Drug Safety Oversight Gaps Put South African Patients at Risk

Pharmacovigilance is often described as the science of watching medicines. Most South Africans have never heard the word, yet every time they visit a doctor, clinic or pharmacy, they depend on it.

The court case involving Pretoria-based compounding pharmacy iDexis has drawn public attention to how medicines are prepared, regulated and accessed in South Africa. Much of the debate has centred on intellectual property rights, regulatory authority and the surging demand for medicines containing semaglutide, the active ingredient in products such as Ozempic. Those legal questions matter and will be resolved through the courts and South Africa’s regulatory processes. But they risk obscuring a more fundamental issue affecting every person who takes a compounded medicine: how do we know these medicines remain safe once they are being used by thousands, or even millions, of people?

Additional reference context is available at https://www.spotlightnsp.co.za/2026/07/22/when-medicines-are-made-outside-the-factory-why-pharmacovigilance-matters-more-than-ever/.

The answer begins with understanding what pharmacovigilance actually does. The World Health Organization defines it as “the science and activities concerned with the detection, assessment, understanding and prevention of adverse effects or any other medicine-related problem.” In practical terms, it means continuously monitoring whether medicines perform as expected in real-world conditions, identifying unexpected safety concerns as early as possible and acting when necessary to protect patients.

Most people encounter pharmacovigilance without realising it. A healthcare professional reports an unexpected side effect. A patient submits a report after an adverse reaction. A pharmaceutical company notices an unusual pattern across several countries. Regulators analyse these signals, compare information from multiple sources and determine whether further investigation is needed. Sometimes the outcome is reassuring. Occasionally it leads to updated prescribing information, additional warnings, restricted use or, in rare cases, withdrawal of a medicine from the market.

Before any medicine is registered by the South African Health Products Regulatory Authority (SAHPRA), it undergoes years of laboratory research and clinical trials to demonstrate safety, effectiveness and quality. Those controlled environments, however, cannot fully capture the complexity of real-world healthcare. Rare adverse reactions occurring in only one out of every 20,000 to 50,000 patients may never surface during trials involving a few hundred or a few thousand participants. Once a medicine enters the market, it reaches populations that were underrepresented in those trials, including older adults, pregnant women and people living with multiple chronic illnesses. Age, underlying conditions, living environments and the use of other medicines all influence how adverse events occur and how severe they become. Medicine safety evaluation is therefore an ongoing process that extends far beyond initial approval.

Pharmacy compounding has existed for centuries and remains essential to modern healthcare. Some patients require dosages that are not commercially available. Some children cannot swallow tablets and need a liquid formulation. Some individuals are 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. Compounding was never intended, however, to replace pharmaceutical manufacturing or to serve as an alternative route for producing medicines at commercial scale.

South African law recognises the value of compounding while placing clear boundaries around its practice. Pharmacists may compound medicines as part of their professional practice, but within a regulatory framework governed by the Medicines and Related Substances Act, the Pharmacy Act and the rules of the South African Pharmacy Council. The underlying principle is that compounding addresses the needs of an identifiable patient based on a legitimate prescription or clinical requirement. Once medicines are prepared in larger quantities, supplied routinely or begin to resemble commercial manufacturing, additional regulatory questions inevitably arise.

The growing popularity of glucagon-like peptide-1 receptor agonists, including semaglutide-containing medicines used for diabetes and obesity, illustrates this challenge sharply. Global demand has outpaced supply in many countries, creating shortages that have prompted some pharmacies to compound formulations intended to meet patient demand. This may improve access in some circumstances, but it also raises serious questions about quality assurance, regulatory oversight and ongoing medicine safety monitoring.

When a medicine is registered, regulators have already evaluated an extensive body of evidence on quality, safety and efficacy. Manufacturers must comply with internationally recognised Good Manufacturing Practice standards, ensuring consistency from one batch to the next. They 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. Every adverse event contributes to a growing body of evidence informing future regulatory decisions.

Compounded medicines exist in a different environment. By their nature, they are often prepared in smaller quantities for individual patients, meaning they are generally not supported by the same volume of clinical evidence or the same extensive manufacturing validation required for registered products. This does not mean they are inherently unsafe, nor does it imply that pharmacists cannot prepare high-quality medicines. It does mean the evidence base is often more limited, making robust quality assurance and careful post-dispensing monitoring all the more important.

International experience has shown that when problems 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 affect medicine quality and 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. Those 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.

One concept becomes especially important here: traceability. Whenever an adverse drug reaction is reported, investigators need to know exactly which product was used, including the formulation, strength, batch number, date of preparation, expiry date and the pharmacy that prepared it. Without this information, it is extremely difficult to determine whether an adverse event is isolated or whether other patients who received medicines from the same batch could also be at risk. Traceability has become a cornerstone of modern pharmacovigilance, allowing regulators to identify safety signals, investigate preparation problems and, where necessary, initiate recalls before larger numbers of patients are affected.

From a public health perspective, the iDexis case raises a question that extends well beyond this particular dispute. If compounded medicines are increasingly being prepared and supplied to larger numbers of patients, what systems should be in place to ensure their safety continues to be monitored after they leave the pharmacy? The answer is not that compounded medicines should be treated identically to registered pharmaceutical products. Compounding fulfils an essential role in modern healthcare and remains indispensable for patients whose clinical needs cannot be met by commercially available medicines. Overly restrictive regulation could reduce access to important treatments for vulnerable patients.

Equally, patients should not be expected to accept a lower standard of safety simply because a medicine has been compounded rather than manufactured. The principles underpinning medicine safety remain the same regardless of where a medicine is prepared. Patients deserve confidence that medicines are produced according to recognised quality standards, that unexpected adverse events can be investigated promptly and that appropriate action can be taken if safety concerns emerge.

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 followed. Such documentation is not an administrative exercise. It forms the foundation of effective pharmacovigilance.

Meanwhile, 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 monitored over time and, where appropriate, information 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.

None of this is novel. These are 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 apply whenever compounded medicines are supplied beyond the occasional, patient-specific prescription.

The discussion surrounding compounded medicines should not become polarised into a debate about regulation versus access or innovation versus enforcement. A well-functioning health system can support innovation while maintaining rigorous standards for patient safety. It can enable pharmacists to use their professional expertise to meet individual patient needs while ensuring appropriate safeguards exist whenever medicines are supplied more broadly. The iDexis case has shone a spotlight on pharmacy compounding, but its most enduring consequence may be something quite different: a reminder that medicine safety does not end when a medicine is approved, dispensed or injected. The question now is whether South Africa’s pharmacovigilance systems, and the professional obligations that support them, are keeping pace with the scale at which compounded medicines are reaching patients.