Abstract
Today, we are experiencing unprecedented growth and innovation within the pharmaceutical industry. Established protein therapeutic modalities, such as recombinant human proteins, monoclonal antibodies (mAbs), and fusion proteins, are being used to treat previously unmet medical needs. Novel therapies such as bispecific T cell engagers (BiTEs), chimeric antigen T cell receptors (CARTs), siRNA, and gene therapies are paving the path towards increasingly personalized medicine. This advancement of new indications and therapeutic modalities is paralleled by development of new analytical technologies and methods that provide enhanced information content in a more efficient manner. Recently, a liquid chromatography-mass spectrometry (LC-MS) multi-attribute method (MAM) has been developed and designed for improved simultaneous detection, identification, quantitation, and quality control (monitoring) of molecular attributes (Rogers et al. MAbs 7(5):881–90, 2015). Based on peptide mapping principles, this powerful tool represents a true advancement in testing methodology that can be utilized not only during product characterization, formulation development, stability testing, and development of the manufacturing process, but also as a platform quality control method in dispositioning clinical materials for both innovative biotherapeutics and biosimilars.
Highlights
Today, we are experiencing unprecedented growth and innovation within the pharmaceutical industry
Multi-attribute method (MAM) has been applied to several early stage clinical programs with different classes of protein therapeutics and compared to current practices. This experience shows that the multi-attribute method (MAM) technology can be utilized for different types of protein therapeutics delivering highly specific and quantitative information, which is invaluable during process development and essential for molecular characterization
new peak detection (NPD) automatically identifies new peaks in samples tested in comparison with a reference, with some preset peak selection criteria implemented with the intention of minimizing false-positive peak detection
Summary
The AAPS Journal (2018) 20: 7 specific characterization work performed during product development (Fig. 1). As defined in ICH Q6B, product-related impurities are BMolecular variants of the desired product (e.g., precursors, certain degradation products arising during manufacture and/ or storage) which do not have properties comparable to those of the desired product with respect to activity, efficacy, and safety.^ CQAs in the category of product-related impurities can be related to the post-translational modifications (PTMs) and chemical modifications of various amino acid residues of the drug product, amino acid misincorporations (sequence variants), or cleavage of its primary sequence due to hydrolysis during production and storage [25] Conventional purity assays such as CEX-HPLC, cIEF, and CE-SDS used for lot release and stability testing are profile based and are often not capable of identifying and quantifying residue-specific CQAs. Each conventional assay is designed to primarily monitor one type of CQA and, in general, has limited resolution and specificity. As a result of such advancement in the use of mass spectrometry, it is feasible and common practice that detailed product characterization is performed earlier in the
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
