Substandard Medicines

For many years, the response to this important threat to public health was embroiled in the discussion complex definitions that means different things to different people. Reflecting this complexity, until May 2017 WHO used the term “substandard/spurious/falsely-labelled/falsified/counterfeit medical product” (SSFFC). The WHO Member State mechanism on SSFFC medical products was tasked with revising these definitions to ensure that they were based on a public-health perspective, with no account taken of intellectual property concerns. Based on their deliberations, the World Health Assembly, which governs WHO, adopted the following definitions:Substandard medical products : also called “out of specification” these are authorized medical products that fail to meet either their quality standards or their specification, or both.

When medicines do not work the way they should (as is the case with most substandard and falsified medical products), they can prolong illness and the inconvenience, time off work and often the misery that go with it. Doctors and other health workers waste precious time trying out alternative treatments, when all that is really needed is a quality version of the same treatment. In the worst cases, several of which are described in this report, people die, either from untreated disease or because the product itself kills them.

According to WHO 2017, substandard and falsified medical products can be:

• Endanger health, prolong illness and even kill;
• Promote antimicrobial resistance and the spread of drug-resistance infections;
• Undermine confidence in health professionals and health systems;
• Create distrust about the effectiveness of vaccines and medicines;
• Eat into the limited budgets of families and health system;
• Provide income to criminal network.

Research conducted by WHO, existing data show that:

• Substandard and falsified medical products exist in every region;
• The more one looks, the more one finds;
• The problem affects a wide range of products, including vaccines, common antibiotics, antimalarials, cancer medicines and other lifesaving medical products;
• Those falsifying medical products target both generic and innovator products.

According to Almuzaini et al, the prevalence of substandard antimicrobials is high throughout Africa and Asia in lower income countries and lower middle-income countries. The prevalence of substandard/counterfeit medicines was significantly higher in the unlicensed markets. Inadequate amount of active ingredients were the largest problem identified. Substandard and falsified (SF) medicines are a “wicked problem” and a global issue with substantial estimated economic and public health impact (Ozawa S, et al. 2018). They affect countries across the full spectrum of financial levels, from low-income countries (LICs) to high-income countries (HICs) 6. SF medicines exist in many different therapeutic classes, are sold with the explicit intent to deceive the end user of their origin, authenticity and efficacy and can have wide ranging effects including failure of treatment, toxicity and antimicrobial resistance (Renshler JP, et al. 2015). Arguably, the most morally reprehensible crime is the willing sale of falsified lifesaving treatments, such as antimalarial products, in area where the disease is endemic, a practice that continues at great cost to human life (Bassat Q, et al. 2016).

In cases of substandard medication that arise through inadequate production processes, rather than through deliberate falsification of drugs, the lack of quality may be the result of a variety of factors, including the following: inadvertent use of substandard or incorrect APIs or excipients; poor control of drug quantity; manufacturing processes that cause contamination or do not adequately ensure sterility; and inadequate packaging design or quality. In addition, ineffective quality-control measure, either on the part of the manufacturer of the NMRA, allow such faults to remain undetected. Any formulation of medication may be regarded as substandard if it has either too much or too little of the API compared with the formulation specifications. Official national pharmacopoeias, such as the British Pharmacopoeia (BP) and United States Pharmacopeia (USP), publish the quality standards for medicinal substances and preparations manufactured or sold in the country. The information given specifies the acceptable limits for the amount of the API that should be present in a given formulation. However, many examples from a range of drug classes have been published of over/underconcentration of APIs in marketed drugs. In some cases, all sampled antibiotics or antimalarial were found to contain API concentrations outside the officially specified limits (Johnston & Holt, 2013).

In short, substandard and falsified medical products are most likely to be found at the intersection where:

• Access to affordable, quality, safe and effective medical products is constrained
• Standards of governance are low, from poor ethical practices in health care facilities and medicine outlets, through to corruption in both the public and private sectors.
• The tools and technical capacity to ensure good practices in manufacturing, quality control and distribution are limited

Very broadly speaking, substandard medical product reach products reach patients when the tools and technical capacity to enforce quality standards in manufacturing and the supply chain are limited. Technical limitations also affect falsified products, but their circulation in the market is further promoted by corruption and other shortcomings of regulation and governance, including unethical practice by wholesalers, distributors, retailers and health care workers. However, a high proportion of cases so far reported to WHO occur where these problems overlap with constrained access.