5. 4 BioPharm International®
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M
edicineshaveexistedsincethebeginning
of time—from what nature provided to
the evolution of modern science. There
has been a rapid evolution of APIs over
the years, driven by innovation with different thera-
peutic modalities, which, due to varying challenges,
require manufacturers to continuously learn and op-
timize their design processes. From antibodies to vi-
ral vectors to messenger RNA (mRNA) to oligos, each
modality comes with its own ecosystem for manufac-
turing that requires the flexibility to grow quickly.
It’s not just about the molecule mRNA. It’s the right
molecule at the right time. Thanks to the rapid devel-
opment of mRNA vaccines for COVID-19, the industry
now has the momentum to overcome the challenges
to realize the enormous potential of this technology.
Long before COVID-19, a small group of dedicated
scientists and researchers had been studying and ad-
vancingthistechnologyforcancerandotherdiseases.
Ittookmorethan30yearstoovercomeobstacles,such
as mRNA destruction by chemicals in the blood. For-
tunately, for the pandemic, scientists figured out how
to teach the immune system cells to consume mRNA
without drastic immune reactions.
Now, innovation is accelerating the development of
these therapeutics. With proven potential, the indus-
try will see the creation of new molecules that will
hopefully lead to improved treatments for patients.
With these advancements come process challenges
and the need to build resilient and flexible manu-
facturing strategies that can adapt to the changing
needs in a nascent industry.
Benefits of mRNA therapeutics
It may take years to reach the next breakthrough in nu-
cleicacid-basedtherapeutics,butthepotentialformRNA
technologytotransformglobalhealthcareisenormous.
Therearesomedistinctbenefitstothetechnology:
• Speed. Most traditional vaccines against viral
diseases are grown in chicken or mammalian
Accelerating the
Development of
mRNA Therapeutics
Scott Ripley
is the general manager,
nucleic acid, for Cytiva.
Manufacturing and processing challenges surrounding
mRNA can be overcome in order to realize the true
potential of a technology 30 years in the making.
DAN
RACE
-
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cells. This process and the associated shipping
of collected viruses can be complex, requires
many chemicals, and might take many months.
Incomparison,mRNAvaccinesarecell-freeand
grown from a DNA template. This template can
be sent electronically and synthesized quickly.
• Safety. In traditional vaccines, collecting and
growing vast quantities of a virus can be dan-
gerous, whereas no virus is needed for mRNA
vaccines. mRNA is non-infectious. Because it
does not enter the nucleus, there is no concern
for DNA integration.
• Efficacy. The mechanisms for delivery of
mRNA allow for stability and increased cell
delivery efficiency. This increases the amount
of spike protein produced—compared to tra-
ditional vaccines—and enables an effective
immune response.
• Flexibility and cost. In traditional vaccines,
each vaccine needs a bespoke manufacturing
process. mRNA vaccines can be scaled and stan-
dardized quickly; therefore, minimal changes
will be needed to the manufacturing process;
thus, reducing overall cost.
These are some of the characteristics that make
this technology promising for some of the world’s
most challenging infectious diseases, like the flu,
zika virus, and potential new pandemics. The ad-
vances made in mRNA vaccines for infectious dis-
eases are renowned, but less is known about the new
therapeutics being developed by reimagining what is
possible with existing technologies. In vivo gene-edit-
ingtechniquesarebecomingmorecommon.RNAcell
therapy is often selected as a more stable alternative
to CAR-T therapy, and mRNA can be used to deliver
the sequence of an antibody as an alternative to viral
vectors. In addition, mRNA therapeutics are being re-
searched for use in allergen-specific immunotherapy
and agriculture to replace pesticides. Clustered reg-
ularly interspaced short palindromic repeats-based
gene editing opens new pathways, gene-modified cell
therapies open new modes of action, and mRNA is the
way to access these modes.
Hurdles ahead
Despite the clear advantages of mRNA, there are
some obstacles to overcome. With the scope of
such a wide range of scales, it’s important to rec-
ognize that the broad spectrum of applications
and their needs will have an impact on the man-
ufacturing strategy adopted. The biopharma in-
dustry needs to establish a development toolbox
that is fit for its purpose. Legacy methods are de-
signed and optimized for monoclonal antibodies
or traditional vaccines, rather than mRNA, lead-
ing to bottlenecks in manufacturing. (See Figure 1
for the range of molecules in clinical development).
In addition, process is central to biomanufactur-
ing. The elements of process, facility, resources, and
infrastructure are integrated and influence each
other. Holistic solutions and incorporating these el-
ements can reduce project risks, stabilize costs, max-
imize capacity, and help speed up time to market.
Few manufacturers are equipped to handle all parts
of this process, and distributed processes are leading
to bottlenecks in logistics and the supply chain.
Challenges and bottlenecks in the development
of key materials, processes, and manufacturing are
contributing to challenges researchers and drug
developers are facing. mRNA and viral vector-based
therapies rely on plasmid DNA (pDNA), and the
good manufacturing practice (GMP)-quality sup-
ply has been significantly strained. Using cell-free
technologies to generate pDNA is a possible solution
that could reduce process timelines and improve
product quality.
Drug developers and manufacturers will need to
work collaboratively to address the challenges of the
in-vitro transcription process. This part of the process
can be costly because it is so complex and requires
the careful addition of multiple diverse components
to the pDNA template. All reactions are currently
batch-based; therefore, developing alternate reac-
tor designs that reduce the inventory of expensive
raw materials could make a significant difference
in productivity and costs.
Purification can be more challenging for mRNA
molecules. Due to their size and varying impurity
profiles, they do not interact well with traditional
chromatography resins. Flexibility in purification
technologies—i.e., allowing process development
scientists to mix and match media based on the spe-
cific characteristics of the molecule—could help al-
leviate this problem.
Encapsulation using lipid nanoparticles is another
critical step in mRNA processing. The lipid nanopar-
ticles used in mRNA delivery protect the nucleic
acid from degradation as the therapeutic makes its
way through the patient’s body. The lipids must be
dissolved in an organic solvent, which is typically
[T]he potential for
mRNA technology
to transform
global healthcare
is enormous.
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7
Development
ethanol, a highly flammable substance. Man-
ufacturers will need to have the capabilities to
ensure the safe use of these materials or use an ex-
perienced contract development and manufactur-
ing organization. Additionally, the lipids currently
in use were developed for small interfering thera-
pies. Investing in the development of better lipid
nanoparticle formulations or alternative delivery
technologies that improve conditions required for
storage stability could have a significant impact on
the delivery of mRNA therapeutics.
Currently approved mRNA vaccines have a degree
of temperature sensitivity, and cold chain logistics
are required to deliver these life-saving therapeu-
tics around the world. There is ample room for im-
provement here, and researchers can assess different
formulation technologies to achieve better stability
(and already are).
The future promise of personalized medicine
One approach to cancer immunotherapy involves the
use of personalized vaccines designed specifically for
individual patient’s tumors. The speed and flexibility
of the mRNA platform make this a promising technol-
ogyforpersonalizedtherapies.Asthepopulationisone
patient, the manufacturing is a small batch. This is an
area where we can expect to see future innovation that
willintensifyandcollapsetheworkflowintomicro-fac-
tories,efficientlyproducingoneproducttoonepatient.
Though the manufacturing processes can be similar
for personalized medicine, individual small-batch
scales will have some different manufacturing re-
quirements. Large population vaccines are usually
large-scale manufacturing, but those targeting a
smallerpatientpopulationwillmostlikelyneedaflex-
ible manufacturing line, which can handle multiple
products and offer the ability to scale out if needed.
With the scope of such a wide range of scales, it’s im-
portant to recognize that this broad spectrum of ap-
plications and their needs will have an impact on the
manufacturing strategy adopted.
Despite the challenges, mRNA therapeutics—more
than any other drug modality—have the potential to
go from mass population therapies, like the pandemic
response,totrulypersonalizedvaccinesbasedonthege-
nomeofagivenpatient.Whilethisbringsaspectrumof
risks and initially high costs, this could transform the
way chronic diseases are treated.
If small batches are needed for personalized medi-
cine as opposed to research, then traceability becomes
a major concern. Hence, the needs of medicine makers
become more focused on quality control (QC), patient
tracking,andautomatingtheprocesstocontrolasmuch
as possible. In small-batch manufacturing, the cost of
goods will be a hurdle for many manufacturers.
mAb
~5 nm
Adeno-
associated
virus (AAV)
~25 nm
Adenovirus
~90 nm
Plasmid
100–300 nm
Exosome
(EV)
30–200 nm
Enveloped
virus
(lentivirus)
Enveloped
virus
(other)
80–120 nm 80–450 nm
Lipid nanoparticle
(LNP)
50–1000 nm
mRNA
20–40 nm
Option 2D
FIGURE 1. Approximate sizes of a range of molecules used in therapeutic development.
The elements of
process, facility,
resources, and
infrastructure are
integrated and
influence each other.
FIGURE
COURTESY
OF
THE
AUTHOR.
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Flexibility to scale
Withmoremodalityandscalediversitythaneverbefore,
it’simportanttobuildinflexibleandresilientsolutions
thatallowresearcherstohavetheabilitytoscalewhere
needed. One way to look at the scale of manufacturing
istoestimatemarketsize,theuptakeofapotentialther-
apy, and the dosing strategy, and then calculate back-
ward from that. Investing in flexible manufacturing
processeswillmakeitpossibletogrow,allowingasmall
fast start with something that is easy to scale up or out.
Toavoidproblemslaterintheprocess,considerman-
ufacturability and scaling up from the beginning. A
protocolormethodthatquicklygivesapureproductfor
earlyclinicalmaterialmightbegreat,butifitcan’tscale
up or be used in manufacturing, this will be an issue.
Manufacturabilityincludesassessingmaterialsuitabil-
ityandthinkingaboutmaterialsourcingearly.Contin-
uous planning, a close relationship between customer,
manufacturer,andsupplieraswellasregularcommuni-
cationwithsuppliersarecriticalfortherapidexpansion
of manufacturing facilities. It is also essential to know
the quality attributes of the product; so, early thinking
on QC testing can save time later in the process.
There are a few steps that manufacturers can take
to reduce unknowns. Networking and collaboration
areessential,suchascommunicationandengagement
withscientists,tostayinformedonwhatisinthepipe-
line and innovations in manufacturing techniques.
Manufacturers can build flexibility into their
processes by ensuring equipment is scalable and
supports the transfer from process development into
GMP manufacturing.
For a manufacturing line, organizations can model
different scenarios to ensure that the core equipment
willperformintherangeneededtoreachthegoal.The
greatestflexibilityisusuallyachievedwithequipment
that has a single-use flow path that can be sized for
each product. The modeling will also show where you
shouldscaleoutinsteadofscalingup.Thinkflexibility
and optimized manufacturing for an investment.
Future strategies for therapeutics will rely on a
toolbox, including product innovations and applica-
tion data for antibody variants and novel therapies.
Researchers are continuously developing support for
current and future molecules. This diversity requires
an agnostic platform approach. ■
Drug Solutions Podcast:
How Pfizer Views Partnering and Investing for Emerging Therapies
BioPharrm International’s sister publication, Pharmaceutical Technology, presents the Drug Solutions podcast, where
the editors chat with industry experts from across the pharmaceutical and biopharmaceutical supply chain. Experts
share insights into the technologies, strategies, and regulations related to the development and manufacture of
drug products.
In a podcast that aired on Sept. 6, 2022, Chris Spivey, BioPharm and PharmTech’s editorial director, interviewed Uwe
Schoenbeck, senior vice president and chief scientific officer for emerging science and innovation at Pfizer. Some of
the areas discussed include repeat expansion disorders, senescence, DNA damage response and nucleic acid sensing,
deubiquitinase pathways, and neuroinflammation. Pfizer feels these hold special promise for new innovative therapies.
Through research collaborations, consortia, licensing, investments, and acquisitions, the emerging science and
innovation team at Pfizer seeks to harness external, cutting-edge preclinical assets and novel technologies in
emerging therapies. Increasingly, the focus is on true first-in-class mechanism, if not only in class programs, that
would allow us to bring real breakthroughs to patients.
Visit PharmTech.com/drug-solutions-podcast to learn how Pfizer’s external-facing research and development
scientists uncover the most promising emerging therapy concepts and ideas in thepharmaceutical landscape.
— The editors of BioPharm International
How Pfizer Views Partnering
and Investing for Emerging Therapies
September 6, 2022
PharmTech.com/drug-solutions-podcast
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T
here are many avenues that researchers
can—and do—pursue in the hopes of
finding treatments for a given disease,
condition, or disorder. One of those av-
enues is the research of oncolytic viruses to treat
cancer. BioPharm International spoke with Boris
Minev, president, medical and scientific affairs,
Calidi Biotherapeutics, about how oncolytic vi-
ruses can be harnessed for use in treatments, how
stem cells are utilized, how oncolytic viruses com-
pare to other methods of treatment on the market
today, and challenges encountered during devel-
opment and manufacturing.
Oncolytic viruses: an overview
BioPharm: Your company develops allogeneic
therapeutics in which oncolytic viruses are housed
within stem cells to treat cancer. To start, what are
oncolytic viruses, and how do these viruses have
the potential to be used to treat cancers?
Minev:Oncolyticvirusesselectivelyinfectandmulti-
plyinsidecancercells.Theyuseavarietyofmechanisms
to target and infect cells, which often involve recogniz-
ing a molecular marker of a cell’s uncontrolled growth
or ability to evade homeostatic checks and balances.
Whileoncolyticvirusesoccurinnature,manyhavebeen
modifiedinthelabtocarryspecificmutationsthatmake
themtargetandkillcancercellsmoreeffectively,which
improves their safety profile and increases their thera-
peuticpotential.
Oncolytic viruses have great potential to be har-
nessed to treat cancers because they replicate within
tumor cells in a targeted fashion, leaving healthy
cells unharmed. Oncolytic virus therapy is espe-
cially potent because it kills cancer cells in two ways.
First, the oncolytic virus selectively infects and rep-
licates within the cancer cells at the tumor site, caus-
ing them to burst. Second, this cellular debris and
viral antigens activate the patient’s immune system,
triggering it to seek and destroy cancer cells near and
Treating Cancer with
Oncolytic Viruses
Meg Rivers,
senior editor
Research into oncolytic viruses shows promise for treating cancer.
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far from the tumor site. Thus, all cancer cells at the
tumor site, circulating in the blood, and at distant
metastases—and any tumor cells that arise in the fu-
ture—are subject to thorough eradication by the im-
mune system, which reduces the risk of recurrence.
More importantly, the oncolytic virus therapies have
a high therapeutic index due to the following fea-
tures: minimal systemic toxicity, non-overlapping
with the toxicity of standard of care drugs; non-over-
lapping mechanisms of action with the standard of
care drugs, allowing effective treatment combi-
nations; low probability of generating treatment
resistance (not seen so far); and virus dose in targeted
tumors increases over time, as opposed to classical
drug pharmacokinetics where drug concentration
decreases over time.
BioPharm: Has other research been done on onco-
lytic viruses, or are there any oncolytic virus-based
drugs currently on the market?
Minev: Decades of research on oncolytic viruses
have been conducted before our work. But because
thehumanimmunesysteminactivatedtheseviruses,
they were largely ineffective in human trials. The
only oncolytic virus therapy in the US market today,
called talimogene laherparepvec (T-VEC), leverages
the oncolytic herpes virus to treat advanced, inop-
erable melanoma (1). T-VEC consists of unprotected
virus particles modified to activate some cells of
the patient’s immune system. Thus, the virus can-
not persist long enough to have a significant thera-
peutic effect because it is eliminated by the patient’s
immune system.
Our strategy of loading oncolytic virus particles
into stem cells takes a different approach. Because
we allow the oncolytic virus to amplify inside the
stem cells and to produce important virally encoded
factors prior to reaching the tumor, our therapies de-
liver a tidal wave of oncolytic virus particles primed
and ready to infect and kill tumor cells together
with important virus-derived and stem cell-derived
factors that are able to instantly modify the tumor
microenvironment to enhance the treatment effects.
Therefore, our therapy is more complex and effective
than just viruses packed inside cells.
Deciding what to pursue
BioPharm: What made you choose to research these
viruses for potential research? What potential did it
show at the onset?
Minev: I was deeply impressed after seeing the
results of the Phase I trial in glioblastoma, which
lengthened patients’ overall survival in this very
difficult-to-treat tumor from 14.6 months to 18.4
months (2). Importantly, in the subset of patients
with glioma with an unmethylated O6-methylgua-
nine-DNA methyltransferase (MGMT) promoter, the
median progression-free survival, and overall surviv-
als were 8.8 vs. five months and 18.0 vs. 10 months,
respectively (2). This was a remarkable achievement,
as this tumor type is largely non-responsive to the ex-
isting chemotherapy treatments. In this setting, the
safety and tolerability of this drug were significantly
impactful: it extended patients’ lives and caused only
mild side effects (i.e., symptoms of cold or flu). I saw
the potential for future trials testing more intensive
treatments with NeuroNova (NNV) with the poten-
tial for affecting more dramatic improvements in
survival without diminishing quality of life. In
parallel, Calidi sought to utilize a similar approach
to treat patients with advanced metastatic solid tu-
mors. In a clinical trial, patients with a wide variety
of solid tumors, including head and neck cancers,
melanoma, and breast cancer, were treated using our
approach (3). Again, side effects were minimal, and
we were astounded to see some of these patients’ tu-
mors shrink significantly because of our treatment.
Utilizing stem cells
BioPharm: Why are oncolytic viruses housed within
stem cells? What led to the discovery of using stem
cells rather than other vectors?
Minev: Oncolytic virus therapies over the years
could not achieve their therapeutic potential because,
when delivered to a patient unprotected, the viral
particles were destroyed by the patient’s immune sys-
tem before they could affect the cancer cells. That’s
Oncolytic viruses
have great potential
to be harnessed
to treat cancers
because they
replicate within
tumor cells in a
targeted fashion,
leaving healthy
cells unharmed.
— Boris Minev,
president,
Calidi Biotherapeutics
Development
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where stem cells come in. The role of stem cells is
three-fold. Stem cells:
• Protect the oncolytic viruses from elimination
by the patient’s immune system
• Amplify the viral particles, serving as mini
bioreactors for this therapy
• Produce potent immune modulators, able
to modify instantly the tumor microenviron-
ment to support virus multiplication and tumor
cell targeting.
Calidihasbeendevelopingcells,derivedfromfattis-
sue,suitedtodeliveranoncolyticvirustosolidtumors,
as was shown in a Phase I trial of an oncolytic vaccinia
virusdeliveredbyautologousstromalvascularfraction
cellsforthetreatmentofsolidtumors(3).Similarly,the
labs of Matt Lesniak and Karen Aboody have been de-
velopinganoncolyticadenovirus,which,whenloaded
into a neural stem cell line, displayed enhanced ther-
apeutic efficacy in a mouse model of glioblastoma—a
veryaggressivebraintumor(4).Theirongoingworkled
to a Phase I clinical trial of a drug named NeuroNova
(NNV), with results demonstrating NNV’s strong po-
tential to treat glioblastoma in humans (2).
Oncolytic viruses vs. other methods
BioPharm: How does the use of oncolytic viruses
as a method of treatment compare to the methods
that are on the market today? What are the differ-
ences in how they function?
Minev: Cancer treatments today are highly var-
ied, but one thing they have in common is that they
often come with severe side effects that diminish
the quality of life. For example, while many chemo-
therapies are toxic to cells proliferating rapidly and
out of control, they do not specifically target cancer
cells. Therefore, these drugs kill healthy cells in ad-
dition to cancer, which causes severe side effects.
Immunotherapies on the market today are designed
to treat cancer in a more targeted way. These include
monoclonal antibodies, checkpoint inhibitors, T cell
therapy, and cancer vaccines. Harnessing the im-
mune system to seek and destroy cancer cells the-
oretically leaves healthy cells unharmed. In prac-
tice, however, the different immunotherapies can
be remarkably effective but come with a range of
immune-related side effects.
Oncolytic viral therapy is a type of immunother-
apy that is exceptionally powerful because of its
dual mode of action: initially, the oncolytic virus
infects, multiplies, and spreads, directly killing can-
cer cells. As the contents of the tumor cells dissipate
into the tumor microenvironment alongside viral
antigens, the patient’s immune system activates to
clear away any remaining cancer cells. Moreover,
the safety profile of oncolytic virus therapies is bet-
ter than other immunotherapy drugs. For example,
chimeric antigen receptor T cell therapies can trig-
ger life-threatening toxicity events in the patient. In
contrast, oncolytic virus therapies cause only mild,
flu-like symptoms in patients.
Developing treatments
BioPharm: What has the development of treatments
using oncolytic viruses been like? What challenges
did you encounter along the way?
Minev: In the last seven years, Calidi’s scientific
and manufacturing teams led by Antonio Santidrian
have overcome numerous challenges. We were able
to develop many optimized protocols for stem cell
expansion and characterization, including the de-
velopment of specific media and growth factor cock-
tails as well as precise protocols for stem cell loading
with oncolytic viruses. Importantly, we perfected the
freezing and thawing protocols for our therapies to
allow instant preparation of our products without
the need for any additional processing steps at the
clinical sites. This development is essential to allow
effective commercial development of our products
to be able to treat thousands of patients with cancer.
FDA reviewed investigational new drug (IND) ap-
plications for NNV swiftly and has reviewed a draft
of an IND for SuperNova, providing invaluable advice
and recommendations for the final IND submission.
Additionally, the scientific community has shown a
great deal of support and excitement for the promis-
ing early preclinical and Phase I data.
Manufacturing challenges
BioPharm: Do you foresee any challenges in manu-
facturing treatments using oncolytic viruses?
Minev: As already mentioned, due to the exten-
sive manufacturing development and optimization,
we do not foresee any significant challenges during
the scale-up of our therapeutic products. The core
components of our therapies are allogeneic stem
cells and viral particles, which are straightforward
and cost-effective to expand commercially. The
subsequent production step of the therapy is highly
streamlined: the components are combined and the
process of loading the oncolytic virus into stem cells
has been optimized extensively at our company over
the past seven years.
References
1. National Cancer Institute, “Talimogene Laher-
parepvec,” www.cancer.gov, accessed July 2022.
2. J. Fares et al., Lancet Oncol, DOI:10.1016/S1470-
2045(21)00245-X (June 29, 2021).
3. B. Minev et al., J Transl Med, DOI:10.1186/s12967-
019-2011-3 (Aug. 19, 2019).
4. A. Ahmed et al., Mol Ther, DOI:10.1038/mt.2011.100
(Sept. 1, 2011). ■
14.
15. 14 BioPharm International®
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T
he rapid growth of the cell and gene therapy
(CGT) industry has highlighted a need
for more universally accepted definitions
and processes involving chain of identi-
ty (COI) and chain of custody documentation for
raw materials. Current good documentation prac-
tices (CGDP) exist and are enforced by regulatory
bodies, but large differences remain in how these
practices are implemented across the industry.
What’s more, diverse protocol operations cause chal-
lenges with individual practices.
Theindustrymusttakestepstoimprovedocumenta-
tion integrity and standardize when possible to reduce
risk.Errorscanleadtomanufacturingholdsanddelays
or, worse, cause a negative outcome for a patient.
Documentation integrity is fundamental to health-
care and critical for the successful manufacturing of
cellular starting material. Standardization is not easy
or quick, however, and customization will be needed
in some situations.
Until standardization occurs, ensuring a system
for real-time post-apheresis raw material documen-
tation and labeling review prior to release can reduce
delays to manufacturing and increase document and
labeling integrity.
Neccesity of real-time
documentation and labeling review
Document and labeling integrity—meaning the doc-
ument or label is completed per the set requirements
andislegibleandaccurate—canbedifficulttoachieve
because of the variability in processes, protocols, doc-
uments, and standard operating procedures.
All centers that collect allogeneic and autolo-
gous starting material will have individual quality
systems that outline the expectations within that
system. CGT sponsors or manufacturers may have
their own quality systems by which a collecting
center must abide. These varying systems often
are not the same, and a center may be collecting for
Real-Time Post-Apheresis
Documentation
Decreases Errors
Julie Tilbury,
is a collection
network liaison at
Be The Match BioTherapies.
Document integrity is critical in the provision of raw
materials for cell and gene therapy manufacturing.
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15
multiple sponsors all with varying protocols and
documentation requirements.
Theinconsistenciesacrossorganizationscanleadto
documentation errors due to unfamiliarity. Some of
theseerrorscanleadtoamanufacturinghold,suchas:
• a mismatch of information (i.e., volume on a
certificateofanalysisdoesnotmatchthevolume
on the product label)
• incomplete or missing information or data
• information that is not legible
• test results that are out of client specifications
• any issue with the COI.
These types of issues must be corrected to avoid
manufacturing delays. A real-time raw material
documentation and labeling review is intended to
catch these types of errors prior to product release
from the collection site.
A real-time post-apheresis review process
Researchers tested a real-time post-apheresis raw ma-
terial documentation and labeling review system in
January 2018. An organization that became opera-
tional in 2016 had gained visibility within a year of its
launch because of its documentation collection pro-
cess across centers that were collecting allogeneic raw
material. Researchers at the organization conducted a
retrospective review in December 2017 of six months’-
worthofcollectiondocumentation,whichrevealeder-
rors in the documentation that accompanied the raw
materials that were delivered to the manufacturer.
Based on the documentation errors found in this
review, a pilot program was launched in January 2018
to establish a real-time, pre-release review of collec-
tion documents. The goal of the pilot program was
to enhance collection-site support and reduce docu-
mentation errors.
After six months, the program realized a 60% re-
duction in documentation quality incidents (1). This
success, along with the evaluation of product labels,
led to the inclusion of the product label in the re-
al-time, pre-release review.
Documentstypicallyreviewedinreal-timeincluded:
• certification of analysis
• certificateofcompliance,perregulatoryauthority
• reviewofhealthhistoryscreeningquestionnaires
and record of physical exam
• Information Standard for Blood and Transplant
(ISBT) 128 label
• biohazard tag(s), as applicable
• donortestresults(e.g.,completebloodcount[CBC]
with differential)
• product test results (e.g., CBC with differential,
flow cytometry, etc.)
• institutional collection procedure records.
Over the next year, documentation errors contin-
ued to decline. January 2018 and June 2019 demon-
strated a 90% reduction in documentation and label-
ing quality incidents (1). In June 2019, the real-time
review moved from a collection network support
team within the organization doing the review to
that organization’s quality control (QC) unit, and the
reduction in documentation and labeling quality in-
cidents continues to be maintained.
This error reduction has been maintained even as
more collection facilities began providing raw mate-
rialatincreasingvolumesformultipleprotocols.While
thiscollectionvolumeincreaseledtomoreerrorsbeing
identified, the review process resulted in a significant
decreaseindocumentationerrorsthatgotcarriedover
to the manufacturer and which could lead to a hold.
In addition, the organization found that individual
sites are conducting a more robust review and verifi-
cation process prior to sending documents for the re-
al-time review. Therefore, errors are being identified
and corrected earlier in the supply process, leading to
greater efficiencies and fewer delays in the packaging
and release of the product.
The reviews have also allowed for the identification
ofcommonerrorsacrosssites.Asaresult,theorganiza-
tion has been able to make improvements in training,
document design, and documentation instructions.
These results all demonstrate the critical value of
a real-time, post-apheresis review.
Steps to a real-time review
The real-time review process begins after the product
has been collected and any processing steps are com-
plete. Once the site has completed all its required doc-
umentation and labeling, it submits a scanned copy of
the required documents and product labels (including
aliquots or product parts) via secure email to the orga-
nization conducting the real-time review.
The QC unit of that organization communicates to
thesitethatthedocumentshavebeenreceivedandthe
review has started. If there are no errors, the QC unit
sendsanemailwiththeapprovaltoreleasetheproduct
to the manufacturer.
Iferrorsaredetected,thesitereceivescommunication
identifyingtheerrors.Thesitethencorrectstheerrors
and resubmits the documents or labels for review. The
The industry must
take steps to improve
documentation
integrity and
standardize.
Manufacturing
17. 16 BioPharm International®
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QC unit reviews the revised documents or labels to
ensure they are correct. The approval for product
release is provided only after all identified errors have
been corrected.
Currently,apost-apheresisreviewofdocumentation
and labeling requires a minimum of 40 minutes.
A real-time review process in action
Prior to creating a real-time review process, organi-
zations that support both collection sites and CGT
sponsors can support protocol development. This
assistance helps ensure that the research protocol
requirements for documentation and labeling are
within the abilities and regulatory standards of the
institutions collecting the raw material.
Once the sponsor’s protocol is complete and
the sponsor’s requirements and documents are in
place, the standard review process design can begin.
This is the first step in putting the real-time review
process into action. The process must be designed to
be time-sensitive, precise, accurate, and repeatable
for every review.
The review organization will determine each ele-
ment of the form or label that will be reviewed for
each specific document. The process design will
occur with every new protocol—and sometimes on a
site-by-site basis—because different collection sites
may document a specific parameter in a different
location on the institution’s document, for example.
This process-design step builds a controlled work
aid checklist that enables a standard review process
for each protocol that encompasses all the protocol
requirements and all the documents.
Training raw material collection sites
Training the sites that will collect raw material for
the protocol is the next critical step. One collection
site may be collecting for six or seven protocols. Be-
cause the desired level of documentation standard-
ization has not been achieved in the industry yet,
each protocol may have slight variations. Therefore,
this training must happen for each protocol.
The training goal is to help the site understand the
documentation requirements of the protocol, what
the real-time review process entails, and the site’s
role and responsibility to documentation, real-time
review, and product release.
Ultimately, the initial documentation, the docu-
mentation review, and the documentation verifica-
tion is the role and responsibility of the collection
site. A focused verification at the collection facility
prior to a pre-release document review creates an effi-
ciency that will reduce review time and avoid cellular
raw material release delays.
The real-time review by the QC unit is intended to
catch errors that were not discovered during the site’s
documentation review and to correct those errors to
avoid manufacturing delays.
How CGT industry can support document integrity
Document integrity is a critical element in the CGT
industry. The varying protocols among CGT sponsors
could increase the likelihood for document or labeling
errorsasmoreprojectsreachclinicaltrialsandcommer-
cialization.Whileareal-timerawmaterialdocumenta-
tion and labeling review such as that described in this
articlecanreduceerrors,theindustrymustworktoward
standardization in the areas where it makes sense and
agree on the areas where customization is necessary.
By aligning in these areas, the industry can avoid
the risks associated with document errors that could
lead to a negative patient outcome.
Aligning will require stakeholders across the in-
dustry to get involved in efforts, such as those led by
the Standards Coordinating Body (SCB). For example,
different stakeholders use different tracking systems
andformats.AnSCBworkinggroupiscurrentlywork-
ing on definitions and key requirements for a stan-
dard COI identifier that would allow for consistent
and efficient tracking of CGTs throughout collection,
production, and delivery. The SCB group’s goal is to
avoiderrorsthatcouldleadtothewrongtherapybeing
administered to a patient (2).
Industry stakeholders must be willing to review,
evaluate, and revise their documents and standardize
wherepossible.Theevaluationincludesreviewingthe
errors that are occurring and determining if some er-
rors are due to form design or lack of clarity and could
be avoided with revisions.
Finally, the real-time feedback loop described in
this article should be a standard implementation. It is
not valuable to provide only an annual performance
report. It is more impactful to provide immediate
feedback to the team involved in that collection to
immediately resolve an error and provide a greater
understanding of the requirement.
In CGT, the stakes are high. The therapies in de-
velopment provide hope and opportunity for people
who oftentimes have no other treatment options. The
industry must act to ensure document integrity and
avoid errors to avoid risk to patients.
References
1. E. Schaller and J. Tilbury, “Criticality of Document
Integrity in Provision of Raw Materials for Cell and
Gene Therapy Manufacturing,” poster presentation
at the ASFA 2022 annual conference (Philadelphia,
Pa., May 4–6, 2022).
2. Standards Coordinating Body, “Project: Chain of
Custody/ChainofIdentity,”www.standardscoordinat-
ingbody.org/project-chain-custody-identity, accessed
May 20, 2022. ■
18. Certainty
is Our Commitment
Your products improve lives every day. We help leading
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T
he field of cell and gene therapy has deliv-
ered personalized and, in some cases, cura-
tive therapeutics for various conditions in-
cluding cancer and monogenetic disorders.
Cell and gene therapies have been studied in various
forms for decades, primarily in academia, and in re-
cent years have gained traction in treating real-world
conditions. The tide began to change in cell therapy
about a decade ago with the treatment of the first pa-
tients with CTL-019, the first chimeric antigen recep-
tor T cells (CAR-T) approved by FDA, now known as
Kymriah, at the University of Pennsylvania to treat
acute lymphoblastic leukemia (ALL). And in gene
therapy, Zolgensma took center stage for its ability
to provide children with certain forms of spinal mus-
cular atrophy (SMA), many times lethal by age four, a
potentially curative treatment.
As the pace of commercial approvals begins to gain
steam, there are key questions about how to effi-
ciently develop and, potentially more importantly,
manufacture these therapeutics at a cost that bal-
ances revenue with affordability. It’s well known that
cell and gene therapies are driving massive innova-
tion in medicine. According to a report, the market
for cell and gene therapies is expected to reach more
than $36 billion by 2027, driven by the increasing
number of clinical and commercial cellular and gene
therapy products (1).
While cell and gene therapy approvals are increas-
ing and moving into larger indications (e.g., the de-
velopment of a cell therapy for multiple myeloma)
challenges remain. Many therapeutic developers
both large and small lack critical expertise to effi-
ciently advance cell and gene therapies to clinic and
commercial production. These gaps span the devel-
opment journey, from how to structure preclinical
studies through chemistry, manufacturing, and
controls (CMC) filings and regulatory submissions.
Compounding a complex cell and gene therapy devel-
opment framework is its fragmented nature, which
The Road to Personalized
Medicine: Reimagining
Drug Manufacturing
Matt Hewitt
is executive director,
Scientific Services
Cell and Gene Therapy
at Charles River.
For cell and gene therapies to reach their full
potential, changes in manufacturing must be explored.
ANDRII
YALANSKYI
-
STOCK.ADOBE.COM
20. www.biopharminternational.com Emerging Therapies 2022 eBook BioPharm International®
19
results in developers managing numerous external
relationships. This might represent a small inconve-
nience for large therapeutic developers, but for small
start-ups, it can be a significant hurdle to hire nu-
merous project managers and other subject matter
experts to choose and manage external vendors. Fur-
ther, because program development is many times
iterative, delays occur at various points which put
developers in a challenging position to realign time-
lines across multiple external vendors. As a result,
therapeutic developers are increasingly searching
for a cell and gene therapy portfolio that can support
them throughout program development.
Evolving traditional manufacturing models
The biggest hurdle to cell and gene therapies realizing
theirfullpotentialisefficientclinicalandcommercial
manufacturing. Therapeutic developers need practi-
cal solutions so these potentially curative therapies
can reach the patients that need them most. There
are also business considerations; if stable, robust,
cost-efficient manufacturing processes cannot be es-
tablished, progress of therapeutics development for
rare and ultra-rare disorders with small patient pop-
ulations, where patient need is highest and little to no
other therapeutic options exist, may be limited.
Whether therapeutic developers are manufactur-
ing viral vector gene therapies such as AAV or cell
therapies like tumor-infiltrating lymphocytes (TILs),
CAR-T or T-cell receptor (TCR-T), they are becoming
increasingly savvy in exploring closed, automated
(and potentially scalable) manufacturing platforms.
Amongst the field, most agree additional automa-
tion is needed to reduce manufacturing costs, but
the key question is when to implement manufactur-
ing automation. As part of their early-phase clinical
activities, specifically Phase I, therapeutic devel-
opers are required to dose multiple patient cohorts
with increasing doses of their experimental therapy.
Focusing on cell therapy, dose-escalation studies
often cover a wide dose range, typically low tens of
millions to billions of cells. It is difficult to utilize
a single closed, automated manufacturing platform
efficiently that can accommodate all dose levels.
Early-phase clinical activities also serve as a value
inflection point for many therapeutic developers in
cell and gene therapy; until they see positive safety
as well as potential efficacy signals, therapeutic de-
velopers are hesitant to invest in closed, automated
manufacturing platforms.
Aside from decisions about manufacturing plat-
forms, therapeutic developers also develop robust
and consistent analytical suites for product release.
Analytical development and qualification for cell and
gene therapy products can be challenging, especially-
the product-specific identity and potency (function-
ality) assays. These assays are particularly challeng-
ing in cell therapies where unmodified cells are used
as the drug product and are truly personalized, such
as autologous tumor-infiltration lymphocyte (TILs)
or autologous neo-antigen T-cell receptor (TCR) ther-
apies. The regulatory agencies have been clear that
a significant (positive) clinical result is not enough
to gain commercial approval and analytical develop-
ment should start as early as possible to prevent any
regulatory filing delays.
As the industry continues to see development of
next-generation cell and gene therapies, there is a
need to reimagine how these therapies are manu-
factured. Today, traditional centralized manufactur-
ing models are employed for manufacturing other
biologics such as monoclonal antibodies (MAbs) and
antibody-drug conjugates (ADCs) candidates. In cell
and gene therapy, this model may prove sufficient
for plasmid, viral vector, and allogeneic cell therapy
manufacturing, but autologous cell therapies may
require a different approach.
While centralized manufacturing is the current
manufacturing model for autologous cell therapies,
it’s important to remember the current commer-
cial therapies are addressing small patient popula-
tions (several thousand per year). This is likely to
change as additional therapies are approved for
larger patient populations, like patients with solid
tumors or type-1 diabetes.
Because autologous cell therapies require cells from
a specific patient to be shipped to a manufacturing
site where cells are good manufacturing practice
(GMP)-processed into the drug product and then
shipped back to the patient, the logistics are complex.
Generally, all cell and gene therapy products require
ultra-cold chain logistics (below -150 °C) for shipment
and storage. What’s unique about autologous cell
therapies is the number of logistics interactions that
As the industry
continues to see
development of next-
generation cell and
gene therapies, there
is a need to reimagine
how these therapies
are manufactured.
Manufacturing
21. 20 BioPharm International®
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must occur for a single therapeutic dose. If the cen-
tralized manufacturing model is scaled out to meet
the demand of a large patient population, it’s likely
the logistic interactions will become unsustainable
and further add to therapeutic costs. If autologous
cell therapy continues to comprise a significant por-
tion of cell therapies, other manufacturing models
must be evaluated.
Moving towards decentralized manufacturing
One answer to efficiently manufacture autologous
cell therapies at scale is adopting a hub-and-spoke de-
centralized manufacturing model in which therapeu-
tic developers partner with contract development and
manufacturing organizations (CDMOs) who manage
decentralized manufacturing networks to efficiently
manufacture therapies. In principle, manufactur-
ing hubs would be located in strategic geographical
locations where they can manage multiple spokes
and be utilized for early-phase clinical cell therapy
manufacturing, commercial cell therapy manu-
facturing (primarily allogeneic products), housing
quality personnel who release drug products to pa-
tients. The manufacturing spokes primary tasks are
manufacturing cell therapies and performing quality
control (QC) release testing. The release test data
package would be sent to the manufacturing hubs
for review and release. Additionally, when organi-
zations place spokes in strategic locations based on
where therapies need to be distributed, the facilities
are closer to the point-of-care and significantly sim-
plify shipping logistics while reducing vein-to-vein
times. This partnership model also serves to adjust
manufacturing demand for therapeutic developers
because curative therapies have different demand
curves than maintenance therapies.
While therapeutic developers can build their own
manufacturingnetworks,considerationssuchasfacil-
ity size, utilization rate, and costs can pose significant
challenges. Both capital expenditure costs and oper-
ational expenses cannot be overlooked, especially in
thecurrentenvironmentwheretalentistight.Bypart-
nering with CDMOs, developers gain the knowledge
CDMOs have gleaned from prior experience as well as
accesstoGMPmanufacturingfacilitieswhileshedding
anyfacility,staffing,andmaintenanceresponsibilities.
Cell and gene therapies continue to show promising
results in multiple modalities. For cell and gene thera-
pies to reach their full potential, changes in manufac-
turing must be explored to lower costs and improve
product consistency which will ultimately increase
patient adoption.
Reference
1.
Research and Markets, Cell Gene Therapy Market–
GlobalOutlookForecast2022–2027, January 2022. ■
Drug Digest: Development and Scalability of ADCs and CGTs
Drug Digest, a tech talk with BioPharm International’s sister publication’s, Pharmaceutical Technology, editors, discusses
emerging opportunities, obstacles, and advances in the pharmaceutical and biopharmaceutical industry for the re-
search, development, formulation, analysis, upstream and downstream processing, manufacturing, supply chain, and
packaging of drug products.
InthisexclusiveDrugDigestvideo,editorsMegRiversandFelizaMirasolinterviewexpertsincellandgenetherapiesand
antibody-drug conjugates. Specifically, they discuss the factors that could influence an organization to pursue specific
biomolecules for development; key considerations for scalability; capacity issues; trends; chemistry manufacturing and
controls; and how to ensure consistency and reproducibility. Experts from Roche and MilliporeSigma divulge factors
that could influence an organization to pursue specific biomolecules for development. Featured in this video are Lisa
McDermott, director of Process and Analytical Development Global Contract Manufacturing Services, MilliporeSigma,
the US and Canadian Life Science business of Merck KGaA Darmstadt, Germany, and Jasna Curak, Global Quality and
External Collaboration Manager, Hoffmann-La Roche Ltd.
Visit PharmTech.com/drug-digest for more videos on a variety of bio/pharmaceutical manufacturing topics.
—The editors of BioPharm International
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T
he importance of messenger RNA (mRNA)-
based vaccines and therapies in global
healthcare is growing, spurred on by the
success of Moderna’s Spikevax and Pfizer–
BioNTech’s Comirnaty COVID-19 vaccines. Such ef-
forts towards precision medicine, however, come with
thechallengeofincreasingcomplexity(e.g.,compared
to small-molecule drugs). This complexity demands
drug developers and manufacturers use the right ana-
lytical tools to fully understand their products.
Nowhere is this complexity more evident than in
the lipid nanoparticles (LNPs) used to encapsulate
fragile mRNA cargo. Size, composition, aggrega-
tion, surface charge, and structure of LNPs can all
have significant effects on a therapeutic molecule’s
success; and optimizing one property may come at
the detriment of another. These interdependent char-
acteristics can impact stability during production,
transport, and storage, or affect the delivery and re-
lease of the drug product in target tissues.
Challenges of LNP characterization
Unlike small-molecule drugs or protein therapeutics,
which are chemically or biologically synthesized,
LNPs self-assemble during the mixing of their com-
ponent ingredients. These components can include
cationic lipids, helper lipids such as distearoylphos-
phatidylcholine (DSPC), sterols such as cholesterol,
and polyethylene glycol-containing (i.e., PEGylated)
lipids (Figure 1). To ensure drug formulators achieve
their final product, they must optimize the ratios of
these ingredients and perfect the way in which these
ingredients are mixed.
Small batch-to-batch differences in mixing can re-
sult in products that have significantly different com-
positions. Similarly, changes in ingredient flow rates
can alter the size of the final product. For example,
faster flow rates produce smaller LNPs than slower
ones. Throughout process development and optimi-
zation, drug manufacturers need to confirm they are
producing LNPs consistently and to specification.
Shining a Light
on Lipid Nanoparticle
Characterization
Hanna Jankevics
Jones, PhD, and Natalia
Markova, PhD, are
pharmaceutical segment
marketing managers at
Malvern Panalytical.
Using an orthogonal approach to lipid nanoparticle
analysis can increase the odds of project success.
LIKANARIS
-
STOCK.ADOBE.COM
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Particle size is critical because it has implications
for drug function. Particles that are too small may
be cleared from the bloodstream by the kidneys
before they can take effect, whereas larger or aggre-
gated particles may fail to penetrate cells or could in-
duceunwantedimmuneresponses.Thus,drugdevelop-
ersneedtoensurethattheLNPstheyareproducingare
theoptimalsizeandthatthesizedistribution(polydis-
persity)fallswithinacceptableparameters.Unexpected
changesinsizeorpolydispersitycouldsignalproblems
in manufacturing processes or product degradation.
Another factor crucial to the success of an LNP is
stability. Solvents used during production may need
to be removed before administering the product to
patients. Drug developers, therefore, need to be sure
that the product created remains stable in the sol-
vent’s absence. They also need to know that the prod-
uct holds its structure during transport and storage.
Drug developers must also ensure that LNPs main-
tain their structure and successfully protect their
mRNA cargo until the therapeutic is delivered to the
target site in the patient’s body. As such, scientists
must analyze LNP performance under conditions
that mimic the bloodstream or target tissues as well
as inter- and intracellular environments.
Thesurfacechargeisanothercriticalfactorthatdic-
tates how well an LNP functions within the body. For
example, while LNPs with a positive charge have been
investigated,theycantriggerinflammatoryresponses,
inducingproblemssuchashepatotoxicity(1).Negative-
ly-charged LNPs avoid these toxicity issues; however,
thisisnottheonlyplacewherethechargeisimportant.
LNPsneedtorespondtochangesintheendosomalpH,
oftenbychangingcharge,whichcaninfluencetheen-
dosomal escape of their mRNA payload.
Expanding the use of LNPs from intramuscular
injections for vaccines to other applications such as
cancer vaccines or gene therapies, in which the LNPs
need to enter other cell types, the surface charge can
impacttheuptakeoftheLNPstodifferentcelltypes(2).
Thus, formulators need to monitor surface charge to
identify LNPs that can access the target cells. It can
also be informative to understand how this surface
charge varies across relevant pH ranges.
Techniques proven to meet the challenge
With such a complex range of attributes to navigate,
developers must use complementary analytical tech-
nologies to provide a full understanding of LNPs.
Fortunately, they don’t need to develop these meth-
ods de novo. Rather, LNP specialists can tap into the
well-established field of lipid-based drug character-
ization, where proven analytical technologies have
long helped ensure product quality and function.
Size matters
To monitor LNP size and sample polydispersity,
LNP specialists can rely on dynamic light scatter-
ing (DLS)—whether single-angle or multi-angle
(MADLS)—and nanoparticle tracking analysis (NTA).
Usingthesemethods,LNPsinsuspensionscatterlaser
light as they diffuse through a sample. Changes in the
scattering pattern are translated to particle size and
size distribution, with larger particles diffusing more
slowly than smaller particles.
DLS offers the lowest resolution of particle size de-
termination but gives a good indication of the size of
LNPs in a sample. Using back, side, and forward de-
tection angles, MADLS offers a higher resolution than
DLS, allowing it to identify additional populations of
LNPs that DLS might miss. NTA offers even higher
resolution but often requires sample dilution, which
can perturb LNP stability. The choice between these
complementary techniques depends on factors, such
as LNP size and polydispersity, sample heterogeneity,
and the questions being asked.
When Pfizer–BioNTech contracted Polymun
ScientifictoscaleuptheprocessofproducingLNPsfor
the Comirnaty program, Polymun needed to develop
robust manufacturing processes to support large-
scale production (3). Key to this development were
FIGURE 1. Schematic of a messenger
RNA (mRNA)–lipid nanoparticle
(LNP) complex (4). DSPC is
distearoylphosphatidylcholine.
Analytics
ALL
FIGURES
ARE
COURTESY
OF
THE
AUTHORS.
25. 24 BioPharm International®
Emerging Therapies 2022 eBook www.biopharminternational.com
analytical methods, including those described in this
article, to guide process development and control man-
ufacturingprocesses.Sucheffortsallowedthecompany
toconfirmbatch-to-batchconsistencyandlong-termsta-
bilityofitsliposomalandLNPformulations(Figure 2).
MADLS and NTA also offer the opportunity to de-
termine particle concentration, which provides quick
information on process yield and any potential losses
from process steps. Recently, researchers applied these
methodstoliposomesamplesandshowedthattheacces-
sibleconcentrationrangeforMADLS(108
to1012
particles/
mL) overlapped with and extended that for NTA (107
to
109
)(Figure 3).MADLSofferedasimilarrangewhenthe
methodwasappliedtoLNPs.
Taking charge
As pH can differ significantly between production and
storage conditions as well as physiological environ-
ments, it is vital to monitor surface charge throughout
the product’s life cycle. Electrophoretic light scattering
(ELS)isapowerfultoolthatcandeterminetheapparent
chargeofaparticleindifferentconditions;forexample,
mimickingapHrangefromslightlyalkalinebloodtothe
acidicendosome.Theobtainedsurfacechargemeasure-
ments allow developers to balance the needs of product
development and long-term storage with the require-
ments for clinical efficacy, optimizing cellular delivery
whileminimizingtoxicityrisks.
The heat of the moment
Production, storage, and application add temperature
stresses to LNPs, which can be investigated using DLS
thermal ramp experiments or differential scanning
calorimetry (DSC). Thermal ramps use DLS to monitor
particle stability over a temperature range, while DSC
measures heat uptake or release linked to structural
transitionsorchangesinmolecularinteractions.
Drug developers can use these methods to examine
the thermal stability of both the LNP delivery vehicle
anditsmRNAcargo.Suchinformationiscriticalduring
LNP formulation as developers optimize ingredient
combinations to improve stability without negatively
impacting efficacy. Furthermore, as the DSC thermo-
gramisalsoafingerprintofmRNAandLNP’shigher-or-
derstructure,companiescanuseittoinformtheselec-
tion of mRNA sequence variants during design stages
and to compare different formulations and batches of
the LNP product. This detailed characterization helps
support intellectual property protection.
A rapid look at composition
Amethodcommonlyusedtomonitorparticlesizeand
polydispersityissize-exclusionchromatography(SEC)
coupled to static light scattering (SLS) or another de-
tection system. But beyond questions of particle size,
developers continue to evolve the applications of SEC–
SLS to help answer questions about LNP composition,
monitoring not only the lipid complexes but also the
mRNA cargo. For example, researchers used SEC–SLS
to perform compositional analysis of two mRNA–
LNPs (4). Monitoring the concentrations of the mRNA
andLNPsacrosstheentireparticledistribution,there-
searcherscoulddeterminetherelativeweightfractions
ofthecomponents—ameasureoftherapeuticpayload.
In both mRNA–LNPs tested, the scientists observed
variation in mRNA loading across the population.
SEC–SLS offers analytical insights in minutes, ac-
celerating throughput across development and man-
ufacturing. The analysis also eliminates the need for
multiple analytical steps and fluorescent reagents
and reduces operator impact on measurement con-
sistency. Although still relatively new to LNP man-
ufacture, compositional analysis has proven vital to
other medical applications, such as studies of viral
FIGURE 2. Analysis showing the size distribution of a lipid nanoparticle preparation to
monitor product stability over time.
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25
Analytics
vectors in gene therapy, antibody-drug conjugates,
and antibody aggregation.
The power of orthogonal approaches
InthecomplexworldofmRNA-basedvaccinesandther-
apies, tried and tested analytical technologies, such as
DLS/MADLS, NTA, and ELS, are shining a light on the
LNPsthathelpthosemedicinessurvivethejourneyfrom
lab to factory to cellular site-of-action. Researchers are
further augmenting those insights by evolving and ex-
panding the applications of DSC and SEC–SLS to build
furtheramorereliablepictureofLNPattributes,improv-
ingthechancesforprojectsuccess.
Although individual biophysical characterization
techniques provide valuable insights into the nature
of LNPs, no single technology can provide a complete
picture. Instead, orthogonal and complementary ap-
proaches are needed to provide a more comprehensive
understanding of the critical quality attributes that de-
fine product quality, consistency, and, ultimately, effi-
cacy(Table I).
This prospect may be daunting if a company is unfa-
miliar with some of these techniques. The broad exper-
tise of an analytical partner can, therefore, help in the
development of the applications needed to achieve a
deeperunderstandingofLNPs.
References
1. R. Kedmi, N. Ben-Arie, and D. Peer, Biomaterials 31
(26) 6867–6875 (2010).
2. R. Pattipeiluhu, et al., Advanced Materials 34,
2201095 (2022).
3. Malvern Panalytical, Developing an Analytical Work-
flowforNanomedicineand3rdGenerationVaccinePro-
duction at Scale, Whitepaper (2022).
4. N. Markova, et al. Vaccines 10, 49 (2022). ■
FIGURE 3. Using size-exclusion chromatography–static light scattering (SEC–SLS) to show
that the weight fraction (Wt fr) of messenger RNA (mRNA) within mRNA–lipid nanoparticles
(LNPs) varies across both a single formulation and between different formulations: (a)
mRNA–LNP1; (b) mRNA–LNP2 (4). RI is refractive index.
TABLE I. Proven analytical technologies monitor a range of lipid nanoparticle attributes (4).
DLS is dynamic light scattering. MADLS is multi-angle light scattering. NTA is nanoparticle
tracking analysis. ELS is electrophoretic light scattering. SEC–SLS is size-exclusion
chromatography–static light scattering. DSC is differential scanning calorimetry.
Particle
size
Polydispersity
Particle
concentration
Surface
charge
Thermal
stability
Higher-order
structure
Particle
composition
DLS ✓ ✓ ✓
MADLS ✓ ✓ ✓
NTA ✓ ✓ ✓
ELS ✓
SEC–SLS ✓ ✓ ✓ ✓
DSC ✓ ✓
27. 26 BioPharm International®
Emerging Therapies 2022 eBook www.biopharminternational.com
W
hen attempting to gauge the future of
emerging therapies, it’s important to
also look to the past for clues on what
may be lurking beyond the horizon.
Knowledge of what FDA has approved in the past is in-
strumental not only in understanding the current reg-
ulatory landscape, but also in determining the types of
therapies that are likely to be approved going forward.
Of the 16 novel molecular entities and therapeutic
biological products that have been approved by FDA
in 2022 at the time of this article’s writing, the three
discussed in this article are all but one of the biolog-
ics (1). While this is a significant decrease from 2021,
which saw four biologics approved in November and
December alone, it is notable that novel approvals as
a whole are down significantly; at this time last year,
there were 35 total approvals (i.e. both new drug appli-
cations and biologic license applications) approved (2).
While there are many reasons why such a decrease
can occur, including simple random chance, it none-
theless places greater emphasis on what therapies are
getting through the approvals process. Examining
the biologics that are getting through could provide a
baseline for the requirements needed to get through
future approval processes.
Roche’s multiple eye disease treatment
Just days after the approval of tebentafusp-tebn, FDA
approved Vabysmo (faricimab-svoa) for treatment of
wet age-related macular degeneration (AMD) and dia-
beticmacularedema(DME).Theindication,whichwas
grantedtoGenentech,aRochegroupcompany,onJan.
28, 2022, is the first granted to a bispecific antibody for
treatment of the eye (3).
TENAYA and LUCERNE are two identical, random-
ized, multicenter, double-masked, global studies
evaluating the efficacy and safety of faricimab-svoa
compared to aflibercept in 1329 people living with wet
AMD (671 in TENAYA and 658 in LUCERNE). The pri-
mary endpoint of both studies was based on average
Novel Therapies of 2022 Grant Playter,
assistant editor
Looking back at the biologics and large molecule drugs approved
by FDA in the past year can give us hints toward what will be
approved in the future.
AKSANA
KAVALEUSKAYA
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STOCK.ADOBE.COM
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27
Quality/Regulations
change in best-corrected visual acuity score (the best
distance vision a person can achieve—including with
correction such as glasses—when reading letters on
an eye chart) from baseline.
Both studies met their primary endpoint, wherein
faricimab-svoa given at intervals of up to four months
was found to be non-inferior to aflibercept given every
two months. Additionally, average vision gains from
baseline at one year in the faricimab-svoa arms were
+5.8 and +6.6 letters, respectively, compared to +5.1
and +6.6 letters in the aflibercept arms.
YOSEMITE and RHINE had a similar experimental
design, except the patient population was 1891 people
with diabetic macular edema (940 in YOSEMITE and
951 in RHINE) and each study had three treatment
arms,ratherthantwo:faricimab-svoaadministeredup
to every four months after four initial monthly doses
using a treat-and-extend approach; faricimab-svoa
administered at two-month intervals after six initial
monthly doses; and aflibercept administered at fixed
two-month intervals after five initial monthly doses.
InYOSEMITE,theaveragevisiongainsfrombaseline
at one year were +11.6 and +10.7 eye chart letters in the
faricimab-svoatreat-and-extendandtwo-montharms,
respectively,and+10.9lettersintheafliberceptarm.In
RHINE, the average vision gains from baseline at one
year were +10.8 and +11.8 letters in the faricimab-svoa
treat-and-extend and two-month arms, respectively,
and +10.3 letters in the aflibercept arm.
Sanofi’s intravenous hemolysis treatment
FDA approved Sanofi’s Enjamo (sutimilamab-jome)
as an intravenous treatment for hemolysis in adults
withcoldagglutinindisease(CAD)onFeb.4,2022.The
first and only FDA-approved treatment for people with
CAD, sutimilamab-jome is a humanized monoclonal
antibody designed to selectively target and inhibit C1s
in the classical complement pathway; through this, it
inhibits the activation of the complement cascade in
the immune system, in turn inhibiting C1-activated
hemolysis(andtheresultingdestructionofhealthyred
blood cells) in individuals with CAD (4).
Sutimilamab-jome’s approval was based on the
CARDINAL study, a 26-week open label, single arm,
pivotal Phase III study examining 24 patients with
CAD who had a recent history of blood transfusion.
Thestudymetitsprimaryefficacyendpoint,acompos-
ite endpoint defined as the proportion of patients who
achieved normalization of hemoglobin (Hgb) level ≥12
g/dLandtheproportionofpatientswhodemonstrated
an increase from baseline in Hgb level ≥2 g/dL at the
treatment assessment time point without receiving a
blood transfusion or medications prohibited per the
protocol in weeks 5 through 26.
Inthestudy,54%ofthepatientsmetthecompositepri-
mary endpoint criteria with 63% of patients achieving
hemoglobin ≥ 12 g/dL or an increase of at least 2 g/dL
and 71% of patients remaining transfusion-free after
week five. All but two patients (92%) did not use other
CAD-related treatments. As a whole, the patients also
experienced a mean increase in hemoglobin levels of
2.29 g/dL (SE: 0.308) at week 3 and 3.18 g/dL (SE: 0.476)
at the 26-week treatment assessment timepoint from
the mean baseline level of 8.6 g/dL.
Bristol Myers Squibb’s oncology drug
BristolMyersSquibb’sOpdualag(nivolumabandrelat-
limab-rmbw) was approved by FDA on March 18, 2022
as a treatment for patients with unresectable or meta-
staticmelanoma.Thenoveldrugisafixed-dosecombi-
nation of the LAG-3-blocking antibody relatlimab and
the programmed death receptor-1 blocking antibody
nivolumab. Prior to its approval, nivolumab and relat-
limab-rmbw received Priority Review, Fast Track, and
Orphan Drug designations (5).
Approval of nivolumab and relatlimab-rmbw was
based on the results of RELATIVITY-047, a random-
ized, double-blind clinical trial evaluating 714 pa-
tients with previously untreated metastatic or un-
resectable Stage III or IV melanoma. Patients were
randomized to receive 480 mg of nivolumab and 160
mg of relatlimab by intravenous infusion every four
weeks or 480 mg of nivolumab by intravenous infu-
sion every four weeks until disease progression or
unacceptable toxicity.
The major efficacy outcome measure was progres-
sion-free survival (PFS) determined by Blinded Inde-
pendentCentralReview(BICR).Thetrialdemonstrated
a statistically significant improvement in PFS by BICR
fornivolumabandrelatlimabcomparedtonivolumab;
median PFS was 10.1 months in the nivolumab and
relatlimab arm and 4.6 months in the nivolumab arm.
An additional analysis of overall survival (OS) was not
foundtobestatisticallysignificant;medianOSwasnot
reached in the nivolumab and relatlimab arm and 34.1
months in the nivolumab arm.
References
1. FDA, “Novel Drug Approvals for 2022,” www.FDA.
gov, accessed Aug. 13, 2022.
2. FDA, “Novel Drug Approvals for 2021,” www.FDA.
gov, accessed Aug. 13, 2022.
3. Genentech, “FDA approves Genentech’s Vabysmo,
the First Bispecific Antibody for the Eye, to Treat
Two Leading Causes of Vision Loss,” Press Release,
Jan. 28, 2022.
4. Sanofi, “FDA Approves Enjaymo (sutimlimab-jome),
First Treatment for Use in Patients with Cold Agglu-
tinin Disease,” Press Release, Feb. 4, 2022.
5. FDA, “FDA Approves Opdualag for Unresectable
or Metastatic Melanoma,” Press Release, March 18,
2022. ■
29. 28 BioPharm International®
Emerging Therapies 2022 eBook www.biopharminternational.com
T
he life sciences industry is seeing a robust
trend in biotech incubator spaces geared to-
ward fostering the growth of new and emerg-
ing biotech startups. Incubators on a global
scale are determined to grow life sciences innovation
in tandem with economically developing local regions.
Establishing an ecosystem
AlloyTherapeutics,headquarteredinWaltham,Mass.,in
theUnitedStates,isabiotechnologyecosystemcompany
that enables biologics drug discovery, for instance. The
company offers “pre-competitive technologies and ser-
vices” to the drug discovery community as whole in an
affordable,non-exclusivemanner,saysErrik Anderson,
founder, CEO, and chairman of Alloy Therapeutics.
“Our biotech ecosystem encompasses our affiliated
Venture Studio, 82VS, which pairs our platforms and
services with a team of company creation experts who
can rapidly establish and successfully build new as-
set-centric companies. 82VS provides these new com-
panieswiththelaboratoryspaceandresourcesofatyp-
ical biotech incubator but goes far beyond what other
incubators offer,” Anderson says.
The company thus provides cutting-edge scientific
knowledge and insights, creates new platforms and
services on demand as needed to support individ-
ual company needs, and offers well-honed company
launch processes across legal, human resources, fi-
nance, operations, and marketing. “Collectively this
minimizes startup time and allows scientists to focus
on advancing their novel ideas and promising thera-
peutic pipelines,” Anderson states.
Meanwhile, LabShares Newton, a biotech incubator
based in Newton, Mass., “provides lab space, extensive
lab equipment, and a variety of services (e.g., environ-
mental,safety,maintenance,purchasing)tohelpstartup
biotechfirmsquicklyinitiateandconductresearch.Our
members can focus on their science, and avoid having
todealwithcomplexandexpensiveinfrastructureand
logistics,” says Jeff Behrens, CEO, LabShares Newton.
Biotech Incubators
Cultivate a Global Scene
Feliza Mirasol,
science editor
The growth of the biopharmaceuticals market
is feeding back into economies and, in part, is
driving the boom in life sciences and biotech ecosystems.
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“LabShares was ‘born’ out of Siamab Therapeutics
(where Jeff Behrens was CEO), which developed anti-
body-based cancer medicines and was sold to Seagen
in 2018. Siamab built a small lab in Newton, Mass.
in 2014, and had enough space to share the lab with
several other companies, helping Siamab defray the
costs of building and running the lab,” explains Beh-
rens. After Siamab’s exit, LabShares was then formed
to take over lab operations and expand the business
model. Today, the organization is growing with the
build-out of a fourth lab expansion, bringing its lab
space to 40,000 ft2
in August 2022 with about 30 com-
panies in residence, says Behrens.
Skill sets and resources
Among the advantages of an incubator are certain re-
sourcesandskillsetsofferedtostart-ups.Forexample,
LabShares is run by a small team of lab management
expertswhofocusonenvironmentalhealthandsafety
issues, equipment maintenance, reagent purchasing,
and other logistical and support issues. Their exper-
tise enables member companies to focus on their own
science, and member companies can start generating
data quickly and efficiently, says Behrens.
In particular, for reagent purchasing, the organiza-
tion has partnered with several companies, including
Zageno, a Cambridge, Mass.-based provider of labora-
tory supplies, and ThermoFisher Scientific to offer
centralized reagent purchasing services for member
companies. “We have been able to negotiate signifi-
cantdiscountswithanumberofvendorswhichweare
able to pass on to our members through this program,
and we have also found that centralizing the purchas-
ing function ensures that orders are correct and filled
rapidly and efficiently,” Behrens notes.
Moreover, LabShares provides centralized equip-
ment maintenance for a broad set of shared equip-
ment provided to member companies. The orga-
nization uses a home-grown annual maintenance
scheduling and planning system to track periodic
maintenance requirements. It also partners with
several service firms to ensure biosafety cabinets
are certified and measurement equipment is cali-
brated appropriately. The organization also makes its
facilities and equipment available to member com-
panies to conduct their own sample preparations
and data interpretation; members are thus able to de-
velop their own individual processes and practices,
Behrens adds.
With Alloy Therapeutics, all new asset-centric
companies that are launched through its Venture
Studio group have access to a full suite of drug dis-
covery platforms and services, emphasizes Anderson.
“We are committed to continually adding additional
platforms and services to our portfolio, and often do
so in response to the needs of our partners and 82VS
NewCos. Through 82VS, we also provide the labora-
tory resources and operational processes (legal, HR,
finance, etc.) that allow startups to launch quickly
and focus their internal resources on asking and an-
swering critical scientific questions,” he explains.
Across five research sites in three different coun-
tries, Alloy Therapeutics’ scientists work collabora-
tively with more than 130 ecosystem partners and
their respective scientific talent. “This democratized
approach gives us—and our partners—access to an
incredible pool of talent much more efficiently and
cost-effectively than could be built in-house by a sin-
gle company,” Anderson states.
A global scene
Outside the US, life science sectors around the world
are invigorated by efforts on the part of various en-
tities—including government, industry, and aca-
demia—to foster the growth of burgeoning regional
biopharmaceutical industries by providing the space,
talent, funding, and resources required by biotech
start-ups. Some examples are included as follows.
Lithuania
Innovation Agency Lithuania is a non-profit agency
undertheMinistryofEconomyandInnovationofLith-
uania.TheagencywasestablishedinApril2022bythe
mergingofthreegovernmentagencies:EnterpriseLith-
uania, Lithuanian Business Support Agency, and the
Agency for Science, Innovation, and Technology.
The agency is responsible for Lithuania’s innovation
ecosystem (1)—the promotion of Lithuania’s business
sectors and their innovations at all stages of business
development, which includes the development of ideas
and the delivery of products and services to end-us-
ers. It collaborates with all participants in the life
sciences field, including the Lithuanian Biotechnology
Association, all types of companies, and academic
institutions,suchasVilniusUniversityandLithuanian
University of Health Sciences, says Rasa Uždavi-
nytė, Director of International Trade Development at
Innovation agency Lithuania.
“Since one of Lithuania’s priorities now is the life
sciences sector’s growth, the Ministry of Economy
Incubators on a
global scale are
determined to
grow life sciences
innovation.
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31
BioBusiness
and Innovation of the Republic of Lithuania decided
to provide more than €13 million [US$13.6 mil-
lion] to life sciences startups’ projects. In this case,
Innovation Agency administers an initiative called
‘Biotechnology industry development in Lithuania’,”
says Uždavinytė.
At the end of 2021, companies were able to apply
for financial support in Lithuania for their projects.
Startups could receive up to €200,000 (US$209,000),
and private companies could receive up to €500,000
(US$523,000), according to Uždavinytė. After evalu-
ating applications, 25 of 43 different companies have
received an overall €5.8 million (US$6.1 million) in
financing, she adds.
Sweden
Karolinska Institutet (KI) Innovations Incubator
supports life science start-ups. Focus is on evidence
based human life science, mainly deep-tech compa-
nies with a strong potential impact on society and
major patient benefit. KI Innovations Incubator is
financed by the state via the Vinnova Excellens pro-
gram and Karolinska Institutet, and the incubation
program involves both individual and group coach-
ing and offers a broad range of education, events,
professional networks, financing, expert competence
in entrepreneurship and business development. The
start-ups also have access to wet-labs and co-working
space within the community.
Although the life science business incubator only
works with start-up companies, KI Innovations also
encompasses early support and inspiration within a
pre-incubator and academic innovation support pro-
gram. Since the start, it has worked with more than
1800 projects and companies, and the return on in-
vestment has been substantial.
“We aim at having a diversity of start-ups, both sci-
ence-heavy, long-reaching pharma companies and
faster moving eHealth-based companies—these typ-
ically comprise different types of founders/entrepre-
neurs,” says Christian Krog-Jensen, PhD, head Busi-
ness Incubator at KI Innovations
Dr. Krog-Jensen notes that KI Innovations aims
to “use” success stories as learning cases, and some
of the serial entrepreneur members are utilized in
group discussions to share their experiences in de-
veloping a start-up that is subsequently launched
onto the market.
“We are also putting in extra effort in inspiring
women to apply to the incubator with their start-up,
this is key to attracting both male and female
entrepreneurs and investors to the environment,”
Krog-Jensen emphasizes. “We also demand that all
companies work on sustainability, they are coached,
has to build a forward directed plan, taking into ac-
count their operational area.”
According to Krog-Jensen, the organization has
brought onboard a set of experts within the relevant
technological and legal areas to play important roles
within the incubator environment. “A network of
external business coaches has been employed by us,
giving scalability and the possibility to meet the spe-
cific demands of the great variation of start-ups. From
a business perspective, we have, over the years, built
up our industry experiences and personnel and have
built a good network of investors and buyers/partners
within pharma and healthcare,” Krog-Jensen states.
SmiLe Incubator, a life science business incuba-
tor, is based in the life science hub of Lund, Sweden.
Founded in 2007, this incubator aims to facilitate
business success for startups and entrepreneurs who
are involved in developing next-generation health-
care and life science technologies. The organization
has become an important national and international
player in the life science startup space in the past five
years. “Since the start, more than 100 startup com-
panies have joined the incubator program, of which
86% are still growing, 20 companies have launched
IPO’s [initial public offerings], and five companies
were merged or acquired,” states Ebba Fåhraeus, CEO
of SmiLe Incubator.
“Since 2014, the incubator companies, together
with alumni companies, have raised approximately
€650million(US$682million)inventurecapital.With
diversity as one of our key success factors, we take
great pride in the fact that some 50% of the founders
and CEO’s of our companies are women and that
these women also raise 50% of the venture capital,”
emphasizes Fåhraeus.
SmiLe´s offerings include business coaching by
senior coaches who have been previously active in
the life sciences industry (e.g., bio/pharmaceutical
RD, business development, marketing, governance,
and finance); access to a large international network
of investors and industry experts; access to a unique
lab infrastructure consisting of 10 laboratories that
house state-of-the-art instrumentation suitable for
Among the
advantages of
an incubator are
resources and
skill sets offered to
start-ups.
33. 32 BioPharm International®
Emerging Therapies 2022 eBook www.biopharminternational.com
bio/pharmaceutical development and cell handling,
for instance; a large community of life science com-
panies; and a wide range of business development
programs tailor-made to support any stage of an en-
trepreneur’s journey, says Fåhraeus.
Switzerland
Switzerland is another country where the life sciences
sector is being driven in part by the presence of bio-
pharma majors headquartered within its borders.
“The incubator scene in Switzerland is flourishing
for a number of reasons. Firstly, proximity in Basel
to the major pharma companies Roche and Novartis
and, secondly, the growing start-up culture in the
main universities such as EPFL [École Polytechnique
Fédérale de Lausanne],” says Sirpa Tismal, director
of Investment Promotion, Switzerland Global Enter-
prise, the official Swiss organization for export and
investment promotion. “Furthermore, the incuba-
tors themselves are very varied—some specialize in
a theme, such as the new Femtech Incubator in Laus-
anne, others [specialize] in disease areas, such as the
Diabetes Center in Berne, while others cover the full
spectrum of life sciences.”
BaseLaunch, based in Basel, Switzerland, for in-
stance, helps launch and build ventures to the point
where they can complete a Series A financing or sim-
ilar. The organization focuses on venture companies
specializing in innovative therapeutics. “We provide
a diverse range of support, from financing to strategic
advice for de-risking the science and building-out the
companies from scratch. We partner with key play-
ers from the biotech sector, leading pharmaceutical
companies, and venture funds: Roche, Pureos Bio-
ventures, Roivant Sciences, Bridge Biotherapeutics,
CSL Behring, Johnson Johnson, and China Medi-
cal System, which also finance the pool out of which
BaseLaunch funds ventures,” says Stephan Emmerth,
PhD, director Business Development Operations,
BaseLaunch.
These key partnerships give BaseLaunch access to
the scientific and commercial know-how of its part-
ners, Emmerth points out. The organization is run by
BaselAreaBusinessInnovation,whichalsofinances
its operations, which are additionally also supported
via its domain partners—KPMG, SpiroChem, Vossius
Partner, Walder Wyss attorneys at law, KPBMA,
WuXi AppTec, Alloy Therapeutics (a reflection of how
the efforts of these incubators often intersect and am-
plify one another), Lonza, and Charles River Laborato-
ries—In addition, BaseLaunch collaborates with the
TechPark Basel and the Switzerland Innovation Park
Basel Area for infrastructure access.
“We provide convertible loan financing of up to
$500,000 per venture. And on top [of that] we work
closely with each venture to help them build the
company to the stage where they can raise venture
capital financing. We are completely customized,”
emphasizes Emmerth.
Emmerth explains that BaseLaunch typically also
gets involved in other aspects that foster a venture
company’s devopment, such as building the team—
bringing in drug development and commercial ex-
pertise, as needed, and establishing fair ways to com-
pensate early team members; providing support with
intellectual property licensing and incorporating the
company; and providing introductions, globally, to
venture funds as well as assisting in negotiations
with these funds.
“Through all of this, ventures retain full entrepre-
neurial freedom to decide what they want to do, and
how they want to do it. Importantly, ventures retain
control over the extent to which our partners become
involved. We believe that this overall set-up was in-
strumental in being successful building new biotech
companies: Since supporting our first ventures in
early 2018, nine of our portfolio companies (of a total
of 19 counting the just recently added) have, in total,
raised over $450 million in financing from European
and US Venture funds,” Emmerth states.
Another Swiss organization, StartLab, located
on the Biopôle campus in Lausanne, Switzerland, is
an incubator that offers 1500 m2
of fully equipped
shared lab space. Biopôle is one of the largest life
sciences parks in Europe, according to Nasri Nahas,
CEOofBiopôle.StartLaboffersspacestailoredtocom-
panies operating in wet-lab biology and chemistry
environments for drug discovery, diagnostics, syn-
thetic biology, medtech, and other areas of the life
sciences, Nahas states.
“We offer individual named lab benches as well as
hotdesking—for employees who are between exper-
iments—and shared specialized labs, including cell
culture, centrifuge, PCR [polymerase chain reaction],
chemistry, and microbiology. Our infrastructure in-
cludes shared general service rooms—such as au-
toclave/washing, machinery, and cold rooms—and
there’s a laboratory manager who takes care of the
facility,” says Nahas, detailing the resources that the
incubator offers.
Life science
sectors around the
world are invigorated
by efforts of
various entities.
