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By Hanns-Christian Mahler and Satish K. Singh

Hanns-Christian Mahler-finalSatish Singh-finalPolysorbates (PS) (or surfactants in general) are commonly added to biopharmaceuticals as stabilizers against interface-mediated stresses. They are recognized as critical excipients by the industry as well as regulators. In the last few years, a number of studies have explored PS as raw material, its stability, and its impact on product quality including Borisov et al. (2011), Hewitt et al. (2011), Kishore et al. (2011 and 2011a), Labrenz, and Borisov et al. (2015).

At the 2015 AAPS National Biotechnology Conference (NBC), we organized the symposium How Stable Is the Stabilizer? Polysorbate Degradation and Impact on Biopharmaceuticals where we explored (novel) analytical aspects as well as stability and degradation of polysorbates. As a follow-up, we want to discuss control strategies for this critical excipient both as raw material as well as in product formulations. New analytical methods enable detailed characterization of the raw material, beyond the compendial requirements. Methods to analyze polysorbates in products have also improved, although recovery in high concentration products can be challenging. The importance of this excipient, coupled with the heterogeneity of the raw material, the relatively low concentrations at which it is used, and the complexity of the degradation pathways and the degradation products has led to a resurgence of interest in all questions related to the use of polysorbates in biotherapeutics.

As the technical ability to monitor these compounds improves, there is a need to develop a control strategy for them. Also, regulatory authorities have been increasingly interested in these excipients, their analysis, and in the control strategy being used by companies for their products. The surfactant is usually added to a product at a set level based on its weight, which is controlled through the batch record. Many questions need to be considered and answered:

  • Should the excipient be monitored, and if so, how?
  • Should the monitoring be in-process or on release, and on stability?
  • Since some of the degradation products are “functional,” how should they be treated?
  • What should be monitored, since depending on the assay, different parts of the molecule may be tracked?
  • Are limits necessary? If so, how should they be determined?
  • How can risk assessment be used to guide decisions?

The 2016 AAPS NBC session Surfactants in BiopharmaceuticalsControl Strategy will provide an update on control strategy considerations related to surfactants and discuss these and other questions. Join us on Monday, May 16 from 8:00–10:30 am. Registration is open—visit the AAPS website today!

If you have any suggestions or questions that you would like to see addressed or discussed, please submit them in the comment section below.

Hanns-Christian Mahler, Ph.D., currently is head of drug product services at Lonza AG and was recognized as an AAPS Fellow in 2013.
Satish K. Singh, Ph.D., is a research fellow at Pfizer in the Biotherapeutics Pharmaceutical Sciences group. He has expertise in formulation, product and process development activities for biologics and therapeutic vaccines, and is involved with regulatory aspects of biologics development.