By Herman F. Bozenhardt and Erich H. Bozenhardt
Project execution and project management are probably two of the topics that are most written about but least understood by the biopharmaceutical industry. Suffice it to say that execution of any project in our business can only be properly done when the operating company, engineer, and builder have sufficient talent and understanding of the process and facility to collaborate on an equal basis. The danger occurs when one of the parties does not have the necessary skillset, as this leads to confusion and misunderstanding, which manifests in schedule slips, cost overruns, and poor quality.
This article is not about the theory of management, but it is a primer on approaches to project execution, some of which may assist the reader in understanding their path of least risk.
Project Inception — Goals And Expectations
As the biotech world continues on the path of faster, better, and lower cost, we are reminded of the old saying that you can pick only two of the following three attributes of a project to control: quality, schedule, or cost.
The third aspect will drift into an equilibrium of necessity.
This makes a great saying but oversimplifies the balance on any project. In order to understand how to balance and control our critical objectives, we need to define the business needs or project objectives. This is the first step of a project, and it drives all subsequent decisions. Unstated objectives may be present, and they will impact decisions and are the ultimate check of whether the project is successful. Transparency is critical for parties in the project to have a clear path to success. Consider these possible pitfalls:
- Cost is always a carefully guarded secret, because either the project is not funded properly, or management does not want it revealed, as they might appear weak or not in control.
- Schedule is typically the most critical driver for getting the product into clinical trials or into the commercial market. It is typically a hard constraint.
- Quality is the one area that, from patient and regulatory perspectives, cannot be compromised.
- With schedule and quality both given, cost will fluctuate.
In order to understand our project and control it, we must learn how to define our path forward taking the business needs into account. Those can be stated as: what product into the clinical trials or launch and when. This is actually simple; however, we need to find out all the real constraints. Turning those business needs into a business plan (cost, schedule, who, what, how, when, where, etc.) is the inception of a project. In broad strokes, this includes defining all the knowns and planning for the discovery of the unknowns. The project inception should, at a high level, address the following:
- Capture the technology and process to be implemented.
- A physical feasibility fit should be done to determine what is the right site and where it is.
- Is this a renovation or new build? How big?
- A high-level milestone schedule should be generated to get an appreciation of the implementation deadlines, especially the dates needed to enter the products into clinical trials or into the commercial market.
- That implementation must have a probable (+/- 50 percent) cost against it. There can be several options that can support the business needs and the same questions and answers should be generated for all options to facilitate a financial evaluation.
- As part of the project inception, checkpoints/stage gates are implemented at critical points in the project to determine risk assessment, regulatory compliance, and affordability.
Understanding what level of regulatory impact and notification/approval is needed is often treated by handing it off to another party. But a project’s overall schedule can be shortened by realizing up front the tipping points (go vs. no-go) and taking a coordinated approach to completing the chain of necessary events:
- Facility and process qualification
- Environmental monitoring
- Machinability process runs
- Media fills
- The actual product batch
- IND or NDA filing
When do you write the validation plan? How to qualify and what needs qualification is an early stage-setting philosophy. It will determine the value of off-site fabrication (as compared to “stick built” on-site) based on the ability to leverage the facility acceptance test (FAT) as the commissioning, installation qualification (IQ), and operational qualification (OQ) effort. For new automation systems or automated equipment, it will define scope. As much as we focus on lead time of equipment or time to build, the back-end qualification time can just as easily make or break a project schedule. For example, going with an equipment vendor that has never manufactured a particular type of equipment or a highly customized version of a system can be successful, but will likely take longer to qualify.
Project Design And Execution — Select A Model
After determining the feasibility of a project through the business case, the project can progress to conceptual design. Concept design validates the business case and further develops it into a plan for execution. The estimate of size becomes an architectural floor plan, and the technology selection becomes process flow diagrams and an equipment list. The compliance and regulatory classifications become HVAC air handling unit zoning and pressurization diagrams. Delivery times of long-lead equipment are checked with vendors and evaluated against the schedule.
After approval of the conceptual design and assuming the project still meets business needs, we are now in a position to select an execution model.
There are a variety of project execution methods that strike different balances of risk, speed, and cost.
- Traditional design-bid-build (DBB) with stage gates has been the tried and true method of project execution. This model provides a high level of control at the cost of speed. The stages include stepwise engineering efforts following conceptual design, which include basis of design (BOD) and detailed engineering. Each step improves the detail, cost estimates, and schedule revision. No construction is executed until detailed design completes with the issue for construction (IFC) documents, and the costs are refined to +/- 10 percent or better.
- Another popular model is design-build (DB). Design-build can have the same stage gates, but the most effective use of this model is to have rolling reviews to enable some level of parallel design with ongoing construction activities. There is the potential to contract design-build as a lump sum to reduce the risk of project cost inflation. However, changes from the basis still represent a cost and schedule risk if all aspects of the facility or process technologies are not perfectly known. The key to this is to have all the decision and permitting parties in one location. The best example of this is the $2 billion NFL Las Vegas stadium build going on now, where a design section is completed on Thursday; the approval from the owners, constructors, permitting officials, and the NFL is received on Friday; and the concrete is poured on Sunday. The key is having all the parties in one place, communicating with the same level of knowledge.
Another avenue to accelerate the schedule that has been tested by several projects is skipping the BOD/preliminary engineering. In this case, the basis for the project becomes the conceptual design. To execute this successfully, there needs to be a clear communication of the project requirements in the concept. This eliminates a formal stage gate of the complete project engineering and should be supplemented with rolling reviews of appropriate work streams. This model is most successful where the project is a clear-cut facility or where the process is well known and tested.
The accelerated models require teamwork and a clear way to come to decisions. While companies are outsourcing more of their engineering, the condensed timelines for reviews may require more owner involvement or a clear understanding up front that the designers will make decisions to keep the project moving. This is a serious risk for newer technologies or complex processes.
In recent years. the desire to limit capital expenditure has led to executing projects through developers and contract manufacturers (CMOs). This path can be advantageous for companies lacking resources (financial and personnel) to support a project. Large companies can sometimes find using a CMO advantageous because it can execute the project faster than their internal practices will allow. The danger in this approach is the CMO will have a profound impact on the technology and implementation, while the operating costs could be excessively high.
Demystifying The Terminology
We hear many buzzwords in the industry. Discerning between marketing hype and successful implementation can be difficult. The following are some common terms and explanations that should demystify these concepts:
- Modular – Off-site fabrication of systems and/or facility components. This can be as simple as skidded equipment or modular cleanroom walls or as complex as a completely prefabricated cleanroom. This practice can allow parallel activities, improve safety/quality by taking work out of the uniqueness of the site, and thorough off-site testing reduces the time to commission/qualify.
- Design Assist – Craft subcontractors and the design engineers work together in the design and construction of the project. This is not a hand-off of the project to the subcontractor but is an extension of the design team that enables a life cycle retention of the project knowledge.
- Lean – All parties act as one team to deliver a project through streamlined methods. The Lean Construction Institute defines Lean Construction1 as, “A collaboration-based system that is founded on commitments and accountability. It requires a significant shift in the trust that each stakeholder places on another. The adversarial relationship that has existed in the industry between contractors and design teams over many centuries is challenged, with all stakeholders having to align with goals and objectives. In projects where Lean construction management principles are applied, teams integrate through collaborative tools and search for ways to eliminate waste. Teams seek to continuously improve through reflection. Lean processes are designed to remove variation and create a continuous workflow to drive significant improvement in predictability and strongly encourages respect for all people involved.”
- Pull Planning – This method involves developing a schedule starting from the end date and working backward as part of the collaborative “Last Planner System.” The Last Planner System relies on those executing the work, the “last planners,” to provide input.
- Turnover Package – This is the complete set of documents from the engineer and constructor that has all the construction detail, construction tests, vendor packages, and vendor equipment details.
- As-Builts – These are the drawings of record provided by the construction subcontractor of exactly what they installed.
- Commissioning – These are the qualification activities (similar to IQ/OQ) performed during construction by the owner’s engineers in conjunction with the subcontractors doing the actual building. This allows the owners to gather validation data, assure their systems are functioning properly, and have the constructors assist and correct any deficiencies found quickly.
- Qualification – This is the general term used for the efforts of commissioning and validation that overlap, especially IQ and OQ of equipment done efficiently. Qualification should look to leverage the supplier as much as possible. Having a meaningful FAT means there will be less troubleshooting and more proving that the system is performing repeatably within specification.
Defining Project Completion
The final aspect of any project is the definition of “When is the project really done?” This can only be answered when the project delivers a facility and a technology transfer that meet the business objectives defined at the project initiation. This includes but is not limited to mechanically complete, completed and approved commissioning, qualification, validation, and EM/media fills that allow the facility to operate the equipment successfully. “Really done” may not be until six to 18 months after mechanical completion.
In the end, a project can only be successful when the owners, engineers, qualification personnel, and builders have a working relationship built on knowledge and understanding of the project goals. Equality in technical skills is critical, as well as the ability to communicate quickly in a collective team environment.
About The Authors:
Herman Bozenhardt has 43 years of experience in pharmaceutical, biotechnology, and medical device manufacturing, engineering, and compliance. He is a recognized expert in the area of aseptic filling facilities and systems and has extensive experience in the manufacture of therapeutic biologicals and vaccines. His current consulting work focuses on the areas of aseptic systems, biological manufacturing, and automation/computer systems. He has a B.S. in chemical engineering and an M.S. in system engineering, both from the Polytechnic Institute of Brooklyn. He can be reached via email at firstname.lastname@example.org and on LinkedIn.
Erich Bozenhardt, PE, is the process manager for IPS-Integrated Project Services’ process group in Raleigh, NC. He has 13 years of experience in the biotechnology and aseptic processing business and has led several biological manufacturing projects, including cell therapies, mammalian cell culture, and novel delivery systems. He has a B.S. in chemical engineering and an MBA, both from the University of Delaware. He can be reached at via email at email@example.com and on LinkedIn.