Two presenters at the BPI European Conference and Exhibition were unable to get corporate approval to comment without remaining anonymous. But we’re grateful for their help anyway and wanted to present their remarks here. . .

Interview #1: A researcher in formulations at a major pharmaceutical company

Q: Protein aggregates seem to be the most prevalent visible/subvisible particles that plague biopharmaceutical drugs (especially highly concentrated liquid formulations). What are some other contaminants that fall into this category?

A: “A lot of protein aggregates are soluble and subvisible. Whereas protein aggregates are almost universal, contaminants are evaluated case-by-case (such as degrading enzymes and leachables).”

Q: Will different methods work for detecting both, or do they require different analytical approaches?

A: “Most contaminants (such as metals) will likely need different analytical tools.”

Q: Is this becoming a bigger problem with highly concentrated formulations — or do certain types of products seem to be plagued more than others?

A: “High concentration generally exacerbates the aggregation process, but the inherent tendency is protein-dependent.”

Q: Can you explain a little bit about biophysical analysis in biopharmaceutical development?

A: “Some instrumental analysis falls into this category. The analysis is based on measurement of biology-relevant physical properties of proteins (such as higher-order structures). The results from some of the analysis can be linked directly to bioactivity.”

Q: Is it newly elevated to importance in formulations (and why), or has it always been a priority?

A: “I think that regulators’ increasing expectations of characterizing protein products led to the current efforts.”

Q: What analytical methods are most often involved?

A: “Fluorescence, CD, UV, IR, and so on.”

Q: Is DoE new to formulators, or have they been using it longer than other folks in biopharmaceutical development?

A: “DoE has a long history. Whether and how one should use it for biopharm development varies.”

Q: Is it true that DoE is requiring analytical laboratory and formulations personnel to learn more about the discipline of statistics?

A: “Recommended but not necessarily a requirement.”

Q: Or are companies hiring statisticians to help them?

A: “It depends.”

Q: What kind of work has DoE replaced in these laboratories?

A: “Any type of work that needs optimization.”

Interview #2: A department director at another major pharmaceutical company

Q: Protein aggregates seem to be the most prevalent visible/subvisible particles that plague biopharmaceutical drugs (especially highly concentrated liquid formulations). What are some other contaminants that fall into this category? Will different methods work for detecting both, or do they require different analytical approaches?

A: “Immunogenicity concern has led industry and regulatory authorities to use protein aggregation as a critical quality attribute, and highly concentrated liquid formulations are becoming more common industry-wide. I would caution one to say that aggregates are the most prevalent visible/subvisible particles. There are probably more cases of product recalls due to extraneous particles such as stainless steel particles and particles related to container–closure components. Analytical techniques are lacking for high-throughput evaluation of different types of particles and for differentiating proteins from nonproteins. There is also a heightened awareness of the gap in understanding 0.1- to 10-µm particle quantitation and identification of source and link to detection of aggregates below and above this size range.”

Q: Can you explain a little bit about biophysical analysis in biopharmaceutical development? Is it newly elevated to importance in formulations (and why), or has it always been a priority? What analytical methods are most often involved?

A: “Biophysical analysis is the evaluation of protein higher-order structure. It has been used for many years in biopharmaceutical development and is especially useful in formulation development. Circular dichroism, differential scanning calorimetry, and FTIR are common methods involved.”

Q: Certain speakers at BPI-Europe will discuss high-throughput approaches to forced degradation studies and preformulation product characterization work. In what other formulations/analytical laboratory work are such assays making a difference?

A: “High-throughput approaches can be very useful in cutting down formulation development time as a way to quickly cut down the formulation candidates before optimization.”

Q: Is design of experiments (DoE) new to formulators, or have they been using it longer than other folks in biopharmaceutical development? Is it true that DoE is requiring analytical laboratory and formulations personnel to learn more about the discipline of statistics? Or are companies hiring statisticians to help them?

A: “I would not say DoE is new to formulation, but a stepwise approach to look at one excipient at a time during formulation development is not uncommon. It is requiring formulators to know more about statistics, and in some cases work closely with in-house statistical experts to design/interpret study results. DoE also allows one to discuss ‘design space’ around formulation targets, which is in-line with QbD thinking.”

Check out what those and other presenters have to say in these five tracks of this year's BPI-Europe in Vienna, Austria (19-20 May 2010)!

• Scale-up, Economics, Manufacturing Strategies and QbD
• Cell Culture and Upstream Processing
• Recovery and Purification
• Formulation Strategies
• Analytical Methods

—cscott@bioprocessintl.com