There is a shift in the industry towards biopharmaceuticals, but there is still great demand for synthetic APIs. We catch up with Richard Hercek, Head of API Engineering and IPC, and Boris Petrusek, EU Project Manager, at Saneca Pharma to discuss the latest trends in small-molecule API manufacture.
What are the biggest changes you have seen in the field of pharma API manufacturing?
For more than 70 years, APIs have been manufactured at our site in Hlohovec, Slovakia. API manufacture started with the isolation of opium alkaloids and then semi-synthetic and synthetic controlled substances were added. Subsequently, lipophilic vitamins were introduced, and beta blocking agents and other cardiovascular active agents were developed and manufactured – to mention just a few. The biggest changes, however, have occurred in the last 25 years following the introduction of Good Manufacturing Practice, as well as legislation concerning the safety of manufactured entities, such as REACH. REACH (Evaluation, Authorisation and Restriction of Chemicals) is a regulation on chemical substances strictly followed in Europe, but not in other regions. It’s quite a challenge because the same legislation and guidelines should apply to all API manufacturers.
What are the biggest trends in API manufacturing today?
Because of the increasingly competitive global API manufacturing environment, we have witnessed a dramatic increase in requirements relating to the purity of APIs, particularly when it comes to genotoxic impurities, which in several cases should be on the level of homeopathic concentration. In the last 10 to 15 years, more focus has been placed on the polymorphism of APIs and special requirements for particle size distribution (PSD). PSD is sometimes obtained by controlled crystallization and sometimes by final treatment physical operations, such as sieving, milling and micronization. The last two topics are a logical consequence of changes in development processes for new innovative dosage forms.
Some companies are also active in using specialized, niche technologies. However, there are a growing number of customers looking for a complex solution - where a full set of services is required from a contract services partner. In addition, there is an increasing trend towards high potency API production lines.
Despite the low costs offered by Asian manufacturers, we’ve seen many customers looking to return to the European manufacturing space for their API projects, due to the high levels of quality and expertise that are on offer. Central and Eastern European countries, such as Slovakia, are well positioned to deliver a service in line with stringent European quality standards, while still providing affordability.
In what ways would you like to see API manufacturing advance in the future?
There is, of course, a shift towards biopharmaceuticals since they present new medical possibilities for patients, but there is still a huge volume of small-molecule drugs – and great demand for synthetic APIs. However, as there is some visible slowdown in the development of synthetically prepared New Chemical Entities, there are often longer life cycles seen in the market of older molecules. Increasing pressure on costs, quality and safety should be expected to continue.
Future API manufacturing trends include the use of online monitoring techniques such as process analytical technology in order to help obtain as much information from your manufacturing process as possible.
What are the challenges of implementing sustainable development and green chemistry?
We have already started applying green chemistry principles in our technologies and we have abandoned the use of chlorinated solvents on an industrial scale at our manufacturing site. We have also started to use some green solvents, while others are being tested.
Factors to consider when using new solvents include differences in selectivity and the impact on the yield or purity of the advanced intermediate and/or final product. For example, we intended to exchange the use of diethyl ether in Grignard reactions with a green solvent. For some processes, however, it was simply not effective at all.
Saneca recently received 1.5 million Euros in funding….
Yes, the grant came from the Slovak Ministry of Education, Science, Research and Sport. The funding has allowed us to strengthen our pharma development services and establish a new R&D department. We believe it is important to provide a full-service API and finished dose development and manufacturing service from farm to pharmacy. The investment into our R&D offering, including the introduction of new technology and expertise through our expanded team, will enable us to enhance the portfolio of services we can offer. New modern equipment will also enable us to study chemical processes in more detail, which will in turn help us to achieve further quality goals and safety measures through additional improvements.
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