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Problems related to quality of antibiotics

As for any medicine, it is crucial that antibiotics are of high quality. However, problems related to the quality of antibiotics do arise, some unintentionally and others due to fraud.

There are many ways in which antibiotics can be of poor quality:

  • Low antibiotic content
  • Poor formulation
  • Containing impurities, intermediary compounds or isomers

The World Health Organization (WHO) addresses the issue through The Medicines Quality Assurance Programme. The program develops norms, guidelines and provides country support. WHO has also set up a Member State Mechanism for substandard and falsified medical products to cover the issue comprehensively.

Terminology

The terminology regarding quality problems with medical products has been difficult to comprehend; the terms have partially overlapped and have been used differently in different countries or settings. In the international debate, this has caused confusion and hindered progress as it also often addressed counterfeit medical products that infringe on intellectual property in parallel to the quality issues.

As a result, WHO has adopted the following terminology for quality related problems with medical products:Substandard products

Substandard medical products

Authorized medical products that do not meet quality standards or specifications, or both. Also called “out of specification”.

Unregistered/unlicensed medical products

Products that have not been evaluated and/or approved by regulatory authorities for the market in which they are marketed, distributed or used.

Falsified medical products

Products that deliberately or fraudulently misrepresent their identity, composition or source.

Additionally, a category of degraded medical products defines medicines of poor quality as a result of exposure of good-quality medicines to light, heat and humidity, as described in the WHO good distribution practices guidelines. It can be difficult to distinguish degraded medicines from those that left the factory as substandard, but the distinction is important as the causes and counter-measures are different.

In the Toolbox, we use the term poor quality antibiotics to encompass all quality-related problems and strictly refrain from involving intellectual property considerations when discussing quality of antibiotic products.

Effects of poor quality antibiotics

It is often difficult to prove causal relationships between poor quality antibiotics and immediate health outcomes in countries without functional surveillance systems. The effects often do not manifest immediately, and confounding factors make it difficult to identify causality correctly. However, the predictable consequences of poor quality antibiotics are treatment failure, prolonged illness, greater risk of complications and adverse drug reactions, and increased rates of morbidity and mortality. For end users, therapeutic failure is often the only indication of poor quality medicines.

Fragmented health services and lack of access to quality-assured medicines at an affordable price often lead patients to take incomplete courses of treatment and may also increase exposure to medicines with illicit origin. All of these not only endanger patient safety, but consequently also risk loss of patients’ trust in the health care system..

Poor quality antibiotics can lead to resistance

In addition, poor quality antibiotics may lead to lower, subinhibitory concentrations of the active pharmaceutical ingredient. Too low antibiotic concentrations can in turn lead to treatment failure, and may also fuel resistance development. If the antibiotic concentration is lower than what is needed to kill or inhibit growth of bacteria, there may be room for resistance to develop and be selected, as has been observed in Mycobacterium tuberculosis as well as in other bacteria.

How big is the problem?

Many countries have weak or no quality assurance systems for medicines due to limited resources of Medicines Regulatory Authorities and lack of qualified personnel. Also, despite a significant proportion of countries’ health expenditures going towards medicines procurement, there are usually no harmonized quality assurance systems for the procurement organizations involved. But substandard and falsified medicines are not only a problem for low- and middle-income countries, they are found also in high-income countries with developed regulatory systems.

According to a report from the WHO Global Surveillance and Monitoring System, approximately 10% of all medicines globally are substandard or falsified. However, the numbers in the report are expected to be underestimates: many countries have not reported to the system, and even more countries do not have the capacity to find all poor quality drugs.

Of all reports in the system, 17% were on antibiotics and 20% on antimalarials, making antimicrobial drugs the largest category of falsified and substandard drugs. This is serious, not only due to the concerns of resistance, but also because these drugs are in fact life-saving. According to a model that estimates the effect of poor quality antibiotics on childhood pneumonia, up to 72000 deaths are attributable to these. In a worst case scenario, where the antibiotics are assumed to contain no active ingredient at all, the death toll would increase to up to 170000 deaths.

Example cases

WHO: Six falsified antimalarial and antibiotic medical products were discovered in Niger in September 2014. All of them have been intentionally falsified and found in pharmacies of public health facilities, but were purchased from private wholesalers. Specifically, the antibiotic amoxicillin contained almost no active ingredient.

EUCAST: Several antimicrobial disks to test susceptibility of antimicrobials were found out of quality control criteria range and therefore considered substandard. Poor-quality testing materials can provide unreliable data for clinical and public health purposes. Find out more about reported cases of poor quality antibiotics in MEASURE: Access existing data – Quality of antibiotics.

Selected Resources

Resource Description
WHO Global Surveillance and Monitoring System for substandard and falsified medical products Report based on the data/case studies collected by the WHO Global Surveillance and Monitoring System (GSMS) for substandard and falsified medicines. Antibiotics are among the most reported medicines in the database. Puts forth “prevent, detect, respond” strategy to tackle the issue.
A study on the public health and socioeconomic impact of substandard and falsified medical products Literature review of the impact of poor quality medicinal products with impact models for childhood pneumonia and malaria. Lays out key areas for further investigation.
Quality Assurance of Pharmaceuticals: Meeting a Major Public Health Challenge WHO Expert Committee on Specifications for Pharmaceutical Preparations provides guidelines for pharmaceutical ingredients, good manufacturing practices, testing of products, regulatory guidelines for authorization of marketing, and correct storage and distribution practices. It aims to ensure that all medicines listed in essential medicines lists meet identical standards of quality, safety and efficacy.

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