In the biopharmaceutical industry, the cost of failure—or not failing fast enough—can be high.
Recently, a large biopharma company was forced to pay a $100M fee to their partner after halting commercialization of a biosimilar. Three years after they started the commercialization project, the company cited the cost of manufacturing the drug as too high and its projected selling price too low to justify bringing it to market.1
Here, in a nutshell, is the challenging reality for biopharma today. Not only do companies have to grapple with increasingly complex large molecules and regulatory requirements that are becoming more stringent—they must also find ways to develop, manufacture, and analyze these molecules in a more efficient and cost-effective manner.
Regulatory bodies around the world continue to update their guidance for the industry with more stringent requirements for analyte monitoring in development and QC.2 Both the U.S. FDA and the European Committee for Medicinal Products for Human Use have recently rejected biologic license applications (BLAs) for insufficient data concerning overall quality, impurities, and stability.3,4
Yet the volume of attribute testing for large molecules is already high—roughly 5 to 10 times that used for small molecules.5 Adding more testing to this load does not in itself result in better analysis and understanding, and it certainly won’t help these companies to be more productive. Instead, better testing makes for better understanding, and for the biopharma industry that will require making better techniques more accessible. Gold standard techniques, such as liquid chromatography-mass spectrometry (LC-MS), analysis have to become routine.
LC-MS analysis offers the ability to directly measure multiple molecular properties/attributes simultaneously, often with greater sensitivity and selectivity than can be achieved by more traditional assay techniques.
Highly trained MS specialists, who have spent years learning the relevant instruments and techniques, carry out upstream “characterization” work for biologics through which a quality target product profile (QTPP) for each drug candidate is established. QTPPs typically include a full array of molecular attributes that should ideally be monitored throughout ongoing development work, including analytical method development and optimization, clone selection, process development, formulation development, and stability testing; in keeping with Quality by Design (QbD) principles.
Through extensive development testing, a subset of these attributes is then defined as critical quality attributes (CQAs). If altered, these attributes could potentially impact the purity, safety, and/or efficacy of the final biotherapeutic drug product. Broader access to LC-MS analysis for monitoring of product attributes throughout late-stage development, manufacturing, and even QC would not only enable better, more precise data to be captured, but it could be done so more efficiently as well.
As development and therapeutic use of biologics grows, expanding access to high-powered LC-MS analysis—in other words, making LC-MS monitoring routine—will increase in importance.
Register for our launch event to learn about a new, more accessible LC-MS system designed for laboratories that monitor biotherapeutics … Coming soon from Waters!
1. Stanton D. (2018) Merck drops Lantus biosimilar, blames pricing and production cost concerns. Bioprocess International.
2. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Veterinary Medicine (CVM). Bioanalytical Method Validation: Guidance for Industry. (2018).
3. Scavone C, Rafaniello C, Berrino L, Rossi F, Capuano A. Strengths, weaknesses and future challenges of biosimilars’ development. An opinion on how to improve the knowledge and use of biosimilars in clinical practice. Pharmacol Res. 2017 Dec;126:138-142. DOI: 10.1016/j.phrs.2017.11.002.
4. Price WN, Rai AK. Manufacturing Barriers to Biologics Competition and Innovation. 101 Iowa L. Rev. 1023 (2016).
5. Imarc Global Biopharmaceutical Market Report and Forecast 2012-2017.
6. Michnowicz J. (2011). Mass spectrometry in drug discovery and development. Nature Reviews Drug Discovery.
7. Analytical Testing Outsourcing Trends Update. (2017) Contract Pharma.
8. Haigney S. Outsourcing Analytical Processes in Biologics Development. (2018). BioPharm International.
SOURCE: Waters Corporation