In 11 June this year, the World Health Organisation (WHO) declared Paraguay to be malaria- free, making it the first country in the Americas to be granted this status since Cuba in 1973.
However, malaria still exists in many countries worldwide, and is an especially serious problem in Africa. Part of the explanation for the persistence of malaria in developing countries is the prevalence of substandard and counterfeit drugs being used to treat the disease.
Substandard drugs are those produced by legitimate manufacturers, but which do not contain sufficient amounts of artemisinin, the key active pharmaceutical ingredient (API). Falsified, or counterfeit, medicines are those that have been deliberately mislabelled and do not contain any APIs.
Statistics vary about the precise number of counterfeit or substandard antimalarial drugs in distribution in South East Asia and sub-Saharan Africa.
The WHO estimates one in ten medical products circulating in low and middle-income countries are substandard or falsified, with antibiotics and antimalarials being the most commonly reported.
A 2012 study of 1437 samples of drugs in five classes from seven countries in South East Asia and 21 surveys from six drug classes from 21 countries in sub-Saharan Africa conducted by the US National Institutes of Health (NIH) found that one in three antimalarials distributed in the two regions were of poor quality. The study was unable to determine for definite what proportion of antimalarials were substandard and what percentage were fake.
However, the London School of Hygiene and Tropical Medicine (LSHTM) found in a 2008-2016 research project, which was part of the Artemisin-based combination therapy Consortium Drug Quality programme, that only 1.9% of the more than 10,000 samples collected in six malaria- endemic countries, including Cambodia, Bioko Island in Equatorial Guinea, Ghana, Nigeria, Rwanda and Tanzania, were falsified antimalarials. These counterfeit drugs were exclusively found in Equatorial Guinea and Nigeria.
LSTHM professor and lead on the 2008-2016 project Harparkash Kaur tells Pharmaceutical Technology that her team found more substandard drugs than falsified and in every country studied, however the total was not as many as the 30% observed by NIH.
She believes the reason why her team did not find as many substandard antimalarials as they expected was “because of the representative sampling approach that we used”. The three pronged system included going to the nearest shop to find out what they were selling, then returning to all pharma outlets on their list pretending they needed to purchase drugs and, finally, returning to half of the total to find out “how much they knew about what they were selling and what was their level of education”.
The existence of substandard and counterfeit medicines for malaria, as well as other diseases in low-income countries, is primarily attributed to the lack of regulation and technical capacity, as well as a low poor supply of legitimate drugs.
However, the increasing complexity of global supply chains and the spread of e-commerce haves only worsened the issue.
Low quality malaria drugs: a worry for patients and the pharma industry
Taking low-quality or fake medicines can delay clinical recovery and increase mortality rates in patients. They can also promote resistance to the drug by introducing small, insufficient proportions of the active ingredients into the body.
In addition to the medical threat to patients, there is the financial waste aspect. Although these drugs are often cheaper than the genuine products, the fact that they will often fail to cure malaria means patients are forced to spend more money than they needed to on treatments. This is especially problematic if the poor-quality drugs actually cause more health problems.
The existence of substandard and fake drugs is also an issue for healthcare providers and has reputational and real costs for pharmaceutical companies, from the obvious lost profits to being blamed when products with their label fail to cure life-threatening diseases.
The WHO has estimated these types of drugs may be responsible for up to 116,000 deaths from malaria per year in Sub-Saharan Africa. The LSHTM says this costs patients and healthcare providers $38.5m in future care needs due to the failure of the first treatment.
Tackling counterfeit and substandard drugs for malaria
Previously only laboratory tests using expensive machinery operated by trained professionals could determine if medicines contained the correct amounts of APIs, however, both regulators and technology companies have begun to develop devices and tools to improve on-the-ground detection of substandard and counterfeit drugs.
PwC’s strategy consulting businesses Strategy& notes that drug regulators across the world have implemented serialisation to encode each drug package with unique identifiers and track-and-trace technology at different points in the supply chain.
Global Good, a collaboration between the Bill Gates Foundation and technology company Intellectual Ventures has designed a portable infrared scanner aimed at testing for fake or substandard artemisinin combination therapies that is affordable for charities or pharmacies in developing countries. The device is currently in the field in South East Asia, but not at the commercial stage.
The Global Good team, led by Ben Wilson, purchased a spectrometer called Scio from Israeli start-up Consumer Physics that uses an LED light, rather than a laser, and cannot detect individual drugs but can determine the overall spectral fingerprint of the product. Scio connects to a smartphone app, which, according to Wilson, can “work in remote locations in India or Africa where there is no data service”.
They tested the device on the samples collected from Bioko Island, Equatorial Guinea by Professor Kaur’s team at LSHTM. Although the system managed to detect every fake, this device and other similar ones struggle to spot some substandard antimalarials with the tags of reputable manufacturers, as Kaur confirmed.
Progression and technical developments by companies have been supported by the WHO, which established the Global Surveillance and Monitory System (GSMS) for substandard and falsified products in 2013. The aim of the institution is to improve local reporting of bad medicines to higher organisations and to create an interconnected network of national regulatory authorities.
This includes working with partners to develop a smartphone application to speed up the reporting of suspect medical products to national regulators, as well as developing an assessment tool to allow countries to compare their systems and resources with international quality benchmarks.
The GSMS published data from its first four years of operations in June 2017. 920 suspected products have been reported from 83 countries, and the most common were fake antimalarials, with 286 products reported from 26 countries.