A high-profile court case has thrust the legalities of compounding medicines in South Africa into the spotlight. Behind the immediate legal issues hide a series of unresolved questions about how we should ensure that compounded medicines used in South Africa are safe, argue Professor Renier Coetzee and Lara van Niekerk.
The recent court proceedings involving the Pretoria-based compounding pharmacy, iDexis, have generated considerable public interest. Much of the discussion has focused on access to medicines, intellectual property, regulatory authority and the growing demand for medicines containing semaglutide, the active ingredient used in products such as Ozempic. The legal questions are important and will ultimately be resolved through the courts and South Africa's regulatory processes.
But beneath the legal arguments lies a different question that deserves far more public attention. How do we know that medicines remain safe once they are being used by thousands - or even millions - of people?
The answer lies in a discipline that most South Africans have probably never heard of, despite benefiting from it every time they visit a doctor, clinic or pharmacy. It is called pharmacovigilance, and although the term may appear technical, the underlying principle is relatively straightforward. Medicines do not stop being monitored once they are approved for use.
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Risks and benefits
Every medicine has both potential benefits and associated risks. Before a medicine is registered by the South African Health Products Regulatory Authority (SAHPRA), it undergoes years of laboratory research and clinical trials to demonstrate its safety, effectiveness and quality. However, clinical trials involve carefully selected participants, and these controlled environments cannot fully capture the complexity of real-world healthcare settings.
Rare adverse reactions that occur in only one out of every 20 000 to 50 000 patients may never be detected during clinical trials involving only a few hundred or a few thousand participants. As a result, these reactions often only become apparent once a medicine is used more widely in routine clinical practice. Once a medicine enters the market, it may be used in populations that were underrepresented in clinical trials, such as older adults, pregnant women or people living with multiple chronic illnesses. Age, underlying medical conditions, living environments, and the use of a range of other medicines can influence the occurrence and severity of adverse events.
This is why the evaluation of medicine safety is an ongoing process.
The World Health Organization defines pharmacovigilance as "the science and activities concerned with the detection, assessment, understanding and prevention of adverse effects or any other medicine-related problem". In practice, this means continuously asking whether a medicine is performing as expected in the real world, identifying unexpected safety concerns as early as possible, and taking action when necessary to protect patients.
Most people encounter pharmacovigilance without realising it. A healthcare professional may report an unexpected side effect after prescribing a medicine. A patient may submit a report after experiencing an adverse reaction. A pharmaceutical company may notice an unusual pattern emerging from reports received across several countries. Regulators analyse these signals, compare information from multiple sources and determine whether further investigation is required. Sometimes the outcome is reassuring. Occasionally, it may lead to updated prescribing information, additional warnings, restricted use or, in rare cases, withdrawal of a medicine from the market.
Importantly, pharmacovigilance is not simply about monitoring side effects. It is about understanding why they occur, identifying who may be at greater risk, determining whether the medicine itself is responsible, and ensuring that the benefits of treatment continue to outweigh the risks. It is a shared responsibility involving healthcare professionals, pharmacists, nurses, patients, pharmaceutical companies, regulators and public health authorities. Each report contributes to another piece of the evidence needed to enhance the safety of medicines.
In South Africa, pharmacovigilance forms part of SAHPRA's broader responsibility to protect public health. Manufacturers of registered medicines are expected to maintain formal pharmacovigilance systems, collect reports of suspected adverse drug reactions, investigate emerging safety concerns and submit ongoing safety data to regulators. Healthcare professionals are encouraged to report suspected adverse reactions, even when they are uncertain whether the medicine caused the event. Patients themselves increasingly play an important role by reporting their own experiences.
When these systems function well, pharmacovigilance is largely invisible. Medicines continue to be used safely, emerging risks are identified before they become widespread, and patients remain protected. It is only when an incident occurs that most people notice these systems exist at all.
The current debate surrounding compounded medicines provides precisely such a moment. While much attention has focused on whether particular products may legally be prepared and supplied, an equally important question is whether the systems needed to monitor their ongoing safety are sufficiently robust. That is where the discussion moves beyond pharmacy practice and into the broader realm of public health.
The role of compounding
Understanding that distinction begins with understanding what pharmacy compounding really is and why it exists.
For centuries, pharmacists compounded medicines for individual patients. Although industrial manufacturing has largely replaced routine compounding, it remains an essential part of modern pharmacy practice. Some patients require dosages that are not commercially available. Some children cannot swallow tablets and need a liquid formulation. Some individuals may be allergic to an ingredient in a registered product. In these circumstances, a pharmacist may prepare a medicine to meet the unique clinical needs of that individual patient since no suitable alternative exists.
However, it was never intended to replace pharmaceutical manufacturing or to serve as an alternative route for producing medicines on a commercial scale. That distinction, while seemingly straightforward, has become increasingly blurred as demand has grown for medicines that are in short supply or are not readily accessible through conventional supply chains.
South African law recognises the value of pharmacy compounding while also placing clear boundaries around its practice. Pharmacists are permitted to compound medicines as part of their professional practice, but this occurs within a broader regulatory framework governed by the Medicines and Related Substances Act, the Pharmacy Act, and the rules of the South African Pharmacy Council (SAPC). Collectively, these instruments seek to ensure that medicines prepared by pharmacists continue to meet appropriate standards of quality, safety and professional accountability.
Where the lines get blurred
The underlying principle is that compounding is intended to address the needs of an identifiable patient based on a legitimate prescription or clinical requirement. Once medicines start being prepared in larger quantities, supplied routinely, or resemble commercial manufacturing, additional regulatory questions inevitably arise. This distinction is not unique to South Africa. Around the world, regulators continue to grapple with where compounding ends and pharmaceutical manufacturing begins, particularly as advances in medicine create new therapeutic opportunities and growing public demand.
The increasing popularity of glucagon-like peptide-1 (GLP-1) receptor agonists, including semaglutide-containing medicines used for diabetes and obesity, illustrates this challenge well. Global demand has outpaced supply in many countries, creating shortages that have prompted some pharmacies to compound formulations intended to meet patient demand. While this may improve access in some circumstances, it also raises important questions about quality assurance, regulatory oversight and, critically, ongoing medicine safety monitoring.
This is where pharmacovigilance becomes particularly relevant and necessary.
When a medicine is registered, regulators have already evaluated an extensive body of evidence relating to its quality, safety and efficacy. Manufacturers are required to comply with internationally recognised standards of Good Manufacturing Practice, ensuring consistency from one batch to the next. They must validate manufacturing processes, monitor product stability, investigate deviations, maintain comprehensive records and operate formal pharmacovigilance systems throughout the product's lifecycle. Every batch can be traced, and every adverse event contributes to a growing body of evidence that informs future regulatory decisions.
Less oversight
Compounded medicines exist in a different environment. By their very nature, they are often prepared in smaller quantities and for individual patients, meaning they are generally not supported by the same volume of clinical evidence or the same extensive manufacturing validation expected for registered pharmaceutical products. This does not mean they are inherently unsafe, nor does it imply that pharmacists are unable to prepare high-quality medicines. Rather, it means that the evidence base surrounding compounded medicines is often more limited, making robust quality assurance and careful post-dispensing monitoring all the more important.
International experience has shown that when problems do occur with compounded medicines, they are frequently related not to the active ingredient itself but to the compounding process. Variability in concentration, contamination during sterile preparation, reduced stability, inappropriate storage conditions or inconsistencies between batches can all influence medicine quality and, ultimately, patient safety. Some of the most serious international medicine safety incidents over the past two decades have involved compounded sterile products that became contaminated during preparation, leading to outbreaks of severe infection and, in some cases, loss of life. These events prompted regulators in several countries to strengthen oversight of large-scale compounding and to place greater emphasis on surveillance systems capable of detecting problems early.
The scientific literature reflects these concerns. Reviews examining compounded medicines consistently identify recurring challenges around quality assurance, standardisation and traceability. While many compounded medicines are prepared safely and provide essential clinical benefits, there is often less published evidence regarding long-term safety, effectiveness and product consistency than exists for registered medicines manufactured under industrial conditions. The consequence is not necessarily a greater risk for every patient, but greater uncertainty. And uncertainty is precisely what pharmacovigilance seeks to reduce.
One concept becomes especially important in this context: traceability.
Whenever an adverse drug reaction is reported, investigators need to know exactly which product was used. This includes the formulation, strength, batch number, date of preparation, expiry date and details of the pharmacy that prepared it. Without this information, it is extremely difficult to determine whether an adverse event represents an isolated incident or whether other patients may have received medicines from the same batch and could also be at risk.
Traceability has become one of the cornerstones of modern pharmacovigilance. It allows regulators to identify safety signals, investigate manufacturing or preparation problems and, where necessary, initiate recalls before larger numbers of patients are affected. Pharmaceutical manufacturers have well-established systems to support this process. As compounded medicines are prepared and supplied more widely, similar principles of documentation and traceability become increasingly important if patients are to receive the same level of protection.
This brings us back to the questions currently being debated in South Africa. While much of the public discussion has centred on whether certain products may legally be compounded and supplied, an equally important question is whether the systems needed to monitor their safety after dispensing are sufficiently developed. Ultimately, the value of any medicine is determined not only by whether patients can access it, but also by whether there are robust systems capable of recognising and responding quickly when unexpected harms arise.
It is against this backdrop that the current legal dispute involving iDexis has attracted such widespread attention. At its core, the matter raises questions about the regulation of compounded medicines, the distinction between pharmacy compounding and pharmaceutical manufacturing, and the authority of SAHPRA to oversee these activities. The courts will ultimately pronounce on the legal issues before them.
What systems do we need?
From a public health perspective, however, the case raises another question that extends well beyond this particular legal dispute. If compounded medicines are increasingly being prepared and supplied to larger numbers of patients, what systems should be in place to ensure that their safety continues to be monitored after they leave the pharmacy?
The answer is not necessarily that compounded medicines should be treated identically to registered pharmaceutical products. Compounding fulfils an essential role in modern healthcare and remains indispensable for many patients whose clinical needs cannot be met by commercially available medicines. Overly restrictive regulation could unintentionally reduce access to important treatments for vulnerable patients.
Equally, however, patients should not be expected to accept a lower standard of safety simply because a medicine has been compounded rather than manufactured. The principles that underpin medicine safety remain the same irrespective of where a medicine is prepared. Patients deserve confidence that medicines are produced according to recognised quality standards, that any unexpected adverse events can be investigated promptly, and that appropriate action can be taken if safety concerns emerge.
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For pharmacies undertaking compounding, particularly where medicines are prepared repeatedly or supplied to substantial numbers of patients, this raises important professional and regulatory considerations. Robust record keeping becomes essential. Every preparation should be traceable to the patient who received it, the ingredients used, the supplier of those ingredients, the batch numbers, the date of preparation, the pharmacist responsible, and the quality assurance processes that were followed. Such documentation is not simply an administrative exercise; it forms the foundation of effective pharmacovigilance.
Similarly, mechanisms should exist to capture reports of suspected adverse drug reactions associated with compounded medicines. Healthcare professionals and patients should know how and where to report concerns. Reports should be investigated systematically, trends should be monitored over time, and where appropriate, information should be shared with SAHPRA to support broader national pharmacovigilance activities. If a pattern of unexpected adverse events emerges, there should be sufficient information to determine whether the problem relates to a specific batch, a particular preparation process, an individual ingredient or another contributing factor.
These are not novel expectations. They reflect internationally accepted principles of medicine safety that have evolved over decades of experience. Pharmacovigilance has repeatedly demonstrated its value in identifying rare adverse reactions, detecting manufacturing problems and preventing further harm. While much of this work has traditionally focused on registered medicines, the same public health principles are relevant whenever compounded medicines are supplied beyond the occasional, patient-specific prescription.
'The science of protecting people'
Ultimately, the discussion surrounding compounded medicines should not become polarised into a debate about regulation versus access, or innovation versus enforcement. These are important issues, but they are not mutually exclusive. A well-functioning health system should be capable of supporting innovation while maintaining rigorous standards for patient safety. It should enable pharmacists to use their professional expertise to meet individual patient needs while ensuring that appropriate safeguards exist whenever medicines are supplied more broadly.
The iDexis court case has shone a spotlight on pharmacy compounding, but its greatest legacy may be something quite different. It has reminded us that medicine safety does not end when a medicine is approved, dispensed or injected. Every medicine continues its safety journey long after it reaches the patient.
Pharmacovigilance is often described as the science of watching medicines. In reality, it is much more than that. It is the science of protecting people. Most people in South Africa will never notice its merits, and that is precisely the point. The safest pharmacovigilance systems are those that detect problems long before they become headlines.
*Coetzee is a Professor in the School of Public Health at the University of the Western Cape and NRF SARCHi Chair in Health Systems Governance. Van Niekerk is a researcher at the Centre of Excellence for Pharmacovigilance in Southern Africa (CEPSA).
Note: Spotlight aims to deepen public understanding of important health issues by publishing a variety of views on its opinion pages. The views expressed in this article are not necessarily shared by the Spotlight editors.
