Though several South African companies are producing HIV and TB medicines, the active ingredients that go into these medicines are usually imported from India or China. Now, a local company is planning to break new ground by making the active ingredients for two important TB medicines in Pretoria.
Catherine Tomlinson, writing for Spotlight, zooms in on the company’s efforts and outlines some of the obstacles to getting such local production off the ground.
South Africa has a relatively robust pharmaceutical sector. About 60% of the medicines sold here are locally produced, according to Dr Senelisiwe Ntsele from the Department of Trade, Industry & Competition (DTIC).
But most of the time we are not producing these medicines from scratch. In fact, like most countries worldwide, we mostly import the ingredients that make the medicines work – the active pharmaceutical ingredients, or APIs. In addition to APIs, medicines contain inactive substances that maintain their form and structure and assist in their delivery, like binders, stabilisers and disintegrants.
Around 98% of the APIs used in locally formulated medicines are imported. South Africa spends around R15bn a year importing APIs, according to Ntsele.
The government has tried to address its dependence on imported APIs as part of its broader strategy to bolster the local pharmaceutical industry, which is identified as a priority sector for investment in the Industrial Policy Action Plan.
Several government departments provide support to the pharmaceutical sector, including for local establishment of API manufacturing capacity. They include the DTIC, the Department of Science & Innovation (DSI), the Technology Innovation Agency (TIA), and the Industrial Development Corporation (IDC).
In efforts to reduce reliance on imported APIs, Ketlaphela, a state-owned API manufacturing company, was announced in 2012. The plan was it would produce APIs used in HIV medicines – but after multiple setbacks the initiative never got off the ground.
Turning to the private sector
Less well known than Ketlaphela are the government’s efforts to support API manufacturing capacity in the private sector. One private company that has received such government support and is likely to start delivering is Pretoria’s Chemical Process Technologies Pharma (CPT Pharma), established in 2014.
CPT Pharma is a subsidiary of Chemical Process Technologies, a company with many years of experience in chemical manufacturing and synthesis, including manufacturing of APIs for animal medicines.
Human medicines, CPT Pharma’s core business, have stricter production management and quality control standards than those for animal medicines.
Dr Hannes Malan, MD of CPT Pharma, told Spotlight the company has 14 APIs in its pipeline, with a strong focus on TB medicines.
In 2023, the company secured a licence from USAid to produce API for rifapentine, a TB-prevention drug, and in 2022, another from the Medicines Patent Pool to produce API for molnupiravir, a treatment for Covid-19.
Malan said these two licences were agreed with organisations aiming to expand the presence of API manufacturers in Africa – unlike typical arrangements driven by pharmaceutical companies looking to secure their own supply chains.
“For all the other APIs that we’re working on (beyond molnupiravir and rifapentine), we’re either working on technical packs (technical information about the API) that were available in the public domain or technologies we’ve developed ourselves,” he said.
“Our approach has always been to look at the molecules, the market value, the technology, and then see if there’s an opportunity for us to develop technology that allows us to produce these compounds competitively.
“We really believe that to be competitive and independent, you have to have your own technology. Doing a technology transfer from Big Pharma does not make you independent.”
How to fund it all?
In 2017, the company completed a pilot plant for making APIs. Then in 2020 it received approval from the SA Health Products Regulatory Authority (SAHPRA) to produce APIs for human use. The plant was built for R50m, funded jointly by the IDC, TIA, and CPT Pharma.
Malan said the IDC and TIA also supported trial runs to test CPT Pharma’s manufacturing processes and technology. These tests included several APIs in development, such as isoniazid, a drug commonly used to prevent and treat TB.
The company has also secured funding from several international donors. The Gates Foundation provided support to develop manufacturing technology for the anti-malarial drug amodiaquine, as well as TB medicines bedaquiline and pretomanid.
GIZ, a German development agency involved in a European Union project to boost vaccine and health product production in Africa, supported the company’s work on molnupiravir and dolutegravir – a widely used HIV medicine. USAid and the DSI are supporting the company’s work on developing rifapentine API manufacturing capacity.
Most of this financial support has been via grants.
Still building new plants
While CPT Pharma has secured local and international funding to help construct a pilot plant and to develop its API manufacturing technology and processes, Malan said more investment is needed to support the construction of two commercial-scale manufacturing facilities: an isoniazid API manufacturing plant and a multiple API manufacturing facility.
Construction of the isoniazid manufacturing plant has already started using existing land and infrastructure with support from the IDC, but it is short of around R20m to complete it, said Malan.
Although the plant is not yet operational, he added that a company has already expressed interest in buying CPT Pharma’s locally produced isoniazid API. This company, Malan said, is contracted to supply isoniazid to government. The plan is to initially supply the company with isoniazid API produced at its pilot plant.
He told Spotlight that when built, the commercial plant will be able to manufacture enough isoniazid API to supply around 60% of local demand.
Things are less far down the road with plans for a plant to produce multiple different APIs at commercial scale, and more work is needed to understand the financing requirements for this type of facility, he said.
“We want to do a bankable study and a concept design for such a plant.”
Based on CPT Pharma’s own experience, published data, and the required complexity and capacity of the plant, it is estimated that construction for the multi-API plant will cost around US$100m.
Plans to commercialise
Meanwhile, the company is progressing with plans to commercialise isoniazid and rifapentine API from its pilot plant. Isoniazid and rifapentine are increasingly used together as TB preventive therapy.
“For rifapentine, our pilot plant is seen as the commercial plant,” said Malan. “At this stage, we can use the pilot facility and the pilot reactor to produce enough rifapentine to get into the market and to grow the market.” But in the long term, the company hopes to transfer rifapentine manufacturing to a larger commercial plant.
The company is also planning to apply for World Health Organisation (WHO) pre-qualification status for its rifapetine API. The goal is to conduct demonstration runs in the pilot plant by June 2025 and validate the WHO pre-qualification application in September 2025.
If achieved, WHO pre-qualification of CPT Pharma’s rifapetine API would show that the company’s APIs meet high-quality standards.
It would also allow CPT Pharma to supply rifapentine API to companies producing medicines for the broader African market, for which a significant proportion of medicines are procured by donors requiring WHO PQ approval.
See more from MedicalBrief archives:
State-owned pharma ‘exists just in name’, Blade tells Parliament
African drug makers urged to adopt a regional approach
Local drugmakers must move to top of registration queue – SAHPRA