Helene Pora, PhD, is vice-president of Technical Communication and Regulatory Strategy at Pall Corporation.

Helene Pora

Both suppliers and users of single-use technologies (SUTs) recognize the need for more efficient and effective training to support the handling and use of SUTs to ensure the biopharmaceutical workforce can successfully and reliably operate good manufacturing practice (GMP)-compliant, aseptic, SUT-based bioprocesses. Establishing adequate training solutions has become increasingly imperative as SUT use at the commercial scale accelerates.

, “Addressing the Training Gap for Single-Use Technologies”(1), the authors discussed reasons for the SUT training gap and why SUT training is crucial to biopharmaceutical manufacturing. This follow-up article outlines the fundamental aspects of training and adult learning styles, elucidates the value of digital and virtual learning, and explains the approach adopted by Pall and Lonza in a collaboration intended to address the SUT training gap.

The first project involved the joint development of a training program for tangential-flow filtration (TFF); additional training modules are planned to follow. Leveraging Lonza’s understanding of the fundamental aspects of training and adult learning styles and Pall’s knowledge of SUT handling and operations of the specific TFF equipment, this novel approach combines digital tools and virtual reality solutions with in-person and hands-on training sessions.

The goal of any training program is to get everyone who receives the training to execute the same tasks in the same manner and in the same timeframe, leading to the same output every time. To achieve that essential goal for product quality and patient safety, it is essential to identify training needs and address them holistically. In essence, training must support transfer of knowledge as well as skills and behaviors required for consistent high-level performance (see 

Figure 1. Key components of effective training programs. Courtesy of Pall.

Adult learning styles must also be considered. There are generally four ways to learn: listening (auditory), viewing (visual), reading/writing, and doing (hands-on). These learning styles can be addressed with either passive or participatory teaching methods. The former includes lectures, reading, audiovisual tools, and demonstrations, while the latter comprise group discussions, practice, and teaching others.

Adult learners are focused on learning what they need to be successful in their current role, and therefore want to learn about the things they need to know to reach assigned goals and objectives. Some of the best practices for adult learning, therefore, include face-to-face interactions and participatory programs that require problem-solving, are topic-centered, and involve real-life scenarios linked to actual daily tasks so that everyone remains interested and engaged.

Each of these different learning methods has unique benefits and advantages/disadvantages. According to the National Training Laboratories, retention of learning content ranges from 5–30% for passive methods and 50–90% for participatory methods (2). Inaddition, adults often learn as much from committing errors (trying and failing), because they must think about what went wrong and why, which leads to greater understanding of the process and prevents reoccurrence.

Criteria for successful SUT training programs

Training on SUTs requires addressing the specific training needs for SUTs while keeping in mind adult learning preferences and the different needs to ensure essential transfer of knowledge, skills, and attitude, including understanding of overall process implications caused by potential variations in the individual tasks.

The design of efficient training programs focused on the handling and use of SUTs must be accomplished by applying the best learning and training methodologies while understanding the specific requirements when operating SUTs. The programs must be suitable for employees with limited or no experience in biopharmaceutical manufacturing, be largely self-directed, be available in several languages, include instructions on the rules and procedures for maintaining aseptic conditions, and take into consideration the fact that access to actual, installed single-use systems and cleanroom suites is limited.

To be competent with SUTs, operators must be not only provided knowledge about the do’s and don’ts of proper handling, but also understand and be able to apply that way of operating consistently; they must exhibit a special attitude when working with SUTs. Training must be provided on the skills and behaviors necessary to touch and handle SUT materials, maintain awareness about the environment, and perform specific tasks reliably.

In addition, effective SUT training goes beyond meeting compliance requirements; it ensures that operators can perform the jobs competently under real-life conditions. Typically, however, access to commercial-scale equipment, particularly equipment located in a cleanroom setting, is severely limited for training purposes. Conditions within a cleanroom may also be limited with respect to training needs (i.e., number of people allowed, ability to bring in training materials during commercial production). Trainer resources may also be limited.

When the needs and available methods are considered, it can be concluded that face-to-face training, e-learning, virtual classrooms, virtual reality training, and mixed reality training represent the best options.

Face-to-face training provides the opportunity for intense, hands-on experiences, while e-learning with enhanced interactive videos and checklists (including assessments) provide a level of active and participatory learning. Virtual classrooms combine group discussions with some listening and watching, and virtual reality and mixed reality training simulate real-life activities with muscle memory and are expected to enable new operators and lab personal to learn operating procedures much faster—anywhere at any time.

Leveraging existing digital training methods already in place at Pall, the two companies developed a proprietary training platform consisting of a series of online training tools specifically covering SUT use, handling, and operations. The initial focus was to create a tool for classifying defects in biocontainers, thus enabling better identification of defects and more systematic trending for systematic learning, which would better prevent bag breakage. A library of defects was developed, along with a training package that includes videos and checklists that can be incorporated into standard operating procedures. Operators are trained to differentiate between cosmetic and actual defects as well as what might be the potential causes for each.

Virtual training tools for aseptic practices

While virtual reality (VR) training might seem like science fiction or gaming, it is advanced and increasingly used in various manufacturing and other settings, including training surgeons, helicopter pilots, and astronauts. The biopharmaceutical industry is already using this approach in several areas (3). Takeda, for example, employs VR to train operators on aseptic practices (4). Leveraging proven digital technology such as VR and augmented reality or mixed reality (MR) for SUT training can decrease the training time of new operators and increase training efficacy. In addition, such training can reduce training costs, eliminate the trainer-time bottleneck, increase the productivity of new hires, and enable on-demand retraining of employees without additional expense. By providing better, more engaging training, training effectiveness can be improved, leading to decreased human errors and therefore increased reliability of supply.

Learning how to move and perform proper cleaning in a cleanroom is a priority module because it applies to all GMP production sites. Operators in a virtual cleanroom can train on aseptic practices (e.g., movement speed, placement of objects, correct cleaning procedures) and establish muscle memory to improve quality and decrease the risk of contamination.

Lonza provided the information to establish a virtual suite with an exact, fully interactable replica of the equipment to be used in production. Employees can train in this virtual, safe environment at their individual learning pace on how to handle and use the equipment, even before a production line is installed. Furthermore, they can also jointly perform and discuss in the same VR room with colleagues and trainers located at other sites around the world without traveling.

VR training is preceded by virtual classrooms to establish a basic understanding of the equipment and process to be learned using VR/MR. Additional requirements, such as watching videos, reading assignments, online assessments, and paper analyses, together with the virtual classrooms ensure that all trainees begin the VR/MR portion of the training with the same level of understanding.

The virtual cleanroom has been outfitted with equipment such as pipettes and biosafety cabinets (BSCs) so users can experience sterile pipette assembly and realistic cleaning and movement techniques. VR technology enhancements like haptic gloves allow higher immersion.

A beta version for selected basic standard unit operations in cleanrooms and BSCs was piloted mid-2020. Goals of the VR training program include 25% reduction in human-caused errors compared to traditional training and a 20% decrease in training time.

Collaboration led to the development of training modules with shop floor relevance that are helping to reduce the time required for operator training while resulting in operators that are better trained. Working jointly in one direction resulted in a win-win situation for all involved.

In the current environment where SUT adoption is accelerating, the biopharmaceutical industry is expanding rapidly, manufacturing paradigms are continuing to evolve, and new hires are entering the workforce at an unprecedented rate, manufacturers must respond quickly to ensure that training programs are compliant to enable accelerated learning for competence.

Collaboration between SUT suppliers and end users, meanwhile, helps shorten timelines for training program development while also enhancing program quality. It also enables the development of comprehensive training portfolios comprising a wide range of training tools so that training solutions can be matched to the specific needs of trainees and the intended goals.

A combination of different personal and digital training methods affords practically helpful training solutions that, based on operator feedback, are more engaging and useful. Digital technology is a strong enabler for accelerating the deployment and enhancing the efficiency of SUT training when combined appropriately with hands-on training.

Starting Strong: A Guide to Pre-Service Training

 (Washington DC, Mosaica, AmeriCorps National Provider, 1996).

F. Kansteiner, “Takeda Lays Out $126M to Tap Robotics, Virtual Reality and More at California Production Site,” 

Michael Moedler, PhD, is head of Training at Lonza Biologics Operations Visp, and Helene Pora, PhD, is vice-president of Technical Communication and Regulatory Strategy at Pall Corporation.


Vol. 46, No. 2
February 2022
Pages: 30–31, 48

When referring to this article, please cite it as M. Moedler and H. Pora, “Accelerating Workforce Training on Single-Use Technologies,” 

Articles

Training is crucial for supporting GMP operations in commercial-scale bioprocessing.

Accelerating Workforce Training on Single-Use Technologies

Deployment of single-use technologies (SUT) has accelerated over the past few years as manufacturers adopt SUT at the commercial scale. The spike in demand has exacerbated an existing shortage of employees trained in the handling, installation, and use of disposable production systems. Knowledge transfer regarding how to use SUT must be achieved in a rapid and scalable manner to enable the workforce to operate good manufacturing practice (GMP)-compliant, aseptic, single-use bioprocesses successfully and reliably.

A collaborative investigation of the specific training requirements around SUT and key aspects of adult learning led to the joint development of an integrated SUT training approach by Lonza Pharma and Biotech and Pall Corporation. The program relies on digital technologies, such as virtual classes, enhanced digital videos, and virtual reality, but also includes face-to-face courses and hands-on learning. The result is an effective, accelerated training program with reduced time spent in cleanrooms.

In this two-part article series, the authors begin by exploring the reasons for the SUT training gap. Part one addresses why SUT training is crucial to biopharmaceutical manufacturing. Part two outlines the fundamental aspects of training related to adult learning principles, the value of digital and virtual learning elucidated, and an approach to training.

The biopharmaceuticals sector has seen a flurry of activity further driven by the COVID-19 pandemic. Growth rates continue to expand, as do capacity constraints. A critical factor of capacity is experienced labor force. Even though the sector currently employs more than 200,000 operations personnel, lack of access to technical and production staff is one of the top constraints noted to be challenging the industry (1).

The need for rapid deployment of novel therapies and vaccines against the SARS-CoV-2 virus has accelerated the deployment of SUT from clinical manufacturing to full commercial upstream/downstream with fill/finish production. This move to SUT is occurring at a time when several drugs whose clinical batches were manufactured using SUT are receiving fast-track approvals and scaling almost immediately to commercial production.

Given the highly regulated nature of the pharmaceutical industry, including requirements for training of manufacturing staff according to current GMPs (CGMPs), effective and efficient training is essential. It imparts safety and quality as well. It has, in fact, become crucial to the continued, successful expansion of the industry considering that more than 40% of new hires over the next five years are expected to support bioprocessing operations (1).

Achieving the appropriate level of training during a period defined by rapid expansion combined with accelerated implementation of SUT solutions is creating challenges for many biologic drug and vaccine manufactures.

According to CGMP regulations, training is compulsory and must be properly documented to achieve compliance. New employees must receive adequate training to become competent to fulfill all tasks associated with their jobs. Despite the importance of ensuring employees have the knowledge required to perform their jobs safely and effectively, gaps in employee and contractor training remains one of the frequent observations that drug manufacturers receive in GMP compliance inspections by regulatory authorities (2).

There are several causes for the existence of training gaps. A general challenge is the need to get to the clinic and the market as quickly as possible. Training is planned, but with time of the essence and employee turnover combined with workforce shortages, companies easily find themselves putting training off until there is “spare” time on the production line—a situation that is unlikely to occur any time soon.

In some cases, training gaps can be linked to the recent arrival of new equipment or the implementation of new manufacturing processes and/or introduction of products. Comprehensive employee training is essential under these circumstances to ensure reliability of supply and to stay fully compliant.

Single-use systems are now widely used for all bioprocessing unit operations in the manufacture of biologic drug substances and drug products, including critical steps, from lab to commercial scale. Despite the extensive effort made by SUT vendors to ensure the integrity of their single-use systems and components, as illustrated in 

, improper handling once the SUTs are in the hands of the end user can easily cause damage, leading to leakage/breakage of sterile barriers of SUT equipment and causing contamination and loss of product (3).

Figure 1. Integrity assurance throughout the single-use (SU) technology product lifecycle. Figures are courtesy of Pall. Click to enlarge.

Most established commercial bioprocessing facilities were initially designed around the use of stainless-steel equipment for all aspects of manufacturing and waste disposal. Operators are familiar with these conventional processes, which largely involve making non-sterile connections and sterilizing assemblies afterwards.

In single-use processes, operators must unpack, visually inspect, and install large biocontainers as well as make sterile connections right first time, then disassemble and dispose the used biocontainers. This sequence of operations (see 

) is clearly more complex with numerous manual operations than what is required for processes performed in permanent stainless-steel equipment. In addition, single-use materials become vulnerable once removed from the packaging; therefore, special precautions must be taken.

Figure 2. SUS system lifecycle. Click to enlarge.

Operator training regarding the installation and use of SUTs is essential to ensure aseptic or sterile operation as well as avoiding damage that can lead to leaks, contamination, and ultimately to batch failures.

In a 2021 survey of biologics manufacturers conducted by BioPlan Associates, single-use biocontainer (bag) breakage was found to remain a key concern and one of the top three reasons preventing more widespread use of SUT (1). This concern is reasonable, given that integrity failure of single-use systems can have major consequences on safety, quality, delivery, and cost, negatively affecting employees and patients.

The same BioPlan Associates survey further found that operator error was considered one of the top causes of batch failures. Survey respondents said that approximately 4.3% of commercial batches and 3.5% of clinical batches at their facility were lost annually to operator error (1). Overall, it has been reported that approximately 50% of all deviations can be attributed to human error (4).

Any failures at commercial scale, in particular, are serious and costly. Leakage of a single-use bag was reported by BioPhorum (a global collaboration of biopharmaceutical industry leaders and subject matter experts) to cost from $50,000 to more than $20 million depending on the type of bag and the material it contains (4).

The expenses associated with single-use bag leakage can be numerous. Reprocessing is often not possible, and product marketing and sales can potentially be disrupted, which can be disastrous, both for patients and drug companies. Costly and time-consuming forensic studies may also be required to identify the cause(s) of the failure to ensure safety of patients and proof for regulators.

Notably, the BioPhorum also acknowledged that improved training methods would considerably decrease the occurrence of leakage (4). In a 2004 presentation, for example, Bayer reported details of damage that caused bag chamber failures at its Berkeley, Calif. manufacturing site, which used bag assemblies of 4 to 2000 L in combination with single-use tubing, manifolds, and aseptic connections (5). Nearly three quarters of the 4% leak rate were found to be attributed to improper handling during insertion, hoisting, and filling of the bags and operator error during fluid transfer. Most leaks were due to chevrons that occurred during bag adjustment and installation. In addition to bin and bag design changes and supplier corrective actions, Bayer identified increased training to educate operators and increase their awareness of proper single-use bag handling and use as effective means for significantly decreasing the percentage of leaks. The training program was designed by a single-use subject matter expert and included information on the site’s leak history and trends, the root cause analysis identifying key factors leading to bag leakage, how chevron damage occurs, and proper bag filling techniques. Once training was complete, the percentage failure rate was consistently reduced, as tracked over several months. Bayer concluded that effective training is crucial, along with in-house technology and knowledge, detailed equipment design and a good material management program, for operation of reliable single-use systems (5). 

The design of efficient training in the handling and use of SUTs must be accomplished by applying the best learning and training methodologies while understanding the constraints of single-use technologies. 

Training alone will not solve all the challenges posed by the rapid adoption of single-use technologies in bioprocessing. History has shown that improving the design of SUTs and components and driving for more standardization both contribute substantially to reducing failure rates (6).

One of the first issues to address is the complexity of current SUT workflows and the need to design new workflows that better integrate with other bioprocess operations. Some areas that can be improved include organization of systems storage areas; materials interlocks; inspection area designs; and mobile equipment. These workflows can then be incorporated into training programs.

Joint efforts by suppliers and end users under the auspices of BioPhorum have led to the development of good concepts geared toward performing root cause analyses of SUT failures and new training tools (4). The development and deployment of effective training methodologies, however, has not yet been achieved throughout the industry.

When thinking about effective and fast SUT training deployment in the biopharmaceutical industry today, several important aspects must be taken into consideration:

Most of new employees have limited or no experience in practical biopharmaceutical manufacturing.

Training must be more self-directed when there are travel restrictions.

Training must be available in several languages.

Accessibility of actual installed single-use systems and cleanroom suites is limited.

It is important only to place operators in real situations once the discovery phase and initial training on basics and fundamentals are completed.

Specially designed training rooms and practices will be required for this initial introduction to SUT handling.

In addition to training on SUT handling, it is essential to ensure that operators also fully understand the rules and procedures for maintaining aseptic conditions throughout a given bioprocess.

In the second part of this article, the authors will take a deeper look at key considerations for SUT training and the blended approach developed that shifts the “one-size-fits-all” training paradigm by combining digital and virtual learning with face-to-face and hands on training.

Annual Report and Survey of Biopharmaceutical Manufacturing Capacity and Production A Study of Biotherapeutic Developers and Contract Manufacturing Organizations

Online GMP Training, “Top 10 GMP Audit Failure Reasons: FDA and TGA Inspection Findings,” 

BPSA Alliance, “Design, Control and Monitoring of Single-Use Systems for Integrity Assurance” (July 7, 2017). 

Biophorum, “Disposables: Single-Use Systems Bag Assembly Leakage and Defect Toolkit,” biophorum.com (Oct. 23, 2020). 

W. Beh, “Operational Considerations for Robust Single-Use Systems,” Presentation at IBC’s 5th Single-Use Applications for Biopharmaceutical Manufacturing (San Diego, June 2, 2008).


Vol. 46, No. 1
January 2022
Pages: 28–31

When referring to this article, please cite it as M. Moedler and H. Pora, “Addressing the Training Gap for Single-Use Technologies,” 

Workforce training is crucial for biopharmaceutical manufacturing.