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Unveiling the peril of substandard and falsified medicines to public health and safety in Africa: Need for all-out war to end the menace

Abstract

The peril of substandard and falsified medicines (SFM) risk complete failure of the United Nations Sustainable Development Goals on access to safe, effective, quality, and affordable essential medicines in African countries. The global market volume of SFM could be up to US$200 billion, and up to 70% of the total medicines in circulation could be SFM in some parts of Africa. This dominance in the region is a clear sign of SFM proliferation, which continues to cause avoidable health hazards leading to severe adverse effects and devastating loss of human lives, by compromising treatment of chronic, infectious, and life-threatening diseases, such as malaria, cancer, pneumonia, tuberculosis, and diabetes. Besides these consequences to public health and safety, the economic and societal detriments are also grave. Although the recent advancement in detection technology coupled with increased collaborative efforts among some African drug regulatory agencies has led to a considerable success in countering the SFM pandemic, there is need to amplify and intensify such efforts in order to curb or totally eradicate the menace. Here, we provide an overview of the detrimental impact of SFM on the healthcare system in African countries and highlight various strategies for curbing the menace in order to arrest its hazardous consequence to the public.

Med Access @ point care 2017; 1(1): e145 - e154

Article Type: REVIEW

DOI:10.5301/maapoc.0000023

OPEN ACCESS ARTICLE

Authors

Nafiu Aminu, Abubakar Sha’aban, Abdulhakim Abubakar, Mahmud S. Gwarzo

Article History

Disclosures

Financial support: No grants or funding have been received for this study.
Conflict of interest: None of the authors has financial interest related to this study to disclose.

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Introduction

There are many problems bedeviling most of the African countries that require holistic and urgent attention, and one of them is the proliferation and circulation of substandard and falsified medicines (SFM). This has grossly affected the healthcare systems and treatment outcomes in the African continent. The menace of SFM is not receiving adequate attention in the region with regards to decisively abating and tackling it. The United Nations Sustainable Development Goals’ Article No. 3.8. is targeted access to safe, effective, quality, and affordable essential medicines (1, 2). However, this goal seems to be unachievable in the near future in low-income African nations because of the menace of SFM. SFM are still taking a devastating toll on human lives silently and regularly, especially in poor African, Asian, and Latin American countries (3).

Substandard or sometimes poisonous medicines can harm patients directly by compromising the treatment of many life-threatening diseases in these countries. An estimated 627,000-1,238,000 deaths occur each year as a result of malaria – the majority of which are in Africa (4). A study conducted in the sub-Saharan African countries on the cause of mortalities associated with poor quality medicines, which were referred to as “falsified, substandard, or degraded” antimalarial medicines, revealed that 122,350 children under 5 years old died in 2013 alone due to reliance on poor-quality antimalarial medicines for the treatment of malaria (4).

Although adulteration, falsification, and fraudulent manufacture of medicines is not a new problem, the recent expansions in industrialization and trade have aggravated the scale of the problem (5). The global sales of falsified medicines are rising significantly, which is evident by the increasing number of countries that report breaches of their supply chain, as well as product falsifications (6). The reported scale of this crime and its potential hazardous effects on the health of the public is quite alarming. In January 2017, it was reported that 113 million potentially dangerous and illicit medicines (estimated to be worth €52 million) were seized during an operation called Action Against Counterfeit and Illicit Medicines (ACIM) which was conducted in the African continent in September 2016 (7). The operation, which lasted 10 days, was jointly organized by the World Customs Organization (WCO) and the International Institute for Research Against Counterfeit Medicines (IRACM), and it involved 16 African customs administrations, with the largest interceptions in Nigeria, Benin Republic, Kenya, and Togo (7). According to the World Health Organization (WHO), between 2005 and 2010, the sales of SFM increased up to 90%, and the market size surpassed US$75 billion (8) – or between US$70 billion and US$200 billion, according to another source (9). It is estimated that about 15% of total medicines sold worldwide are SFM (10). This percentage can be as high as 70% in some parts of Africa and Asia (9). Asia accounts for the largest volume of the trade of SFM (8), with China and India being the major sources (3, 11, 12), and recently Russia became involved (9). Internet marketing of pharmaceuticals through online chemists has further contributed to the pervasion of SFM (10). WHO estimates that up to 50% of the medicines being sold on the internet are fake (9).

Despite the report that a lot of people suffer unnecessarily prolonged illness or become disabled or even die due to lack of adequate access to effective healthcare rather than because of medicine falsification (13), curbing medicine falsification is still pertinent to effective healthcare delivery. A safe, reliable, effective, qualitative and affordable medicine is essential for quality healthcare delivery, but unfortunately, this is largely missing in nations with weak regulatory bodies (14), many of them in Africa. This prompted the call for strengthening the drug regulatory systems, especially in the African continent. Poor-quality medicines lead to a compromise in the therapy of chronic and infectious diseases, which, in turn, could result in drug resistance, worsening of the disease, and ultimately death (5). A strong drug regulatory system is required to overcome the menace of SFM and its consequences (15).

The problem of SFM is not limited to African continent alone; it is a global phenomenon that has spread to even highly regulated countries in Europe and America (16). This emphasizes the need for sound collaborative efforts between the national drug regulatory authorities in Africa and the rest of the world, along with the WHO, nation states’ governments, pharmacies, pharmaceutical manufacturers, enforcement agencies (e.g. Police, Customs, Immigration), legitimate drug supply organizations and nongovernmental organizations (NGOs), in order to effectively fight the menace of SFM by disrupting its supply chains and bringing the culprits to justice, as well as preventing the medicines from reaching the innocent patients (13, 17, 18).

However, it is worth mentioning that there have been commendable increased efforts in Africa to counter the menace of SFM in recent years by both national and international regulatory agencies. The inter-governmental operations that led to the seizures of counterfeit and illicit medicines in the continent over the last few years, which amounted to around 900 million packets of SFM, is a good step in the right direction (7). In another development, a recent study conducted to determine substandard and falsified antimicrobial medicines’ prevalence in faith-based and public healthcare centers of part of Malawi revealed some encouraging findings, because out of the 155 samples investigated, only 1 sample was found to be falsified and 6 were found to be substandard medicines (1). The drug regulatory agencies in Nigeria, Ghana, Kenya, Rwanda, and a few other countries have intensified their efforts in curbing the menace by employing state of the art detection instruments and increasing public awareness (3, 15, 18). The recent amendment and passage of falsified related medicines bill in Nigeria into law, which provided tough penalties, such as life imprisonment and expensive fines for SFM offenders, is also a remarkable development (19). Ziemer (20), in his correspondence, argued that although there is a need for regulatory authorities of medicines in Africa to be strengthened, important progress is being made (20). Although these recent developments are highly commendable but the prevailing SFM pandemic signifies that they are grossly inadequate for the attainment of the desired quality of healthcare delivery and for safeguarding the public health in the region.

This review was aimed to update its readers on the latest dangers posed by SFM to the African healthcare sector and to public safety. The magnitude and the actions being taken to address the problem have been extensively discussed.

Definitions

There is lack of consensus on a common definition of what constitutes falsified/counterfeit medicine, as the current definitions vary from one country to another (21). This disagreement had a negative impact on the efforts to stop the SFM peril in developing countries. According to the WHO, counterfeit medicine is defined as “the one which is deliberately and fraudulently mislabeled with respect to identity and/or source. Counterfeiting can apply to both branded and generic products and counterfeit products may include products with the correct ingredients or with the wrong ingredients, without active ingredients, with an insufficient active ingredient or with fake packaging” (22). The term “counterfeit” is increasingly being replaced with “falsified” because of the argument for emphasis on intellectual property rights and commercial interests rather than public health and safety (23, 24). Therefore, we avoid using “counterfeit” in this article because of these concerns.

In a typical expression, falsified medicines were referred to as those medicines that have been fraudulently fabricated and distributed and which failed to meet the quality criterion for that particular medicine (18). The meaning of other related terms has been defined elsewhere, such as substandard (out of specification), unregistered/unlicensed (25), degraded, poor quality (18), and fake medicines (5). Among these terms, counterfeit, falsified, fake and substandard medicines are used interchangeably (11, 26), so we grouped them under the umbrella of “substandard and falsified medicines (SFM),” except in some areas where the original source of information specifically referred to a particular term.

The WHO, in its 70th World Health Assembly, adopted the term “Substandard and Falsified (SF) medical products” to replace the erstwhile term “substandard/spurious/falsely-labelled/falsified/counterfeit (SSFFC)” (25). This is part of its effort to promote a universal understanding of SF, global data comparison and analysis, and to redirect stakeholders to the public health implications of SF rather than debating over intellectual property rights.

Extent of the problem

The clinical effect of substandard and falsified medicines in Africa

Falsification of medicines may have a number of clinical consequences ranging from poisoning, drug resistance, treatment failure, the masking of clinical symptoms of ailments, and ultimately death in the worst cases. There are some reported poisoning incidences in Africa, which occurred as a result of the contamination of medicines. In 2008, a tragic incident occurred in Nigeria where many children developed acute kidney injury and later died due to the consumption of a supposed teething problem remedy called “My Pikin,” which was contaminated by the inadvertent or deliberate addition of diethylene glycol (DEG) as a solvent in place of propylene glycol (27-28-29). DEG is cheap but lethal, and it looks, smells, and tastes like glycols and glycerine, which are harmless but more expensive (27). Similar incidences happened earlier where the same DEG was used instead of propylene glycol in South Africa in 1969 and in Nigeria in 1990, which resulted in 7 and 47 deaths, respectively (27). In another tragic story, a Ghanaian woman developed a serious skin cancer when she consumed SFM that contained a carcinogenic substance (3).

Consumption of SFM – especially antibiotics, antimalarials, and other antimicrobials – by patients may result in the subtherapeutic blood concentration of such medicines, and that may lead to drug resistance (15, 30) and/or treatment failure (31). A study of uterotonic medicines in Ghana found that 89% of the analyzed samples were less than the requirements of British Pharmacopoeia for an active pharmaceutical ingredient (API) (32). Postpartum hemorrhage was the primary cause of 16.8% (33) and 22.5% (34) of maternal deaths in Ghanaian hospitals during the study period (33, 34). Although the deaths were not directly linked to SFM, but considering the high level of substandard injectable uterotonic medicines (ergometrine and oxytocin) found in a region of Ghana (32), it may be reasonable to speculate that SFM has contributed to the problem, since it is these medicines that are mainly used for both inducing labor and controlling postpartum hemorrhage in the country.

A team of researchers investigated the quality of metformin tablets in Nigeria and found that half of the popular tablet’s products that were sampled failed at least 1 pharmacopoeia test of bioequivalence (5). A similar study, which was conducted to assess the stability of medicines in Rwanda revealed that up to 20% of the medicines sampled was substandard at the time of purchasing them in public and private pharmacies (5). These are the kinds of medicine hazards that could lead to the deterioration of a patient’s condition and to treatment failure. For example, the incidence of recrudescence of seizures and death due to falsified antiepileptic medicines were reported in Guinea-Bissau and Nigeria (35). In Uganda, an appalling incidence of lethal bacterial meningitis, which is likely due to substandard ceftriaxone, was reported (36). A patient (an adolescent boy) failed to respond to the treatment and eventually died after being treated according to the Standard Treatment Guideline. As part of the investigation of what possibly caused the treatment failure and eventual death of the patient, an untampered vial of a similar ceftriaxone product that was used to treat the patient was sent for analysis by mass spectrometry at the University of Ottawa, Canada. The result revealed that the product contained only 0.455 g of the API, which was contrary to the claimed 1 g by its manufacturer (36). This means that a subtherapeutic dose of ceftriaxone had been administered to the patient, if similarly compromised vials of the product were used on him, and this may have contributed to the failure of the treatment (36). The fact that the report highlighted limitations – some of which arose from resource-poor settings, such as deficiency of reliable diagnostic tools, delayed or inadequate interventions, and an uncertainty as to whether the analyzed vial belonged to the same lot as those used to treat the patient – precluded a 100% causal link to the substandard ceftriaxone. However, the finding that the analyzed ceftriaxone contained less than 50% of the stated API cannot be ignored, because therapy of bacterial meningitis with such a product has a high propensity of causing drug resistance, treatment failure, and/or death. Therefore, substandard or falsified ceftriaxone medicine may be a contributing factor to the problem of treatment failure in bacterial meningitis therapy in Africa (36).

Findings from a review article, which included 21 surveys of antimalarial medicines from 21 countries in sub-Saharan Africa, revealed that from the analyzed samples, 35% (796/2297) failed chemical analysis and 20% (79/389) were identified as falsified medicines (37). Similarly, a survey that was conducted in parts of Africa and Asia to evaluate the level of SFM in 10 faith-based drug supply organizations using a low-cost Global Pharma Health Fund (GPHF) Minilab, revealed that 2.4% (i.e., 21 out of 869) of the tested samples were confirmed to be substandard or falsified medicines (17). GPHF is a charitable organization assisted by a pharmaceutical company from Germany (Merck KGaA), while its Minilab is a detection technology that is capable of analyzing up to 85 different essential medicines by using thin-layer chromatography (TLC). The GPHF Minilab is a simple detection tool that can be used as a field test kit to identify and estimate the amount of API (17). The results of the SFM surveillance shows that Cameroon possessed the highest proportion of SFM, followed by the Democratic Republic (D.R.) of Congo, and Nigeria, and that antimalarial medicines have the highest frequency of falsification among the medicines studied (17). In Malawi, a falsified antimalarial tablet product, which contained a mixture of paracetamol and co-trimoxazole tablets instead of the claimed sulfadoxine/pyrimethamine tablets, was detected by the GPHF Minilab and confirmed by high performance liquid chromatography (HPLC) (33). The absence of the declared antimalarial agent and the presence of another API (paracetamol and co-trimoxazole), which can mask the feverish symptoms of malaria, represented a potential threat to public health (38).

The economic effects of substandard and falsified medicines in Africa

Besides the discussed clinical and public health consequence associated with SFM in Africa, SFM also constitutes a substantial economic problem for the patients, the pharmaceutical companies, and the governments in the continent. This economic effect is like a chain reaction, whereby one factor may lead to the other. The SFM may inflict economic burden on: (i) individual patients and their families, by wasting their funds in the purchase of useless, if not harmful, medicines, which, unknown to them, are SFM; (ii) legitimate pharmaceutical companies, by losing huge revenues due to competition for the market with SFM; and (iii) the governments, through the loss of revenue from unpaid taxes and spending money in fighting the SFM menace (3, 5, 21, 39).

The global market size of falsified medicines has been estimated to reach about US$75 billion annually (6, 39, 40), which is far less than the estimated 2016 global pharmaceutical market value of US$1,105 billion (41). This could be a potential opportunity cost attributable to global SFM business. In Africa, the estimates of the United Nations Office on Drugs and Crime (UNODC) for the sales of falsified antimalarial medicines in West Africa alone is US$438 million (12), which indicated a huge market loss for pharmaceutical companies that manufacture and trade legitimate antimalarial medicines in this region. This amount, which is being lost for antimalarial medicines alone, has exceeded the Gross Domestic Product (GDP) of Guinea-Bissau (42).

Falsified medicines have caused governments in African countries to lose tax revenues estimated to be worth hundreds of millions of U.S. dollars. The East African countries, which include Tanzania, Burundi, Kenya, Uganda, and Rwanda, have reported unremitted taxes related to falsified medicines and other goods to be more than US$500 million, and the worst scenario is in Tanzania, which is annually losing up to US$617 million as a result of tax evasion associated with falsified products (42). The overall detrimental effects of SFM in Africa could lead to: (i) loss of revenues by pharmaceutical firms and governments; (ii) poor or no investment from industrialized countries due to fear of losing revenue to counterfeiters; and (iii) job losses.

Inadequate health financing in Africa is another obstacle that has further compounded the healthcare problem in the region. The weaker economy of some African countries, increasing healthcare costs, and the recent economic downturn arising as a result of a crash in the price of crude oil (which was heavily relied upon by some of the African countries such as Nigeria, Angola, D.R. Congo, Sudan, etc.) may have contributed to the acute shortage of funds that prevent adequate financing of healthcare sectors in some African countries. However, lack of commitment by the government of these countries is another key setback, which has further exacerbated poor health financing, as the majority of the countries failed to fulfil the year 2001 adopted Abuja Declaration, which set a target of allocating a minimum of 15% of the annual budget for each member state to its health sector (43). As of 2011, only Rwanda and South Africa were able to achieve the “at least 15%” target of the Abuja Declaration (43). Similarly, a report from the WHO revealed that the average total health expenditure for the year 2010 in African countries to be US$135 per capita, which is more than 20 times less than the one spent (i.e., US$3,150) by affluent countries (44). The majority of African citizens are not covered by a reliable and affordable health insurance scheme. It is reported that household out-of-pocket payments account for 40% or more of the total health expenditure in about half of the African nations, and this may create financial barriers that may block people from accessing health services, and may put them at the risk of impoverishment (44). To address this problem, there is an urgent need for the African countries to significantly improve the funding of their health systems. Affordable insurance schemes should be provided to enhance access to quality health services by the populace. This may reduce demands for cheaper medicines, which in many cases are SFM.

The social effects of substandard and falsified medicines in Africa

The healthcare systems in the majority of African countries are underdeveloped. SFM further undermine the already weak confidence in all public health institutions as well as the entire healthcare system in many African countries. Victims of SFM are usually unaware they are victims (5); what they often think is that they are not responding well to the treatment. This sometimes creates mistrust in pharmacies, and in the physicians because the patients question the accuracy of their diagnosis. A systematic review suggests that patients in approximately 39 Sub-Saharan African countries and some parts of Asia have a negative impression on their healthcare systems. They are especially doubtful of the staffs’ clinical skills and professional competence, and the availability of medicines (45).

The proliferation and trade of SFM can cause other social troubles such as: (i) encouraging corruption, as many counterfeiters use bribery to persuade corrupt officials responsible for regulating the import and circulation of medicines; (ii) increasing criminal activities, as the business is often conducted by criminal cartels that usually generate huge amounts of money from the sale of falsified medicines and use it to purchase ammunition, cause public disorder, and influence corrupt officials (12, 46); and (iii) deteriorating the already weak political infrastructure that permits their continuous circulation (5).

Approaches for combating substandard and falsified medicines in Africa

National approaches: a Nigerian experience

In Nigeria, unregulated open medicine markets have been identified as a major element contributing to the prevalence of SFM. These are markets where medicines are being sold outdoors on the street and in illegal kiosks (47). The great danger is that they even supply some wholesale and retail pharmacies and some health institutions in the country. In an attempt to curb the menace of SFM, in 2012 (and launched in 2015) the Nigerian government initiated a guideline for National Drug Distribution to change the medicine distribution pattern in the country. Proper implementation of this guideline will ensure that all medicines in circulation are from a known and reliable source. It is also part of the benefits of the National Drug Distribution Guideline to ensure medicines are affordable. This will reduce the demand among the general public for buying medicines from unregulated outlets. Another medicines regulation law of Nigeria called “Counterfeit and Fake Drugs (miscellaneous provisions) Act, Cap 73 of 1990” has prohibited the sale of medicines in an open market without proper permission from the designated authority (48). The supplementary part of this law, called “Counterfeit and Fake Drugs and Unwholesome Processed Foods (Miscellaneous Provisions) Act of 1999, also contains similar prohibition quoted as “Any person who- (i) hawks or sells; or (ii) displays for the purpose of sale; or (iii) aids or abets any person to hawk, sell, display for the purpose of sale of any drug or poison in any place not duly licensed or registered by the appropriate authority, including any market, kiosk, motor park, road-side stall or in any bus, ferry or any other means of transportation, is guilty of an offence under this Act and shall, accordingly, be punished as specified in this Act” (49). However, ineffectual enforcement of such laws still allows illicit practices to prevail.

Earlier, in 2010, the National Agency for Food and Drug Administration and Control (NAFDAC) of Nigeria in collaboration with Sproxil® launched NAFDAC Mobile Authentication Service (MAS). It gives the consumer the power to instantly authenticate a medicine free of charge by 3 simple steps: (i) scratching the Sproxil label on the product; (ii) sending the unique personal identification number (PIN) to a short code 38353; and (iii) receiving a response within seconds indicating if the product is genuine or not. This technology was also deployed in Ghana. Other cutting-edge technologies used to curb SFM, especially in the West African region, include TruScan, a handheld Raman spectrometer (Deployed in Nigeria, Ghana, and Sierra Leone), GPHF Minilab (Deployed in Nigeria, Liberia, and Sierra Leone), Black Eye (i.e., infra-red-based detection technology) and Radio Frequency Identification (RFID) both adapted by Nigeria (3). The TruScan RM by Thermo Fisher Scientific is a useful instrument for the analysis of solid dosage forms, such as tablets, capsules, and powders. It is equipped with a laser excitation wavelength of 785 nm, spectral resolution between 8 and 10.5 cm−1, and Raman shift between 250 and 2,875 cm−1 (50). However, adapting the TruScan for falsified medicines identification in field settings has been limited due to its cost implication (US$17,000-$50,000 per device) driven by some of its components (31).

Global approaches by WHO through surveillance and monitoring system

In an effort to fight SFM peril in Africa, the WHO inaugurated a global surveillance and monitoring system in West Africa in July 2013 for what it then called SSFFC, the terminology which was recently replaced with “substandard and falsified medical products” (on May 29, 2017) (25, 51, 52). This African region surveillance and monitoring system was made based on the experience of a similar one called Rapid Alert System in the Western Pacific Region, which was operational much earlier. From its inception, more than 550 regulatory personnel from 141 collaborated countries were educated on how to operate the system. Since then, 20 global medicine alerts and many regional warnings have been issued, and more than 100 cases have been provided with technical support by WHO as at November 2017 (51). It aims to work in collaboration with the benefiting countries to protect public health in their region by accessing correct data related to SFM and using the data to adequately address issues of medicine falsifications (52). Ten West African countries were selected for a pilot run of the system in late 2012 to early 2013 after a training workshop that was carried out in the Philippines, and the implementation which began in mid-2013 during the regional workshop conducted in Nigeria. Since then, several other training workshops have been conducted in the region up to this year (2017). Attendees of the workshops are selected from national regulatory authorities and are nominated as the focal point of their respective organizations at the end of the workshop (52). The system works through a coordinated mechanism whereby the Member States submit reports of either suspected or validated SFM via the system. The report is then automatically uploaded to a secure database of the WHO and processed immediately. The results are then shared with the reporting country within 24 to 72 hours, depending on the nature and extent of the case (52).

An extension of the global surveillance and monitoring system is the WHO Medical Product Rapid Alert system, which is an innovation developed to facilitate a rapid and accurate response to incidences related to SFM that pose eminent danger to international public health and safety (53). The WHO Medical Product Rapid Alert system updates the Member States on the presence of potentially hazardous SFM and encourages them to take the necessary measures to protect their supply chains and safeguard their citizens. When an incident that poses a public health risk has happened and has been validated, the WHO immediately issue the alert and allow it to remain on its website for 5 years before archiving. In order to increase the impact of the alert, medical personnel and relevant staff of drug regulatory authorities need to be more aware of its existence and use. The published complete details of WHO Medical Product Rapid Alert system can be found at http://www.who.int/medicines/publications/drugalerts/en (53). The system has shown that antimalarial and anti-infective medicines seem to be the most common group of medicines falsified in Africa (53).

Impacting awareness and the utilization of the Medical Product Alert system in Africa can be achieved through proper collaboration between the WHO and Member States’ national regulatory agencies, and by creating a direct link on their websites for the WHO Medical Product Alerts. With the current globalization of smartphones, creating a mobile application of these systems by the WHO could maximize its benefits. However, some peculiar challenges, such as an intermittent power supply and poor internet infrastructure, which affect several African countries, may hamper the full benefits of these systems. These limitations may result in the under-reporting of SFM incidences in Africa. Nevertheless, measures such as increasing the frequency of workshops for the surveillance and monitoring system, and intensifying enlightenment campaigns may translate the reports into more conspicuous actions. Additionally, improving collaboration by engaging more stakeholders through prompt inter-professional collaboration among the healthcare teams and intersectoral collaboration with other agencies, such as drug regulatory agencies, policymakers, customs and excise, etc., also could be helpful.

Methods and technologies for the detection of substandard and falsified medicines

Swift detection methods are the cornerstone of any successful response to epidemic afflictions. Suitable methods for early diagnosis are indispensable to the national drug regulatory bodies and the global health community in their effort to counter the pandemic of SFM by detecting the medicines before it could penetrate supply chains and reach patients (6). The rapid advancements in science have yielded immensely sensitive instruments for forensic chemistry that can provide accurate information of a pharmaceutical product. These analytical techniques can give prosecutors sufficient proof to bring the culprits to justice.

Kovacs et al (54) found that there are 42 unique detection technologies that can identify SFM, of which more than half are readily available in the market. A summary of some of these technologies is provided in Table I. Such technologies provide a different level of qualitative and quantitative data for pharmaceutical products. Methods that give qualitative data usually generate information about the medicine’s qualities; that is, parameters that show identities, such as color, labelling, or the active ingredient of the medicine. On the other hand, quantitative techniques provide measurable data for the medicine; that is, its content. Qualitative techniques may be more helpful in the swift detection of a less sophisticated SFM, such as the ones with the wrong or no active ingredient, while the quantitative techniques are the most relevant when it comes to the determination of the pharmaceutical product’s defects, such as the content of impurities or an unacceptably high or low content of API (5).

Available detection approaches and technologies for substandard and falsified medicines

Approach/technology Detection range Affordability Reference
API = active pharmaceutical ingredient; SFM = substandard and falsified medicines.
Visual inspection Physical appearance: color, shape, size, etc. Less expensive Martino et al (21)
Packaging: mPedigree, Sproxil® Can detect fake packaging Less expensive Hibberd (55)
Colorimetry Can identify and quantify various types of API Less expensive Green et al (56)
Thin layer chromatography Can identify and quantify various types of API Less expensive Khuluza et al (38)
Disintegration and friability tests Can determine the product ability to disintegrate correctly Less expensive Buckley and Gostin (5)
Dissolution tests Can determine the product ability to dissolve correctly Can indicate bioavailability Less expensive Nayyar et al (11)
Capillary electrophoresis Can identify various types of API Less expensive Marini et al (57)
Portable device: near-infrared spectrometer Found promising in identifying SFM and for detecting certain medicines with an insufficient concentration of API Less expensive Wilson et al (31)
Fourier-transform infrared spectroscopy Can provide the chemical profile of various types of API and excipients Medium expensive Kovacs et al (54)
Portable device: Raman spectroscopy Can identify API, excipients, and provide relative concentration of ingredients Medium expensive Lawson and Rodriguez (58)
High-performance liquid chromatography Can identify and quantify various types of known API and impurities Medium expensive McCord et al (59); Shi et al (60)
Liquid chromatography-mass spectrometry Can rapidly identify and quantify various types of API and excipients with higher selectivity Expensive Lebel et al (61)
High-performance liquid chromatography- electrospray ionization mass spectrometry Can rapidly identify and quantify various types of API and excipients with higher selectivity Expensive Panusa et al (62)
Gas chromatography Can confirm the identity and quantity various essential oils; volatile active constituents and contaminants; residual solvents; and unknown compounds Expensive Deconinck et al (63)
Nuclear magnetic resonance Can confirm the identity of various types of API and excipients, and provide structural information for even closely related compounds Expensive Balayssac et al (64); Nuhu (65)
X-ray diffractometry Can provide the chemical profile of various types of API and excipients Expensive Martino et al (21)
Key points
SFM are serious public health risks but are a neglected problem in Africa.
The United Nations Sustainable Development Goals on access to safe, effective, qualitative, and affordable essential medicines may not be achieved in many African countries because of the SFM peril.
The problem of SFM is not limited to the African continent alone but is a global phenomenon that has spread to even highly regulated countries in Europe and America; hence the need for a concerted international effort to counter it decisively.
There has been some progress in the war against SFM in Nigeria, Ghana, Kenya, Rwanda, and a few others, as a result of the increased awareness campaigns, collaboration with the WHO and the use of effective detection techniques.
The high cost of some detection technologies limits regulatory agencies in many African countries to acquire them, consequently lowering their capability of fighting the SFM war. Therefore, the availability of cheaper and effective detection instruments is paramount in countering the SFM pandemic in Africa.
There are some social problems that are indirectly emanating from the proliferation and trade of SFM in Africa, such as corruption, crimes (including violent crime), and the erosion of the political infrastructure.
There is need to improve health financing and to provide affordable insurance schemes in Africa to enhance accessibility to quality health services and to decrease the dependence on household out-of-pocket payments for health expenditure.
African countries must exercise a high level of commitment toward the implementation of the agreed health treaties, such as the Abuja Declaration and must also ensure that their stakeholders are exercising their duties with due diligence and with determination to end the SFM menace.

The cost of some of these detection technologies is over US$100,000 per instrument (54), and this limits the ability of regulatory agencies to acquire them in many less affluent countries, which are also the ones most badly hit by the menace of SFM. Therefore, the availability of cheaper detection instruments for SFM is paramount in countering the SFM pandemic in Africa. Even the poor countries are supposed to afford rapid detection tools in order to be able to identify these bad medicines in their supply chain and at the points of entry into their countries.

The advent of a less expensive, hand-held near-infrared spectrometer (NIRS) as a portable device for the detection of quality assured and SFM of artemisinin-based combination therapy (ACT) medicines is important progress (31). NIRS, which cost only around US$1,000 has shown promising results for the screening of falsified ACTs samples from Equatorial Guinea and Ghana, and it can facilitate cheaper rapid testing at any country’s point of entry and in the supply chain (31). Similarly, the GPHF Minilab is another affordable detection tool that can make a significant impact in the war against SFM in Africa. This detection kit is less expensive, is not sophisticated, does not require extensive training to operate, and has already been employed in testing the quality of medicines in Cameroon, D.R. Congo, Nigeria, Kenya, Uganda, Ghana (17), Malawi (38), and some other African, Asian, and Latin American countries.

A good strategy for detecting and confirming SFM during an operation is to use portable devices, such as a handheld NIRS, a Raman spectrometer, or an infrared spectrometer for initial screening, followed by confirmatory forensic tests by more powerful and highly sensitive instruments such as liquid chromatography-mass spectrometry (LC-MS), nuclear magnetic resonance (NMR), etc. (50). The low-cost portable detection devices, such as NIRS and GPHF Minilab, would be very useful to African countries in the identification of SFM at the point of entry, considering that a large volume of such medicines are being illegally imported from other countries.

Pharmacists’ roles in combatting substandard and falsified medicines

Pharmacists have a vital contribution to the fight against SFM. As trained custodians of medicines, they have the pivotal role of controlling the infiltration of such medicines into the supply chain (66). Pharmacists should purchase their medications only from known and reliable sources. They must also confirm from distributors that the medicines were purchased directly from manufacturers or other reliable sources. They should educate themselves, their co-workers, and the patients about the risks of SFM. They should keep themselves up to date with any SFM alert (e.g., the WHO Medical Produce Alert system). Also, they should educate and caution patients on the dangers of purchasing medications from online or unregistered sources. They should synchronize their training and technology in order to detect SFM. They should physically examine medicines for suspicious appearance and use scanning and other technologies in the pharmacy as part of a medication and prescription verification process. They should ensure the quality control and quality assurance of medicines. They should ultimately collaborate with other stakeholders and report suspicious medicines to the national drug agencies, the distributors, and the legitimate manufacturers (18, 66). These actions may, in turn, lead to a significant reduction of SFM in the medicines supply chain and prevent patients from ingesting them.

However, pharmacists are just one of the integral professionals in the medicines supply chain, which comprises various other key players, such as the executive arm of governments, policymakers, regulators, health and nonhealth professionals, law enforcement bodies, customs and excise, community health workers, among others. Therefore, for African countries to achieve meaningful success in their fight to arrest the SFM menace, all stakeholders must exercise their duties with due diligence and must act vehemently within the provisions of law.

Conclusion

Despite some recorded successes, SFM still poses a serious threat to public health and safety in Africa. Many people are disabled or die needlessly, not for being unable to access or afford medication but for being a victim of SFM. No country is completely free of the risk of SFM, including the developed nations with highly regulated drug agencies and sophisticated detection equipment. However, the most susceptible are the middle- and low-income countries, most of which are in Africa. There is an urgent need for the African countries to significantly improve funding for their health systems and provide affordable insurance schemes that will enhance the public’s accessibility to quality health services. This may reduce demands for cheaper medicines, which in many cases are SFM.

Advancement in detection technologies has been a turning point in the war against SFM in most African countries. However, there are other strategies that can significantly enhance this war, which include: (i) extensive public enlightenment and awareness campaigns should be extended to consumer education and advocacy through print and electronic media, religious organizations, and health workers’ education; (ii) review of existing legislation and regulations for SFM; (iii) strong political will and enforcement of legislation, which will enforce zero tolerance of governments on medicines falsification and impose tough punishment for SFM offenders, such as arrest, prosecution, confiscation of all proceeds from SFM transactions, or the death penalty in the event of loss of life associated with SFM; (iv) determination and commitment for implementing the agreed health treaties, such as the Abuja Declaration; (v) fight corruption vehemently; and (vi) strong inter- and intrainstitutional and governmental collaboration, including relevant regulatory agencies, civil forces (Police, Immigration, Customs, etc.), professional associations, civil societies, and NGOs. Executives, policymakers and all relevant stakeholders in Africa need to consider these strategies for possible implementation in order to provide effective, safe, quality, and affordable medicines to their citizens.

Disclosures

Financial support: No grants or funding have been received for this study.
Conflict of interest: None of the authors has financial interest related to this study to disclose.
References
  • 1. Khuluza F Kigera S Heide L Low prevalence of substandard and falsified antimalarial and antibiotic medicines in public and faith-based health facilities of southern Malawi. Am J Trop Med Hyg 2017 96 5 1124 1135 Google Scholar
  • 2. United Nations. Transforming our world: the 2030 Agenda for Sustainable Development. http://undocs.org/A/RES/70/1. Accessed December 17, 2017. Google Scholar
  • 3. Aminu N Gwarzo MS The Eminent Threats of Counterfeit Drugs to Quality Health Care Delivery in Africa: Updates on Consequences and Way Forward. Asian J Pharm Clin Res 2017 10 7 82 86 Google Scholar
  • 4. Renschler JP Walters KM Newton PN Laxminarayan R Estimated under-five deaths associated with poor-quality antimalarials in sub-Saharan Africa. Am J Trop Med Hyg 2015 92 6)(Suppl 119 126 Google Scholar
  • 5. Buckley GJ Gostin LO eds. Countering the problem of falsified and substandard drugs. Washington D.C. National Academies Press 2013;55-290. Google Scholar
  • 6. Nayyar GML Breman JG Herrington JE The global pandemic of falsified medicines: laboratory and field innovations and policy perspectives. Am J Trop Med Hyg 2015 92 6)(Suppl 2 7 Google Scholar
  • 7. Institute of Research Against Counterfeit Medicines. New record seizures of illicit medicines in Africa 2017 http://www.iracm.com/en/2017/01/new-record-seizures-illicit-medicines-africa-counterfeit-medicines-africa-time-assessment-2/. Accessed December 17, 2017. Google Scholar
  • 8. World Health Organisation. Growing threat from counterfeit medicines. Bull World Health Organ 2010 88 4 247 248 Google Scholar
  • 9. Clark F Rise in online pharmacies sees counterfeit drugs go global. Lancet 2015 386 10001 1327 1328 Google Scholar
  • 10. Fadlallah R El-Jardali F Annan F Azzam H Akl EA Strategies and Systems-Level Interventions to Combat or Prevent Drug Counterfeiting: A Systematic Review of Evidence Beyond Effectiveness. Pharmaceut Med 2016 30 5 263 276 Google Scholar
  • 11. Nayyar GML Attaran A Clark JP et al. Responding to the pandemic of falsified medicines. Am J Trop Med Hyg 2015 92 6)(Suppl 113 118 Google Scholar
  • 12. United Nations Office on Drugs and Crime (UNODC). Transnational trafficking and the rule of law in West Africa: a threat assessment 2009 https://www.unodc.org/documents/data-and-analysis/Studies/West_Africa_Report_2009.pdf. Accessed December 17, 2017. Google Scholar
  • 13. Kahn U Kreutzer S Gill J Taylor D Falsified medicines and the global public’s health. http://www.globalforumljd.org/sites/default/files/docs/library/UCL-Matrix_Insight-Falsified_Medicines_and_the_Global_Publics_Health.pdf. Accessed December 17, 2017. Google Scholar
  • 14. Ratanawijitrasin S Wondemagegnehu E Effective drug regulation - a multicountry study. http://apps.who.int/medicinedocs/pdf/s2300e/s2300e.pdf. Accessed December 17, 2017. Google Scholar
  • 15. Binagwaho A Bate R Gasana M et al. Combatting substandard and falsified medicines: a view from Rwanda. PLoS Med 2013 10 7 e1001476. Google Scholar
  • 16. LaínAbril J Holt DW Wilson RR Falsified Medicines in the European Union and North America: What are we doing to Protect Public Health? J Pharmacovigil 2016 4 3 213 Google Scholar
  • 17. Petersen A Held N Heide L Difäm-EPN Minilab Survey Group. Surveillance for falsified and substandard medicines in Africa and Asia by local organizations using the low-cost GPHF Minilab. PLoS ONE 2017 12 9 e0184165. Google Scholar
  • 18. Hamilton WL Doyle C Halliwell-Ewen M Lambert G Public health interventions to protect against falsified medicines: a systematic review of international, national and local policies. Health Policy Plan 2016 31 10 1448 1466 Google Scholar
  • 19. LawPavilion. Counterfeit and Fake Drugs and Unwholesome Processed Food (Miscellaneous Provision) Act (Amendment) Bill, 2015 https://lawpavilion.com/blog/counterfeit-and-fake-drugs-and-unwholesome-processed-food-miscellaneous-provision-act-amendment-bill-2015/. Accessed December 17, 2017. Google Scholar
  • 20. Ziemer T Falsified medicines in Africa. Lancet Glob Health 2015 3 2 e82 Google Scholar
  • 21. Martino R Malet-Martino M Gilard V Balayssac S Counterfeit drugs: analytical techniques for their identification. Anal Bioanal Chem 2010 398 1 77 92 Google Scholar
  • 22. World Health Organization. Report of the situation of counterfeit medicines based on data collection tool. http://www.who.int/medicines/services/expertcommittees/pharmprep/WHO-ACM-3IMPACTSurveyDataCollectionToolReport.pdf. Accessed December 17, 2017. Google Scholar
  • 23. Newton PN Amin AA Bird C et al. The primacy of public health considerations in defining poor quality medicines. PLoS Med 2011 8 12 e1001139. Google Scholar
  • 24. Clift C Counterfeit, falsified and substandard medicines. Meeting summary. Chatham House 2010 1– 6 https://www.chathamhouse.org/publications/papers/view/109566. Accessed December 17, 2017. Google Scholar
  • 25. World Health Organization. Definitions of substandard and falsified (SF) medical products 2017 http://www.who.int/medicines/regulation/ssffc/definitions/en/. Accessed December 17, 2017. Google Scholar
  • 26. Gwatidzo SD Murambinda PK Makoni Z Medicines counterfeiting in Africa: a view from Zimbabwe. Med Access @ Point Care 2017 1 1 82– 86 Google Scholar
  • 27. Schep LJ Slaughter RJ Temple WA Beasley DMG Diethylene glycol poisoning. Clin Toxicol (Phila) 2009 47 6 525 535 Google Scholar
  • 28. Akuse RM Eke FU Ademola AD et al. Diagnosing renal failure due to diethylene glycol in children in a resource-constrained setting. Pediatr Nephrol 2012 27 6 1021 1028 Google Scholar
  • 29. Bonati M Once again, children are the main victims of fake drugs. Arch Dis Child 2009 94 6 468 468 Google Scholar
  • 30. Newton PN Tabernero P Dwivedi P et al. Falsified medicines in Africa: all talk, no action. Lancet Glob Health 2014 2 9 e509 e510 Google Scholar
  • 31. Wilson BK Kaur H Allan EL Lozama A Bell D A new handheld device for the detection of falsified medicines: Demonstration on falsified artemisinin-based therapies from the field. Am J Trop Med Hyg 2017 96 5 1117 1123 Google Scholar
  • 32. Stanton C Koski A Cofie P Mirzabagi E Grady BL Brooke S Uterotonic drug quality: an assessment of the potency of injectable uterotonic drugs purchased by simulated clients in three districts in Ghana. BMJ Open 2012 2 3 e000431. Google Scholar
  • 33. Lee QY Odoi AT Opare-Addo H Dassah ET Maternal mortality in Ghana: a hospital-based review. Acta Obstet Gynecol Scand 2012 91 1 87 92 Google Scholar
  • 34. Ganyaglo GYK Hill WCA A 6-year (20042009) review of maternal mortality at the Eastern Regional Hospital, Koforidua, Ghana. Semin Perinatol 2012 36 1 79 83 Google Scholar
  • 35. Otte WM van Diessen E van Eijsden P et al. Counterfeit antiepileptic drugs threaten community services in Guinea-Bissau and Nigeria. Lancet Neurol 2015 14 11 1075 1076 Google Scholar
  • 36. Nickerson JW Attaran A Westerberg BD Curtis S Overton S Mayer P Fatal Bacterial Meningitis Possibly Associated with Substandard CeftriaxoneUganda, 2013. MMWR Morb Mortal Wkly Rep 2016 64 50-51 1375 1377 Google Scholar
  • 37. Nayyar GML Breman JG Newton PN Herrington J Poor-quality antimalarial drugs in southeast Asia and sub-Saharan Africa. Lancet Infect Dis 2012 12 6 488 496 Google Scholar
  • 38. Khuluza F Kigera S Jähnke RWO Heide L Use of thin-layer chromatography to detect counterfeit sulfadoxine/pyrimethamine tablets with the wrong active ingredient in Malawi. Malar J 2016 15 1 215 Google Scholar
  • 39. Chaccour C Kaur H Del Pozo JL Falsified antimalarials: a minireview. Expert Rev Anti Infect Ther 2015 13 4 505 509 Google Scholar
  • 40. Blackstone EA Fuhr JP Jr Pociask S The health and economic effects of counterfeit drugs. Am Health Drug Benefits 2014 7 4 216 224 Google Scholar
  • 41. International Federation of Pharmaceutical Manufacturers & Associations (IFPMA). The pharmaceutical industry and global health 2017 https://www.ifpma.org/wp-content/uploads/2017/02/IFPMA-Facts-And-Figures-2017.pdf. Accessed December 17, 2017. Google Scholar
  • 42. Wilson JM Fenoff R The health and economic effects of counterfeit pharmaceuticals in Africa. Michigan State University http://a-capp.msu.edu/sites/default/files/files/AFRICABACKGROUNDERfinal.pdf. Accessed December 17, 2017. Google Scholar
  • 43. World Health Organization. The Abuja Declaration: ten years on http://www.who.int/healthsystems/publications/Abuja10.pdf. Accessed December 17, 2017. Google Scholar
  • 44. World Health Organisation. State of health financing in the african region. WHO 2013 http://www.afro.who.int/sites/default/files/2017-06/state-of-health-financing-afro.pdf. Accessed December 17, 2017. Google Scholar
  • 45. Berendes S Heywood P Oliver S Garner P Quality of private and public ambulatory health care in low and middle income countries: systematic review of comparative studies. PLoS Med 2011 8 4 e1000433. Google Scholar
  • 46. Finlay BD Counterfeit drugs and national security. https://www.stimson.org/sites/default/files/file-attachments/Full_-_Counterfeit_Drugs_and_National_Security_1.pdf. Accessed December17, 2017. Google Scholar
  • 47. Fatokun O Curbing the circulation of counterfeit medicines in Nigeria. Lancet 2016 388 10060 2603 Google Scholar
  • 48. Erhun WO Babalola OO Erhun MO Drug regulation and control in Nigeria: the challenge of counterfeit drugs. J Health Popul Dev Countries 2001 4 23 34 Google Scholar
  • 49. United Nations Office On Drugs and Crime (UNODC). Counterfeit and Fake Drugs and Unwholesome Processed Foods (Miscellaneous Provisions) Act (Nigeria) https://www.unodc.org/res/cld/document/nga/counterfeit-and-fake-drugs-and-unwholesome-processed-food-act_html/Nigeria_Counterfeit_and_Fake_Drugs_and_Unwholesome_Processed_Food_Act.pdf. Accessed December 17, 2017. Google Scholar
  • 50. Dégardin K Roggo Y Innovative strategy for counterfeit analysis. Med Access @ Point Care 2017 1 1 65 71 Google Scholar
  • 51. World Health Organization. Substandard and falsified medical products. http://www.who.int/mediacentre/factsheets/fs275/en/. Accessed December 17, 2017. Google Scholar
  • 52. World Health Organization. WHO global surveillance and monitoring system. http://www.who.int/medicines/regulation/ssffc/surveillance/en/. Accessed December 17, 2017. Google Scholar
  • 53. World Health Organization. WHO medical product alerts http://www.who.int/medicines/regulation/ssffc/medical-products/en/. Accessed December 17, 2017. Google Scholar
  • 54. Kovacs S Hawes SE Maley SN Mosites E Wong L Stergachis A Technologies for detecting falsified and substandard drugs in low and middle-income countries. PLoS ONE 2014 9 3 e90601. Google Scholar
  • 55. Hibberd R Combating falsified medicines in Africa through digital artefacts. http://eprints.lse.ac.uk/79513/1/Delivering Digital Drugs (D3) – Combating Falsified Medicines in Africa through Digital Artefacts.pdf. Accessed December 17, 2017. Google Scholar
  • 56. Green MD Mount DL Wirtz RA Authentication of artemether, artesunate and dihydroartemisinin antimalarial tablets using a simple colorimetric method. Trop Med Int Health 2001 6 12 980 982 Google Scholar
  • 57. Marini RD Rozet E Montes MLA et al. Reliable low-cost capillary electrophoresis device for drug quality control and counterfeit medicines. J Pharm Biomed Anal 2010 53 5 1278 1287 Google Scholar
  • 58. Lawson LS Rodriguez JD Raman Barcode for Counterfeit Drug Product Detection. Anal Chem 2016 88 9 4706 4713 Google Scholar
  • 59. McCord J Mavity M Damayo S Wintczak D Universal HPLC Analysis for Counterfeit Medication: A Partnership of Purdue University and the Kilimanjaro School of Pharmacy. Purdue J Serv Int Engagem 2015 2 1 23 26 Google Scholar
  • 60. Shi YQ Yao J Liu F et al. Establishment of an HPLC identification system for detection of counterfeit steroidal drugs. J Pharm Biomed Anal 2008 46 4 663 669 Google Scholar
  • 61. Lebel P Gagnon J Furtos A Waldron KC A rapid, quantitative liquid chromatography-mass spectrometry screening method for 71 active and 11 natural erectile dysfunction ingredients present in potentially adulterated or counterfeit products. J Chromatogr A 2014 1343 143 151 Google Scholar
  • 62. Panusa A Multari G Incarnato G Gagliardi L High-performance liquid chromatography analysis of anti-inflammatory pharmaceuticals with ultraviolet and electrospray-mass spectrometry detection in suspected counterfeit homeopathic medicinal products. J Pharm Biomed Anal 2007 43 4 1221 1227 Google Scholar
  • 63. Deconinck E Sacré P-Y Courselle P De Beer JO Chromatography in the detection and characterization of illegal pharmaceutical preparations. J Chromatogr Sci 2013 51 8 791 806 Google Scholar
  • 64. Balayssac S Gilard V Delsuc M-A Malet-Martinoa M DOSY NMR, a new tool for fake drug analyses. Spectros Eur 2009 21 10 14 Google Scholar
  • 65. Nuhu AA Recent analytical approaches to counterfeit drug detection. J Appl Pharmaceut Sci 2011 1 6 13 Google Scholar
  • 66. Chambliss WG Carroll WA Kennedy D et al. Role of the pharmacist in preventing distribution of counterfeit medications. J Am Pharm Assoc (2003) 2012 52 2 195 199 Google Scholar

Authors

Affiliations

  • School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang - Malaysia
  • Faculty of Pharmaceutical Sciences, Usmanu Danfodiyo University, Sokoto - Nigeria
  • Faculty of Pharmaceutical Sciences, Ahmadu Bello University, Zaria - Nigeria
  • Faculty of Pharmaceutical Sciences, Bayero University Kano, Kano - Nigeria

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