Unique Challenges of Providing Bioanalytical Support for Biological Therapeutic Pharmacokinetic Programs

Abstract

Regulatory recommendations for providing bioanalytical support for biological therapeutics have co-evolved with the increasing success of these unique pharmaceuticals. Immunoassays have been used to quantify biological macromolecules for more than 50 years. These assays rely on the use of antigen-specific antibodies. More recently, LC-MS methods have being adapted to quantitate biologics. LC-MS has attributes that complement the limitations encountered by immunoassays. Whether employing immunoassay or LC-MS methods, compared with traditional chemical-based therapeutics, biological therapeutics present unique analytical challenges to analysts. In this article, we review bioanalytical strategies for supporting biologics and discuss the regulatory and analytical challenges that must be met.

Strategic Approaches to Optimizing Peptide ADME Properties

“…Displacement proteins (e.g., serum albumin) or peptides (structural analogs) are sometimes added to compete for the surface-binding sites (40). Organic solvents, acids, salts, or surfactants (e.g., Triton X-100 or Tween-20) can be added to overcome nonspecific binding by increasing peptide solubility (40,42).…”

“…For peptides with poor stability, blood/plasma samples need to be stabilized once they are removed from the in vivo systems (41). Protease inhibitors or cocktails (e.g., aprotinin to avoid proteolysis or oxidation of cysthiols) are usually added to the collection tubes on wet ice to cool the samples immediately after blood collection and to prevent further hydrolysis during sample preparation and analysis (42). Nonabsorptive collection tubes are used to minimize nonspecific binding (http://www.labonline.com.au/ products/48460-Eppendorf-LoBind-Tubes-and-Plates-andepT-I-P-S-LoRetention-pipette-tips).…”

Application and Challenges in Using LC–MS Assays for Absolute Quantitative Analysis of Therapeutic Proteins in Drug Discovery

“…A number of reviews have been published in recent year detailing protein quantification [20][21][22][23][24][25][26]; however, they were mostly focused in protein ana lysis in the development stage. This review will describe the key benefits and applications, as well as the techniques and challenges for applying LC-MS to support protein quantification in drug discovery.…”

Comprehensive Review on Manufacturing Process and Characterization of Biosimilar Drugs

“…Scientific advancements in recombinant genetic engineering techniques and refinements in manufacturing processes has made its path to success at a very great pace in the field where biological proteins are used in disease treatment (Cai et al, 2011;Tsiftsoglou et al, 2013;Lee et al, 2012;Nowatzke et al, 2011). Biological medicines play pivotal role in treatment for harmful and fatal diseases, such as cancer, hepatitis, autoimmune disorders, neurodegenerative diseases, and orphan diseases.…”