Biotechnology Operations

Principles and Practices, Second Edition

John M. Centanni, Michael J. Roy

• Publisher: CRC Press
• Year: 2016
• ISBN:
  9781498758857
• Edition: 2
• Topic: Medicine
• Subtopic: Biotechnology in Medicine

This book describes seven areas in the field of biotechnology operations as practiced by biopharmaceutical firms and nonprofit institutions. Revisions focus upon changes that have occurred in several areas over the past six years, with emphasis on regulatory, biomanufacturing, clinical and technical information, along with processes and guidlines that have added to the discipline. Examples are increased for new technical fields such as cell and tissue engineering. Further, illustrations or figures are added to each chapter to emphasize particular points.

1

Introduction to Biotechnology Operations: Planning for Success

Biotechnology Operations

Biotechnology encompasses a wide variety of scientific, business, and operational endeavors in life sciences. It is applied across a broad range of specific disciplines, for example, plant, animal, medical, microbiological, biopharmaceutical, agricultural, and environmental to name just a few. Biotechnology is practiced worldwide and at many institutions: small private firms, large public corporations, nonprofit organizations, universities, and research institutes. Those practicing biotechnology include individuals with diverse skills and backgrounds: entrepreneurs, scientists, business-persons, managers, product developers, and other highly educated and motivated specialists. As seen by the inexperienced and at the macro level, biotechnology appears to be a vast three-dimensional matrix, broad and oftentimes baffling in scope and operation. However, to those experienced in biotechnology, there is organization and rationale. The keys to successfully managing a biotechnology firm are a focus on carefully crafted plans and efforts to accomplish a specific objective and to integrate operational activities within the operational matrix. This is especially true for biotechnology product development operations, where the objective is to increase the value of specific products by moving them through sequential phases and to the marketplace.

Virtually every aspect of biotechnology has two common themes: (1) to extend our knowledge of life sciences and (2) to produce a product or service that someday will improve the condition of humankind. In the commercial sector of biotechnology, there is also the objective to profit financially. There are subplots to every biotechnology endeavor as well. Developing a novel biotechnology product, especially a biopharmaceutical, is an extremely technical, highly regulated, complex, expensive, and long process. Biopharmaceuticals are in development for more than 5 years, and it is not unusual for schedules to extend, from research to market approval, beyond 10 years. The risks associated with biotechnology are tremendous, since most biopharmaceuticals fail at some point in development. Yet, there are compelling reasons to undertake biotechnology product development. The profits can be substantial, and there are needs and markets for useful products. For some individuals, it is not financial incentives, but altruistic purposes or the challenge of pursuing an ambition and lifelong dream. This provides a stream of bright individuals willing to labor at bringing biotechnology products to market. So, biotechnology development continues to grow in importance, size, and scope, and is highly regarded by the public.

Biotechnology has its own jargon as evidenced by terms used in this book and other references listed in the Additional Readings, and a great amount of operational information, notably regulatory, is available at websites and some of these are identified in this book.

Words, some considered jargon, have developed to describe certain aspects of the biotechnology operational trades, and these can be confusing, even counterintuitive, to the uninitiated. The reader may refer to Glossary for definitions used in this book.

This book focuses on biotechnology product development, specifically the scientific skills commonly applied worldwide to move in an ordered manner a product from concept at the laboratory bench to the marketplace. It emphasizes product design, development planning, project management, and elements of each major operational function applied to the development process. These combined activities we refer to as biotechnology operations. The seven major functional areas of biotechnology operations, identified in Box 1.1, are further described in individual chapters of this book. Additional functional areas, such as business development and finance, also directly impact biotechnology operations, and these are recognized because they are keys to success.

The focal point of a biotechnology operation is the product, and at the heart of product development are the user and intended use. The operational team of professionals works together to add value, bring the product to market, and ultimately to the end user. Hence, a key to building a successful biotechnology operation is to maintain this focus on product and its intended use and the user. In biopharmaceutical development, the intended use is the product indication, a word that will be used repeatedly in this book. In medicine, an indication is defined as the reason a product is used to diagnose, prevent, or treat a specific disease or condition. An indication also identifies, to a great extent, the intended user of a biotechnology product. This is especially true for biopharmaceuticals. In addition to having an indication, biotechnology development is also based on an understanding of the molecular or cellular nature of a product and on the product’s safety, strength, purity, and potency.

Seven major areas of biotechnology operations are listed in Box 1.1. In addition, there is a need to integrate and coordinate each of these skills in an effective and timely manner, focusing on making operational headway, and moving the product toward market approval. Given the complexity of biotechnology operations, the need for careful planning is intuitive. Planning is an activity that results in a written strategy. Together they establish the objectives and also map out a means of integrating the skills and events that lead to success. Indeed, a product development plan (PDP) allows a development program to be successful. Without a carefully crafted and functionally integrated plan, biotechnology operations typically fail.

BOX 1.1 SEVEN MAJOR AREAS OF BIOTECHNOLOGY OPERATIONS

Operational Area	Definition	Chapters
Project Management	Lead the planning, organization, and management of the overall development project and associated resources.	2
Regulatory Affairs	Advise on regulatory aspects and climate for product development, coordinate activities with regulatory agencies, and ensure regulatory compliance.	3 and 4
Quality Assurance	Provide support to ensure that all efforts and the product are of highest quality through quality management, audits, documentation, and other quality functions.	5
Biomanufacture	Produce the highest quality product through phased manufacturing development and final commercial production.	6
Quality Control	Ensure quality product through laboratory testing.	7
Nonclinical	Develop pharmacology and toxicology laboratory and animal studies and reports to ensure the safe and proper use of the product.	8
Clinical	Determine the safety and effectiveness of the product when used to treat human subjects.	9

To begin our journey through biotechnology operations, this chapter introduces the planning process for product development. Think of the plan as a skeleton and each element of the plan a bone that gives structure to the overall operation. Chapters 3 through 9 describe individual functional areas that execute or flesh out the plan and provide operational activities (Box 1.1). The functional areas do the heavy lifting, so to speak, in an operation, and six of them are considered the muscles of an operation. Chapter 2 describes project management, the operational function that serves as the neural system to a biotechnology operation, coordinating movement of operational elements according to the plan.

Marketing, Financial, and Business Considerations for Development

Biotechnology products in general and biopharmaceutical products in particular, with their stringent regulatory guidelines and strict need for a high benefit-to-risk ratio, are particularly expensive to develop. So expensive, in fact, that investment capital and public funding often provide insufficient resources to support the complete product development cycle. Today, the total development cycle costs for a biopharmaceutical can reach or exceed one billion U.S. dollars. Although somewhat less expensive to develop, other types of biotechnology products, such as those in the agricultural or environmental sectors, might still cost in excess of one-half billion U.S. dollars. Indeed, some biotechnology firms never even enter the development arena because of high cost and inability to raise capital to meet projected expenses.

Biotechnology firms rely on both public or private financing and partnerships with traditional pharmaceutical firms to provide capital needed to reach their development goals. Of course, money always comes with tradeoffs and an investor or partner may hold definite ideas and opinions regarding how the biotechnology firm should develop the product. In the end, some biotechnology firms are acquired by the partner during the development cycle and well before a product comes to market. Raising capital is not a subject of this book, but one must consider expenses and budgets during development planning and again at every milestone.

Once a project has begun, financing and budgets continue to have an impact on decisions made both in planning and in executing a project. Indeed, they are often the primary consideration regarding a decision on whether or not to continue a product development project. There are tradeoffs for the biotechnology firm. Development of a specific product may necessitate the sacrifice of other endeavors, such as pursuing promising lines of research. The philosophy of a company may have to be changed to pursue development, with hiring of development staff offset by the loss of research scientists. Facilities inevitably must be added or modified to suit development efforts and, as noted later, this can be extremely resource intensive. Once these resources have been committed, there is no turning back without incurring significant loss of time and money. No wonder biotechnology executives typically refer to the decision to embark on development as betting the farm or entering the valley of death.

Given all these warnings, what is the prudent way for a biotechnology firm to enter product development? The answer is simple: one step at a time, with a market analysis, a carefully defined product and indication and a well-considered PDP.

Earlier in this chapter, a metaphor—skeletal, muscular, and neural systems—was used to introduce the concepts of biotechnology development plans, operational elements, and integration by project management, respectively. This metaphor is further explained and developed in Box 1.2. Further to this metaphor, consider that these three organ systems would not function properly in any animal without support provided by other organs: the heart, liver, and kidneys for example. So, it is in biotechnology development, where support from research, marketing, business development, management, and other areas is essential to the life of the operation. An important element of any good development program is the need to consider the advice, expertise, and support of individuals with skills that do not apply directly to the technical agenda of an operation but have great impact nonetheless. We have mentioned financing and now consider input from the business and marketing professionals. While these professionals might seem at times to perceive situations and issues differently from operational staff, their skills and judgment are indeed important throughout the development process and their input is especially critical to success at the planning stage.

BOX 1.2 A BIOLOGICAL METAPHOR FOR PLANNING BIOTECHNOLOGY OPERATIONS

A metaphor to planning a biotechnology operation is taken from the organized development of the mammalian neural, muscular, and skeletal systems. This metaphor seems relevant, given the biological nature of our professional work.

An organism is composed of individual organs and tissues, and as they develop and function they work together in harmony and allow the animal to function and survive. The skeletal, muscular, and neural tissues provide functions, respectively of support, movement, and perception of or reaction to stimuli. Each tissue arises in an exact manner, shaped according to a plan programmed in the genetic code. The developing skeletal system is composed of bones, logically arranged and able to provide the outline of a unique organism.

To begin the metaphor a biotechnology operation functions, or should function, in the manner of a healthy organism, with the individual organs and tissues coordinated and working in harmony. An operational plan, the PDP, is the skeleton of that operation. It provides shape to the overall project. Although the individual bones of an animal form a strong framework, they must move in an integrated and coordinated manner. For this to happen in an organism, muscle is the organ system holding bones in a particular manner, yet moving them so they are useful s...