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This book is dedicated to our families, who tolerate and endure the consistently inconsistent nature of our schedules and timeline when developing this type of knowledge tool. Your patience is both appreciated and amazing.
Jeffery Odum and Michael C. Flickinger
Contributors
Josh Capparella
Precis Engineering, Inc.
Ambler
Pennsylvania
USA
Samuel Colucci
Precis Engineering, Inc.
Ambler
Pennsylvania
USA
Daniel Conner
Precis Engineering, Inc.
Ambler
Pennsylvania
USA
Jonathan Crane
HDR, Inc.
Atlanta
Georgia
USA
Robert Dick
Precis Engineering, Inc.
Ambler
Pennsylvania
USA
Beth H. Junker
Bioprocess R&D
Merck Research Laboratories
Rahway
New Jersey
USA
Flemming K. Nielsen
NNE A/S
Gentofte
Denmark
Jeffery Odum
NNE
Durham
North Carolina
USA
Larry Pressley
IPS
Morrisville
North Carolina
USA
Kip Priesmeyer
Kip Priesmeyer & Associates, LLC
St. Louis
Missouri
USA
Hartmut Schaz
NNE
Frankfurt
Germany
Henriette Schubert
NNE A/S
Gentofte
Denmark
Amanda Weko
AGW Communications
Haddonfield
New Jersey
USA
Mark F. Witcher
NNE
Durham
North Carolina
USA
Foreword
Architecture evokes an interaction between fabricated space, form, and human activity. It can be a modest human-scale design or an awe-inspiring monumental work of art. Every architecture has both synergy and limitations. The synergy and limitations can be site, materials, artisanship, climate, government regulations, and certainly resources and budget.
Process Architecture in Biomanufacturing Facility Design is the first volume specifically written for architects, designers, and facility engineers to introduce the unique synergy between bioprocessing–biological medicines–people–facility and the limitations imposed by government regulatory requirements for the safe production of complex human biologics or vaccines by living cells.
Jeffery Odum has carefully assembled contributions into a unique and useful volume that explains the synergy of biopharmaceutical product, a carefully controlled process, equipment, GMPs, and facility design. This work explains how bioprocess architecture—the actual steps in the manufacturing process—affects the design of the manufacturing space and how people operating biological processes within this space produce, purify, formulate, and minimize contamination of potent human medicines.
Training a new generation of architects, designers, and engineers is particularly important now as the types and scale of biological medicines derived from living cells are rapidly expanding. Facilities to manufacture biological medicines for long-term care of chronic or degenerative human diseases are being built today. These new facilities will be capable of producing very large volumes of biologics (10,000 kg of active pharmaceutical ingredient or biologic per year) to meet the anticipated demand for treating hundreds of millions of patients over a long period. Examples of these large-scale biomanufacturing needs are facilities to produce biological medicines for treating diabetes, or Alzheimer's.
These facilities also need to be flexible. Many new facilities will be significantly smaller (reduced footprint, reduced construction costs, reduced utility, water, and solid waste requirements per kg product) to speed construction, reduce financial risk, and to meet requirements of new sites. Examples are new facilities to rapidly manufacture millions of doses of vaccines and adjuvants to meet global pandemics that have recently been built to improve regional vaccine quality. Vaccines can be complex multicomponent biologics manufactured by multistep processes. However, they must be manufactured as new products each year (often combining new antigens) seasonally. These facilities need to be operated efficiently with standardized automation for biologics to be compliant and cost effective.
In contrast, the emerging field of patient-specific biologics and cell therapy requires a completely different process architecture approach to facility design as each product may be derived from cells from a single patient destined to be immunologically or genetically altered and returned to that same patient. Product isolation and facility design to minimize product bioburden contamination are critical for these types of processes.
Process Architecture in Biomanufacturing Facility Design is an important new work to accelerate the design of a new generation of efficient, flexible, cost-effective, and compliant biomanufacturing facilities to deliver life-changing biologics and vaccines to patients worldwide.
Michael C. Flickinger, Professor, PhD
Preface: Why a Book on Process Architecture?
Process Architecture may not be a term that many people are familiar with in the context of this field. Most people relate this term to computer hardware and software design or business processes such as logistics or enterprise systems. The structure of a process system, or its architecture, is viewed as the hierarchy and relationship of a process system's components. But within the global biopharmaceutical industry, the term has a completely different meaning and holds a key strategic place in the list of activities necessary to develop a drug or biologic manufacturing facility design that meets regulatory compliance requirements.
For biopharmaceutical drug and vaccine manufacturing facilities, the relationship between product, process, and facility requires synergy across architecture and engineering disciplines, which is driven by a set of legally binding guidelines known as current good manufacturing practices, or the cGMPs.1 These strict regulatory guidelines are the foundation of current drug safety practice related to how these specialized facilities are licensed and operated. The critical first steps in developing concepts for proper operational effectiveness and regulatory compliance involve the execution of process architecture as presented for the first time in this book.
Biopharmaceutical process architecture involves the integration of process understanding and facility architecture concepts to create a design that meets the regulatory compliance guidelines for the manufacture of quality, safe drug, and biologic products. Product attributes, process parameters, and operational philosophy are defined and integrated via architectural programming activities that will define the solution(s) to an architectural problem, in this case, how best to provide a regulatory compliant manufacturing facility design.
This book focuses not only on the regulatory considerations driving facility design decisions but also on many of the different aspects of design specific to biomanufacturing pilot and production facilities for both biological therapeutics and vaccines. As the global biotech industry continues to grow into its fourth decade, more facility design companies will find themselves in a position to both understand and define facilities in a manner where the architectural program not only addresses function, form, economics, and time but also does so in a manner that will withstand regulatory scrutiny from different global agencies. Operational efficiency, flexibility, high-utilization rates, and a stringent focus on quality will take precedent over image. The practitioner leading the programming effort must not only establish the considerations, limits, and possibilities of the design but must also understand the product–process–facility relationship and be able to apply cGMP in all elements of the conceptual design.
The global biotechnology industry focused on drug and vaccine manufacturing will continue to grow; the execution of sound process architectural programming to define compliant facilities will be an essential part of this growth process. The authors contributing to this book are thought leaders within this industry and bring, along with their skills, a broad depth of experience in process engineering, architectural programming, regulatory compliance, facility operation, and aseptic manufacturing. Their willingness to contribute their time and energy to this project is not only greatly appreciated but is also a valuable and unique contribution to the expansion of the industry's body of knowledge.