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perform a given task in the human body. To achieve this, laboratories
must make timely, confident decisions at early stages of development
- for which they need accurate and reliable quantitative bioanalysis
of a substance's pharmacokinetics and pharmacodynamics (how
a drug will be absorbed or metabolized in the body over time, for
instance). Given that just one in 5,000 preclinical candidates (inclusive
of chemically synthesized small molecules and biological entities) is
estimated to reach the commercial market4 - and considering the cost,
regulatory and ethical risks, and time delays accrued by progressing a
candidate that fails - achieving precise, reliable preclinical screening
is a matter of priority for the pharmaceutical industry.

Accelerated Drug Development with
Advanced Immuno-MS

Overcoming the Challenges of
Conventional Bioanalysis
LBAs, such as enzyme-linked immunosorbent assay (ELISA), are a
leading method of biotherapeutic analysis. These plate-based assay
techniques bring high sensitivity and throughput, but unfortunately
suffer from limitations.
In its simplest form, an ELISA comprises a multi-well plate of numerous
sample antigens, to which a mAb is applied and allowed to bind. To
perform successfully, an ELISA requires the generation of specific,
high-quality antibodies with specificity to the target antigen, which
can take a great deal of time and resources to develop. The method is
also sometimes limited in linear dynamic range as it quickly becomes
saturated over the drug profile, and can, therefore, be inadequate to
meet pharmacokinetic requirements without being recalibrated and
run multiple times. Furthermore, alongside their aforementioned
sensitivity to matrix interference, LBAs are highly susceptible to
anti-drug antibodies in animal studies, raising concerns around the
method's ability to pick out an analyte of interest from the copious
other constituents of a sample.
Based on advances in targeted proteomics technology, strategies
based on liquid chromatography-mass spectrometry (LC-MS) have
emerged as a promising way forward for bioanalysis. One of the
most common methods for protein quantitation by LC-MS is an
approach based on surrogate peptides, by which intact proteins are
digested and broken down into smaller, easier-to-analyze peptides.
Appropriate peptides are then chosen as a surrogate measure for
the protein and monitored via either triple quadrupole or highresolution MS. However, identifying a single low-level peptide
within a protein-filled sample - and differentiating between highly
similar peptides - remains challenging. Also, the sample preparation
procedures for surrogate peptide LC-MS may be an obstacle
to achieving the sensitivity required for precise and complete
quantitation at the low levels required.
Hybrid methods that unite LBA and MS (immuno-MS) bring the best
of both worlds to bioanalysis by combining the specificity of LBA
and the powerful and specific detection techniques of MS. ImmunoMS provides unparalleled selectivity and sensitivity and offers a
swift, streamlined universal method for preclinical bioanalysis of
mAb therapeutics.2
Pharmaceutical Outsourcing |


At the preclinical stage, methods of bioanalysis for biotherapeutics
must be robust, reproducible, and able to capture a humanized
mAb of interest from an animal sample (a humanized mAb being a
non-human antibody with a modified protein sequence to optimize
its similarity to naturally occurring antibody variants in humans).
Given the potential of immuno-MS, numerous pharmaceutical and
contract research organizations are opting for this technique in their
preclinical analysis of mAb therapeutic candidates. With immuno-MS,
targeted molecules are extracted from a sample using immunoaffinity
chromatography, during which biomolecules are separated based
on their specific binding interactions with another substance: in this
case, antibody and antigen. Targets are then digested (for peptidebased quantitation) and analyzed using MS.
Immuno-MS has proven beneficial in the case of preclinical analysis
of IgG-1 type mAbs.2 The high precision, selectivity, and sensitivity
of the technique facilitate earlier and more precise identification of
drug candidates that are likely to fail later in the drug development
process, enabling organizations to abide by the principle of 'fail fast,
fail cheap'. By identifying areas in which investment may be wasted,
and, conversely, areas in which it could lead to the most successful
outcome, drug developers can maximize their chances of success
at preclinical and even earlier points in the pipeline. As a result,
organizational profitability and reputation can be protected.
Advances in speed and simplicity through automated, bead-based
enrichment and digestion have enhanced the application of immunoMS by removing numerous time-consuming and error-prone manual
steps from such workflows. Automation increases analytical accuracy
by minimizing opportunities for manual error, in turn improving
reproducibility and protecting the integrity of analytical data. A
preclinical study may involve up to 100 samples, each of which
requires tedious immunoaffinity capture, digestion, sample transfer,
denaturation, reduction, and subsequent manual cleanup steps. By
implementing such procedures in parallel, and eliminating the need
for some steps, immuno-MS can shorten the time required for this
process to a matter of hours.
Through removing the need to generate specific antibodies per
biotherapeutic candidate, immuno-MS enables a universal method
| October/November/December 2020



Table of Contents for the Digital Edition of PharmaceuticalOutsourcingQ42020

Editor's Message
Editorial Advisory Board
CN Perspectives
Social Media Connections
Insider Insight - Price
Insider Insight - Ventura
Contract Manufacturing
Supply Chain
Contract Manufacturing
Interview with Yourway
Supply Chain
Clinical Trials
Supply Chain
Analytical Testing
Supply Chain
Clinical Trials
Analytical Testing
Horizon Lines
Industry News
Advertiser's Index
PharmaceuticalOutsourcingQ42020 - Cover1
PharmaceuticalOutsourcingQ42020 - Cover2
PharmaceuticalOutsourcingQ42020 - 1
PharmaceuticalOutsourcingQ42020 - Editor's Message
PharmaceuticalOutsourcingQ42020 - 3
PharmaceuticalOutsourcingQ42020 - 4
PharmaceuticalOutsourcingQ42020 - 5
PharmaceuticalOutsourcingQ42020 - Editorial Advisory Board
PharmaceuticalOutsourcingQ42020 - 7
PharmaceuticalOutsourcingQ42020 - CN Perspectives
PharmaceuticalOutsourcingQ42020 - Social Media Connections
PharmaceuticalOutsourcingQ42020 - Insider Insight - Price
PharmaceuticalOutsourcingQ42020 - 11
PharmaceuticalOutsourcingQ42020 - Insider Insight - Ventura
PharmaceuticalOutsourcingQ42020 - 13
PharmaceuticalOutsourcingQ42020 - Contract Manufacturing
PharmaceuticalOutsourcingQ42020 - 15
PharmaceuticalOutsourcingQ42020 - 16
PharmaceuticalOutsourcingQ42020 - 17
PharmaceuticalOutsourcingQ42020 - Supply Chain
PharmaceuticalOutsourcingQ42020 - 19
PharmaceuticalOutsourcingQ42020 - Contract Manufacturing
PharmaceuticalOutsourcingQ42020 - 21
PharmaceuticalOutsourcingQ42020 - Interview with Yourway
PharmaceuticalOutsourcingQ42020 - 23
PharmaceuticalOutsourcingQ42020 - Supply Chain
PharmaceuticalOutsourcingQ42020 - 25
PharmaceuticalOutsourcingQ42020 - 26
PharmaceuticalOutsourcingQ42020 - 27
PharmaceuticalOutsourcingQ42020 - 28
PharmaceuticalOutsourcingQ42020 - 29
PharmaceuticalOutsourcingQ42020 - Clinical Trials
PharmaceuticalOutsourcingQ42020 - 31
PharmaceuticalOutsourcingQ42020 - 32
PharmaceuticalOutsourcingQ42020 - Roundtable
PharmaceuticalOutsourcingQ42020 - 34
PharmaceuticalOutsourcingQ42020 - 35
PharmaceuticalOutsourcingQ42020 - Supply Chain
PharmaceuticalOutsourcingQ42020 - 37
PharmaceuticalOutsourcingQ42020 - 38
PharmaceuticalOutsourcingQ42020 - 39
PharmaceuticalOutsourcingQ42020 - Analytical Testing
PharmaceuticalOutsourcingQ42020 - 41
PharmaceuticalOutsourcingQ42020 - 42
PharmaceuticalOutsourcingQ42020 - 43
PharmaceuticalOutsourcingQ42020 - Supply Chain
PharmaceuticalOutsourcingQ42020 - 45
PharmaceuticalOutsourcingQ42020 - 46
PharmaceuticalOutsourcingQ42020 - 47
PharmaceuticalOutsourcingQ42020 - Clinical Trials
PharmaceuticalOutsourcingQ42020 - 49
PharmaceuticalOutsourcingQ42020 - 50
PharmaceuticalOutsourcingQ42020 - Analytical Testing
PharmaceuticalOutsourcingQ42020 - 52
PharmaceuticalOutsourcingQ42020 - 53
PharmaceuticalOutsourcingQ42020 - Horizon Lines
PharmaceuticalOutsourcingQ42020 - 55
PharmaceuticalOutsourcingQ42020 - 56
PharmaceuticalOutsourcingQ42020 - 57
PharmaceuticalOutsourcingQ42020 - Industry News
PharmaceuticalOutsourcingQ42020 - 59
PharmaceuticalOutsourcingQ42020 - 60
PharmaceuticalOutsourcingQ42020 - 61
PharmaceuticalOutsourcingQ42020 - 62
PharmaceuticalOutsourcingQ42020 - 63
PharmaceuticalOutsourcingQ42020 - Advertiser's Index
PharmaceuticalOutsourcingQ42020 - Cover3
PharmaceuticalOutsourcingQ42020 - Cover4