A cross-sectional analysis of falsified, counterfeit and substandard medicines in a low-middle income country

The availability of low quality and/or counterfeited pharmaceutical products is one of the major barriers to provide quality essential health care in developing countries [1, 2]. Indeed it is also an issue in some high-income countries [3, 4].

According to the World Health Organization (WHO), substandard medicines also called “out of specification”, are authorized medical products that fail to meet their quality standards or specifications, or both. Unregistered medical products have not undergone an evaluation and obtained approval by the National Regulatory Authority for marketing. Falsified medical products deliberately/fraudulently misrepresent their identity, composition or source [5].

Recently, Ozawa et al. completed a systematic review of 44 extracted prevalence studies, conducted in 25 different countries. The median prevalence of substandard/counterfeit medicines was 28.5% (11–48%) [6]. Comparable findings were also reported by the WHO in 2017 [7] and in other studies [8‐10]. Moreover, the WHO has estimated the cost to procure substandard and falsified medicines to be approximately US$30.5 billion worldwide [7]. Substandard and falsified medicines impact the community at patient-level, and if antibiotics pose a risk of antimicrobial resistance, cause ineffective treatment outcomes and unnecessary increased cost and health burdens [11].

The WHO reported surveillance of antibiotic consumption data worldwide and Mongolia was one of the countries with the highest antibiotic consumption (64.4 DDD per 1000 inhabitants per day) [12]. A pilot study of counterfeit medicines in Mongolia was undertaken by the Ministry of Health (MOH) of Mongolia and 3.5% were considered possibly counterfeit [13]. A larger scale study at the nationwide level indicated a higher prevalence of 14.6% (13.2–17.8) in 2012. The mission of the National Medicines Policy of Mongolia (NMPM) is to provide continuously, equitable and adequate supplies of medications for individuals, health facilities and veterinary services which are effective, safe, of good quality and affordable; and to promote the rational use of medicines [14]. Nevertheless, despite the Government’s efforts to achieve successful implementation of the NMPM [14], the situation has deteriorated with respect to availability [15, 16], quality [13, 17, 18] and rational use [19, 20].

The current study aimed to perform a repeat survey to assess and compare the quality of current medicines, including those manufactured in Mongolia.

A cross-sectional study followed the WHO Guidelines on the “Conduct of Surveys of the Quality of Medicines” [21]. This methodology was adapted to the Mongolian context, in particular the selection of medicines and pharmacy entities.

A total of 1770 samples were purchased from 118 pharmacy entities a majority of which were obtained from retail pharmacies in urban areas (n = 1110, 62.7%). When the samples were not available or there were insufficient samples, the study team randomly selected the next pharmacy entity to make up the samples. From each entity, the same brands, but different batches of pharmaceutical products were purchased and analysed.

Of note, Revolving Drug Funds (RDF) operate only in rural areas and 135 (7.6%) were acquired from RDFs. Similarly, to other areas, the same brands but different batches of products were collected from RDFs.

More samples were purchased from wholesalers in urban areas when compared to their counterparts in rural areas [(n = 210, 11.9% vs n = 60, 3.4%, p = 0.001)]. Data regarding individual samples purchased from pharmacy entities in urban and rural areas are presented in Table 2. Samples of one brand could include different batch numbers, due to out-of-stock or unavailability.

This cross-sectional study investigated the quality of 1770 samples of 15 specific medicines collected from various types of pharmacy entities located in four districts of Ulaanbaatar city and four rural provinces in Mongolia. It was found that 10.1% of the total samples were substandard. In a comparison with a survey performed in 2012 [18], the proportion of substandard medicines had slightly decreased from 14.6 to 10.1% found in this study. However, the prevalence of substandard products was three times higher for locally manufactured products (18.6%) than for imported counterparts (6.1%). Local manufacturing of medicines is promoted in the NMPM and it is mainly to improve the access to essential medicines in Mongolia. However, implementation of good manufacturing practices (GMP) requires significant expenditure for pharmaceutical companies. Large companies operate on a scale that allows them to recover the costs of running high-quality factories, but this is not the case for smaller manufacturers in developing countries [34]. In India, a number of small manufacturers struggle to implement quality-assurance and quality-control procedures even with a large population. Similarly, a majority of locally produced cotrimoxazole were reported to be substandard when evaluated in Indonesia [35].

A systematic review on the prevalence of substandard/falsified medicines from 2007 to 2016 by means of electronic databases reported that it was 10.5% in low-middle income countries. The results in the WHO report are based on studies with the objective to quantify quality problems regarding specific drug classes, including antimalarials and antibiotics [36].

In this study, most of all failed tests were due to assay, content uniformity, dissolution and disintegration. These failures were related to citramon-P (acetylsalicylic acid+acetaminophen+caffeine), 240 mg + 180 + 30/450 mg tablets), omeprazole 20 mg, ciprofloxacin 500 mg and diclofenac sodium, 100 mg tablets owing to poor weight uniformity. Samples of amoxicillin 500 mg and omeprazole 20 mg failed due to dissolution test results in this study.

Apart from being substandard or falsified at the manufacturing stage, the quality of pharmaceutical products is affected by inappropriate storage and transportation conditions during the supply chain [37].

The Mongolian climate is known to be very harsh, with temperatures below − 30 °C in winter. Some rural areas are hot (> 30 °C) in summer. Medicines can deteriorate during storage and transportation in extreme weather conditions and degraded medicines might be distributed in the market [38, 39]. All standard protocols on transportation and storage requirements were complied with during the sample collection and quality assurance was maintained throughout study, including data analysis. However, the samples were collected from different pharmacy entities, meaning that there might be potential risks during distribution or transportation until pharmaceutical products are delivered to each pharmacy entity. Hence, more information to identify the impact of climate during supply and storage chain on drug quality needs to be further investigated.

Good pharmacy practice is promoted by the MOH and enforced by the GASI. However, due to financial constraints and limited human resources, strict quality control measures are yet to be implemented [40, 41].

In this study, one fake sample of sildenafil citrate 100 mg was found. The quantitative content of active ingredient was 45.3–65.4% well below the pharmacopoeial limit (95–105%). Problems with phosphodiesterase type 5 inhibitors (PDE5) have been reported elsewhere, for example an Italian survey on the PDE5 medicines was completed between 2005 and 2011 [42]. It found that 24.0% of the analyzed samples were counterfeit and 54.0% were illegal medicines. In 12.0% of the cases an intermediate classification (illegal/counterfeit) was assigned, whereas only 7.0% of the samples were original [42].

The study showed a decreased prevalence of unregistered medicines, when compared with the previous findings [18]. This could be due to the MOH’s efforts to strengthen the drug registration as well as development of an online database “Licemed” to check and verify drug information. However, discrepancies in outer packaging and information on package inserts can potentially contribute to the inappropriate use of medicines [43].

Research shows that multi-faceted interventions including a mix of regulations, training of inspectors, public-private collaborations and legal enforcement actions are useful in combating substandard and falsified medicines [44]. At the time of writing the manuscript, the regulation of drug registration has been revised and approved by the Mongolian Government [45]. It is envisaged that with revised legal requirements, implementation and enforcement of quality assurance will be improved in Mongolia.

Overall the national law coordination and law enforcement on registering medicines is in place in Mongolia. Nevertheless, echoing previous findings, the current study results suggest that substandard and falsified medicines are still prevalent in Mongolia. Prevalence of low quality medicines indicate that licensing of manufacturing plants and pharmacy outlets is not fully effective.