The dangers of substandard and falsified medical products

The dangers of substandard and falsified medical products (SFMPs) and their related poor regulation on the African continent featured prominently at the sixth Biennial Scientific Conference on Medical Products Regulation in Africa (SCoMRA) that was held in Cairo, Egypt from December 5 - 7, 2023.

 A recent example of the SFMPs scourge was the contaminated Naturcold cough syrups that were detected in Cameroon in March 2023, which resulted in the death of 12 children. A World Health Organisation Regional Office for Africa (WHO-AFRO) field investigation team deployed to Cameroon between May 9 and June 7, 2023, identified 60 cases of anuria (a condition where the body is not producing enough urine).

 Results of a preliminary analysis released on July 6, indicated very high levels of Diethylene Glycol (DEG). Samples of Naturcold syrups received at WHO headquarters in Geneva, Switzerland, on July 27 were sent to a laboratory. An analysis in a WHO-prequalified laboratory detected excessive levels of DEG, up to 300 times the acceptable level. A report of criminal investigation in Cameroon was registered in August 2023. 

 On September 6, 2022, the WHO Country Office reported that the Gambian Ministry of Health (MoH) was investigating up to 40 deaths of children, most of them under 5 years of age, which are suspected to be linked to the use of “paracetamol syrup. “The deaths were suspected to have been caused by “kidney failure.” Information suggested that MoH was aware of 49 cases as of August 29.

 On September 7, 2022, the Gambian Government suspended the use of all paracetamol syrups. An initial list of six suspect paracetamol syrup products was identified. WHO was requested to support analysis for the presence of contaminants. Results of several lab analyses released on September 19 and 23 detected and quantified DEG and Ethylene Glycol (EG) in samples of the syrups.

 On October 5, 2022, WHO issued a Medical Product Alert #6 for four contaminated syrups. All the four products were manufactured in India. The Gambian Medicines Control Authority initiated the national recall of all paracetamol, promethazine and cough syrups.

 The Technical Officer, Incidents and Substandard and Falsified Medical Products (ISF) at WHO, Dr Leticia Megias Lastra, said the possible causes of the incidents in Gambia and Cameroon include contamination of excipients at point of manufacture impacting the global supply chain (propylene glycol, sorbitol or glycerin). 

 In her presentation “WHO response to over-the-counter syrups for children with confirmed or suspected contamination with high levels of diethylene glycol and ethylene glycol,” Dr Lastra said it could have been falsification (or adulteration) of excipients at some point in the global supply chain.

 She said it could have been accidental or intentional substitution of industrial grade propylene glycol glycerin or sorbitol solution in place of pharmaceutical grade product - in supply chain or at the manufacturing site.

 “There is significant global public health risk unless causes are identified,” Dr Lastra warned.

Uganda

 The National Drug Authority (NDA) has discovered several nutritional supplements, beverages, herbal and alcoholic products adulterated with drugs for erectile dysfunction.

 On August 22, 2023, the NDA warned the public against the consumption of L-Power Coffee, which its laboratory tests had confirmed was adulterated with Tadalafil, a prescription drug.

 According to a press statement issued by the drug regulator, its imports control team intercepted a consignment of L-Power Coffee, which was being concealed as a nutritional supplement. The regulator sent samples to its quality control laboratory and after the positive results, the NDA formally informed the importers of L-Power Coffee to take full responsibility for its destruction and recall (collect off the market) and products that could have been sneaked into Uganda. 

 Tadalafil is a drug for erectile dysfunction, which must be used under strict instructions by a qualified medical professional as it has side effects which include; extreme respiratory and cardiac problems, urinary disorders and sometimes leading to coma and death, the NDA warned.

 On previous occasions, the NDA had discovered M-Magix Coffee, the alcoholic product “Stronger Weekend” and the herbal product Embaloka hardcore drink, which were all adulterated with high amounts of the drugs for erectile dysfunction.

 “Counterfeit and substandard medical products are those products that contain inadequate amounts of active ingredients, contain the wrong active ingredients, be contaminated with harmful substances, and/or be falsely labeled. These are a public health issue globally, and their presence continues to grow, driven by demand and money,” NDA’s Public Relations Manager, Abiaz Rwamwiri told Daily Monitor  last week. 

 He added: “Counterfeit medications are produced without regulatory oversight and are distributed illegally. Use of these medications can result in adverse effects or a lack of improvement in a person’s health condition. In practice, one difference between falsified and substandard medicines is that the drugs regulator, having the authority to license manufacturers and register medicines, can act against unscrupulous or careless manufacturers. There is no such remedy when the manufacturer is falsely represented. This is a lucrative business run by criminals.”

 Mr Rwamwiri said this problem is, however, not limited to developing countries. In Uganda, the NDA which is mandated to regulate drugs and healthcare products, has established mechanisms to ensure the drug supply chain is protected from infiltration by these impure products.

 The IGAD Region

 When asked how the Intergovernmental Authority on Development (IGAD) Member States are being impacted by SFMPs, the Head of Post-market Surveillance at the Pharmacy and Poisons Board (PPB) in Kenya and the Promoting the Quality of Medicines Plus (PQM+) programme, Mr Karim Wanga, responded: “The IGAD Member States are at different levels of maturity regarding capacity for regulation of medical products. The countries also share long porous borders where there is free movement of people and goods.”

 He added: “This poses a risk to quality and safety of medical products circulating on the markets. There is risk of substandard or falsified products being smuggled or illegally imported across the borders. SF products cause morbidity and mortality as well as economic losses to communities and the member states.”

 On the diseases that drug criminals target in the IGAD region for their illegal trade, Mr Wanga, said: “We have not done this study. However, generally, individuals who intend to falsify medicines target fast-moving medicines as well high-cost medicines like anti-cancer medicines, medicines for HIV, malaria and medicines for erectile dysfunction.”

Regulatory challenges

 According to Dr Lastra, the forces that drive SFMPs in Africa include constrained access, poor governance and weak technical capacity.

 On his part,  Mr Wanga lists a lack of awareness of the SFMPs burden and threat by the healthcare workers, law enforcement agencies and members of the public, among the challenges that regulators face in the IGAD region.

 “The costs of post-market surveillance activities are very high. Technology has helped the criminals to make their activities more sophisticated and difficult to detect. Political fragility and security challenges affect delivery of quality medical products and healthcare,” Mr Wanga added.

 The Technical Officer from the Regulatory System Strengthening Team at WHO, Dr Andrea Keyter, identified seven major challenges to regulatory systems activities in Africa.

 “There are frequent changes in leadership and priorities along with management instability,” Dr Keyter said in her paper “Progress on regulatory systems strengthening efforts, challenges and opportunities: the contribution to Africa regulatory.”

 She said there is a lack of sustainable financing and yet regulatory activities are a resources-intensive undertaking.

 Dr Keyter observed that there are inadequate human resources, numbers and skills to undertake regulatory activities.

  “Infrastructure is lacking including quality, information and risk management systems as well as quality control laboratories,” she said.

 Dr Ketyer added: “There are challenges in generating and maintaining reliable and high-quality data on medical products regulation.”

 She said there is political support for regulatory systems strengthening activities in some countries.

 “There is a lack of legal frameworks for effective medical products regulation including in support to implementing good regulatory and reliance practices,” Dr Keyter said.

 Dr Lastra said  the WHO is offering technical support to African states by strengthening the capacities of National Regulatory Authorities (NRAs) in market surveillance and control, developed risk communication tools, and a new WHO Pharmaceutical Starting Materials Certification Scheme (SMACS). 

 She reported that WHO has also improved regional capacity for testing; the development and inclusion of screening or detection and testing methods for DEG/EG in raw materials and medicines; reviewed and updated WHO guidance on control of raw materials and manufacturing process.

Dr Lastra added that the WHO is supporting Member States investigations into production and distribution of contaminated products; identify manufacturers, supply-chain vendors, repackagers, and distributors; and issue Medical Product Alerts, among others.

 “The most important thing is to report as soon as a contaminated drug is identified,” she said.

About SCoMRA

The African Union Development Agency-NEPAD (AUDA-NEPAD), WHO, and the African Medicines Regulatory Harmonisation (AMRH) partners collaborated to bring this conference that was held in Cairo, Egypt.

 Since 2013 The SCoMRA has brought together policymakers, regulators, industry, academia, research organisations, and scientists to network and exchange knowledge on innovative approaches for pharmaceutical sector development in Africa.

 The first SCoMRA was held in South Africa in 2013. Ethiopia hosted the second SCoMRA in 2015. In 2017, the third SCoMRA was convened in Ghana. The fourth SCoMRA was held in Zimbabwe in 2019. Following the outbreak of Covid-19, the fifth SCoMRA was held virtually in 2021.

The seventh SCoMRA is scheduled to be held in Kenya in 2025.

recommendations 

The sixth SCoMRA urged countries to: enhance data and information sharing on SF medical products among the member states; improve legal framework and strengthen intersectional collaboration on SF issues; report SF incidents (through the WHO Global Surveillance and Monitoring System) promptly, since reporting is key to fight SF; and also recommended the need for sensitisation and trainings.

The conference  urged the international actors to integrate continental and regional efforts against SFMPs and African Union Development Agency-NEPAD (AUDA-NEPAD) to coordinate harmonised efforts to fight SFMPs on the continent.

   Held under the theme “Strengthening regulatory systems for the advancement of local production and increased access to medical products and technologies for Africans” this year’s SCoMRA was convened to reflect on the progress that has been made in strengthening regulatory systems and harmonisation in Africa; and share scientific advances and current best practices in regulatory science disciplines.

   The conference also provided a platform for regulators, manufacturers, government entities, and civil society to share information to create an appetite for investment in the local production of medical products and technologies, which will contribute to the overall socio-economic development of the continent.

   The AUDA-NEPAD, WHO, and the African Medicines Regulatory Harmonisation (AMRH) partners collaborated to bring this conference that was held in Cairo, Egypt.

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