Biomedical Engineering Reference
In-Depth Information
2.10 SUMMARY
There has been significant progress in developing Quality by Design approaches to small
molecules. Many of the principles used for small molecules, such as design space, risk
assessments, design of experiments, and PAT, apply to biotechnology products. Howev-
er, biotechnology manufacturing involves both complex products and complex process-
es. This combined complexity leads to greater uncertainty for biotechnology product
design spaces. Approaches to this uncertainty include a greater use of biological
characterization, mechanism(s) of action, and structure/function analysis in risk assess-
ments for product attributes. Appropriate statistical support for modeling, platform
approaches, conservative boundaries, and risk-based strategies for movement within a
design space can also provide confidence. Experience with actual applications in a pilot
program could provide information on organization, content, and appropriate evaluation
of QbD for biotechnology products.
A QbD application is not a requirement, but some level of product and process
knowledge is generally necessary for complex products. Although many safe and
effective products have been brought to market without demonstrating all the features
of QbD, the proactive and systematic use of risk management and science inmanufactur-
ing will ultimately make safer, better products at lower cost. In addition, leveraging some
of the structure/function information associatedwith QbDmay have added benefits, such
as facilitating clinical development and drug discovery.
Over the past two and a half decades, biotechnology-based pharmaceuticals have
moved from a single marketed product to a prominent role in treatment of many diseases.
Over this period, there have beenmany advances in the development, manufacturing, and
regulation of these products [56]. QbD can be an important step forward in this evolution.
ACKNOWLEDGMENTS
The authors acknowledge Keith Webber for his valuable comments in review of this
chapter. This chapter reflects the current thinking and experience of the authors.
However, this is not a policy document and should not be used in lieu of regulations,
published FDA guidance, or direct discussions with the agency.
REFERENCES
[1] U.S. FDA. Pharmaceutical cGMPs for the 21st Century: A Risk-Based Approach: Final
Report, 2004.
[2] U.S. FDA. Science Board Executive Summary November 16, 2001.
[3] ICH. Q8: Pharmaceutical Development, 2005. http://www.fda.gov/cder/guidance/6746fnl.
htm.
[4] U.S. FDA. Guidance for Industry PAT—A Framework for Innovative Pharmaceutical
Development, Manufacturing, and Quality Assurance, 2004. http://www.fda.gov/cder/
guidance/6419fnl.pdf.
