Pretoria company aims to lead South Africa in making key TB drug ingredients

South Africa has a relatively robust pharmaceutical sector. About 60% of the medicines sold in South Africa are locally produced, according to Senelisiwe Ntsele, writing in an opinion piece for 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, we mostly import the ingredients that make the medicines work — commonly referred to as active pharmaceutical ingredients (APIs). In addition to APIs, medicines contain other inactive substances that maintain their form and structure and assist in their delivery, such as binders, stabilisers and disintegrants.

About 98% of the APIs used in locally formulated medicines are imported and South Africa spends about R15bn a year importing APIs, according to Ntsele.

The government has tried to address South Africa’s 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 country’s Industrial Policy Action Plan. Several government departments provide support to the local pharmaceutical sector, including for local establishment of API manufacturing capacity. These departments include the DTIC, the department of science & innovation (DSI), the Technology Innovation Agency (TIA), and the Industrial Development Corp (IDC) — South Africa’s development finance instrument.

In a bid to reduce the country’s reliance on imported APIs, Ketlaphela — a state-owned API manufacturing company — was announced in 2012. The plan was that Ketlaphela would produce APIs used in HIV medicines, but after multiple setbacks the initiative never got off the ground. Spotlight reported on the history of Ketlaphela in more detail here.

Turning to the private sector

Less well known than Ketlaphela are government’s efforts to support API manufacturing capacity in the private sector. One private company that has received such government support and seems set to start delivering is Pretoria-based 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.

Hannes Malan, MD of CPT Pharma, tells Spotlight that the company has 14 APIs in its pipeline, with a strong focus on TB medicines.

In 2023, the company secured a licence from the US Agency for International Development (USAID) to produce API for rifapentine, a drug widely used for TB prevention, and in 2022 it secured a licence from the Medicines Patent Pool to produce API for molnupiravir, a treatment for Covid. Malan points out that 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 that we’ve developed ourselves,” says Malan.

“Our approach has always been to look at the molecules, look at the market value, look at the technology, and then see if there’s an opportunity for us to develop technology that allows us to produce these compounds cost competitively,” he says.

“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,” Malan adds.

How to fund it all?

In 2017, the company completed a pilot plant for making APIs. Then in 2020 it received approval from the South African Health Products Regulatory Authority to produce APIs for human use. The plant was built for R50m, funded jointly by the IDC, TIA, and CPT Pharma.

Malan says 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 antimalarial drug amodiaquine, as well as TB medicines bedaquiline and pretomanid. GIZ, a German development agency involved in an EU 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 in the form of 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 says 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 started using existing land and infrastructure with support from the IDC, but it is short of about R20m to complete it, says Malan.

Though the plant is not yet operational, he says a company has already expressed interest in buying CPT Pharma’s locally produced isoniazid API. This company, says Malan, is contracted to supply isoniazid to the government. The plan is to initially supply the company with isoniazid API produced at its pilot plant.

Malan says the commercial plant, when built, will be able to manufacture enough isoniazid API to supply about 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, says Malan. “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, he says it is estimated that construction for the multi-API plant will cost $100m.

Plans to commercialise

Meanwhile, the company is moving forward 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,” says 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 he says 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 rifapentine 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 rifapentine 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 pre-qualification approval.

This article was first published by Spotlight — health journalism in the public interest. Sign up to the Spotlight newsletter.