Background
Defining and quantifying the problem
Definitions
Prevalence of poor-quality anti-malarial medicines
Region/country and year | Product and number of samples | Source(s) and sampling | Key results |
---|---|---|---|
Africa | |||
Tanzania 2010 [24] | Artemisinin-containing N = 1737 | Source: private retail outlets Sampling: nationally representative sample | All samples contained an API Artemisinin-containing derivative: 4.1 % substandard (outside the 85–115 % API range) PQ drugs had 10 % of the odds of being poor-quality vs non-PQ Partner drugs 12.1 % substandard PQ had 4 % of the odds of being poor-quality |
Ghana, Togo 2010–2011 [28] | Artemisinin-containing N = 132 | Source: retail outlet Sampling: convenience sample | Only one sample lacked an API Combination products: 83.7 % (outside 90–110 % API) Monotherapy: 57.9 % substandard |
Nigeria 2012–2013 [23] | Artemisinin-containing N = 3024 | Sources: pharmacies (35.6 %), patent medicine vendors (60.6 %), public health facilities (3.6 %), market stalls (0.2 %) Sampling: mostly mystery client (63.5 %), then overt (6.6 %) or convenience (29.9 %) | 9.2 % poor-quality: 6.8 % substandard; 1.3 % degraded; 1.2 % falsified Convenience sampling yielded a significantly higher prevalence of poor-quality |
Democratic Republic of Congo 2014 [25] | Artemisinin-containing N = 238a
| Source: private licenced wholesalers Sampling: cross-sectional, mystery client | 21 % were found non-conform for the content in API 48 % were under-dosed in artemether |
Southeast Asia | |||
Cambodia 2010–2011 [30] | Artemisinin derivatives N = 291 | Sources: private health provider Sampling: mystery client | All samples contained an API Overall: 31.3 % substandard (outside range of 85 % and < 115 %) 24.7 % were expired Artesunate tablets: 25.8 % (60/233) substandard Co-blistered mefloquine: 73.4 % (149/203) substandard Considering both drugs: 77.3 % (157/203) substandard |
Lao People’s Democratic Republic (Laos) 2012 [31] | Various anti-malarial medicines N = 146 | Source: Private retail outlets Sampling: Cross-sectional random sample, mystery client | All samples contained an API 25.4 % substandard (outside 90–110 % API) |
Multi-level factors and consequences
Global
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Lack of effective surveillance the absence of a global system for the mandatory reporting, assessment, and dissemination of information on falsified and substandard medicines is a major obstacle to measuring the scale of the problem, raising sufficient awareness, and improving global medicines supply [33]. This problem is amplified by deficits in national-level quality surveillance in many malaria-endemic countries [34].
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International supply chain regulation the globalized marketplace means that medical products can be manufactured in one country, packaged in another, and supplied to others with limited international oversight of manufacturing, testing, or storage practices for legitimate medicines or the introduction of deliberately falsified products into the supply chain [7].
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Legal insufficient legal action against falsified and substandard (if negligence could have been corrected) medicines are facilitated by inadequate and/or unharmonized international and national laws and law enforcement against this form of fraud. The regulation of legitimate medicines manufacture is also hampered by the lack of a consistent legal framework [35].
National
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National regulation the weakness of national medicine regulation authorities (NMRAs) in many countries is a central concern with regard to both falsified and substandard medicines. Documented shortfalls in national regulation in developing countries include: low prioritization of regulation within health systems; fragmentary, out-dated, and poorly coordinated regulatory frameworks; uneven and weak implementation of functions; inadequate adaptation and use of guidelines; inappropriate organizational structures (not able to ensure transparency, independence, and accountability); weak inter-sectoral collaboration nationally and among countries; shortages of qualified staff; and inadequate and unsustainable funding [34, 36].
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Access to good-quality medicines limitations on access to affordable good-quality treatment can drive demand for poor-quality medicines, or for monotherapy. A shortage of medicines can also lead to a reliance on unknown suppliers and illicit/uncontrolled supply chains, where the risk of poor-quality medicines may be greater. The introduction of falsified meningococcal vaccines during the 2015 outbreak in Niger illustrates the rapid capability of this organized crime [37].
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Costs of testing for medicine quality standard methods of testing drug reliability, such as high-performance liquid chromatography and spectroscopy, require high-cost instruments, expensive maintenance, and trained proficient staff. These constraints, in addition to less-than-optimal operational conditions, inhibit the use of these techniques in low-income malaria-endemic countries [38]. Development of portable rapid-testing methods, which are discussed in more detail in the surveillance and quality testing section below, offer the prospect of introducing less expensive and more sensitive technologies. However, the absence of a single affordable, reliable, validated, and portable technology currently remains a barrier [39].
Population and individual
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Public confidence ineffective treatments can result in a loss of public confidence in drugs, pharmacies, and healthcare providers, as well as in anti-malarial programmes [15].
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Public awareness evidence suggests that levels of public awareness about poor-quality medicines in malaria-endemic areas are sub-optimal [41]. This is particularly important given the frequency of self-medication.
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Treatment failure inadequate therapy leads to extended, more severe illness, and increased fatalities compared with recommended therapy [11].
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Financial loss of income and increased expenses for patients and families.
Improving quality standards
Surveillance and quality testing
The WHO prequalification of medicines programme
Other initiatives
Health policy issues
National registration process
Prioritize the development of medical products regulation |
Strengthen the coherence and performance of the medicines regulatory system (including dialogue among stakeholders)a
|
Adapt and use guidelines in line with WHO recommendations |
Increase implementation of regulatory functions |
Enhance the status of NMRAs |
Institute sustainable mechanisms to effectively manage conflicts of interest |
Strengthen inter-sectoral collaboration between relevant stakeholders |
Ensure availability of qualified human resources for regulation of medical products |
Ensure adequate and sustainable financing of the medicines regulatory system |
Improve collaboration, coordination, and harmonization of medical products regulation |
National Medicines Regulatory Authorities (NMRAs) and World Health Organization (WHO)
Today’s current environment | A harmonized future environment |
---|---|
~50 different NMRAs (working
independently) to register medicines across Africa
| ~5 or 6 regional groups (each with
harmonized technical requirements) coordinating registration across the entire
African continent |
Different administrative and technical
requirements, processes, and procedures for
medicines registration across NMRAs | Common (harmonized) registration documentation (format and technical
requirements),
procedures, and decision-making processes across African regional groups |
No clear indication of the time taken, or the
maximum
times allowed, for regulators to
assess and register medicines | Streamlined processes that are faster, more
predictable, and better aligned to public health needs (in terms of prioritization, conditional approvals, etc.) |
Limited transparency before or during the registration process | Transparent and clear procedures and a good understanding of registration
requirements and processes by all stakeholders |