A student practices laboratory techniques in a 2015 BARDA Fundamentals course conducted through the Biomanufacturing Training and Education Center (BTEC). (WWW.BTEC.NCSU.EDU)
Today’s bioprocessing technicians are highly skilled professionals who can operate large automated equipment, juggle numerous support activities, and document manufacturing deviations. In coming years, their jobs will become even more rigorous as companies push more decision-making to the production floor to save time and resources. With the trend toward smaller batches made in bench-scale and/or single-use equipment, this strategy becomes easier to implement. One way to foster improved decision-making on the production floor is to hire or promote employees who understand the basic scientific principles underlying a bioprocess. What abilities and skills does the workforce of the future need to make the best decisions? And how can that workforce be developed?
A Changing Paradigm
The typical biomanufacturing company advances a drug substance from research to the marketplace by navigating though a rigorous gating process that enables process development, technology transfer, process performance qualification, and production. Subject-matter experts (SMEs) in each phase conduct the work in their project plans and then communicate their findings to those working in the next phase. Their efforts encourage specialization and facilitate attention to certain details, but also can lead to resource inefficiency, longer cycle times, and greater risk of miscommunication. By the time a bioprocess makes it into manufacturing, it may no longer be optimized, and much of its development history will be buried in multiple laboratory notebooks. Time, and maybe product, can be wasted when production personnel need to contact the original development engineers or support staff to help troubleshoot a process failure. Fortunately, several industry trends are challenging this paradigm and fueling a demand for new skills on the production line.
Pressure to reduce prices has forced companies to take a closer look at the cost to commercialize and manufacture a drug product. They are asking tough questions such as, “How much will all this specialization cost?” and “Will faster decisions on the production floor reduce waste?”
Development of advanced analytics is making it possible to monitor and release products in real time.
Rapid adoption of single-use disposable technologies has reduced the number of routine manual interventions for cleaning, sterilization, and similar operations.
Autologous cell therapies and gene therapies for rare diseases require smaller volumes, and bench-scale equipment is typically used.
A Workforce Transformed
Given these trends, it’s advantageous for companies to build organizations in which production personnel understand underlying scientific and engineering principles that support bioprocesses and can react quickly to manufacturing deviations. In bioprocessing operations that use large, highly automated stainless steel equipment (e.g., for production of monoclonal antibodies), technicians with a background in science will be able to troubleshoot problems and make corrective actions in real time without help from support staff. The growth of advanced analytics and process analytical technology (PAT) is producing more process data, but until every deviation can be predicted and every corrective action can be programmed, the bioprocess technicians’ jobs will become more challenging (1).
Autologous cell therapies and gene therapies for rare diseases require smaller volumes than for production of monoclonal antibodies and often can often use single-use technologies that are facilitate operations. With these products, research scientists can be given a greater role in shepherding a therapy through its life cycle — all the way to the production line. With this goal in mind, a scientist can focus development activities on establishing a commercial manufacturing process capable of consistently producing the specified drug substance according to ICH Q8 (2). Outputs include critical quality attributes, design space, and control strategy. PAT strategy can be developed here, as well. At this point, it would be natural for a scientist to move on to learn about process performance qualification and then production. Such a workflow reduces the time required to commercialize a product and shortens the cycle time to produce each batch, especially when process failures occur.
Bioprocesses of the future will demand more from production personnel. By necessity, autologous therapies require a greater number of production batches. On a given work shift, a great number of critical operations can affect a batch. Because single-use technologies require fewer manual operations than does traditional equipment (e.g., cleaning and sterilization), the proportion of critical operations per shift also will increase. In either case, additional process knowledge will be needed during production.
So How Do We Get There?
Education, recruitment, and training are the interconnected routes to building product and process knowledge.
Education: Students interested in entering the biomanufacturing industry need to learn and understand biology, microbiology, molecular biology, chemistry, and biochemistry. Those who want multiple job offers will supplement their studies with courses on fermentation, cell culture, downstream operations, automation, aseptic processing, and quality principles. Regulatory science, automation and professional skills also are helpful.
Universities are well suited to offer both introductory and advanced courses in scientific principles. Where such programs exist, most include hands-on laboratory activities to support the curricula. Students majoring in the life sciences can be introduced to bioprocessing careers — especially manufacturing positions — during their first year of study. Upperclassmen then can choose electives relevant to drug substance manufacturing and, if available, obtain a major, minor, or certificate in bioprocessing. Graduate courses in bioprocessing can supplement other programs or lead to a master’s degree.
Community college programs also need to deliver introductory courses, hands-on laboratory activities, and career education. Students interested in quickly assimilating into the biomanufacturing industry can take courses in applied microbiology and aseptic processing to learn the core competencies of drug product manufacturing. Unless a community college offers advanced topics and the local industry recognizes that students obtaining a two-year degree have advanced skills, students wishing to perform more complex bioprocessing operations need to transfer into a university that offers the appropriate bachelor degree(s). In this case, articulation programs with life science departments are critical.
Recruitment: The feeder pool for new production scientists is loaded with recent graduates and laboratory workers who know and understand life sciences and chemistry. Some workers even have completed additional education or training in bioprocessing fundamentals, process automation, and quality compliance.
Companies are starting to demand a higher level of education for their bioprocessing workforce. During a recent career fair held at NC State University’s Biomanufacturing Training and Education Center (BTEC), recruiters for manufacturing positions were targeting undergraduates who would graduate with bachelor degrees in biology, microbiology, biochemistry, or bioprocessing science. A quick survey of online advertisements for production positions revealed that the many biomanufacturing companies in and around Research Triangle Park, NC, require a bachelor degree. Other recruiters were looking for candidates with an associate degree and two or more years of experience, but preferred candidates with a bachelor degree. These degree requirements are justified given some of the other job duties listed in the postings:
- Understand process principles
- Understand scientific theory behind operational steps
- Write standard operating procedures (SOPs)
- Troubleshoot processes
- Conduct investigations
- Generate technical reports
- Assist in execution of validation protocols.
Training: Training programs are needed to help employees close gaps in their resumes. Professionals in traditional scientist roles need to learn more about cell culture, fermentation, downstream processes, aseptic processing, process control, advanced process analytics, quality tools (root cause analysis and risk management), and regulatory science. Bioprocessing professionals lacking a formal education in basic sciences will need training in biology, microbiology, molecular biology, chemistry, and biochemistry. The more hands-on the training, the better.
Getting Started
As usual, industry is leading the way by specifying more in-depth qualifications in its job postings. By raising the bar for production personnel’s educational requirements, employers are signaling a call to action by universities, community colleges, and training organizations. It’s time to focus on preparing graduates for positions that demand a unique blend of scientific knowledge, laboratory skills and problem-solving abilities.
The articles that follow in this featured report continue BPI’s focus on biopharmaceutical training trends (begun in its December 2016 special issue) by highlighting selected programs for building professional skills in the modern industry.
References
1 US Food and Drug Administration. Guidance for Industry, PAT: A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance. September 2004; www.fda.gov/downloads/drugs/guidances/ucm070305.pdf.
2 US Food and Drug Administration. Guidance for Industry, Q8(R2) Pharmaceutical Development. Revision 2, November 2009; http://academy.gmp-compliance.org/guidemgr/files/9041FNL%5b1%5d.PDF.
Rick Lawless, CPIP, is the director, industry programs, at the Biomanufacturing Training and Education Center (BTEC), NC State University; rick_lawless@ncsu.edu.