Hospice Africa Uganda (HAU) and the Ministry of Health (MOH) work in close collaboration Other key partners: Palliative Care Association of Uganda (PCAU) African Palliative Care Association (APCA) Population: 33 million Deaths in pain: 69,000 Coverage: 4% Data from 2010 History of access to pain relief HAU began to reconstitute oral morphine in 1993 for hospice patients Govt reconstituted for public sector at the national hospital Specially trained nurses prescribe morphine 3

Disruption in 2010 leads to transformation Public-sector stock-out due to changes in procurement regulations and lack of clarity about the best way forward HAU provided morphine to hospice patients and some public sector facilities GAPRI and APCA invited to assist with finding a solution Extensive discussions with all players led to design of a new approach, starting early 2011 National Medical Stores (NMS) contracts with HAU for an annual order HAU procures powder and produces finished oral solution HAU upgraded and expanded production facility NMS distributes to public and private, not-for-profit facilities NMS provides morphine to all patients for free 4

Experience after one year Price for govt reduced by 40% Cost for HAU reduced from 50,000 USD/year to 4,000 USD/year Oral morphine has been continuously available at central stores 15.9 kg produced in kg produced first half of

Production Based on HAU blue book guidance Some changes to come closer to GMP: Amber bottles Labels with batch no. and expiry Deionized water Product testing HAU uses bronopol preservative Shelf life~6-12 months Alcohol-free Color-code by strength Green: 5mg/5mL –vast majority of use Red: 50mg/5mL Blue: 100mg/5mL 6

Cost in USD Morphine powder $ 0.85 Bronopol crystals $ 0.01 Gauze for filtering water $ 0.04 Water $ 0.11 Bottle: 500mL $ 0.09 Label $ 0.03 Packing $ - Human resources $ 0.38 Adminstrative costs for Hospice Africa-Uganda $ 0.22 Other recurring costs $ 0.15 Total $ 1.86 Cost of 500mg/500mL Cost Current cost is ~1.86 USD for 500mg This is about 1 week of treatment Cost component 45% is morphine powder 20% is human resources 7

Upgrading production GAPRI recently secured 85kg donation of morphine powder for HAU 1 million doses ~3-5 years supply Expected to generate about 170,000 USD surplus for HAU upgrades Renovate space Rainy-day fund Automation equipment 8

Why oral liquid instead of tablets? Patient Reduce pill burden Inability to swallow May be only immediate release option Easy to finely titrate doses Procurement Morphine powder is API-does not need to be registered Volume is small, easy to ship and store Price is about 1/3 of tablet price (~2,000 USD per kg) Distribution Production on demand maximizes shelf-life Can make various strengths on demand Creates local jobs 9

10 Drawbacks Liquid is bulkier to distribute locally Requires technical capacity in country for production Requires supplies and equipment Dosing may be less accurate Drawbacks of oral liquid morphine?

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