The access to quality medicines in developing countries: a neglected scourge
1
The manufacturing market before 1990
Active ingredients: Europe and US: 90 à 95% of « self‐production » (1)
Finished products: Europe and US = main exporters to DC’s
Less than 5% of circulating medicines
are generics (2)
2
The manufacturing market
today
Europe and US active ingredients: More than 80% come from abroad, (mainly from Asia) (3, 4)
India: 1st WW producer and exporter of generics to DC’s
More than 50% of the WW prescriptions are generics (5)
Yearly growth of Chinese and Indian exports: 15 to 20% (6, 7)
3
Poor quality medicines: it happens for real
• The WHO prequalification project assesses the quality of medicines for AIDS, TB, malaria (+reproductive health and avian flu). It publishes the list of pre‐qualified products (product‐manufacturer‐site);
4
Poor quality medicines: it happens for real
• The WHO list of essential medicines: +/‐ 350 medicines, among
them live‐saving ones. About 300 for « common diseases ».
• For those, there is no international mechanism that guarantees
the quality of medicines.
5
Poor quality medicines: it happens for real
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Concentration in API: Over/Under‐dosing
Poor bio‐availability
Unexpected impurities
Decreased efficacy of the active ingredient Contamination with environmental pollutants, pyrogens, microbiological,
Cross‐contaminations with highly active molecules, toxic contaminants, including from the excipient, etc. Lack of stability Alteration of pH
Accelerated deterioration due to poor packaging (e.g., IV fluids)
Leaflet / packaging/labelling (mistakes)
6
Who is responsible for the quality of medicines?
7
Do the NRA’s guarantee
the quality of medicines?
Means?
NRA* 1
NRA 2
Political will?
NRA 3
Interests and lobbies?
NRA 4
* National Regulatory Authority
8
Do the NRA’s guarantee
the quality of medicines?
“The reality is that many regulatory authorities don't have the full capacity to perform all regulatory functions, due to chronic shortages of human, technical, financial and other resources” WHO (8)
PC3
50%
20%
PC1
RA1
RA3
30%
RA4
PC4
Developed
Variable
Limited
9
Do the NRA’s guarantee
the quality of medicines?
33%
Regulatory authorities in 46 African WHO member states. WHO (9)
24%
PC1
4%
RA1
RA3
PC3
RA4
PC4
39%
Developed
Moderate
Basic
Limited
10
Do the procurement centers guarantee
the quality of medicines?
Means?
Political will?
PC 2
PC 1
NRA1
Competition?
NRA2
NRA 3
NRA4
PC 3
PC 4
Interests and lobbies?
* Procurement center
11
Do the int’ organizations guarantee
the quality of medicines?
Means?
Political will?
NGO* 1
IO* 1
PC 2
PC 1
VP* 1
NRA 1
NGO2
NRA 2
NRA 3
Interests and lobbies?
NRA 4
PC 3
Rights and
duties?
PC 4
VP2
* International organization; Non governmental organization; Vertical program
12
Do the donors guarantee
the quality of medicines?
Interests?
Means?
WHO
Political will?
D3
D* 1
NGO1
D2
IO1
PC 2
PC 1
VP1
NRA 1
NGO2
NRA 2
NRA 3
NRA 4
PC 3
PC 4
VP2
* Donor
13
14
18
So …
• Globalization of the market: outsourcing, subcontracting and diversification of the supply chain ‐> Tracability?
• Multiplicity of standards (WHO, ICH, EU ..) and difficulty to apply them;
• Quality control and Quality assurance: Blur concepts for a lot of actors
(quality control is sufficient);
• Counterfeit and informal markets hide the growing issue of substandard
medicines;
• Increasing pressure on price ‐> Affordability vs. Quality;
• Lack of common standards and tools: Same audited entity, different
auditors ‐> different recommendations;
• Lack of cooperation: Solving this problem « on your own » is very difficult
and very expensive.
15
So …
• Each key actor of the procurement chain (regulator / donor / manufacturer / distributor / purchaser) is supposed to play a key role in order to guarantee the quality of the medicines of this chain;
• In reality and very often, each actor forwards this responsability to another one, believing that it has the resources to do it.
► Who is responsible for the quality of medicines?
16
QUAMED strategy
Sharing the information and resources in an independant network:
A new strategy to improve the access to quality medicines.
17
Putting together purchasers and
procurement centers…
PC1
D3
D1
D5
IO1
D2
D4
PC3
VP1
NGO1
NGO2
PC2
NRA1
IO2
NGO3
NRA3
NRA2
NRA4
NRA5
WHO
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QUAMED strategy
Ethics: Right of each organization to have access to reliable
information to ensure that it procures and delivers quality
medicines.
Economics: Better taking into account the economic dimension of this sector and not only rely to regulation as the sole response 
A complementary support to the NRA’s through a market‐driven
push towards quality.
Economies of scale: Pooling of information and resources: “let’s
do it together rather than struggling to do it on our own”.
– Human resources
– Technical resources
– Financial resources
19
QUAMED strategy
Technical: QUAMED supports and strenghtens its partners (WHO MQAS reference); Strategic: A network strategy in such a way that the purchasers are sensitized and educated in QA ‐> The current major weakness of the market.
Market‐driven : – A strong business incentive for the audited entities:
• Clear and common message on the expected quality level;
• Huge gain of time / resources.
• Access to a growing network of partners.
20
QUAMED objectives
QUAMED is a program of the Institute of Tropical Medicine (Antwerp) and has 3 main objectives:
• Raise awareness
• Develop research / capacity‐building activities and collaboration with academic/ research partner
institutions • Improve the technical capacity of organizations involved
in the procurement of essential medicines for populations in LICs;
Quamed
partners
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Activities
• Audits and assessments
– Wholesalers; countries (pharmaceutical markets); manufacturers;
products
• Capacity building
– Quality standards (GMP, GDP, MQAS, GMP…)
– Development or review of QA policies + implementation
– Field and HQ QA trainings
• Access to a “validated” information
– WHO Pre‐Qualification, WHOPIRs, WHOPARs, lists of prequalified
products, EUDRAGMP, Pharmaceutical Inspection Cooperation
Scheme, European pharmacopea (DEQM), US FDA
► Restricted‐access online database
22
Procurement strategy and activities
Information is shared with all partners to ensure that they procure quality medicines.
PC1
IO1
PC3
NGO1
NGO2
VP1
IO2
NGO3
PROCUREMENT
Strenghtening
of QA capacities
Audits of international
wholesalers
Audits of pharmaceutical
markets
Product dossiers reviews Validation of manufacturing sites by SRA’s
QUAMED partners database
Market strategy and activities
The buyers are “educated” and purchase from PCs selling quality medicines.
QA policies for
QUAMED NGO/IO Implementation of QA policies and support to
tenders for QUAMED NGO/IO
VP1
IO1
S1
S4
NGO2
NGO1
QA trainings
field and HQ for
QUAMED NGO/IO
Capacity
building
MARKETING
Market (supply)
D1
D3
NGO3
S2
Support to the review of donors guidelines
PC1
PC3
PC2
D2
S3
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Update of activities – May 2013
Wholesalers :
Countries :
Done (11)
Done (9)
Manufacturing sites :
Done (~140)
25
Update of activities – end of 2013
Wholesalers :
Countries :
Done (16)
Done (9)
Manufacturing sites :
Done (300)
26
QUAMED partners
27
90
€ 300
53
80
€ 250
Millions
Millions
Key figures
70
60
€ 200
50
303
€ 150
250
32
€ 100
€ 50
93
27
€0
‐
‐
‐
Purchases North
Bénéficiaires
30
20
111
10
46
19
2011
(14 partners)
40
Purchases South
0
2012
(23 partners)
2013 (April)
(28 partners)
No figures of beneficiaries from procurement centers + from a part of the northern partners: ‐> Number of beneficiaries underestimated
No figures of local purchases from a sizeable part of northern partners: ‐> Northern purchases underestimated
2010, 2011 or 2012 figures following available data
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Current strategic focus
• Reinforce sustainability of national systems through increased support to southern partners;
• Strengthen and harmonize Quality Assurance guidelines of donors;
• Increase the information provided by QUAMED partners in QUAMED database;
• Increase QUAMED's impact on the market through an extended number of partners;
• Secure additional funding from 2014 on: Institutional + Quamed partners
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Review of audits activity carried out by QUAMED
Outcomes of MQAS assessments
• Level of GDP/GSP varies according to the stringency of authorities:
– Good level for Northern wholesalers;
– Heterogenous for Southern wholesalers with major failures on cold chain.
• Main weaknesses in qualification of sources and monitoring for almost all audited entities (North and South).
• MQAS and even QA concepts often unknown even for Northern wholesalers.
• Full MQAS audit not possible/useless for local wholesalers.
Outcomes of MQAS assessments:
Northern wholesalers
Northern Procurement Agencies
#
Date
Outcomes of the MQAS/GDP audits
GDP
PQ
QC
Monitoring
1
10/2011
4
3,7
4
4
2
12/2011
3,5
3,7
4
3
3
06/2012
3,25
3,7
3
4
4
07/2012
3,5
5
08/2012
3,75
6
09/2012
7
09/2012
3,75
8
10/2012
No stock
9
01/2013
3,75
4
4
None
None
None
4
Range of values : 0 – 4
GDP criteria : control at reception, warehouse management, distribution, QA follow‐up
PQ criteria : product qualification, qualification decision, manufacturing site assessment
Outcomes of MQAS assessments:
Northern wholesalers
Northern Procurement Agencies
#
Date
Outcomes of the MQAS/GDP audits
GDP
PQ
QC
Monitoring
1
10/2011
4
3,7
4
4
2
12/2011
3,5
3,7
4
3
3
06/2012
3,25
3,7
3
4
4
07/2012
3,5
2,3
0
2
5
08/2012
3,75
2
4
2
6
09/2012
2,5
1,3
0
0
7
09/2012
3,75
2
1
4
8
10/2012
No stock
None
None
None
9
01/2013
3,75
2,3
4
1
Range of values : 0 – 4
GDP criteria : control at reception, warehouse management, distribution, QA follow‐up
PQ criteria : product qualification, qualification decision, manufacturing site assessment
Outcomes of MQAS assessments:
Southern wholesalers
Southern Procurement Agencies
#
Date
Outcomes of the MQAS/GDP audits
GDP
PQ
QC
3
4
1
07/2011
2
11/2011
3,5
3
11/2011
3,5
4
10/2012
5
11/2012
6
03/2013
7
03/2013
8
04/2013
Monitoring
4
3
Range of values : 0 – 4
GDP criteria : control at reception, warehouse management, distribution, QA follow‐up
PQ criteria : product qualification, qualification decision, manufacturing site assessment
Outcomes of MQAS assessments:
Southern wholesalers
Southern Procurement Agencies
#
Date
Outcomes of the MQAS/GDP audits
GDP
PQ
QC
Monitoring
1
07/2011
2,25
0
0
0
2
11/2011
3,5
3
4
2
3
11/2011
3,5
1,7
4
1
4
10/2012
1,5
2,3
1
0
5
11/2012
1,75
0,7
1
0
6
03/2013
3
1,6
2
0
7
03/2013
2,25
0
1
0
8
04/2013
2,75
1
2
1
Range of values : 0 – 4
GDP criteria : control at reception, warehouse management, distribution, QA follow‐up
PQ criteria : product qualification, qualification decision, manufacturing site assessment
References
(1) Inspection process differences in Chinese domestic and export APIS. European Chemical News. 31 october 2005
(2) Barnes K. US and EU pharma trade bodies slam poor regulation of foreigh API’s. In‐Pharma technologist.com. 20 october 2006.
(3) http://www.pharmaceutiques.com/phq/mag/pdf/phq149_51_industrie.pdf
(4) http://www.economist.com/node/21564546
(5) Villax G., Oldenhof C. Global API sourcing: What is next for suppliers for the European union? Pharmaceutical Technology Sourcing and Management. July 2006
(6) http://www.aei.org/article/health/medical‐technology/pharmaceuticals/the‐problems‐and‐potential‐of‐chinas‐pharmaceutical‐industry/
(7) http://inde.cnccef.org/542‐pharmacie.htm
(8, 9) Roles of National Medicines Regulatory Authorities, Dr Samvel Azatyan, WHO / Global Fund joint meeting on Quality Assurance of essential medicines, 30‐31 august 2011, Geneva.
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