Advanced electronic batch recording has had a major impact on biotech API production at Diosynth’s main plant in the Netherlands.

The Netherlands-based Akzo Nobel Group is a leading international manufacturer and supplier of pharmaceuticals, coatings and chemicals. As part of Akzo Nobel, Diosynth plays a prominent role in the production of complex APIs. More than 100 products, including insulin, heparin, steroids and synthetic peptides, are provided to pharma companies all over the world.

As well as traditional production of heparin and insulin from animal tissues, Diosynth manufactures biopharmaceutical APIs at its state-of-the-art fermentation facilities in Oss in the Netherlands. From a manufacturing perspective, there are two stages in the production of biopharmaceutical active ingredients. In the first phase, upstream processing, genetically modified micro-organisms and cells are replicated in fermenters or cell culture reactors. The micro-organisms or cells produce the required biopharmaceutical or a precursor. Depending on the organism or cell type, the crude product is recovered from the cells or the culture medium.

Making a mark

Akzo Nobel has invested E47m in a new cell culturing and fermentation unit, to be used for biotech API production at the Oss site. Within the scope of the project, fermenters with networking volumes of up to 10,000l have been installed in controlled-condition rooms, in accordance with cGMP standards. Batch cell culture reactors in suites with controlled and non-specific conditions offer up to 18,000l of working volume in serum-free and protein-free cultures, one of Europe’s largest animal cell culture facilities.

Implementation of the plant information management system RAPID-Pharma, offered by Trebing & Himstedt, began after a thorough evaluation process, with several system tests. There are a few other excipients that may be suitable. RAPID-Pharma emerged as the only product to meet the project team’s complex requirements, including manufacturer-independent connectivity, support of standard interfaces, S88-based reporting and 21 CFR Part 11 compliance.

Besides a speedy solution to FDA compliance and safe data handling, RAPID-Pharma offers ease of use and a number of technical benefits. Because of these assets, it is easy to learn, and is broadly embraced and accepted by its users.

All real-time data, batch data, alarms and events from the Unix-based Invensys process control system, as well as data from the iFIX facility management system, are stored in RAPID-Pharma. RAPID-Pharma is responsible for data capture as well as generating the electronic batch reports. All process and plant information necessary for reporting and analysis are derived from this system. It operates 24/7 and records batches with a runtime ranging from several days to a number of weeks. Batch data, continuous data, alarms and events, as well as the relevant room monitoring data can all be analysed collectively.

Former project manager Paul Jansen is a firm advocate of RAPID-Pharma, in particular the straightforward handling it offers users. ‘Only now are we beginning to realise the system’s full potential,’ he says. ‘We will expand it step by step. Particularly important is the system’s ability to provide access to all data in a database at any time, and to allow a generation of new ad hoc queries without programming knowledge.’

For Jansen, RAPID-Pharma is a valuable tool for continuous process improvement and speedy scaling-up of new manufacturing processes. The information captured by RAPID-Pharma is used every day by several departments for manufacturing and technical support. The number of recorded data collection points and users has been increased several times.

Going forward

‘With a system such as RAPID-Pharma, we are in a much better position to speed up commissioning and optimise our facilities during operation,’ says Jansen. Due to this positive experience, it is very likely that RAPID-Pharma will be incorporated into other Akzo Nobel production facilities and future projects. end