Recently, there has been an increased number of World Health Organization (WHO) alerts targeting substandard and falsified medical products. Given the seriousness of this issue and its potentially devastating consequences on the health of Africans, drastic measures must be taken by African countries to protect their citizens.
Substandard products are those that fail to meet quality standards or specifications or both, whereas falsified medical products are those whose identity, composition or source, is deliberately or fraudulently misrepresented. For the keen observer, the number of medical product alerts issued by WHO in the last few months is alarming.
For instance, on 11 April 2023, WHO published Medical Product Alert No. 3/2023 regarding falsified DEFITELIO (defibrotide sodium) which was identified in the WHO Regions of Europe and the Eastern Mediterranean. An antithrombotic medicine, defibrotide is used for the treatment of veno-occlusive disease (VOD) in paediatric and adult patients undergoing haematopoietic (blood) stem cell transplantation. Patients with VOD have veins in the liver that become blocked, which results in the improper functioning of the organ. The falsified products found in Kyrgyzstan and the United Arab Emirates do not contain any of the stated active ingredients and are in packaging from either the United Kingdom/Ireland or the United States.
Earlier, on 22 February 2023, WHO published a Medical Product Alert No. 2/2023 for batches of TETRACYCLINE HYDROCHLORIDE OPHTHALMIC OINTMENT USP 1%. This product is manufactured by Galentic Pharma (India) Pvt. Ltd. Multiple batches of this product had a variety of quality issues such as black and brown spots and splotches on the tube’s inner foil layer. A minimum of 55 countries are reported to have received the affected batches.
On 11 January 2023, WHO’s Medical Product Alert No. 1/2023 reported two substandard (contaminated) products, AMBRONOL syrup and DOK-1 Max syrup, which were identified in Uzbekistan. Both products had an unacceptable amount of contaminants (diethylene glycol and/or ethylene glycol) which are toxic chemicals used as industrial solvents and antifreeze agents. These contaminants should never be found in medicines as the consumption of even a small amount can result in death. This is not the first time in the last six months that syrups, typically consumed by children under five years of age, have been found to contain these contaminants. In October 2022, WHO identified four products in The Gambia (namely Promethazine Oral Solution, Kofexmalin Baby Cough Syrup, Makoff Baby Cough Syrup and Magrip N Cold Syrup). These products contained unacceptable amounts of diethylene glycol and ethylene glycol as contaminants. Furthermore, eight substandard products (Termorex syrup (batch AUG22A06 only), Flurin DMP syrup, Unibebi Cough Syrup, Unibebi Demam Paracetamol Drops, Unibebi Demam Paracetamol Syrup, Paracetamol Drops (manufactured by PT Afi Farma), Paracetamol Syrup (mint) (manufactured by PT Afi Farma) and Vipcol Syrup) were identified in Indonesia and contained these same contaminants. A medical product alert was then issued about these contaminated products on 2 November 2022. In total, more than 300 children under five years of age who consumed these products died in Uzbekistan, The Gambia, and Indonesia. There are possibly more unreported deaths in other territories.
All these medical product alerts that have been published by WHO over the last six months show the complexity (read criminality) of the global supply chain and how products – genuine or falsified – manufactured in one country can be packaged in another and then distributed across multiple borders to be consumed in a third country. The rise in e-commerce has aided access to medicines, making the unsuspecting public vulnerable to purchasing substandard and falsified medical products.
The Urgent Need for an Operational African Medicines Agency
The responsibility of National Medicines Regulatory Authorities (NRAs) is to ensure that products such as pharmaceuticals, biologicals, and medical devices released for public distribution are subjected to a thorough evaluation and meet required standards of quality, safety, and efficacy. Thus, all countries need an NRA.
All 55 African countries (except perhaps the Sahrawi Republic) have an NRA or an administrative unit that does NRA work. Some countries even have many agencies responsible for the monitoring of medical products. For example, Tanzania has two NRAs: the Tanzania Medicines and Medical Devices Authority (TMDA) and the Zanzibar Food and Drug Agency (ZFDA). All NRAs, regardless of their procurement policies and pharmaceutical manufacturing capacity, must grant marketing authorisations and perform post-marketing surveillance, including monitoring adverse events following immunisation (AEFI). The WHO medical product alerts really shine a spotlight on the importance of medicine regulatory systems and how their inefficiency can lead to preventable deaths.
African regulators face several challenges in executing their mandate. For example, only 7% of the NRAs on the continent have developed the requisite capacity to carry out their functions. Worse off, more than 90% of them are reported to have minimal to no capacity. NRAs also face financial and human resource constraints. Although these challenges are considered to be at the national level, they can have a negative regional or continent impact given the complexity of manufacturing chains.
Fully cognisant of the foregoing, African leaders and NRAs are pushing for the operationalisation of a continental regulatory body, the African Medicines Agency (AMA). AMA will be a specialised African Union (AU) agency that improves access to quality, safe and efficacious medical products on the African continent. It will also work with African NRAs to ensure effective public health protection and promotion. Additionally, it is expected to evaluate medical products for priority diseases and perform risk-based joint Good Manufacturing Practice (GMP) inspections of foreign manufacturing sites that export to Africa. Furthermore, AMA is expected to work with regional economic communities and NRAs in the identification of substandard and falsified medical products as well as facilitate the sharing of information across the continent. All this should assure product quality, safety and efficacy. Although Rwanda was on 16 July 2022 selected by the AU Executive Council in a meeting held in Lusaka, Zambia to host the continental regulator, it is not yet operational and its leadership has not been constituted.
What needs to be done
First and most importantly, African countries that have not signed or ratified the treaty for the establishment of AMA must urgently do so. The operationalisation of AMA must be fast-tracked and its leadership and structures finalised. This will enable the continental regulator to get to work immediately by protecting the African population and curbing the circulation of substandard and falsified products on our continent. The need for robust regulatory systems and the ongoing efforts to strengthen regulatory systems cannot be overemphasised and so should be taken more seriously.
To be sure, AMA cannot single-handedly address the issue of substandard and falsified products. It will need help from the general public who are the end users of the regulated products. It will also need the help of our NRAs, suppliers/procurers, and pharmaceutical manufacturers. As citizens, our role is to ensure that the medical products we consume are approved and we obtain them from authorised or licensed suppliers. We should also check the authenticity of the products and their physical condition. If we are in doubt, we have every right to seek advice from a healthcare professional. I also believe that we need to improve on our culture of reporting adverse drug events or reactions to appropriate healthcare professionals or agencies, our respective NRAs or national pharmacovigilance centres. This will enable the NRAs to investigate suspicious products and withdraw them from the market, ultimately protecting the public and the economy.
Secondly, our governments and NRAs must ensure that all on-the-market medical products in their respective territories are approved for sale and can be purchased from authorised/licensed suppliers. When WHO publishes a medical alert, it is also the responsibility of national governments and NRAs to detect and remove/recall these products from circulation. For this to be possible, there is a need to allocate adequate resources to enable more risk-based GMP inspections of manufacturing facilities to be done. Furthermore, market surveillance needs to be increased, including risk-based targeted testing of on-the-market products, especially those traded in informal markets. Laws and other relevant legal measures must also be put in place to address the manufacture, distribution and use of substandard and falsified medical products. Imposing fines and revoking licenses as punishment clearly does not work, as such fines have not deterred the criminals involved in the ‘business’ of fake medical products. It is time for people to be charged with serious crimes, such as attempted murder, when they trade in substandard or falsified products. After all, these products do result in fatalities.
Thirdly, suppliers and distributors are recommended to always check for signs of falsification and the physical condition of the medicines that they sell. They should also distribute or sell products that have been approved by the NRAs, retain accurate, complete and proper records of the medicines that they distribute/sell, and provide the public with advice on rational medicine use.
Lastly, manufacturers should play their part by purchasing raw materials and active pharmaceutical ingredients from qualified and audited suppliers. They should also conduct full testing of the starting materials on receipt and full testing of the finished pharmaceutical product before it is released to the local or export market. Accurate and complete records of all manufacturing process steps should also be retained to enable traceability.
Evidently, we all have a role to play in the fight against substandard and falsified medical products. We cannot continue to have regulatory system failures at different levels of the supply chain and we most certainly cannot have repeats of avoidable deaths following the consumption of substandard and falsified medicines.