PharmaceuticalOutsourcingQ42020 - 40

ANALYTICAL TESTING

A Brief Guide on Designing a
Comprehensive Cell and Gene
Therapy Bioanalytical Strategy
Janine Micheli, PhD
Senior Group Leader
PPD® Laboratories Bioanalytical Lab

Catherine Vrentas, PhD
Group Leader
PPD® Laboratories Bioanalytical Lab

Panteli Theocharous, FIBMS, MS, PhD, FRCPath
Global Vice President, Cell and Gene Therapy Strategy Lead
PPD

Introduction
The field of cell and gene therapy (CGT) is rapidly developing, with the
number of therapies in development greatly increasing over the last
five years. The application of CGT provides the promise of significant
long-term health benefits to people suffering from a wide range of
diseases, from ophthalmological disorders to cancer.
In cell therapies, cells from a donor (allogeneic therapies) or from the
patient (autologous therapies) are propagated outside the body and
then introduced into the patient.1 In gene therapies, modifications
to the genetic material of somatic cells can be conducted inside (in
vivo) or outside (ex vivo) the body.1 Functional copies of a mutated
gene can be inserted or new proteins related to the therapeutic
approach can be introduced to the patient's genome. For example,
an inherited disease may involve a genetic mutation in a gene for a
key metabolic enzyme, resulting in a nonfunctional enzyme and toxic
accumulation of the enzyme's substrate in the body. A gene therapy
would introduce a functional gene into the body with the use of a
viral vector or lipid nanoparticle. Genetic modifications can allow
for constitutive production of the replacement enzymes, providing
significant advantages over alternative approaches that require
regular dosing of exogenous enzyme replacement therapies. Current
research is also aiming to develop therapeutics that perform finerscale editing of genetic mutations inside cells ( " gene editing " ).1
The transduction of host cells with viral vectors has a relatively high
efficiency compared to non-viral methods. However, challenges of
immunogenicity and cytotoxicity have led to an increase in the use
of non-viral gene delivery vectors for ex vivo and in vivo processes.
In addition to safety benefits, non-viral methods also offer the
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40

advantages of easier preparation, the ability to transfer larger genes
and considerably improved transfection efficiencies. Non-viral
genetic modifications are being explored as potential therapeutics
for HIV, beta-thalassemia and other diseases.

Case Example: CGT in Oncology
The oncology field provides a case example of the utility of CGT.
Historically, cancer treatments were based on surgery, chemotherapy
and radiation interventions. Over the past two decades, targeted
therapies - primarily monoclonal antibodies - have become
the gold standard for many cancer treatments. More recently,
immunotherapies that attack tumors by harnessing the patient's
immune system have emerged as a powerful tool in cancer treatment
regimens.2 One emerging immunotherapeutic approach is cell-based
therapy. Cell-based therapy can involve the transplantation of stem
cells or adoptive cell transfer (ACT), which consists of collecting and
using patients' own immune cells to treat their cancer.2
The advantages of autologous therapies include low immunogenicity
and avoidance of graft-versus-host disease. Conversely, the main
drawbacks are the length of time required for cell expansion, the
variability of the donor's starting material and the logistical challenges
of scaling production of individualized treatments.
Still, challenges such as source material shortage, invasive retrieval
methods, cell heterogeneity and purity have driven the search for
alternatives to allogeneic cell and gene therapies. In response to
these challenges, new methods for creating cells suited for allogeneic approaches are emerging. Mesenchymal stem cells (MSCs)
are derived from induced pluripotent stem cells (iPSCs), offering
| October/November/December 2020



PharmaceuticalOutsourcingQ42020

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
Roundtable
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
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