Edinburgh Research Explorer
Regenerative medicine as a disruptive technology
Citation for published version:
Banda, G, Tait, E & Mittra, J 2019, 'Regenerative medicine as a disruptive technology: Implications for
manufacturing and clinical adoption', Cell and Gene Therapy Insights, vol. 5, no. 10, pp. 1287-1303.
https://doi.org/10.18609/cgti.2019.135
Digital Object Identifier (DOI):
10.18609/cgti.2019.135
Link:
Link to publication record in Edinburgh Research Explorer
Document Version:
Publisher's PDF, also known as Version of record
Published In:
Cell and Gene Therapy Insights
Publisher Rights Statement:
Copyright © 2019 Geoffrey Banda, Joyce Tait & James Mittra. Published by Cell and Gene Therapy Insights
under Creative Commons License Deed CC BY NC ND 4.0.
General rights
Copyright for the publications made accessible via the Edinburgh Research Explorer is retained by the author(s)
and / or other copyright owners and it is a condition of accessing these publications that users recognise and
abide by the legal requirements associated with these rights.
Take down policy
The University of Edinburgh has made every reasonable effort to ensure that Edinburgh Research Explorer
content complies with UK legislation. If you believe that the public display of this file breaches copyright please
contact openaccess@ed.ac.uk providing details, and we will remove access to the work immediately and
investigate your claim.
Download date: 10. Aug. 2022
www.insights.bio
1287
CELL & GENE THERAPY INSIGHTS
DECENTRALIZED MANUFACTURE
ORIGINAL RESEARCH
Regenerave medicine as a
disrupve technology: implicaons
for manufacturing & clinical adopon
Georey Banda, Joyce Tait & James Mira
Although regenerave medicine has been described as a disrupve inno-
vaon, there has been lile crical enquiry into the nature and locaon
of the disrupon. This paper, based on ten cases in the UK, analyses the
nature of disrupon for allogeneic and autologous therapies in terms of
manufacturing, distribuon and adopon in clinical sengs. We discuss
the challenges of dealing with inherent variability in living systems and
how this necessitates co-evoluon of technologies and innovaons. We
propose that understanding of the disncon between disrupve and
incremental innovaon, and of the nature, extent and locaon of the dis-
rupon across sectoral value chains, can help to guide company innova-
on strategies and government innovaon support policies for regenera-
ve medicine, as already proposed for industrial biotechnology.
Cell & Gene Therapy Insights 2019; 5(10), 1287–1303
DOI: 10.18609/cg.2019.135
INTRODUCTION
Regenerative medicine (RM),
which promises to cure disease and
respond to currently unmet medical
needs [1], is frequently described
as a ‘disruptive innovation’ [2,3].
However, there has been little crit-
ical enquiry into the nature and lo-
cation of the disruption, resulting
in missed opportunities to shape
the innovation ecosystem to make
it more supportive of RM therapies.
We have dened disruptive and
incremental innovation as follows
[4,5].
Disruptive innovation involves
discontinuities in innovation path-
ways, requires new areas of research
CELL & GENE THERAPY INSIGHTS
DOI: 10.18609/cg.2019.135
1288
and development (R&D), creation
of new modes of production and/or
new markets. It can lead to sectoral
transformations and the displace-
ment of incumbent companies, or
the creation of entirely new sectors,
all with signicant societal and
economic benets. ere is often
no pre-existing business model on
which to build a strategy for dis-
ruptive innovation and there may
also be a need to create a new value
chain, or a new role for the emerg-
ing technology in an existing value
chain.
Incremental innovation ts well
with the current business model
of a rm. It generates competitive
advantage and contributes to the
economy through more ecient
use of resources, or elimination of
wasteful or environmentally dam-
aging practices, but will not lead to
sectoral transformations.
is paper builds on the authors’
previous research [1,6,7]; providing
new empirical data and analysis to
inform our thinking on disruptive
innovation and how the concept
can be operationalized to deliver a
more supportive policy environ-
ment [5]. e key to this approach is
to attend to the extent of disruption
of incumbent company business
models, the location of that disrup-
tion within specic value chains,
and the impact of regulatory and
policy choices on the location and
extent of disruption. Our case study
of RM encompasses both allogeneic
and autologous therapies:
Allogeneic therapies are developed
by collecting cells from a donor,
manipulating them to form a mas-
ter-cell bank, then using them as
starting material to produce multi-
ple therapies administered to large
numbers of patients, generating at-
tendant economies of scale.
Autologous therapies are based on
collection of cells from a patient,
manipulation in the manufacturing
environment and re-introduction
into the same patient within a clin-
ical setting.
In line with the above deni-
tions, both allogeneic and autolo-
gous RM therapies are disruptive of
the business models of incumbent
small molecule pharmaceutical and
bio-pharmaceutical companies [1],
in that they require radically dier-
ent approaches to R & D, manufac-
turing, distribution and marketing.
Autologous therapies, while equally
disruptive of pharmaceutical busi-
ness models, could be regarded as a
relatively incremental development
for companies involved with organ
transplants or for blood transfusion
services (BTSs), albeit with some
disruptive elements, given the na-
ture of the properties of the material
being handled.
e approach adopted in this
paper contributes to understand-
ing where and to what extent au-
tologous and allogeneic therapies
display disruptive or incremental
innovation characteristics, based on
original case study interviews with
organizations involved in RM de-
velopment in the UK. It builds on
our previous research to show how a
disruptive/incremental lens can add
insights that are valuable in devising
policies to support the development
of innovative technologies.
BACKGROUND
Although there have been signi-
cant advances in scientic knowl-
edge and understanding of RM,
commercialization and large-scale
production of autologous and al-
logeneic therapies have remained
ORIGINAL RESEARCH
1289
Cell & Gene Therapy Insights - ISSN: 2059-7800
challenging. For allogeneic thera-
pies, being developed in large scale,
centralized manufacturing facilities
[8], disruptive challenges include:
the time and eort needed for do-
nor material collection, processing
and storage in a bio-bank under
current Good Manufacturing Prac-
tice (cGMP), followed by further
processing to produce therapies for
patients; cryopreservation of living
material, safe distribution of frag-
ile living materials, ensuring trace-
ability of cells following treatment;
and dealing with immunogenicity
issues in recipient patients. Many
of these factors also apply to autol-
ogous therapies being developed in
localized manufacturing facilities,
with additional challenges related
to the personalized nature of the
therapy, ruling out economies of
scale. e Department of Business,
Innovation and Skills (BIS) in 2011
[9] suggested that manufacturing
viable living cells for RM requires
the development of “new technol-
ogies, tools and techniques” and,
although considerable progress has
been made, for example in manu-
facturing process development, RM
therapy value chains are still a long
way from delivering a reliable, prof-
itable route to market [10,11].
Lipsitz et al. argued that the
new RM-related technologies span
manufacturing, distribution sys-
tems, shelf life enhancement and
automation (especially closed man-
ufacturing systems) [12]. is has
led to further calls for advances in
manufacturing and bio-processing,
because of the non-scalability of
existing technologies [9] and the
need for skills development in the
RM niche-focused areas. Abbasal-
izadeh et al. present a deeper anal-
ysis of the scientic, technological,
and commercialization challenges
of allogeneic therapies, suggesting
that although autologous therapies
are safer and often the preferred
choice, they do not provide a sim-
ple o-the shelf product for clinical
use [8]. ey also argue that produc-
tion of autologous therapies is time
consuming, skilled labor-intensive
and, from an operational perspec-
tive, the mechanics of isolating
cells and delivering the therapy are
problematic for elderly and criti-
cally ill patients unable to tolerate
biopsies. Lipsitz et al. demonstrate
that lack of highly skilled labor is
caused by current manufacturing
process requirements and the costs
incurred in training operators, in-
cluding routine validation of asep-
tic techniques for operators [12].
Additional issues include the need
to independently verify batch re-
cord protocols, active working time
delays due to suiting up procedures
with laboratory garments, and the
need for additional sta to facilitate
gowning. e calls for ‘closed man-
ufacturing systems’ are based on the
need to reduce some of these ‘neces-
sary redundancies’ of current clean
room operation procedures for
cGMP requirements. Other chal-
lenges include lack of value chain
integration, technology delivery
gaps, and arguably inappropriate
or disproportionate governance of
innovative technologies [4,6]. Given
the disruptive nature of RM, new
rm-to-rm linkages are needed to
create new value chains and, during
early development phases, broker-
age is important to create links with
stakeholders [6]. ese disruptive
challenges are not experienced by
manufacturers of small molecules
and other biologicals and they are
important for understanding the
unique hurdles RM manufacturers
face in assuring cellular product
CELL & GENE THERAPY INSIGHTS
DOI: 10.18609/cg.2019.135
1290
safety, quality and ecacy, as well
as traceability and attendant ethical
considerations.
Centralized & locally
distributed manufacturing
approaches
Harrison et al. argue that through-
out history there has been a steady
shift from localized, decentralized
production systems to centralized
production systems, underpinned
by the need to achieve economies of
scale and scope [13]. Centralization
was possible where manufacturers
were dealing with standardized
bulk products, which could be eas-
ily characterized and analyzed and
were accompanied by increasingly
automated processing and quality
assurance systems. Lipsitz et al. ar-
gue that, for RM therapies, scalable
production methods will determine
the cost of goods sold, leading to the
policy focus on allogeneic therapies
because of their potential economies
of scale and investment palatability
making them slightly less disrup-
tive of incumbent pharmaceutical
business models than autologous
therapies [12]. However, allogeneic
RM therapies are inherently dis-
ruptive of this centralizing trend
because of the greater variability of
biological inputs, creating technical
diculties in standardizing manu-
facturing and quality assurance and
creating a need for close collabora-
tion between therapy producers and
clinicians (see ‘RM manufacturing
processes’, ‘e links between man-
ufacturing systems and distribution
models’ and ‘Clinical adoption of
autologous therapies’ sections). For
these reasons, Harrison et al. foresee
autologous therapies being man-
ufactured in locally distributed,
‘near-hospital’ facilities [13]. is
argument informs our focus on the
nature and location of disruption in
the development of RM therapies as
it impacts on manufacturing, dis-
tribution and adoption in clinical
settings.
Given the challenges of producing
autologous cell therapies, decentral-
ized or locally distributed manufac-
ture is the only feasible approach for
autologous and gene-based cell ther-
apies. In response to BIS [9] and Ab-
basalizadeh et al. [8], Harrison et al.
[13] argue that, as a result of recent
advances in technologies that facil-
itate “reproducible, repeatable and
reliable manufacture of highly spe-
cialist products at a small scale” and
real-time monitoring Quality Man-
agement Systems (QMSs), it is in-
creasingly possible to move towards
such locally distributed manufactur-
ing models. ey also claim that this
small scale, locally distributed tech-
nology approach makes it possible to
handle “inherently unstable person-
alized cell and gene therapies”.
Locally distributed manufacture
of autologous cells will be an or-
der of magnitude more disruptive
of the existing pharmaceutical and
biopharmaceutical business mod-
els than current manufacturing
approaches to allogeneic therapies,
hence the lack of interest in these
therapies by these incumbent sec-
tors. For allogeneic therapies, rath-
er than adaptation of the existing
big pharma business model there
is a need to develop new business
models and value chains, involving
new start-up companies or existing
companies moving into health care
from other sectors of the econo-
my (e.g., investment in manufac-
turing processes by Lonza and GE
Healthcare).