Important notice
Please note that the images, figures, and tables for this Review have not been added yet. We are actively working to digitise and include these materials from our past magazines.

Main content

Access to essential medicines, at affordable prices and with appropriate quality standards, is a fundamental prerequisite to ensure universal access to health. In recent years, we witnessed an impressive mobilization of the scientific community and civil society to improve financial access to newly-developed essential medicines, and the lessons learned in the field of HIV/AIDS represent a valuable model for other infectious diseases as well as non-transmissible diseases. Unfortunately, there hasn’t been a comparable mobilization for overcoming the North-South divide when it comes to quality of medicines.

A situation of multiple quality standards

The rapid globalization of the pharmaceutical market observed during the last three decades has not been accompanied by a globalization of pharmaceutical regulation. According to the World Health Organisation (WHO), only twenty percent of countries have fully operational national regulatory authorities (NRAs), while the capacity for medicines regulation (e.g. for thoroughly assessing products’ dossiers before registration) is ‘varying’ in 30% of countries and ‘very limited or absent’ in the remaining 30%. (1) This led to a situation of multiple pharmaceutical standards. The quality of medicines largely depends on the level of income and regulation in the country of final destination, and people in many middle- and low-income countries (LMICs) are exposed to the risk of receiving poor-quality medicines. (2)

Poor quality medications
In general, poor-quality medicines can be lumped into two broad categories.
First, falsified medicines (or falsely-labelled, counterfeits) are products that are intentionally and fraudulently produced. They often contain no or less active ingredient than labelled, or plainly the wrong active ingredient. However, they can confusingly also contain the right active ingredient, in the right quantity, but simply infringe the trademark of a patented product. This latter example does not represent a public health threat for patients but merely an intellectual property problem. Falsified medicines are always the result of a criminal activity, carried out outside any regulatory and legal framework.
The second category consists of substandard medicines which are the result of unintentional actions, such as degradation due to faulty storage conditions or errors during the manufacturing process, which most often results in a different amount of active ingredient than labelled. This is due on the one hand to the manufacturers’ lack of capacity or negligence, and on the other hand to the NRAs’ lack of resources for enforcing regulatory supervision of medicines manufactured, imported and distributed in their territory.

From a public health perspective, substandard and falsified medicines are equally dangerous, (5) i.e. they may all cause direct toxicity, lack of therapeutic efficacy, and emergence of resistances.

There is widespread evidence that poor-quality medicines are prevalent in LMICs. Most data come from the field of malaria, since the steep rise in resistance to old medicines has triggered a strong awareness of the risks linked to poor-quality antimalarials, (6) which will be discussed in more detail by Thomas Dorlo on page 13-15. However, quality problems have been documented also for other medicines, such as those for treating tuberculosis, (7) infectious diseases, (8) tropical neglected diseases, (9) chronic diseases, (10) and others (11). The in vitro diagnostics and medical devices are not spared by this plague, (12) and it is likely that the phenomenon remains underestimated. In fact, evidence from the literature comes either from retrospective surveys or from cases of acute toxicity, (10) while cases of sub-therapeutic efficacy (e.g. due to underdosing of the active ingredient, poor stability or insufficient bio-availability) will often go undetected. The weakness of pharmaco-vigilance systems in many LMICs further aggravates the risk of underreporting.

The way forward

The WHO Pre-qualification project (13) provides a precious support for purchasers of medicines in LMICs for some specific diseases (http://apps.who.int/prequal/), but unfortunately no comprehensive mechanisms exists yet covering all essential medicines. In order to prevent poor quality medicines from reaching patients in LMICs, and to prevent these patients from being harmed rather than cured by a therapeutic intervention, the following measures should be urgently implemented:

Re-enforcing the regulatory capacity in LMICs;

Strengthening the national and international regulation, with special focus on initiatives that promote collaboration, knowledge-sharing, resource-sharing and networking among Northern and Southern NRAs; (14)

Expanding the scope of the WHO Prequalification programme;

Educating and convincing the main public and private stakeholders to adopt and implement procurement practices for medicines and other medical products based on stringent quality assurance criteria. (2)

The enforcement of quality standards in pharmaceutical production and distribution is generally seen as a purely technical subjects. In reality, the poor enforcement of regulatory supervision on medicines’ manufacturers and wholesalers exposes the patients to poor-quality medical products, which will in turn result in avoidable harm. Correcting the current situation of variable pharmaceutical standards is in the first place not a technical problem but an ethical imperative linked to the medical ethics’ principles of beneficence and non-maleficence. (15)

Acknowledgements

The content of this paper is drawn from the experience of QUAMED, a programme of the Institute of Tropical Medicine of Antwerp which brings together humanitarian NGOs and non-profit procurement centres, to promote appropriate quality standards for the procurement of medicines in LMICs (https://www.quamed.org/fr/accueil.aspx).

References

  1. World Health Organisation (WHO). The African Medicines Regulatory Harmonization Initiative (AMRHI): a WHO concept paper. WHO Drug Information 2008; 22 (3): 182-190
  2. Caudron J-M, Ford N, Henkens M, Mace C, Kiddle-Monroe R & Pinel J. Substandard medicines in resource-poor settings: a problem that can no longer be ignored. TMIH 2008; 13, 1062-1072
  3. http://www.who.int/medicines/services/counterfeit/faqs/06/en/ Last accessed on 19th June 2015
  4. WHO Fact sheet N°275. Available at http://www.who.int/mediacentre/factsheets/fs275/en/ Last accessed on 19th June 2015
  5. Newton PN, Amin AA, Bird C, Passmore P, Dukes G, et al. The Primacy of Public Health. Considerations in Defining Poor Quality Medicines. PLoS Med 2011; 8(12): e1001139. doi:10.1371/journal.pmed.1001139
  6. Tabernero P, Fernandez FM, Green M, Guerin P and Newton PN, Mind the gaps the epidemiology of poor-quality anti-malarials in the malarious word – analysis of the WorldWide Antimalarial Resistance Network database. Mal J 2014, 13:19
  7. World health Organisation (WHO) Quality Assurance and Safety: Medicines, Essential Medicines and Pharmaceutical Policies. Health Technologies and Pharmaceuticals. WHO Regional Office for Europe. Survey of the quality of anti-tuberculosis medicines circulating in selected newly independent states of the former Soviet Union. November 2011. Available at: http://apps.who.int/medicinedocs/documents/s19053en/s19053en.pdf Last accessed on 19th June 2015
  8. United States Pharmacopoeia (USP). A review of drug quality in Asia with focus on anti-infective. The USP Drug Quality and Information Program. February 2004. Available at http://pdf.usaid.gov/pdf_docs/PNADH154.pdf Last accessed on 19th June 2015
  9. Dorlo TPC, Eggelte TA, Schoone GJ, de Vries PJ, Beijnen JH (2012) A Poor-Quality Generic Drug for the Treatment of Visceral Leishmaniasis: A Case Report and Appeal. PLoS Negl Trop Dis 6(5): e1544. doi:10.1371/journal.pntd.0001544
  10. Arie S. Contaminated drugs are held responsible for 120 deaths in Pakistan. BMJ 2012;344:e951 doi: 10.1136/bmj.e951
  11. FE Eichie et al., In-vitro evaluation of the pharmaceutical quality of some ibuprofen tablets dispensed in Nigeria. African Journal of Pharmacy and Pharmacology 2009; 3(10): 491-495
  12. Mori M, Ravinetto R, Jacobs J. Quality of medical devices and in vitro diagnostics in resource-limited settings, TMIH 2011, 16(11): 1439-1449
  13. ‘t Hoen EF, Hogerzeil HV, Quick JD, Sillo HB. A quiet revolution in global public health: The World Health Organization’s Prequalification of Medicines Programme. J Public Health Policy. 2014; 35(2):137-61.
  14. Regulator prequalification of medicines: a future concept for networking. WHO Drug Information Vol. 26, No. 3, 2012
  15. Ravinetto R, Schiavetti B. Quality of Medicines: an ethical issue? In press in the Indian Journal of Medical Ethics (http://ijme.in/index.php/ijme/)