Author: John Milne PhD, training manager, National Institute for Bioprocessing Research and Training

Biopharmaceuticals differ in several respects from small-molecule drugs, including the manufacturing process to produce the active ingredient, their overall complexity, molecular weight and their stability. Recombinant proteins manufactured using well-characterised Chinese hamster ovary (CHO) cells constitute the majority of biotherapeutics coming on the market. Mammalian cells are now the workhorse of the biopharmaceutical industry, due to their ability to perform human-like post-translational modifications to proteins, resulting in a better quality product for patients in the clinic. While there has been some rationalisation within the small therapeutic molecule industry due to the expiration of patents, growth forecasts are very positive for biopharmaceuticals over the next decade. Company pipelines are becoming busier, with more biopharmaceuticals entering the clinical phase trial of development. Second-generation monoclonal antibodies and newer product classes such as antibody drug conjugates are generating much interest within the industry, for their potential to treat human disease. Within the context of Ireland while there have been some job losses within the small molecule market, recent positive announcements by the IDA of key investments have clearly demonstrated that Ireland will continue as a hub for the manufacturing of important biopharmaceuticals into the future.

PROTOCOLS AND SINGLE-USE SYSTEMS

Currently, production of recombinant proteins and, in particular, monoclonal antibodies is performed in large-scale reusable stainless steel bioreactors. However, as cell titres have increased along with the necessity for more flexible manufacturing strategies, single-use bioreactors that do not require CIP/SIP Protocols are now becoming significant in manufacturing facilities. There are several advantages in employing such technology and single-use systems can offer a benefit in terms of time to market, reducing validation complexity, process security, production efficiency and cost of goods. Following cell culture and harvesting of the product containing cell culture supernatant solution, the target molecule of interest is purified using a series of discrete unit operations. Such operations typically include filtration and liquid chromatography techniques designed to produce a pure product which is then filled into a suitable delivery system to be used in the clinic.

Once again, for many of the reasons mentioned above, single-use technologies are now beginning to make a real impact on the downstream processing environment and most companies are operating at the very least a ‘hybrid’ approach where single-use systems will be incorporated in a process, where they can demonstrate a clear advantage over reusable systems. With all of these new options for manufacturing, it is clear that engineers will continue to play a key role within modern biopharmaceutical facilities. An additional challenge for some engineers will be the need to transition across from a small-molecule active pharmaceutical ingredient manufacturing environment to facilities where complex biopharmaceuticals are manufactured. Engineers responsible for generating clean utilities and maintaining facilities fit for purpose will, in a general sense, find the transition easier given the similarity in both industries in many areas such as the production of high purity water, water for injection, CIP solutions, clean steam and compressed air. However, given the different unit operations employed in biopharmaceutical manufacture and the nature of the cellular processes used to manufacture complex protein products, there will be obvious learning needs for some engineers looking to upskill or transition to a role in the biopharmaceutical industry.

NIBRT TRAINING AND RESEARCH 

The National Institute for Bioprocessing Research and Training (NIBRT) is a world-class institute that provides both training and research solutions for the bioprocessing industry. The mission of NIBRT is to support industry by providing a unique learning experience for trainees in a state-of-the-art environment that replicates a modern industrial bioprocessing facility. NIBRT can work with engineers directly to increase their knowledge and skillset within biopharmaceutical manufacturing through its customised training programs. NIBRT, along with its education consortium partners (UCD, DCU, TCD and IT Sligo), can offer trainees from an engineering background an opportunity for flexible, competency-based learning solutions that can deliver cost-effective benefits in the workplace. Engineers are offered unrivalled access to a fully operational manufacturing plant, in a simulated good manufacturing practice (GMP) environment that ensures that all trainees gain experience with both the equipment and the regulations pertaining to a facility operating to GMP. NIBRT works closely with Engineers Ireland to jointly promote training courses for engineers that involve both classroom learning and hands-on laboratory sessions. It is hoped to look at increasing the number of courses in the coming months by offering some training solutions in the area of facilities and utilities.

Current training courses run in conjunction with Endress + Hauser ,which has provided a state-of-the-art training system to NIBRT that addresses all elements of instrumentation and associated process control – a key driver in current manufacturing processes. This unique customised training rig is used to deliver an understanding of the theory of process measurement, control and digital communications and its application in an industrial process control environment. This two-day course is practical based so trainees get hands on experience with all the various tools involved in instrumentation. The course is ideal for instrumentation engineers and plant technicians who require greater awareness and understanding of the theory and current industrial best practice of equipment operation. In the ‘Introduction to Biopharma for Engineers’ course, engineers who come from a variety of backgrounds attend NIBRT for an introduction to the biopharmaceutical industry. The course covers such areas as biopharmaceuticals as a class of therapeutics, cell culture processing, protein purification, downstream processing, cleanroom design and control and formulation-fill finish operations. Importantly, the course also affords attendees an opportunity to take part in an interactive tour of the production facility and utilities areas to observe at close quarters the unit operations employed by industry to sustain manufacturing campaigns. The course is designed in a sense to take the mystery out of biopharmaceutical manufacturing and to demonstrate to engineers that transitioning to a career within a biopharmaceutical facility is possible and can be.

SPRINGBOARD INITIATIVE

For those engineers who have unfortunately lost their job and are considering building on their experience to transition to a role within biologics manufacturing, in either a maintenance or production role, it is worth looking at the Springboard initiative, launched in 2011 as part of the Government’s job initiative. Springboard provides free, part-time places in accredited higher education courses in areas where there is an identified skills need. Indeed, target participants in the programme are unemployed people who have lost their jobs as a result of the recession or company closures and who would benefit from up-skilling or cross-skilling to get back into sustainable employment. NIBRT currently has a series of course offerings as part of the Springboard programme that can help engineers to transition into the biopharmaceutical industry. In summary, for engineers that may be looking to transition to a career in the biopharmaceutical sector, there are a series of solutions to suit the need of all individuals. With proper consideration, engineers can arm themselves with the skills and competencies to forge a successful career in what continues to be an exciting, dynamic and rewarding industry.

Further information on courses, course schedules and opportunities for engineers can be found on the NIBRT website or contact NIBRT for informal discussions directly through John Milne PhD, training manager, at john.milne@nibrt.ie. John Milne has a PhD in enzymology from University College, Dublin. He has 14+ years' experience in a variety of roles within the biopharma industry including process development, scale-up, tech transfer, commercial production and ensuring GMP compliance in regulated facilities. Milne has been based at NIBRT since 2013 in the role of training manager.