1. Introduction
Errors are a part of life. In a pharmaceutical context, though, errors affect safety and quality and can lead to issues with supply. Direct financial impact from lost batches, investigations, and remediation activities—as well as compliance issues, higher inventory due to late batch releases, or even lost market share—all have to be considered when thinking about total cost of errors. With existing deviations attributed to human error estimated at 50% within the biopharma industry [internal BioPhorum Operations Group (BPOG) member survey], the vital importance and real-world value of integrating human performance (HuP) principles is obvious.
Despite the high error rate, resistance to the kind of cultural change needed to improve HuP is rooted in past attitudes and paradigms. For example, it is generally accepted as inevitable that more batches mean more deviations, that higher turnover means more deviations, and that new product introductions mean more deviations. Overall, we deliver products that meet rigorous compliance requirements to our patients and have a positive impact on their lives. So why do anything differently?
We can do better. We want to reduce losses so that our patients receive every volume of product we make. We want to reduce production costs so that we can do more to reinvest in our pipelines of new therapies. We want to continue to reliably deliver to market in a changing and dynamic environment. We want to exceed the expectations of our regulators.
So what do we do to overcome a plateau of good performance and achieve enviable levels of operational performance? In researching our historical deviations, we discover an entry point. Industry data shows 50% of deviations are attributable to human error. We have found internally that despite our best efforts the human error rate has been constant over several years. Comparing ourselves to other high-risk industries with unparalleled levels of reliability, such as nuclear power and aviation, we see that we have changes to make. And those changes are all tied to the integration of HuP into our operations.
This article utilizes the experience of two large, global biotech companies to illustrate pathways to integrate HuP and the benefits realized. It is important to recognize that integration of these principles do not merely address human error, but rather have an overall positive benefit to quality, safety, compliance, and on-time delivery—the critical measures that will make or break a biotech company's performance.
2. What Performance Is—and Is Not
There is no such thing as productivity versus quality. Those two major subjects—productivity and quality—cannot be separated but are intrinsic. Everyone involved has to understand that there is no productivity without the best quality. This includes the need to improve operational performance in general, including a culture change towards HuP principles.
The integration of HuP is not about overlaying a program on top of what you already do. It is about change—about breaking long-held paradigms and ways of thinking, and this means the following:
Changing the Way the Organization Deals with Human Errors
Human error is a part of the human condition: people are fallible (1). Reliance on the old view of human error—that punishment, retraining, and firmer discipline will have an impact—has been proven to not drive improvement (2). Organizationally, we need to recognize that performance is not that simple. Our systems and environment are dynamic and complex. Rather than focus on the person, we need to explore the task, tools, and operating environment. This means that human error becomes a starting point for investigation, not the root cause.
Ensuring the Organization Has an Open Reporting Culture
Within good manufacturing practice (GMP) regulations we are accustomed to reporting deviations. When an activity does not go according to expectations or procedure, if we can point to a document or instruction that was violated, we report and investigate a deviation. What we are not necessarily so good at doing is reporting all of the issues that create challenges in operations. What about the time a hose was almost misconnected? What about the time we selected the drain valve to be opened but caught it before we lost product? What about the time we took a chance on automation and batch record instructions that didn't match, and were lucky to get it right? We want to know about those potential error traps—and have our personnel feel open and encouraged to report them. This is foundational to being able to be proactive about addressing system issues before they become deviations, or major events.
Ensuring the Organization Has a Learning Culture
In a learning culture, an organization is focused on gathering as much information as possible in order to identify how it can adjust its systems and processes to achieve higher levels of performance. Based on our historical responses to human error and variable levels of management engagement on the shop floor, we are missing out on opportunities to learn. Data gathered through open reporting processes will provide a wealth of learning. Similarly, implementation of front-line observation and coaching programs create opportunities to gather information about potential break points in operations. The organization needs to take this information and do something about it.
3. Human Performance (HuP)—how To Get Started
This section focuses on how two global organizations, Lonza and Biogen, have made significant progress towards HuP integration. Their paths are similar. Where there are differences, these will be highlighted and discussed to help others shape what integrating HuP may mean for them.
Both organizations started by learning from others. Both conducted benchmarking and learned from high reliability organizations, such as nuclear power and aviation. They also learned from industry peers through BPOG. Drawing upon BPOG resources and examples, learnings were consolidated into a HuP assessment tool. This tool evaluates organizational HuP maturity, and it provides a blueprint for implementation.
HuP is designed to encourage behavioral changes that will lead to dealing differently with human errors and preventing them—for the individual, the leaders, and the organization. Such a HuP effort has to offer positive examples to employees—through a series of different workshops and lessons—of both the kinds of behaviors that exemplify HuP as well as tools and techniques they can use to execute key principles of HuP (Institute of Nuclear Power Operations Handbook—Principles for a Strong Nuclear Safety Culture):
Managers are responsible for, and everyone is personally involved in, HuP.
Leaders demonstrate commitment to HuP.
Trust permeates the organization.
Decision-making reflects error prevention first.
A questioning attitude is cultivated.
Organizational learning is embraced.
Error prevention undergoes constant examination.
Let us make it clear: Even if a company makes HuP a must-do throughout the organization, the implementation cannot be accomplished in one year. This is a multi-year, phased-in process.
The Biogen Story
Biogen's journey towards improved HuP began at its Cambridge manufacturing site. Following initial benchmarking and BPOG activities, the Cambridge team brought a consultant in to perform a current-state assessment of their operating culture. This assessment answered the question, where are opportunities to improve in order to better manage operational risk? This assessment, though performed at one location, became a catalyst for the company's other manufacturing sites. The ideas and recommendations were shared globally within the organization, and in early 2014, it was decided that integration of HuP would be a global strategic effort for all of the company's internal manufacturing sites.
Figure 1 describes Biogen's implementation roadmap to create a culture aligned to HuP principles. Biogen branded their HuP efforts “Hu”, which is reflected in this figure. Details supporting each component of the transition are described in the sections that follow. The desired future state for Biogen once HuP is fully integrated includes
System weaknesses are identified and effectively addressed before they have impact
Documents, software, and hardware are designed for optimal human cognition—significantly reducing error likelihood
Value is placed on technical training for all personnel so they are better positioned to identify and manage risk
Workers apply technical understanding when executing work and utilize HuP tools consistently
Biogen's implementation roadmap to create a culture aligned to human performance (HuP) principles.
Leadership and Governance
Each Biogen site was in a different starting place. Cambridge had started to implement some new tools and was initiating people leader training in early 2014. At the time HuP was declared a global effort, the other manufacturing sites needed to be enrolled. Biogen's approach is to enable site autonomy and ownership while ensuring common philosophies and frameworks at a global level. Therefore, the organization took a site-oriented approach to initiating HuP throughout its manufacturing network. To support HuP, concepts were introduced at each site through its site leadership teams. Each site was asked to identify a site HuP lead, and that lead then assembled a team with cross-functional representation. Site teams establish site implementation plans, and site general managers are the executive owners of HuP for their sites.
Like many companies, Biogen has functions that are led globally, such as manufacturing, quality assurance, quality control, and engineering. Though these organizations were engaged on site teams, focus and attention also needed to be given to global functional leadership to ensure aligned support. Today Biogen has a cross-site/matrix function team that oversees HuP globally. This team includes all of the site HuP leads, and a global HuP lead for each global function.
HuP Integration—Biogen's First Steps and Continuing Efforts
Building HuP Knowledge within the Organization:
Awareness sessions, lunch-and-learns, and general training sessions have been performed at all of Biogen's sites. Training is done top-down, starting with site leadership teams, then people leaders, then associates. The training includes overviews of HuP concepts with focus on how the organization and ways of working need to change.
Implementing New Operational Tools To Identify and Manage Risk:
A concept introduced through Biogen's learning was that of critical steps (3). The first new HuP tool Biogen implemented is pre-job briefs. These were implemented for each unit operation containing critical steps. Pre-job briefs are a structured dialog performed prior to performance of an activity to ensure all involved are clear about what is to be done, roles and responsibilities, what past experiences need to be remembered, and what will be done if something goes wrong.
Implementing New Approach to Task Instructions:
Biogen had initiated improvements to its procedures prior to HuP. The organization's strategic focus on HuP elevated the importance of this work and also expanded it beyond procedures to include all tools utilized during task performance, such as batch records and automation prompts. Applying human factors to all of these elements of the tools used to perform work, and approaching it in a holistic way, are yielding good results (see Early Results section).
Eliminating “Human Error” as a Root Cause:
Biogen is currently implementing a global project to improve its deviation and investigation process. Part of this project is implementing new root cause choices. These new choices do not include “human error” as an option. This ensures appropriate focus on systems and behaviors that drive overall performance. Success criteria for implementation of these new selections include conducting investigations with a systems perspective, uncovering all contributing factors to events, gathering information without hindsight bias and with application of local rationality (2), and most importantly, identifying corrective and preventive actions that improve resilience to errors and enhance system robustness. Implementation is targeted for late 2015.
Including Error Prevention in Equipment and Process Design:
To fully realize the benefits from HuP, it is not sufficient to stop with new behaviors and doing a better job with root cause analysis. Biogen is embracing the need to modify its approaches to equipment and process design so that HuP considerations are built in from the start. Biogen is integrating HuP concepts into its projects that affect how associates interface with production system elements by including deliberate success measures and/or check points for human factors in project plans.
Focusing on Learning—Not Just When Things Go Wrong:
One of the next steps in Biogen's journey is focus on leader observation and providing mechanisms for open reporting. Observation and coaching have started to be implemented as a formal program with associated metrics to reinforce it as a new expectation. Open reporting is a process Biogen plans to use in order to gather information about not just deviations, but when obstacles or unexpected conditions were encountered. For Biogen, this is an important aspect of transitioning to a learning culture and a vital step in being able to proactively address issues.
The Lonza Story
Lonza built its global HuP program on the back of its operational excellence program and BPOG immersion meetings at nuclear facilities, applying lessons learned in building high reliability and preventing human errors. BPOG provided a good overview of what's already in the industry without consultants and helped to avoid many pitfalls and perhaps saved Lonza 1–2 years on its HuP journey.
The overriding theme at Lonza is creating an environment where everyone is involved in identifying pitfalls, habits, and situations that will likely cause errors and then taking actions needed to ”prevent” those errors from happening. The essence of HuP at Lonza is a fundamental cultural change program with five beliefs behind it (Figure 3):
It starts with the understanding that we all make errors, even the best of us—it's simply a part of being human;
Second, we acknowledge that error-likely situations are predictable, manageable, and preventable;
Third, we have to positively influence the behavior of our employees through the right processes and approaches;
Fourth, the way we encourage and give feedback to our employees has a high influence on their individual contributions to the company and their role in safety and quality;
Finally, we have to learn from past mistakes and take into account ways to avoid them from happening in the future.
Similar to production systems in the automotive industry, Lonza branded its HuP program as the error prevention system (EPS) globally across all pharmaceutical sites, making it instantly recognizable to all employees and a part of their daily working life. Rolling it out did not just focus on training (though all of Lonza's pharma & biotech operations staff went through a full-day on sources of errors, and how behavior influences errors) (Figure 2), but the HuP program was based on the broad approaches that proved successful in the nuclear industry and that were adapted for a biopharma setting.
Elements of Lonza's error prevention system (EPS).
The four phases of Lonza's error prevention system (EPS).
Leadership and Governance
In designing EPS, Lonza recognized that a simple top-down approach wasn't the best fit. From the beginning it was easy to convince top management and get buy-in, and from an operator level there was strong support for a structured approach to dealing with issues and to discussing before things are done. There was a passiveness in middle management, though, who saw EPS as “just another initiative”. Lonza's internal set-up, however, made this easier to overcome. Engagement, communications, and most importantly good results were shared across the network. The clarity that EPS is non-negotiable, and building mandatory observation walks into daily practice for managers, removed the resistance.
For successful implementation, the Lonza Executive Committee has the ultimate responsibility to ensure that management puts the right organizational systems in place as well as proper control mechanisms. Consequently, EPS is embedded as a key element in the global quality strategy. EPS experts, site leaders, quality assurance, and operations people are working jointly to set priorities for what needs to be done and to ensure every employee understands and puts the right emphasis on continuous improvement of HuP. The responsibility for creating the EPS culture does not rest only with the individual front-line worker. The area and functional leaders are role models for Lonza EPS and have to make sure the EPS elements are followed, and that they meet the needs of their employees and their own operations so they can achieve their goals.
This cultural change is driven by establishing a system to actively coach employees on expected behaviors by regular “Leader Observation Walks” using cards with error traps and behavioral countermeasures (Figure 4). These frequent interactions are trended for defined traps and measures to identify areas for HuP-related root cause investigation as well as corrective and preventative actions. Also a financial reward system for site people and teams who fulfill milestones along their journey, including awards to honor the areas with the most exemplary performance, has been established. Early results have been encouraging (see Early Results section).
Leader observation walks reinforce and encourage proactive behavior.
In June 2014, the Lonza EPS team met to begin work on the Phase 2 ”Excellence in Documentation and Learning” Planning Workshop. The team reviewed external best practices in the areas of documentation and learning from across the industry as well as internal best practices from several Lonza sites. Guidelines and templates were designed for master batch records, work instructions, and knowledge documents in order to make our documents more logical for users and to reduce error traps:
Master Batch Records provide process specific instructions and are used to record process data.
Work Instructions provide simplified instructions for the operator, with minimized error opportunities.
Knowledge Documents contain background information and context for the process or procedure.
To build the link between theory and practice, a comprehensive learning package concept was outlined. Effective learning is the foundation for consistent knowledge and empowers every employee to anticipate, manage and prevent errors. Proof of concept was piloted at GMP and ISO sites, and demonstrated reduction of errors by 20–40% in pilot areas around filling in batch records as well as errors categorized as omissions, inconsistent execution, or failing to follow instructions. Lessons learned are being used for final adjustment of roll-out plans for EPS Phase 2 in 2015.
4. Early Results
Biogen Case Study
The benefits of integrating HuP are illustrated by a case study performed on the pre-use cleaning steps of an ultrafiltration operation at one of Biogen's manufacturing sites. A project was initiated to analyze this process with a systems perspective in order to reduce the potential for misinterpretation of instruction, produce consistent results, and address human interaction with the process.
Process mapping was conducted of the process, associated documents, and automation steps. This analysis uncovered significant opportunities to improve instruction clarity and reduce automation prompt requirements. Positive results included reduced process time, increased reliability, and decreased error rate. Changes that were made as a result of this analysis, though taken from a HuP perspective, had a broad impact. Following the analysis, a pump was no longer required to be reset prior to starting the automation, which reduced automation calls and associated downtime. By modifying how the operation was performed, the need for cassettes to dry out after blow-down was also completely eliminated. Summarized results are provided in Table I.
Summarized Results of the Process Mapping Analysis Implementing HuP for UF Cleaning Operation
Lonza's Results
In February 2014, the first phase towards deploying HuP tools and principles was launched. By the end of 2014, over 4700 employees participated in 1 day EPS introductory training, more than 3,000 observational field walks by leaders are executed every month, and daily engagement of front-line operators in identifying error traps and opportunities for improvement was practiced. This played a major role in reducing human error–related quality deviations and non-conformities by over 40% (Figure 5) and resulted in an overall reduction in deviations by 30% within the first year for all pharma sites.
Correlation of human error–related deviations and EPS deployment.
That reduction is a remarkable and early achievement! It underscores why a HuP program is not just a passing “management flavor-of-the-month” fad. To the contrary, HuP is a cultural change initiative that comes complete with a full set of powerful, continuous improvement tools—from observational walks to new, simplified, improved ways of writing and formatting work Instructions, batch records, and standard operating procedures. Ultimately, Lonza's aim is to make it harder for an employee to do something wrong than right.
Non-Quantifiable Benefits
At both organizations, positive feedback has been received regarding employee engagement and empowerment to improve how employees work. Integrating HuP helps make jobs easier—the early results from both Lonza and Biogen demonstrate this clearly.
Conclusion
Integration of HuP is starting to make measurable results in biotech. The stories from Lonza and Biogen provide insight for other organizations who are willing to take a step forward to this new operational paradigm. Both companies use the same elements by looking at document and process improvements, observations, focused tools, equipment, and process design. Even as HuP implementation plans are different, the results are similar. What next steps will you take?
Footnotes
BPOG SPECIAL SECTION: The following article is a special editorial contribution from the BioPhorum Operations Group (BPOG). Please note that it did not go through the PDA Journal and Pharmaceutical Science and Technology regular peer review process.
- © PDA, Inc. 2015
