A well-designed study can help a biopharmaceutical company build quality and efficiency into its biopharmaceutical product
design and in-process development and commercialization. This approach provides a knowledge base for a better selection of
product formulation components, with respect to leachables.
Scientific understanding based on data obtained from this particular study can be used to support other pharmaceutical product
development processes. For instance, for different rubber stopper materials or other types of container/closure materials,
the potential leachables profile can be predicted based on its extractables profiles and the intended formulation and excipients
regime with greater accuracy for the model systems studied. The knowledge and understanding accumulated will in turn aid the
product development process and make it possible to develop safer and more efficacious medicines faster.
Based on our study, changes in the components in a biopharmaceutical formulation can lead to appreciable changes in the leachable
profiles. A thorough understanding of how various formulation components may affect a leachables profile can aid in selecting
appropriate formulation constituents based on the container/closure materials and storage conditions. Such an understanding
overcomes the limitations of a traditional selection process and allows the early adoption of a risk-based approach and QbD
at the beginning of product development. Consequently, drug development duration can be shortened significantly while product
quality, safety, and efficacy are maintained.
Xiaochun Yu, PhD, is a senior research scientist, Don DeCou, PhD, is a senior research scientist, Derek Wood is a laboratory manager, Steven Zdravkovic is a senior scientist, Heather Schmidt is an associate research scientist, Laurie Stockmeier is a scientist, Robert Piccoli, PhD, is an associate research scientist, Daniel Rude is a research scientist, and Xiaoya Ding, PhD, is the director of scientific and technical affairs, all at the cGMP laboratory, PPD, Inc., Wilmington, NC, 910.558.7585,
1. Yu X, Wood D, Ding X. Extractables and leachables study approach for disposable materials used in bioprocessing. BioPharm
2. Product Quality Research Institute. Leachables and Extractables Working Group. Safety Thresholds and Best Practices for
Extractables and Leachables in Orally Inhaled and Nasal Drug Products. Arlington, VA; 2006.
3. US Food and Drug Administration. Guidance for industry: Container closure systems for packaging drugs and biologics, chemistry,
manufacturing, and control documentation. Rockville, MD; 1999 May.
4. Europeans Commission (Enterprise Directorate General). EMEA guideline on plastic immediate packaging materials. Brussels,
Belgium; 2005 May.
5. United States Pharmacopeia (USP). General chapter <661> containers—polytethylene containers. Rockville, MD.
6. USP. General chapter <381> elastomeric closure for injections. Rockville, MD
7. European Pharmacopeia. Chapter 3. Materials for containers and containers. Strasbourg, France.