March 2008

Bioassay Survey 2006–2007

Bioassays are required for a variety of purposes in the development and production of biopharmaceuticals including drug candidate selection, product releases, product stability assessment, and comparability to support proposed process changes. However, because of their complexity and susceptibility to many variables, bioassays often prove problematic and difficult to develop. Timely development of suitable assay systems represents a major investment on the part of the biopharmaceutical industry — but late development often results in even more costly clinical holds. PRODUCT FOCUS:…

Appendix 1: Designing for Process Robustness

A rich cup of coffee is what comes to mind for many people when you mention the word robust. For biotechnologists it is often a comfortable term, generally referring to the overall strength or ruggedness of a manufacturing process. However, the origin of the robustness concept for manufacturing is found in the field of robust design, which has for decades been a rigorous discipline with its own metrics, algorithms, and mathematical tools. Lately it has experienced a renewed interest in…

Cell Cultivation Process Transfer and Scale-Up

The introduction of therapeutic monoclonal antibodies (MAbs) has greatly revolutionized therapies for several cancer immune disorders (1,2,3,4,5). Benefits to patients have been substantial, translating into both increased life expectancy and improved quality of life. Currently, twenty-one therapeutic MAbs are registered for marketing in the United States, with the introduction of several more expected in the coming years (6,7,8,9,10,11). PRODUCT FOCUS: MONOCLONAL ANTIBODIESPROCESS FOCUS: Technology transfer (production) and analytical methods developmentWHO SHOULD READ: PRODUCTION AND PROCESS DEVELOPMENT, MANUFACTURINGKEYWORDS: IGF-1R, EXPRESSION, TECH…

A New Era for Bioprocess Design and Control, Part 2

The level or intensity of product and process understanding that can or should be achieved beyond the acceptable minimum level promises to be the scope of a continuing debate among biotech industry and its regulators. In practice, the path of increased understanding may follow a series of incremental steps toward the desired state (Figure 1) after a product launch. Realistically that is expected to occur when the level of product and process understanding has reached or slightly exceeded the minimum…

Shared Risk

Risk is inversely proportional to one’s distance from a problem. For regulators, it seems straightforward to control biopharmaceutical and medical device risk. For pharmaceutical, biotechnology, and medical device executives, however, risk is hardly so clearly defined; it extends, grows, twists, and compounds through a chain of suppliers, consultants, and business partners. So when regulatory officials claim that compliance accountability cannot be delegated, biopharmaceutical and medical device companies are left holding the bag. Years ago, as a C-level executive for a…

A New Era for Bioprocess Design and Control, Part 1

Elements of the biopharmaceutical industry’s new operating paradigm have inevitably created an immediate need to condense, interpret, and relate their implications to existing regulatory and industry practices. This also provides us with an opportunity to look at them in a broader context and in relationship to one another. Such a perspective may open up new directions in discussion on how design and control aspects of biopharmaceutical manufacturing are likely to evolve. These are exciting times for scientists, engineers, statisticians, quality…

The Biopharmaceutical Industry’s New Operating Paradigm

Currently the biopharmaceutical industry is transitioning to a new business model of production efficiency through implementing operational excellence (Op Ex). Borrowing from such principles as “lean manufacturing” and “Six Sigma” (6σ), and incorporating quality by design (QbD) (1), Op Ex is being applied through the implementation of such advanced enabling concepts and technologies as quality risk management (QRM) (2), process analytical technology (PAT) (3), and systems biology (SB) (4). Some people see a conflict here: This paradigm shift is occurring…

Throwing a Flag at Biosimilars

PHOTO COURTESY OF ROGER LUNDBLAD (PICTURED). When I officiated at high school (US) football, I learned a lot from the experience. Contrary to popular opinion, there are rule books referees study. However, although the rule book is modest in size, the case book for interpretations is large. This brings me to the topic of generic or follow-on biologicals and biosimilar products for which there will be rules, and the interpretations will be many. Continuing with the US football analogy, the…

IP Strategies to Combat Distribution of Counterfeit Drugs

Counterfeit products are no longer restricted to Gucci purses and Rolex watches. The pharmaceutical business has seen an alarming rise in the number of counterfeit products entering traditional distribution and supply chains. As a result, consumers can unknowingly purchase counterfeit pharmaceuticals from their local pharmacy and receive little or no therapeutic benefit, or worse, die as a result of ingesting counterfeit products. Pharmaceuticals are subject to counterfeiting in a number of ways. A counterfeit product may contain no active ingredient…

Biological Assay Development and Validation

IBC’s 16th annual Bioassay Conference is the meeting for learning about developing, qualifying, validating, and maintaining important biological assays. Come and discover the newest techniques for streamlining development and validation using easy-to-understand statistical approaches. Hear how other assay developers are accelerating their development plans and meeting aggressive timelines. Learn about use of the newest technology and regulatory trends to develop the right assay, at the right time, in the quickest possible way. After attending this conference, you will catapult your…