Les médicaments en Afrique sub-saharienne : des différents défis, liés à la vulnérabilité des systèmes de santé et des patients

RAFFAELLA RAVINETTO, 24 MARS 2018

Le problème

Le« gap » entre les pays riches et l’Afrique sub-saharienne reste important :

- inaccessibilité financière

- manque des recherche pour les maladies tropicales

- médicaments de mauvaise qualité

- …………………………………………………………

Notre programme

- Essential Medicines

- Medicines ’ quality

- Intellectual property and access

- Research & Development

- Belgian initiatives

1. Essential medicines

http://www.who.int/medicines/about/en/

• 1975: Essential Medicines and National Pharmaceutical Policies

• 1977: the 1st list of Essential Medicines is published

• SDG indicator 3.b.3: proportion of health facilities with a core set of relevantessential medicines available and affordable on a sustainable basis

Essential medicines

http://www.who.int/medicines/publications/essentialmedicines/en/index.html

Essential medicines

Epidemiologic pattern

Efficacy and tolerability

Ratio cost/efficacy

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Essential medicine listThe WHO EM List 2017: not just for “poor countries”?

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• The EML now includes expensive drugs (hepatitis C, HIV, cancer)

• The list should not be considered relevant only for poor countries

• Some drugs are too expensive for rich countries too: “The inclusion on the EML sends a strong message to all public health actors that these medicines provide true public health benefits and really should be made available when needed” (S. Hill)

2. Medicines’ quality

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Assessment of SITE + of PRODUCT

= Quality assurance

(QA)

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Good Manufacturing Practices (GMP)

To ensure that the manufacturer guarantees anhomogenous (within batch) and reproducible (frombatch to batch) quality

Assessment of each product

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Quality of active ingredients

Specifications of final product (Pharmacopoeias)

Proof of stability (shelf life)

Proof of bioequivalence (for generics)

(Primary and secondary) packaging

Labeling, leaflet

Regulatory status

Substandard and falsified medical products

Medicine quality: what is it not?

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World Health Assembly 2017

Substandard medical products: authorized by national regulatory authorities, but fail to meet national or international standards

Falsified medical products: deliberately/fraudulently misrepresent their identity, composition or source.

Unregistered or unlicensed medical products: not approved by the relevant regulatory authority

Medicine quality: sometimes visible

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Probable impurities due to degradation of unstable

acetylsalicylic acid (Togo-2013)

Exposure of glucose 50% at inappropriate temperatures

(South Soudan-2010)

Data source: MSF and QUAMED partners

Microbial contamination of phenobarbital tablets

Friability of pyridoxine tablets

Overheated cloramphenicol vials

(Darfur)

Medicine quality: sometimes not visible - Panama 2006

13Rentz ED. Bull World Health Organ [Internet]. 2008 Oct 1;86(10):749–56.

• Unusual number of unexplained acute renal failure: 12 (57%) of 21 died

• Association between ingestion of prescription cough syrup and illness onset

• Lab analyses:

• diethylene glycol (DEG) in biological samples from case patients

• 8% DEG contamination in cough syrup samples

• 22% contamination in the glycerin used to prepare the cough syrup

• Source of the outbreak: DEG-contaminated cough syrup

Medicine quality: sometimes not visible - DRC 2014

14Rentz ED. Bull World Health Organ [Internet]. 2008 Oct 1;86(10):749–56.

• Cross-sectional survey : paracetamol tablets, amoxicillin and artemether/lumefantrine powders for suspension

• 417 products from 61 wholesalers

• Visual inspection:

• nonconformities in powders for suspension

• poor-quality labels across all medicine types.

• Chemical analysis:

• 27.2% samples of poor quality;

• 59.5% of AL samples underdosed in artemether

• More problems for local manufacturing

Falsified bevacizumab and sunitinib malate in East Africa (2017)

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First quality evaluation of cardiac drugs in Africa (2017)

7 medications in ten Sub-Saharan African countries

Collected from licensed and unlicensed places of sale (2012-2014)

Out of 1530 samples, poor quality was identified in 249 (16.3%)

Higher prevalence in certain drugs (amlodipine 29% and captopril 26%), in generics (23%) and drugs reportedly produced in Asia (35%)

Up to 50% for drugs reportedly produced in Asia and sold in street-markets.

M. Antignac, et al., Fighting fakemedicines: First quality evaluation of cardiac drugs in Africa, Int J Cardiol (2017)

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Medicine quality: who is responsible?

National Medicines Regulatory Authority

(NMRA)

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RA3

4%

33%

24%

39%

Developed

Moderate

Basic

Limited

“….substantially confirm the 2004 results”

“90% of NMRAs in the African region lack the capacity to carry out medicines

regulatory functions”

Differences in regulatory capacity in Africa: 2004, 46 WHO member states

Assessment of regulatory capacity in Africa: 2010, 26 WHO member states

WHO. Assessment of medicines regulatory systems in sub-Saharan African countries. 2010.

Challenges: weak NMRAs

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20-25 years ago

Finished products

• Europe and USA are main exporters to LMICs

• 80% of the trade within HICs and 20% towards LMIC

• < 5% of medicines circulating are generic products

Active ingredients : Europe and USA leaders (90-95% self-production)

Challenges: complex global market

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Finished products

• India is the world leader in manufacturing and distribution of generics

• More than 50% of prescribed medicines are generic products

• 15-20% yealry growth of Indian and Chinese exports

Active ingredients : 80% form abroad (mainly from Asia)

Today

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Challenges: complex global market

Assesses products for HIV, TB, malaria (+ reproductive health, avian flu, hepatitis B and C, some NTDs and twoanti-cancer drugs)

https://extranet.who.int/prequal/content/prequalified-lists/medicines

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WHO List of Prequalified Medicinal Products: An important but limited supporting tool

Publish the list of approvedproducts

T’Hoen at al. Journal of Health Policy 1-25. 2014

Medicine quality: ways forward

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Policy makers

• Strengthening the national and international regulatory oversight

• Increasing transparency on quality information,

• Expanding the scope of the WHO Pre-qualification program

• Adapting the procurement policies of major donors and agencies

Field

• Be aware of the risk!

• Buy at pre-qualified suppliers when possible

• Always report possible quality problems

3. Intellectual property & access

Patents

- A title granted by the publicauthorities to the inventor of aninvention, conferring a temporarymonopoly for the exploitation ofthe invention

- The monopoly prevents others frommaking, marketing and using theinvention

- Created to advance the public good,by encouraging innovation

WTO and TRIPS Agreement

1994: World Trade Organization establishes the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS)

links issues of intellectual property and trade

provides multilateral mechanism for disputes between States

requires Member States to incorporate into their legislation copyright, patents, trademarks

mandates granting of patents in all fields of technology: no possible to exclude medicines, vaccines, diagnostics, food

Patents monopoly high prices that may restrict access

TRIPS and pharmaceuticals

Before ARVs, most essential medicines were not patented

When ART became available at $10,000 per patient/year, the TRIPS impact on access to medicines became evident

Access to essential ARVs

1999:

high prices ART unaffordable in LMICs to patients, state, donors

2000-2001:

Accelerated Access Initiative set preferential prices for LMICs by

innovators limited decrease, a variety of criteria

2002-2008:

quality-assured generics allow scaling up ART programs (WHO

Prequalification) first-line ART may cost down to $87/pat/year

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- Mobilisation of civil society played a key role

- Quality-assured generics from countries such as India, with TRIPS deadline 2005

The effect of generic competition (MSF data)

Beyond ARVs: cancer medicines

• “Even when a higher cure rate is possible, this is often not achieved:

• in low-income settings because of a lack of access to well established and effective treatment and care

• in middle-income countries where often “treatment is only affordable for certain segments of the population, and… good outcomes remain skewed toward those who can pay”

(Union for International Cancer Control 2014)

Access problems are global

US CML experts: prices are too high, unsustainable, compromise access, are harmful to sustainability of national healthcare systems

Cancer drug prices have almost doubled from a decade ago

Beyond ARVs: cancer medicines

The doctrine of Justum Pretium, or just price, refers to “fair value” of commodities: by moral necessity, price must reflect worth

In the doctrine of free market economies, prices reflect “what the market bears”, or what one is willing to pay for a product.

When a commodity affects the lives or health of individuals, just price should prevail because of the moral implications. Examples:

the price of bread during famines

polio vaccine

ivermectin for river blindness

treatments of chronic medical conditions

Beyond ARVs: cancer medicines

Toward a fair pricing…?

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Tri-tryps

= MSF focus

« All NTDs are

tool ready, all

NTDs are tool-

deficient »Hotez & Pecoul,

PLoS NTD, 2010

Neglected Tropical Diseases - NTD

= WHO definition

Poverty-related diseases ≈

G-Finder definition

HATChagas

Leishmaniasis

(inc. Kala azar)Buruli

ulcer

Schistosomiasis

STH

Onchocerciasis

Guinea worm

Rabies

HIV/AIDS

TB

Malaria

Diarrhoeal

diseases

DengueLymphatic

filariasis

So-called

« tool ready »

NTDs

Bacterial pneumonia & meningitis

4. R&D

Source: Chirac P, Torreele E. Lancet. 2006 May 12; 1560-1561.

Back to 2004: a diagnosis of “fatal imbalance”

Tropical diseases:

18 new drugs

(incl. 8 for malaria)

TB: 3 new

drugs

1.3%

21 new drugs

for neglected

diseases98.7%

1,535 new drugs

for other diseases

(1975-2004)

Tropical diseases and TB:

•12% of the global disease burden

•1.3% of new drugs

Pedrique B et al. The drug and vaccine landscape for neglected diseases (2000-11). Lancet Glob Health 2013; 1(6): e371-9

• Neglected diseases: malaria, TB, diarrhoeal diseases, neglected tropical diseases, other diseases of poverty

• 1975–99:

– 1,1% of new therapeutic products developed for NDs

• 2000-2011:

– 850 new therapeutic products: 37 (4%) for NDs

– 336 new chemical entities: 4 (1%) for NDs (3 for malaria, 1 for diarrhoea)

– 148 445 clinical trials: 2016 (1%) for NDs

Persistent insufficiency in R&D, despite a slight improvement over 12 years

Price ProductCost R&D =

High

Prices

No R&D for ‘poor’ markets

A pathway to focus

R&D towards health

needs

R&D priorities driven

by health needs, not

marketing

The way forward: delinkage?

The way forward: delinkage?

Delinkage could take the form of a prize fund, an incentive model that offers a cash prize in return for the development of a target medicine

Products should not be patented

International collaboration by groups of countries, to share the cost burden

This is likely to become a wider conversation, as current medicines prices outstrip the health budgets of even wealthy economies, and needed essential medicines are not developed.

The way forward… equity in access to treatments?

5. Belgian initiatives: QUAMEDhttps://quamed.org/en/home.aspx

TYPE NAME DEPARTMENT IN WINDOW

5. Belgian initiatives: Be-cause Health (medicines WG)https://www.be-causehealth.be/en/bchgroups/access-to-quality-medicines/

TYPE NAME DEPARTMENT IN WINDOW

5. Belgian initiatives: the Committment to qualityhttps://www.be-causehealth.be/en/bch-news/minister-de-croo-and-belgian-actors-from-the-

international-health-cooperation-sign-commitment-on-quality-of-medicines/

TYPE NAME DEPARTMENT IN WINDOW

Raffaella Ravinetto rravinetto@itg.be

For more information, for specific questions from the field, forjoining the Be-cause Health Medicines WG…….