Beyond the Courtroom: Why Compounded Medicines Need Robust Safety Monitoring

A court case in South Africa involving a Pretoria-based compounding pharmacy has forced a reckoning with a question that rarely surfaces in public debate: how do we know that medicines are safe once thousands of people are using them? The legal arguments—about intellectual property, regulatory authority, and access to semaglutide-containing products—will be resolved in the courts. But beneath those disputes lies something more fundamental, and more urgent.

Pharmacies have compounded medicines for centuries. A child who cannot swallow tablets needs a liquid. A patient allergic to an ingredient in a registered product needs an alternative. A person requiring a dose not commercially available needs a custom formulation. These are legitimate clinical needs, and compounding remains an essential part of modern pharmacy. But in recent years, the line between preparing medicines for individual patients and manufacturing them on a commercial scale has blurred. Demand for certain medicines—particularly glucagon-like peptide-1 receptor agonists like semaglutide, used for diabetes and obesity—has outpaced supply in many countries. Some pharmacies have begun compounding these formulations in larger quantities to meet patient demand. This raises a question that most South Africans have never heard of, despite benefiting from the answer every time they visit a doctor or clinic: pharmacovigilance.

The term sounds technical, but the principle is straightforward. Medicines do not stop being monitored once they are approved for use. Before the South African Health Products Regulatory Authority registers a medicine, it undergoes years of laboratory research and clinical trials. But those trials involve carefully selected participants in controlled environments. They cannot capture the full complexity of real-world healthcare. Rare adverse reactions—those occurring in one out of every 20,000 to 50,000 patients—may never appear in trials involving only a few hundred or a few thousand people. Once a medicine enters the market, it reaches populations underrepresented in trials: older adults, pregnant women, people with multiple chronic illnesses. Age, underlying conditions, living environments, and interactions with other medicines all influence whether and how severely adverse events occur. This is why evaluating medicine safety is an ongoing process, not a one-time event.

Pharmacovigilance 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. A healthcare professional reports an unexpected side effect. A patient submits an account of an adverse reaction. A pharmaceutical company notices an unusual pattern emerging 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 leads to updated prescribing information, additional warnings, restricted use, or withdrawal from the market. Importantly, pharmacovigilance is not simply about counting side effects. It is about understanding why they occur, identifying who is at greater risk, determining whether the medicine itself is responsible, and ensuring that benefits continue to outweigh risks. It is a shared responsibility involving healthcare professionals, pharmacists, nurses, patients, pharmaceutical companies, regulators, and public health authorities.

When medicines are registered, regulators have already evaluated extensive evidence about quality, safety, and efficacy. Manufacturers must comply with internationally recognised standards of Good Manufacturing Practice, ensuring consistency from batch to batch. 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. 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. This does not mean they are inherently unsafe, nor does it imply that pharmacists cannot prepare high-quality medicines. Rather, it means the evidence base is often more limited, making robust quality assurance and careful post-dispensing monitoring all the more important. International experience shows 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, or inconsistencies between batches. Some of the most serious 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.

One concept becomes especially important: traceability. Whenever an adverse drug reaction is reported, investigators need to know exactly which product was used—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 problems, and 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.

The iDexis court case raises questions that extend 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 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 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. For pharmacies undertaking compounding, particularly where medicines are prepared repeatedly or supplied to substantial numbers of patients, robust record keeping becomes essential. Every preparation should be traceable to the patient who received it, the ingredients used, the suppliers of those ingredients, the batch numbers, the date of preparation, the pharmacist responsible, and the quality assurance processes that were followed. 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 information shared with the regulatory authority 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. 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 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. 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.