Meg O’Brien, Ph.D.Director, Global Access to Pain Relief Initiative

Procurement & Manufacture of IR Oral Morphine: Uganda experience

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2O’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 millionDeaths in pain: 69,000Coverage: 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

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Disruption in 2010 leads to transformation

• Public-sector stock-out due to changes in procurement regulations and lack of clarityabout 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

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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 2011• 7.0 kg produced first half of 2012

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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

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Cost in USDMorphine 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

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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

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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

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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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