One of the health-related sustainable development goal targets is to achieve “universal health coverage, including financial risk protection, access to quality essential health-care services and access to safe, effective, quality and affordable essential medicines and vaccines for all”. The word “quality” appears twice in that target description, as a requirement for the health-care services delivered and as an essential element of the medicines and vaccines made available.
‘Quality cannot be tested into a product’
There is a truism in the pharmaceutical industry that quality cannot be tested into a product. Instead, quality is assured by the implementation of a pharmaceutical quality system, referred to as current Good Manufacturing Practice (cGMP).
The primary legal enablement is provided by the Medicines & Related Substances Act. Section 1(3) of the act states: “In determining whether or not the registration or availability of a medicine is in the public interest, regard shall be had only to the safety, quality and therapeutic efficacy thereof in relation to its effect on the health of man or any animal, as the case may be.” Evidence for safety and therapeutic efficacy is provided by well-conducted clinical trials. There is a difference, however, between registered medicines and complementary medicines. The latter require a warning on their labels stating: “This unregistered medicine has not been evaluated by the Sahpra [South African Health Products Regulatory Authority] for its quality, safety or intended use.” Complementary medicine manufacturers are being progressively brought in line with GMP.
Evidence of quality is not reliant only on retrospective data, on tests conducted on the medicines used in the clinical trials and the design of the dosage form to be sold, but also on the means to ensure that every batch made will deliver the same results. By requiring that every manufacturer of a medicine be licensed by Sahpra, the entity can ensure compliance with GMP. The ultimate sanction for not meeting GMP standards is withdrawal of licensure and therefore an immediate stop to all manufacturing activities.
New guidelines
Sahpra updated its GMP guidelines in April 2026. The guideline defines GMP as “a set of principles and procedures that, when followed, ensure that medicines and related substances are of high quality, safety and efficacy”, and as a “system that ensures medical products are consistently produced and controlled according to quality standards”. Echoing the truism, it states that GMP is “designed to minimise the risks involved in any pharmaceutical production that cannot be eliminated through testing the final product”.
GMP requires the manufacturer to provide detailed descriptions of the systems to be implemented to document every step in the manufacturing process and the control measures in place to ensure quality. These step-by-step descriptions have to cover every component included in the medicine and its packaging, the premises and equipment used and the training and accreditation of the staff involved in the production process. A risk-based approach is used, for example differentiating between sterile and nonsterile production processes. Quality control testing during the production process is critically important.
GMP places a lot of emphasis on the capability of key personnel, but also the way in which authority and responsibility are assigned, accepted and documented, and how each person fits into the management decision-making process. For example, Sahpra’s GMP guidelines differentiate between the head of quality control, who “should have the authority to establish, verify and implement all quality control procedures such as authority over quality decisions, oversight of testing and results, approval of quality control documentation, laboratory management, validation and method control”, and the head of quality assurance, who “should be part of the decision-making process in all matters that affect the quality of products including development, laboratory, storage, distribution, vendors and third-party contractors”. All staff engaged in production have to be trained on the principles of GMP and the specific duties assigned to them. Continuing training is required, with documented training programmes, training records and checks to confirm that procedures are being followed.
What if medicines are made outside of SA?
That all sounds straightforward, if the manufacturer is located in South Africa and can easily be accessed by a Sahpra GMP inspector. However, the majority of medicines consumed in South Africa are imported, and even those that are made locally mostly rely on imported active pharmaceutical ingredients or drug substances.
That said, even the best-resourced regulatory authorities are struggling to cover a globalised pharmaceutical industry, with many facilities located in China and India
International standards for GMP have a long history. The first draft document was prepared by the World Health Organisation (WHO) in 1968. Since 1969, compliance with WHO GMP has been the basis for the WHO certification scheme on the quality of pharmaceutical products moving in international commerce. However, there has been criticism of the scheme, as certificates can be issued by national regulators that are not considered to meet acceptable maturity standards.
Although there is provision for exceptions, medicines imported into South Africa have to be subjected to post-importation identification and assay (testing of what it contains) by a local accredited laboratory, or samples have to be returned to the manufacturer or an overseas testing laboratory.
Sahpra is a member of two key organisations that are advancing harmonisation of regulatory standards. The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) publishes extensive quality guidelines. ICH Q10, for instance, describes the requirements for a pharmaceutical quality system.
Sahpra is also a member of the Pharmaceutical Inspection Co-operation Scheme (PIC/S), which aims to pursue the “development, implementation and maintenance of harmonised GMP standards and quality systems of inspectorates”. Apart from its work on harmonising GMP standards, PIC/S enables the training of GMP inspectors and the voluntary sharing of GMP inspection reports. PIC/S membership requires an assessment of a regulator’s inspectorate systems and procedures, so provides a quality check at that level. South Africa adopted the PIC/S GMP guide in 2006, updating that status in 2017.
Sahpra’s GMP inspectors are not confined to working within the boundaries of the country. They also inspect pharmaceutical production plants in other countries and work with the WHO prequalification programme to extend their reach. That said, even the best-resourced regulatory authorities are struggling to cover a globalised pharmaceutical industry, with many facilities located in China and India. A recent commentary in the New England Journal of Medicine pointed out how few foreign plants making generic medicines had been inspected by the US Food & Drug Administration, and the problems they encountered when conducting inspections, calling for improved post-marketing surveillance.
The public, patients and health professionals can therefore make a reasonable assumption that medicines produced in a cGMP-compliant production facility meet the required quality standards. However, that is insufficient on its own. Mature regulators are also required to have effective post-marketing vigilance systems in place. Apart from adverse event reporting, these systems should also enable the reporting of quality problems with medicines.
Substandard or falsified medicines
Effective surveillance of the pharmaceutical market assists in the identification of substandard or falsified (SF) medicines. The necessary control measures also have to be in place to enable recalls and the destruction of identified SF medicines.
The WHO Global Benchmarking Tool (GBT) requires evidence that “legal provisions and regulations authorise market surveillance and control activities which include product sampling from different points of the supply chain.” Sahpra does not operate its own testing laboratory but contracts with a WHO-prequalified facility at North-West University. Proactive sampling of medicines from all points in the distribution chain needs to be strengthened, as part of the national action plan to combat SF medicines.
Despite the existence of a global surveillance and monitoring system for SF medical products (both medicines and devices), quantifying the scale of the problem remains challenging. Medical product alerts have been issued in every WHO region, affecting every type of medical product, not only generic medicines. They have been identified in countries with well-resourced, mature regulatory systems and in countries that lack such capacity. Nonetheless, transparent reporting of problems identified, corrective actions taken and regulatory interventions can help to build confidence that quality assurance systems are not only working but are seen to be working. Quality should not have to be assumed without assurance that effective systems are in place and appropriately monitored.
Gray is a senior lecturer at the University of KwaZulu-Natal and co-director of the WHO Collaborating Centre on Pharmaceutical Policy & Evidence-based Practice.
Disclosure: Gray serves on three technical advisory committees at the South African Health Products Regulatory Authority.
This column was published by Spotlight — health journalism in the public interest. Sign up for the Spotlight newsletter.
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