Harry Benson- Global Director of Human Performance Services; Aaron Roth- Associate Director of Global C&Q, Commissioning Agents Inc
Hundreds of thousands of potential drugs die in the pharmaceutical valley of death every year, never making it to the market and patients in need.
The past three years have brought unprecedented difficulties for manufacturing sites, primarily due to supply chain disruptions, escalating raw materials costs, and an ever-changing workforce.
Only around 10% of drug development projects make it from Phase I clinical trials to market launch. This is the pharmaceutical “valley of death.” Though the timeline between drug discovery and product launch is typically 12 to 14 years, emerging therapies and the expectations of a pre-COVID world mean increasingly smaller windows of launch. Many times, the reason drugs don’t reach the market isn’t their inability to treat or cure patients – it’s because pharmaceutical facilities, both clinical and final manufacturing, face system inefficiencies and cannot become operational on time.
Pharmaceutical companies need a solution to identify problems sooner, support project construction, and enable ongoing operations in order to shorten timelines.
The newest solution isn’t a what – it is a who.
Introducing the reimagined role of the system owner. An individual that learns and observes every step of the manufacturing system life cycle, from the engineering team’s strategy development to the facility’s ongoing execution – all to ensure proper communication and confirm drugs are produced efficiently and effectively.
The role of the system owner has existed for decades as an afterthought but has only recently been defined in industry guidance (ISPE Baseline Guide 5 – Commissioning and Qualification, 2nd Ed.) as:
- The person ultimately responsible for the availability, support, and maintenance of a system and for the security of the data residing on that system.
In the ever-changing world of pharmaceuticals, even this definition can be far too limiting concerning its scope and vision, demanding a radical re-imagining of the definition and the corresponding practice.
Facilities can’t hire system owners after transitioning from projects to operations and expect the systems to simply “work.” System owners need to work closely with the earliest groups of engineers through system design, fabrication, and commission, focusing on understanding the system in the context of the intended manufacturing program within an operational facility. They need to be the connection between engineering development and ongoing facility operations – the bridge over the valley of death.
In this article, we will break down the foundation needed for a facility’s operational readiness, the roles and responsibilities of the integrated system owner, and the associated cost justification of early investment in experienced, focused system ownership. Most importantly, we will detail how exactly this reinvented system owner is the intersection between the key disciplines of Good Engineering Practice (GEP) and Human Performance (HP), transforming facility site management to achieve better production results and ensure a drug’s faster speed to market.
The Foundation: Plant, People, and Procedure
The goal of any new life sciences manufacturing facility is to achieve a state of operational readiness that enables the sustained output of drug treatments to market. Before diving into the system owner, we must understand the three interfacing assets of operational readiness – the plant, its people, and its procedures.
These three assets can be viewed as the essential elements of operational chemistry, which can be combined into the compounds, or disciplines, of Good Engineering Practice and Human Performance:
- Plant x People = Good Engineering Practice (GEP)
- People x Procedure = Human Performance (HP)
Each of these disciplines represents a group of people with its own focus. The GEP discipline focuses on delivering the plant and is more prevalent during the project phase before startup.
Alternatively, the HP discipline tends to concentrate on steady-state manufacturing procedures and workflows, and is more prevalent during the operations phase.
It is through the successful combination of Good Engineering Practice and Human Performance that the desired operational posture is achieved where:
- GEP x HP = Steady, Sustained Output of Quality Product
Because these are two separate disciplines, they tend to be executed by two different teams: the project team and the operations team.
Startup represents the transition from project mode to operations mode and is identified by the facility handover from the project team to the operations team. Unfortunately, the operations team is often still in the early stages of group development by the time the project team is ready for this handoff. This is because they have not yet developed a relationship with a critical member of their team–the facility itself.
As a result, the startup phase is where projects often stumble into the valley of death, representing uncertainty for investors and owners. Why not build a bridge?
Our “bridge” is the select group of strategic hires with roles and responsibilities spanning both disciplines, acting as members of both teams: system owners.
The Role and Responsibilities of the System Owner
In typical project delivery models, a site has a few skilled, experienced people present from the start and execute the site vision.
From the engineering team’s perspective, these individuals typically act as loosely affiliated advisors, either busy with their “day job” in another manufacturing facility or playing catch-up with operations planning because they were hired late in the project. Conversely, most GEP experts are contracted resources with the sole mandate to deliver the facility to the end user, not to use it themselves.
From the human performance team’s perspective, those same individuals work independently of the engineering project team. Standard operating procedures (SOPs) are assigned for authoring, and the “qualification” for each role is simply a list of SOPs to read, often chosen haphazardly without focusing on the result. The roles are poorly defined because there hasn’t been sufficient time for detailed operations planning and practice with the equipment.
Enter the reinvented system owner: the long-needed risk control and solution for these issues. Ideally, the system owner would join the project team from day one, fully positioned to straddle the intersecting disciplines of HP and GEP as the facility progresses through the roadmap and into operational readiness.
They will leverage their expertise to assess staff performance risks and gaps in their system area, then participate directly in the engineering process to develop and institute technical, procedural, and behavioral controls in the process design, frontloading the identification of issues and minimizing delays during handover and startup.
Roles of the System Owner in the Engineering Discipline
For the engineering discipline, the system owner should:
- Understand, compile, and, if necessary, define the system user requirements.
- Own and maintain the traceability matrix – the information map illustrating how the design meets those requirements throughout the system life cycle.
In the realm of emerging therapies, many manufacturing facilities focus on “turn-key” operational readiness, utilizing off-the-shelf platforms and vendor-supplied literature and qualification packages.
Despite the convenience, some facilities have failed to achieve startup schedules because they assume that “turning the key” to their facility will be as intuitive as starting a car.
While Commissioning & Qualification (C&Q) contractors can supplement the work of vendors, the operations team would still lack a foundational understanding of the equipment function.
Alternatively, system owners prioritize a complete understanding of the equipment’s function, thus defining the intended use and understanding how and what the vendor initially provides. System owners are actively engaged in the project phase by performing the activities listed above. They can offset the total cost for third-party C&Q, enabling drug companies to shift resources to where they will genuinely pay dividends: pushing forward drug therapy through development, clinical, and commercial use.
Roles of the System Owner in the Human Performance Discipline
For the human performance discipline, the system owner should:
- Define the work breakdown structure as it relates to systems and equipment utilization.
- Establish a staffing plan based on production targets.
- Develop and maintain standard operating procedures and other instruction-focused resources necessary to perform the work.
Recently, a new pharmaceutical manufacturing site hired 75 people who met typical facility staff experience expectations. However, the site didn’t have defined expectations for each staff member’s position. Throughout the facility’s startup phase, team members weren’t clear on responsibilities and scrambled to meet targets. Subsequently, the site suffered from significant post-startup staff turnover, resulting in the inability to sustain its operations.
Companies that leverage system owners can hire, train, and qualify their staff in sufficient time to move directly into an operational state. This is because of the system owner’s role in developing a detailed work breakdown structure in the context of each specific system, including facility design and layout, early in the project phase.
Operational Readiness and the Vertical Startup
In the drug development process, the company sets a targeted capacity of production and release for the new site or expansion, along with a date for capital project completion – typically the time at which the site should achieve targeted capacity consistently and sustainably. A well-defined operational plan and qualified staff are necessary for timely execution.
Experience shows that many production issues that prevent the transition to a steady state of operation occur during the startup phase. These issues can often be traced to a disconnect between operations planning (or lack thereof) and facility design and configuration. As a result, the facility’s output after startup is inconsistent and below the target necessary to achieve the intended return on assets. Survey data suggests a few months’ delay could result in missed revenue equivalent to millions of dollars and the potential for the relevant market windows to close.
Investment in a system owner program can help identify and mitigate production risks, thus reducing post-start-up issues, accelerating the site’s productivity, and preventing unnecessary costs.
Converting the reduced amount of treatment released to market as a result of these inefficiencies into a tangible loss of revenue can establish the business justification for employing experienced system owners early in the project phase.
To summarize, the cost of the system owner program divided by the value per batch presents the number of gained batches needed to break even. If the cost to employ system owners in the early project phase (about one year ahead of startup) was $1.9M, and the value of the treatment per batch was $800K, only an additional 2.4 batches would need to be sold to break even.
Building a New Bridge with System Owners
Expecting the system owner’s responsibility of ensuring ongoing GMP-ready production to be handled by existing team members establishes unrealistic expectations in modern, high-capacity therapeutic production facilities.
In facilities, site leaders and established roles have competing priorities coupled with limited bandwidth. They cannot be expected to have comprehensively mastered the breadth of experience and expertise necessary to “own” all the identified risk factors.
Instead, bringing an experienced system owner on long before the startup phase can forecast, evaluate, and manage the potential risks. By identifying the likely issues and planning for risk mitigation during the pre-startup phase, the site can implement the necessary pre-startup controls to achieve a consistent, sustained output and the release of an on-time, quality product.
The pharmaceutical industry can’t allow the shrinking drug approval rate to continue. Life-saving therapies exist, but due to short-staffed teams and miscommunication, they will never reach patients.
The system owner’s role forms a natural bridge of oversight and risk control over each stage of drug development. They can be leveraged to achieve better production results, a more integrated and diverse organizational culture, and, most importantly, the treatment’s faster speed to market.
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