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Cost drivers of cultivated meat production
Elliot Swartz, Ph.D.
Principal Scientist, Cultivated Meat
@elliotswartz
March, 2024
elliots@gfi.org
Linkedin
The Good Food Institute
Science and Technology
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200+ staff in 6 regions
The purpose of this presentation is to describe our current
understanding of the major cost drivers or cost-influencing factors
of cultivated meat production — how to think about the problem.
The presentation does not comprehensively capture every minor
cost or process consideration. Cell line influences are not
described in detail.
We are still learning about the costs of cultivated meat
production. Some cost factors today may become minor as new
solutions emerge.
Information will change as more data becomes available.
Accordingly, this presentation will be updated annually.
Fundamentals: understanding the cost
drivers of cultivated meat
5
Source: Humbird, 2021.
The cost drivers of cultivated meat
Cell culture media
Infrastructure
Facility 1 Facility 2
6
The cost drivers of cultivated meat
Source: CE Delft Techno-Economic Assessment (2021)
Webinar: The costs and environmental impacts of cultivated meat
Growth media is the
current cost driver
Infrastructure will be a
long-term cost driver
Maximizing process efficiency and
cell-level traits are needed to get into
commodity cost ranges
Two major buckets drive cultivated meat production cost
Cell culture media Infrastructure
Growth factors
Amino acids
Buildings
Bioreactors Labor
Utilities
Other media
components,
equipment,
consumables
Cell culture media
9
Cell culture media composition: basal media
The basal media contains the energy source (glucose, pyruvate), amino acids, vitamins, and inorganic salts.
DMEM/F12 contains 50-52
ingredients and serves as a
starting point for mammalian
cell cultures
DMEM/F12
Leibovitz-15 contains 30-32
ingredients and serves as a
starting point for fish and
crustacean cell cultures
10
Cell culture media composition: added factors
Added factors may include: lipids, antioxidants, growth factors, hormones, small molecules, peptides,
anti-foaming agents, surfactants, etc.
Component
DMEM/F12
Ascorbic acid 2-phosphate
Sodium bicarbonate
Sodium selenite
Insulin
Transferrin
FGF2
TGFb
Essential-8, originally derived
to simplify the growth of human
induced pluripotent stem cells,
contains 7 added factors on top
of the DMEM/F12 basal media
formulation
Complete media = basal media + added factors.
Complete media will differ by the cell type,
species, differentiation state, process
conditions, and intended end-product
Reducing media costs
Use less media
2
● Optimize for feed conversion ratio
(g ingredients/kg meat)
● Tailored to each company’s cells,
process, and products
● Longer timeline for success
Source lower-cost
ingredients
1 ● Optimize for $/L media
● Cross-industry relevance
● Shorter timeline to success
Time
Success in both approaches will be required for
cost-competitive cultivated meat production
Steps to reduce cell culture media costs
1. Source lower cost ingredients ($/L)
a. Pharma-grade → food-grade and feed-grade ingredients
b. New sources for recombinant proteins and amino acids
2. Use less media (g/kg)
a. Formulation discovery: metabolic modeling and engineering to create cultivated
meat with low feed conversion ratios and to inform media formulations and the
future supply chain
3. Scale the new supply chain
$1/L of media is an early target for the industry
Source: Negulescu, 2023.
Source: Lever VC
But commercial stem cell media cost hundreds of
dollars per liter
Source: Kuo, 2020.
Sourcing lower-cost ingredients can reduce
media costs ($/L) by >99%
$40.94 $14.54 $4.71 $3.74 $0.85 $0.35 $0.24
Source: Specht, 2019
● Models suggest media costs below $1/L are tractable and can happen quickly.
● Anecdotally, multiple companies have already broken through this threshold.
Sourcing food-grade ingredients lowers costs
Kanayama, 2022
● Many basal medium ingredients are available
at “food-grade,” with similar purity levels as
pharma-grade ingredients.
● 100% food-grade basal media, such as I-MEM
2.0, have already been created.
Source: Integriculture
Source: Cellular Agriculture Europe
Food- and feed-grade ingredients perform well in
cell culture media
Source: The Good Food Conference, 2021
● Cultivated meat manufacturers and media suppliers are at various stages of replacing
pharma-grade ingredients with food- or feed-grade ingredients.
● Multiple data points suggest replacement of pharma-grade ingredients is a tractable approach
with minimal technical bottlenecks.
● Regulatory issues for food-grade inputs are not expected, as most basal media ingredients are
nutrients found abundantly in the food we eat every day. Safety for some feed-grade inputs will
need to be evaluated.
1. Source lower cost ingredients ($/L)
a. Pharma-grade → food-grade and feed-grade ingredients
b. New sources for recombinant proteins and amino acids
2. Use less media (g/kg)
a. Formulation discovery: metabolic modeling and engineering to create cultivated
meat with low feed conversion ratios and to inform media formulations and the
future supply chain
3. Scale the new supply chain
Steps to reduce cell culture media costs
19
Growth factors and recombinant proteins are cost drivers
If growth factors used in the pharmaceutical sector were used in cultivated meat
production, they would account for 99% of costs at scale.
Source: Specht, 2019
Growth factors: reduce their use
Source: 3DBioTissues
Companies are employing many different
methods to reduce the quantity of growth
factors needed or eliminate them entirely.
Certain supplements claim to show
increased cell growth rates despite using
growth factors at half their normal
concentrations.
Source: Stout, 2023
Cells can be engineered in various ways to
eliminate the need for certain growth
factors such as FGF2.
Read more: Swartz, 2023
Growth factors: scale production with existing
technology
To be suitable for use in a cost-competitive cultivated meat industry, growth
factors should cost at or below $100,000/kg.
Source: Puetz & Wurm, 2019
● These growth factor cost profiles are
readily achievable for suppliers to hit
when scaling existing production and
performing food-grade downstream
purification processes.
● While costs for growth factors are still
high today, the bottleneck is one of
markets, not technology: no single
manufacturer is ready to purchase
kilograms of FGF2, IGF1, TGFb.
Source: Swartz, 2023
Other recombinant proteins are used in significantly
higher quantities than growth factors
99% of recombinant
protein volume would
come from proteins such as
albumin*, transferrin, and
insulin
Source: Swartz, 2023, * not all media formulations will require albumin
Millions of kg of albumin
could be needed to supply
less than 1% of global
meat production volume
Albumin
300-8200x
the current
production
volume for
transferrin
Alternative, non-recombinant sources of albumins, transferrin, and
insulin are needed to supply the cultivated meat industry as it scales
Certain recombinant
proteins are used at 103
to
>106
higher concentrations
than growth factors
New sourcing strategy for albumins, transferrins, insulin
Opportunities to find cell culture functionalities
for other food-grade ingredients:
● Methylcellulose enhances albumin
functionality (Schenzle, 2022). Has also
been shown to have shear protectant
properties.
Plant albumins can functionally replace recombinant animal albumin in cell culture.
The same should be feasible for transferrins from plants or algae.
Source: Stout, 2023
The bulk of cellular biomass in proliferating cells is made from amino acids. Today,
amino acids used to feed cells come primarily from individual fermentation processes,
only some of which are sufficiently scaled.
Facility 1 Facility 2
Source: Humbird, 2021
Amino acids are a cost driver
Catch 22: Amino acid costs only
become low when the cultivated
meat industry is large. But high costs
during the early stages of the industry
would likely prevent industry growth.
25
Amino acids from hydrolysates?
Soybean hydrolysate contains an amino acid
profile that fills most essential amino acid
requirements of an animal cell.
For cultivated meat, can hydrolysates from
plants, microalgae, or other organisms be
used as the primary source of amino acids?
Source: Humbird, 2021
Kerry cell nutrition
Hydrolysates from plants, animals, and
yeasts have been used as supplements
in cell culture for decades.
26
Use of hydrolysates can have large effects on cost
…and result in fewer raw materials
needed for media formulation,
resulting in a more simplified supply
chain.
Source: Humbird, 2021
Facility 1 Facility 2
Cost if soy hydrolysates are used at $2/kg
$3.10 $4.25
27
What is a hydrolysate?
Source: Ho, 2021
High protein raw
materials are
hydrolyzed (i.e., broken
down) by acid or
alkaline pH, heat,
enzymes, or
fermentation processes.
Hydrolysates contain a
mixture of peptides,
amino acids, minerals,
carbohydrates, and
lipids.
28
What materials should be used for hydrolysates?
Using the same animal cell protein requirements, crop sidestreams such
as soy meal, corn DDGS, canola meal, brewer’s spent grain, & corn gluten
meal were determined to have favorable amino acid profiles for hydrolysis.
GFI sidestreams analysis
Soybean hydrolysate contains an amino acid
profile that fills most essential amino acid
requirements of an animal cell.
Source: Humbird, 2021
29
Open questions, challenges, and research priorities
1. What starting material should be used (crops,
microalgae, yeasts, bacteria, etc)?
a. Volume, cost, environmental footprint
2. In what form should the starting material be
obtained (meal, concentrate, isolate; from an
existing sidestream, etc)?
3. What hydrolysis method works best, how much
hydrolysis to perform?
a. Need to characterize peptide, amino acid, vitamin,
mineral composition;
b. Lot to lot variability;
c. Other unique bioactivity (antioxidant, antimicrobial,
anti-nutritional or growth inhibitory factors)
4. Deep, experimental characterization in different
cell types from different species is needed.
Source: GFI sidestreams analysis
30
Open questions, challenges, and research priorities
1. What starting material should be used (crops,
microalgae, yeasts, bacteria, etc)?
a. Volume, cost, environmental footprint
2. In what form should the starting material be
obtained (meal, concentrate, isolate; from an
existing sidestream, etc)?
3. What hydrolysis method works best, how much
hydrolysis to perform?
a. Need to characterize peptide, amino acid, vitamin,
mineral composition;
b. Lot to lot variability;
c. Other unique bioactivity (antioxidant, antimicrobial,
anti-nutritional or growth inhibitory factors)
4. Deep, experimental characterization in different
cell types from different species is needed.
● Results, protocols, & methods should be
published openly to prevent duplication
● Lots of opportunity for collaborative,
public-private work Source: Yamanaka, 2023
Protocol for optimizing
microalgae hydrolysis
31
Amino acids from hydrolysates?
For cultivated meat, can hydrolysates from plants,
microalgae, or other organisms be used as the
primary source of amino acids?
To be determined…
1. Source lower cost ingredients ($/L)
a. Pharma-grade → food-grade and feed-grade ingredients
b. New sources for recombinant proteins and amino acids
2. Use less media (g/kg)
a. Formulation discovery: metabolic modeling and engineering to create cultivated
meat with low feed conversion ratios and to inform media formulations and the
future supply chain
3. Scale the new supply chain
Steps to reduce cell culture media costs
Feed conversion: why $/L is not the correct long-term metric
Data source: Table 1, Sinke et al, 2023.
Most of cell culture
media volume and
weight is water.
Measuring costs on
a volumetric basis
says little about the
amount of actual
ingredients in the
media or how
efficiently those
ingredients are
being converted
into meat.
The question to ask is: what amount (mass) of media ingredients is necessary to
produce 1kg of cultivated meat in your production process?
The importance of feed conversion
A minimum of ~600-800 g of solids per kg of meat (70% of meat is water) was determined (needs further
experimental validation).
The baseline scenario results in a feed conversion nearly 3x as efficient as chicken production.
If feed conversion is inefficient (high medium scenario), the costs would increase dramatically and the carbon
footprint would increase by 73 to 241% compared to baseline, depending on where and how renewable energy is
used in the supply chain.
The medium (in this study)
includes:
● 75% of amino acids derived
from soy hydrolysate
● 25% of amino acids from
fermentation and chemical
synthesis
● Glucose from corn
● Recombinant proteins and
growth factors produced
via microbial fermentation.
Data source: Table 1, Sinke et al, 2023.
35
Raw material estimates from multiple studies
Data source: Table D.9, Sinke et al, 2023.
A large research gap is that more real-world data points from different cells and species, and different
cellular stages (proliferation, differentiation) are needed to estimate the amount of raw materials needed.
Note that including hydrolysates will result in higher overall amounts of amino acids compared to solely
sourcing them from fermentation processes because some amino acids will be in overabundance. But the cost
savings justify these higher amounts.
36
Cell metabolism is central to achieving cost and
environmental goals
Source: Humbird, 2021. Assumes a cell is 15% lipid, 10% carbohydrate, 5% RNA/DNA, and 70% protein.
Hypothetical wild-type metabolism
0.147 glucose + 0.378 O2
+ 0.007Arg + 0.004Cys + 0.022Gln + 0.003His + 0.007Ile + 0.010Lys + 0.002Met
+ 0.005Phe + 0.009Thr + 0.002Trp + 0.005Tyr +0.010Val +0.013Ala + 0.006Asn + 0.008Asp + 0.011Gly +
0.011Leu + 0.007Pro + 0.010Ser →
1DCM + 0.005Glu + 0.070 NH3
+ 0.474 Lac + 0.435 CO2
+ 0.495 H2
0
Hypothetical “enhanced” metabolism
0.147 glucose + 0.378 O2
+ 0.007Arg + 0.004Cys + 0.022Gln + 0.003His + 0.007Ile + 0.010Lys + 0.002Met
+ 0.005Phe + 0.009Thr + 0.002Trp + 0.005Tyr +0.010Val +0.013Ala + 0.006Asn + 0.008Asp + 0.011Gly +
0.011Leu + 0.007Pro + 0.010Ser →
1DCM + 0.005Glu + 0.004 NH3
+ 0.041 Lac + 0.455 CO2
+ 0.613 H2
0
Efficient metabolism means better feed conversion and less waste. But it also translates to creating
fewer toxic metabolic byproducts (i.e., ammonia and lactate).
Stoichiometric/mass balance equations need to be validated based on real biomass compositional
measurements from animal cells used in cultivated meat production. This is a current data gap that is
critical for informing techno-economic and environmental impact models.
Case study: media formulation optimization
Source: Lyra-Leite, 2023
Off-the-shelf media formulations are not tailor-made. They often contain ingredients
that are unnecessary or in overabundance, leading to waste.
Number of ingredients reduced from 52 to 39.
Concentration of several ingredients such as
amino acids and vitamins were reduced.
Fewer ingredients = lower costs.
DMEM/F12 BMEM
Very labor intensive.
Other machine learning and high dimensional
design-of-experiments techniques will also be
valuable in formulation optimization (Cosenza).
38
Metabolic modeling to optimize feed conversion
Source: Romero & Boyle, 2023; more explained in GFI’s solutions database.
The diverse array of species, cell types, and dynamic cellular states (e.g., proliferation,
differentiation) necessitates many custom media formulations catered to individual
metabolisms or metabolic states.
The creation and validation of genome-scale metabolic models can accelerate
formulation discovery and optimize feed conversion in a hypothesis-driven manner.
Recycling and valorization
Ammonia is the metabolite of highest concern because it becomes toxic at
relatively low concentrations (3-5 mM).
● There is a large incentive to lower ammonia production via cell engineering (e.g., glutamine
synthetase) or change in media composition (e.g., avoid feeding glutamine).
● Limiting ammonia production increases productivity and lowers costs.
Lactate is the metabolite produced in the highest quantity.
● How tractable is it to valorize lactate, creating a co-product, revenue stream, and carbon
footprint offset?
● Toxicity of lactate is less of an issue compared to ammonia: less research on how to stop its
production, more research on what we do with it?
More on recycling: Yang, 2023
Recycling water, growth factors, amino acids, or other metabolites may also be
performed, influencing cost and environmental impact of production.
● More research needed to uncover what other inhibitory metabolites may exist.
1. Source lower cost ingredients ($/L)
a. Pharma-grade → food-grade and feed-grade ingredients
b. New sources for recombinant proteins and amino acids
2. Use less media (g/kg)
a. Formulation discovery: metabolic modeling and engineering to create cultivated
meat with low feed conversion ratios and to inform media formulations and the
future supply chain
3. Scale the new supply chain (see slides 70-71)
Steps to reduce cell culture media costs
Summary
1. There is a clear path for the steps to take and major R&D areas of focus to
significantly reduce the costs of cell culture media.
a. The major buckets are (1) sourcing lower cost ingredients and (2) optimizing
formulations for efficient feed conversion.
2. Many pathways to sourcing lower cost ingredients are already known.
a. Many solutions can be used throughout the entire industry.
b. Several examples in the literature already demonstrate tractable approaches.
c. Sourcing lower cost ingredients already gets you to >99% cost reduction compared to
pharma-grade media.
3. Formulation discovery, understanding metabolism, and using media
efficiently with low feed conversion rates will require more R&D time and
effort compared to sourcing lower cost ingredients.
a. Solutions will need to be uniquely tailored to each cell line.
b. This research is just beginning.
Two major buckets drive cultivated meat production cost
Cell culture media Infrastructure
Growth factors
Amino acids
Buildings
Bioreactors Labor
Utilities
Other media
components,
equipment,
consumables
Infrastructure
1. Infrastructure buildout requirements and current
status in scaling to meet market growth estimates
2. Production facility cost estimates
3. Bioreactor types, costs, considerations, and metrics
By 2030, McKinsey
estimates that under
high growth scenarios,
cultivated meat could
account for up to 2.1
million metric tons
(MMT), making it a
$25B market.
This is ~0.56% of
global meat demand
(assuming 375 MMT,
excluding seafood by
2030).
Cultivated meat growth estimates
Source: McKinsey, 2021
A significant amount of new infrastructure will be needed
“Building the infrastructure to make more meat requires a significant amount of capital. The
kind of infrastructure we need is not available on the planet.” - Josh Tetrick CEO, Eat Just
Size range of current global
pharmaceutical capacity
= 10 million liters of capacity
to
to
Capacity range needed for 1.5 MMT of cultivated
meat (~0.4% of 2030 market) is about 22x that of
the current global pharmaceutical industry
Source: McKinsey, 2021
Capacity gap estimations
Source: Ark Biotech, the bioreactor gap
Capacity calculations based on expected yield of 8.2 kg/L/year, which assumes
50% of cultivated meat is produced with an optimized fed-batch process, and 50%
is produced with an optimized continuous process.
Global meat consumption could be satisfied with
60 billion liters* of bioreactor capacity, which
could fit in the size of lower Manhattan
* Assumes more efficient production with Ark’s bioreactors
Scale up terminology and current status
Source: Harsini and Swartz, 2024; GFI facility and capacity tracker.
The largest known installed bioreactors are
6,000L (GOOD Meat, Singapore) and 10,000L
(OMeat, U.S.), although there is no confirmation
that these reactors are currently operational.
The largest known bioreactors in operation within
the cultivated meat industry are 2,000L (several
companies).
There are at least 35 facilities that have been built
or announced around the world.
● The vast majority are pre-pilot or pilot scale
facilities.
● A few facilities (including those currently
under construction) could be considered
industrial scale.
A proposed guide for aligning on scale up terminology.
Cultivated meat industry growth estimates: how are we
tracking?
Source: Harsini & Swartz, 2024. * Assumes 100% cultivated meat production, not incorporation into hybrid products.
1
Based on red meat (beef, mutton, pork) production across 800 federally-regulated slaughterhouses.
Key considerations: commission time of facilities (difference between reactor capacity and
actual production), cultivated meat or hybrid products, actual success in scaling, financing
availability and overall de-risking of business models, regulatory challenges or bans
Survey data: ~25k tons expected from 19
companies by 2026.
Multiply by 5 to account for ~100 B2C
companies.
= A very rough estimate of ~125k tons* of
CM production by the end of 2026 (~4 U.S.
slaughterhouses1
worth of production).
Currently tracking toward the low growth
estimate from McKinsey.
Disclaimer: Caution is advised when interpreting the figures presented, as they are based on a subset of 19 responses, not
representative of all CM companies, and do not fully reflect the industry. Scaling challenges and optimistic projections can
lead to varying production capacity estimations. Technological advancements and process refinements may accelerate
industry growth. The projections do not account for potential innovations or new industry players, which could greatly
influence future production capacity. The higher and lower bounds in the figure refer to the ranges of options selected by
companies. "Max capacity" refers to maximum production capacity, and "estimated production" refers to expected
production amount.
Estimated cultivated meat production by end of 2026 (19 respondents)
Infrastructure
1. Infrastructure buildout requirements and current
status in scaling to meet market growth estimates
2. Production facility cost estimates
3. Bioreactor types, costs, considerations, and metrics
Estimates for new facility CAPEX: example 1
Facility 1 Facility 2
Source: Humbird, 2021
The total capital
investment for a facility
with ~7,000 tons of
annual production
capacity is $325M
(facility 1)*
to $663M
(facility 2)*
.
*Facility 1 uses 20kL bioreactors operating under fed-batch mode. Facility 2 incorporates a 2kL perfusion system.
The total capital
investment of a
10,000 ton annual
production facility is
$450M (-20% to
+40%).
Source: CE Delft Techno-Economic Assessment (2021)
Webinar: The costs and environmental impacts of cultivated meat
Policy recommendations
Technical recommendations
Estimates for new facility CAPEX: example 2
Summary estimates for new facility CAPEX
Study
Negulescu,
2023
Negulescu,
2023
Negulescu,
2023
Vergeer,
2021
Humbird,
2021
Humbird,
2021
Largest
proliferation
vessel
42 kL
stirred-tank
reactor
211 kL
stirred-tank
reactor
262 kL air-lift
reactor
10 kL
stirred-tank
reactor + 2 kL
perfusion system
for
differentiation
20 kL
stirred-tank
reactor
2 kL
stirred-tank
perfusion
reactor
Annual
production
capacity
4,000 tons 20,000 tons 25,000 tons 10,000 tons 6,800 tons 6,900 tons
CAPEX per
facility
$438M $1,172M $366M $450M $325M $663M
Capital cost
per ton
~$109,000 ~$58,000 ~$14,000 ~$45,000 ~$46,000 ~$94,000
*Each study uses different assumptions and in some cases different bioreactor types or modes of operation that can affect overall capital costs. These
numbers therefore are not necessarily directly comparable but can be used to provide a sense of expectations for CAPEX costs. Capital cost per ton is to
get a sense of differences from a normalized value (does not account for amortization).
Size (sq. ft.) 187,000 200,000
Capacity Up to 13,600 tons At least 10,000 tons
Reactor size Up to 100,000 L Not stated
Investment
amount
$140M investment
(~$10,000/ton)*
$123M investment
(~$12,000/ton)*
Real-world production facility announcements
*it is not stated exactly what is accounted for by these investment totals. It is possible that future investments will be
needed to outfit the facility with the necessary equipment to achieve the stated maximum capacities or operational
efficiencies.
Source Source
Ballpark estimates for the cost of new infrastructure
= 10,000 tons annual capacity = ~$300M?
= 150 facilities
= 1.5M tons annual capacity
= 0.4% of 2030 market
= $45B?
● There is high variability in the estimated costs of facilities capable of producing
thousands of tons of cultivated meat.
● Facility costs may vary significantly by region and this has yet to be modeled.
● More data and studies are needed before higher confidence predictions on
anticipated costs of new infrastructure can be made.
Infrastructure
1. Infrastructure buildout requirements and current
status in scaling to meet market growth estimates
2. Production facility cost estimates
3. Bioreactor types, costs, considerations, and metrics
The cultivated meat industry uses diverse bioreactor types
Nearly all TEA studies performed to date focus on the cost of production using stirred-tank
bioreactors. This does not capture the diversity of approaches being pursued.
Different bioreactors may have
different roles in proliferation and
differentiation.
Different bioreactors can have
different components (e.g.,
impellers) that influence material
and utilities costs.
Different bioreactors occupy
different amounts of space in a
facility, influencing overall design
facility footprint, or shipping and
assembly.
Production in different bioreactor
types will have different
techno-economic outcomes.
Source: Harsini & Swartz, 2024.
Source: Negulescu, 2023; Humbird, 2021
1
Total direct cost, 2
Single equipment purchase cost
Humbird: Estimated cost of a 20 m3
stirred-tank bioreactor made of pharma-grade
316L stainless steel: $1.5M1
Negulescu: Estimated cost of a 42 m3
stirred-tank bioreactor made of food-grade
304 stainless steel: $904k2
Negulescu: Estimated cost of a 211 m3
stirred-tank bioreactor made of food-grade
304 stainless steel: $2.38M2
Negulescu: Estimated cost of a 262 m3
air-lift
bioreactor made of food-grade 304 stainless
steel: $313k2
Bioreactors: type, size, and material influences cost
Use of food-grade steel alloys in the cultivated meat industry
The material makeup of the 316
stainless steel alloy makes it
more durable but also more
expensive (~40% higher).
Some cultivated meat companies
are already using the 304
stainless steel alloy, which is
more commonly used in food
production.
Adoption of 304 stainless steel
or other more affordable
materials1
will be important to
track as the cultivated meat
industry scales.
Source: Harsini & Swartz, 2024.
1
Read how sterility controls may influence the types of materials that can be used for bioreactors.
Assumes: 50K MT annual output, fed-batch process reaching 20M cells/mL and no differentiation step;
bioreactors <250K L fabricated in shop with others fabricated in field; 15-year depreciation period with no
salvage value; bioreactor volumes are nominal with 80% working volume.
Source: Ark Biotech TEA
Economies of scale are real. Why?
As the scale of the reactor
increases, production becomes
more efficient.
● (1) fewer reactors (including
seed train vessels and
parts) are needed for the
same production output, (2)
fewer personnel and
utilities are needed to
operate the equipment, and
(3) the cost contribution of
maintenance and
depreciation decreases.
60
Influence of bioreactor size on cost contribution
Source: Negulescu, 2023. This figure assumes a fixed media cost.
With less equipment, total costs become more dependent on cell culture media.
Anticipated bioreactor size in future facilities
Some companies in the
cultivated meat industry
expect to use
bioreactors >50,000L.
The first successful
cultivated meat
production runs in
bioreactors larger than
25,000L (the largest
reactors used in
biopharma) could be a
significant de-risking
event for the industry.
Source: Harsini & Swartz, 2024.
Scaling up vs. scaling out: balancing risk
With larger size comes larger risk, but potentially larger rewards (i.e., lower COGS).
● Technical risk: animal cells have never been grown at such large scales.
● Operational risk: larger vessels increase production time and reactor surface area, which
could increases opportunity for contamination and loss of batches.
Different philosophies: Some believe that scaling out at a
certain “sweet spot” will enable them to achieve favorable
cost profiles for their products, balancing risk vs. reward.
Others believe continuing to scale up is the most prudent
path forward.
Where companies decide to stop scaling up and instead
scaling out will dependent on many factors such as the
process and product.
Additional TEAs are needed to evaluate this under different
scenarios (different bioreactors, different scales, different
process designs, etc).
scale
up
scale
out
Contamination prevention
If pharmaceutical clean rooms are assumed, the costs of the facility as it
increases in size outpace any efficiencies gained from scaling (Humbird).
Cultivated meat manufacturers will need to be able to grow cells in
environments with lower clean room classifications, potentially exposing
them to higher rates of contamination and loss of batches.
Different philosophies: Skeptics believe that growing cells at large scale in
a non-pharmaceutical environment is a dead end. Others believe it not a
big hurdle, it’s just never needed to be done before.
Other potential solutions: food-safe antimicrobial peptides as a second
layer of defense.
Bioreactors: mode of operation
Source: Harsini & Swartz, 2024.
Fed-batch is currently
the most frequent
mode of operation
used for production.
However, companies
throughout the
cultivated meat
industry are exploring
all types of operation
modes for running
production processes.
Bioreactors: mode of operation
Source: Ark Biotech TEA
Many companies
are developing
continuous or
perfusion
processes.
But this may have
operational
limitations at
increasingly larger
bioreactor scales or
higher media costs.
Bioreactors: cell density
Source: Ark Biotech TEA
Note: it is recommended to measure and report cell density in grams
per liter. This normalizes for differences in cells per mL measurements
that are dependent on cell size.
Cell density (g/L) is one of the most important cost variables and metrics to track.
But context matters: achievable cell densities will vary based on the mode of
operation and the type of bioreactor used.
Bioreactors: cell density
Source: Humbird, 2021; Pasitka, 2023
The Humbird report says perfusion
would max out at 195 g/L, given
certain constraints and perfusion
rates.
A study by Believer Meats in Nature Food reports very high densities of 360 g/L
at small scale. But the high perfusion rates (VVD) implies a large amount of
media being exchanged. If these rates are not lowered, media costs at scale
would be very high.
Cell density as a singular metric does not tell the full story. Context matters.
Process intensification lowers CAPEX by reducing the
number of bioreactors and the number of buildings
Source: CE Delft Techno-Economic Assessment (2021)
Webinar: The costs and environmental impacts of cultivated meat
More efficient production processes (e.g, faster cell doubling times, increased cell
densities, reduced media costs) means fewer bioreactors needed in the facility and
fewer personnel to operate and maintain the equipment, reducing overall cost burden.
STAFF
200 130
CAPEX
$450M $250M
Closing thoughts
1. Scaling the supply chain, interventions, and other
factors
2. Where are we and what’s next?
Scaling the supply chain
The supply chain for media, bioreactors, and other equipment will need to be
reshaped to fit the needs of the cultivated meat industry.
Significant investments will also be needed by suppliers to acquire land, build
production facilities, source energy and raw materials, and hire labor to run new
facilities for inputs and equipment.
None of this happens overnight.
Suppliers will need to scale alongside the
growth of the cultivated meat industry.
This will inherently limit how fast certain
costs can be reduced.
Higher
demand
Lower costs,
better products
Scaled
production
CapEx
Longer term, lower cost,
non-VC capital.
Government support:
loan guarantees, tax
credits, grants,
procurement contracts
Source: discussions with Zak Weston (BERA partners)
Supply chain interventions: learnings from past
market-shaping work
Pooled procurement: Creating buyer consortiums for media, media inputs (e.g.,
growth factors), and high-cost equipment (e.g., bioreactors) to combine purchasing
power, provide predictable demand to suppliers, and lower costs.
Coordinated ordering: Multiple buyers use group-negotiated prices and terms derived
from information sharing and joint market research to optimize purchasing strategies.
Variant optimization and standardization: Standardized medium formulations, input
and equipment specifications, and purchasing terms.
Interventions taken to rapidly scale supply chains and lower costs for vaccines and
other medicines can be applied to the cultivated meat industry.
Source: Zak Weston; Parmaksiz, 2022; USAID Market Shaping Primer, 2014.
Learning rates
Could learning curves for bioreactors be analogous
to what learning curves for batteries enabled for
electric vehicle competitiveness?
Modularity and low design complexity for equipment and
processes can help ensure that robust manufacturing
learning curves emerge
Source: Malhotra & Schmidt, 2020.
Ample opportunities for learning rates to emerge
Cultivated meat differs from biofuels —
it does not need to directly compete
with commodities from the get-go.
Meat prices span two orders of
magnitude. The premium and specialty
meat market is ~6 million tons
annually.
Solar gained scaling foothold in the
high-priced satellite industry in space,
then learning rates took over on Earth.
From its current point, cultivated meat
will take ~13-15 doublings in capacity
just to fulfill the premium/specialty
meat demand.
Cultivated meat companies do not need to limit
themselves to just selling meat
Cultivated meat companies can license or sell media formulations, cell lines, or
other process and equipment-related IP.
It is possible that other co-products could be valorized to provide a meaningful
revenue stream for companies.
Closing thoughts
1. Scaling the supply chain, interventions, and other
factors
2. Where are we and what’s next?
76
Summary of select scenarios from select TEAs
Scale of reactor
(L x 1000)
77
Summary of select TEAs
● Contrary to some opinions, scenarios in
multiple cultivated meat TEAs suggest
cost competitiveness could be achieved.
○ Many of these scenarios are at very large
scales or have favorable assumptions.
● Need for more TEAs:
○ There is a large need for TEAs to reflect the
diversity of manufacturing approaches
being taken in the industry. Knowledge
gaps include TEAs with other bioreactor
types (hollow fiber, air lift, fixed bed),
modes of operation, the influence of
accounting for mass gain during
differentiation, and hybrid products.
○ Most TEAs don’t include all of the
production steps (e.g., stop at cell harvest)
or analyze profitability and payback time in
detail.
Scale of reactor
(L x 1000)
78
Predictions by some cultivated meat companies outpace most
TEA outlooks
“Our TEA results show for the first time that a
credible path to sub $7 per kg on beef production
at the first commercial factory,” he writes, “and
can reach sub $5/kg beef at the second commercial
scale facility.”
- Deniz Kent, CEO Prolific Machines
Fast Company, 2023
“We can achieve price parity today if we operate at
scale, without relying on future innovations. And we
can do that with the 10,000-liter bioreactors we’re
planning in our pilot plant, whereas others require
really large bioreactors that haven’t been validated.”
- Ali Khademhosseini, CEO Omeat
AgFunder, 2023
Achieving price parity in the short-term is not predicted by existing public cost
models. Can this actually be achieved?
“We believe we can do profitable production
from 2,000-liter reactors for premium
species [such as eel and grouper], and we as
we go to larger volumes, 10,000-liters makes
sense.” - Mihir Pershad, CEO Umami Bioworks
AgFunder, 2023
*BlueNalu plans to use eight 100,000L bioreactors in their
future facility
Food Dive, 2022
Profitability is usually mentioned in the context of high-priced conventional meat or
seafood products
79
Where do we stand?
As of now, we do not actually know the cost of cultivated meat production today or
in the future. There are many production scenarios and approaches — a single
number cannot be given. Additional studies are needed to get higher confidence in
the expected range.
It is critical to provide the context for the product (chicken vs. foie gras) and
whether it’s a hybrid (100% vs. 5%) when discussing how cultivated meat costs
compare to conventional meat.
Taking the current knowledge of costs and expected progress:
● If pursuing a high-end product type (e.g., foie gras, tuna toro), then a 100% cultivated meat
product (or similarly high inclusion rates) can be a tractable approach to cost-competitiveness.
● If pursuing commodity meats (e.g., chicken, pork, beef, certain seafoods), then hybrid products
at low inclusion rates offer the most tractable way to approach cost-competitiveness. However,
the timeline is uncertain and success will depend on many of the variables discussed in this
presentation.
80
Learn more!
@GoodFoodInst /TheGoodFoodInstitute www.gfi.org

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2024.03.12 Cost drivers of cultivated meat production.pdf

  • 1. Cost drivers of cultivated meat production Elliot Swartz, Ph.D. Principal Scientist, Cultivated Meat @elliotswartz March, 2024 elliots@gfi.org Linkedin
  • 2. The Good Food Institute Science and Technology Advancing foundational, open-access research in alternative proteins and creating a thriving research and training ecosystem around these game-changing fields. Corporate Engagement Partnering with companies and investors across the globe to drive investment, accelerate innovation, and scale the supply chain—all faster than market forces alone would allow. Policy Advocating for fair policy and public research funding for alternative proteins. We work as a force multiplier, bringing the expertise of our departments to the rest of the world. United States Brazil India Europe Asia Pacific Israel GFI is a 501(c)(3)nonprofit developing the roadmap for a sustainable, secure, and just protein supply. We focus on three key areas of work: GFI officially earned Candid’s 2022 Platinum Seal of Transparency—reflecting our commitment to maximum impact, efficiency, and inclusion. 200+ staff in 6 regions
  • 3. The purpose of this presentation is to describe our current understanding of the major cost drivers or cost-influencing factors of cultivated meat production — how to think about the problem. The presentation does not comprehensively capture every minor cost or process consideration. Cell line influences are not described in detail. We are still learning about the costs of cultivated meat production. Some cost factors today may become minor as new solutions emerge. Information will change as more data becomes available. Accordingly, this presentation will be updated annually.
  • 4. Fundamentals: understanding the cost drivers of cultivated meat
  • 5. 5 Source: Humbird, 2021. The cost drivers of cultivated meat Cell culture media Infrastructure Facility 1 Facility 2
  • 6. 6 The cost drivers of cultivated meat Source: CE Delft Techno-Economic Assessment (2021) Webinar: The costs and environmental impacts of cultivated meat Growth media is the current cost driver Infrastructure will be a long-term cost driver Maximizing process efficiency and cell-level traits are needed to get into commodity cost ranges
  • 7. Two major buckets drive cultivated meat production cost Cell culture media Infrastructure Growth factors Amino acids Buildings Bioreactors Labor Utilities Other media components, equipment, consumables
  • 9. 9 Cell culture media composition: basal media The basal media contains the energy source (glucose, pyruvate), amino acids, vitamins, and inorganic salts. DMEM/F12 contains 50-52 ingredients and serves as a starting point for mammalian cell cultures DMEM/F12 Leibovitz-15 contains 30-32 ingredients and serves as a starting point for fish and crustacean cell cultures
  • 10. 10 Cell culture media composition: added factors Added factors may include: lipids, antioxidants, growth factors, hormones, small molecules, peptides, anti-foaming agents, surfactants, etc. Component DMEM/F12 Ascorbic acid 2-phosphate Sodium bicarbonate Sodium selenite Insulin Transferrin FGF2 TGFb Essential-8, originally derived to simplify the growth of human induced pluripotent stem cells, contains 7 added factors on top of the DMEM/F12 basal media formulation Complete media = basal media + added factors. Complete media will differ by the cell type, species, differentiation state, process conditions, and intended end-product
  • 11. Reducing media costs Use less media 2 ● Optimize for feed conversion ratio (g ingredients/kg meat) ● Tailored to each company’s cells, process, and products ● Longer timeline for success Source lower-cost ingredients 1 ● Optimize for $/L media ● Cross-industry relevance ● Shorter timeline to success Time Success in both approaches will be required for cost-competitive cultivated meat production
  • 12. Steps to reduce cell culture media costs 1. Source lower cost ingredients ($/L) a. Pharma-grade → food-grade and feed-grade ingredients b. New sources for recombinant proteins and amino acids 2. Use less media (g/kg) a. Formulation discovery: metabolic modeling and engineering to create cultivated meat with low feed conversion ratios and to inform media formulations and the future supply chain 3. Scale the new supply chain
  • 13. $1/L of media is an early target for the industry Source: Negulescu, 2023. Source: Lever VC
  • 14. But commercial stem cell media cost hundreds of dollars per liter Source: Kuo, 2020.
  • 15. Sourcing lower-cost ingredients can reduce media costs ($/L) by >99% $40.94 $14.54 $4.71 $3.74 $0.85 $0.35 $0.24 Source: Specht, 2019 ● Models suggest media costs below $1/L are tractable and can happen quickly. ● Anecdotally, multiple companies have already broken through this threshold.
  • 16. Sourcing food-grade ingredients lowers costs Kanayama, 2022 ● Many basal medium ingredients are available at “food-grade,” with similar purity levels as pharma-grade ingredients. ● 100% food-grade basal media, such as I-MEM 2.0, have already been created. Source: Integriculture Source: Cellular Agriculture Europe
  • 17. Food- and feed-grade ingredients perform well in cell culture media Source: The Good Food Conference, 2021 ● Cultivated meat manufacturers and media suppliers are at various stages of replacing pharma-grade ingredients with food- or feed-grade ingredients. ● Multiple data points suggest replacement of pharma-grade ingredients is a tractable approach with minimal technical bottlenecks. ● Regulatory issues for food-grade inputs are not expected, as most basal media ingredients are nutrients found abundantly in the food we eat every day. Safety for some feed-grade inputs will need to be evaluated.
  • 18. 1. Source lower cost ingredients ($/L) a. Pharma-grade → food-grade and feed-grade ingredients b. New sources for recombinant proteins and amino acids 2. Use less media (g/kg) a. Formulation discovery: metabolic modeling and engineering to create cultivated meat with low feed conversion ratios and to inform media formulations and the future supply chain 3. Scale the new supply chain Steps to reduce cell culture media costs
  • 19. 19 Growth factors and recombinant proteins are cost drivers If growth factors used in the pharmaceutical sector were used in cultivated meat production, they would account for 99% of costs at scale. Source: Specht, 2019
  • 20. Growth factors: reduce their use Source: 3DBioTissues Companies are employing many different methods to reduce the quantity of growth factors needed or eliminate them entirely. Certain supplements claim to show increased cell growth rates despite using growth factors at half their normal concentrations. Source: Stout, 2023 Cells can be engineered in various ways to eliminate the need for certain growth factors such as FGF2. Read more: Swartz, 2023
  • 21. Growth factors: scale production with existing technology To be suitable for use in a cost-competitive cultivated meat industry, growth factors should cost at or below $100,000/kg. Source: Puetz & Wurm, 2019 ● These growth factor cost profiles are readily achievable for suppliers to hit when scaling existing production and performing food-grade downstream purification processes. ● While costs for growth factors are still high today, the bottleneck is one of markets, not technology: no single manufacturer is ready to purchase kilograms of FGF2, IGF1, TGFb. Source: Swartz, 2023
  • 22. Other recombinant proteins are used in significantly higher quantities than growth factors 99% of recombinant protein volume would come from proteins such as albumin*, transferrin, and insulin Source: Swartz, 2023, * not all media formulations will require albumin Millions of kg of albumin could be needed to supply less than 1% of global meat production volume Albumin 300-8200x the current production volume for transferrin Alternative, non-recombinant sources of albumins, transferrin, and insulin are needed to supply the cultivated meat industry as it scales Certain recombinant proteins are used at 103 to >106 higher concentrations than growth factors
  • 23. New sourcing strategy for albumins, transferrins, insulin Opportunities to find cell culture functionalities for other food-grade ingredients: ● Methylcellulose enhances albumin functionality (Schenzle, 2022). Has also been shown to have shear protectant properties. Plant albumins can functionally replace recombinant animal albumin in cell culture. The same should be feasible for transferrins from plants or algae. Source: Stout, 2023
  • 24. The bulk of cellular biomass in proliferating cells is made from amino acids. Today, amino acids used to feed cells come primarily from individual fermentation processes, only some of which are sufficiently scaled. Facility 1 Facility 2 Source: Humbird, 2021 Amino acids are a cost driver Catch 22: Amino acid costs only become low when the cultivated meat industry is large. But high costs during the early stages of the industry would likely prevent industry growth.
  • 25. 25 Amino acids from hydrolysates? Soybean hydrolysate contains an amino acid profile that fills most essential amino acid requirements of an animal cell. For cultivated meat, can hydrolysates from plants, microalgae, or other organisms be used as the primary source of amino acids? Source: Humbird, 2021 Kerry cell nutrition Hydrolysates from plants, animals, and yeasts have been used as supplements in cell culture for decades.
  • 26. 26 Use of hydrolysates can have large effects on cost …and result in fewer raw materials needed for media formulation, resulting in a more simplified supply chain. Source: Humbird, 2021 Facility 1 Facility 2 Cost if soy hydrolysates are used at $2/kg $3.10 $4.25
  • 27. 27 What is a hydrolysate? Source: Ho, 2021 High protein raw materials are hydrolyzed (i.e., broken down) by acid or alkaline pH, heat, enzymes, or fermentation processes. Hydrolysates contain a mixture of peptides, amino acids, minerals, carbohydrates, and lipids.
  • 28. 28 What materials should be used for hydrolysates? Using the same animal cell protein requirements, crop sidestreams such as soy meal, corn DDGS, canola meal, brewer’s spent grain, & corn gluten meal were determined to have favorable amino acid profiles for hydrolysis. GFI sidestreams analysis Soybean hydrolysate contains an amino acid profile that fills most essential amino acid requirements of an animal cell. Source: Humbird, 2021
  • 29. 29 Open questions, challenges, and research priorities 1. What starting material should be used (crops, microalgae, yeasts, bacteria, etc)? a. Volume, cost, environmental footprint 2. In what form should the starting material be obtained (meal, concentrate, isolate; from an existing sidestream, etc)? 3. What hydrolysis method works best, how much hydrolysis to perform? a. Need to characterize peptide, amino acid, vitamin, mineral composition; b. Lot to lot variability; c. Other unique bioactivity (antioxidant, antimicrobial, anti-nutritional or growth inhibitory factors) 4. Deep, experimental characterization in different cell types from different species is needed. Source: GFI sidestreams analysis
  • 30. 30 Open questions, challenges, and research priorities 1. What starting material should be used (crops, microalgae, yeasts, bacteria, etc)? a. Volume, cost, environmental footprint 2. In what form should the starting material be obtained (meal, concentrate, isolate; from an existing sidestream, etc)? 3. What hydrolysis method works best, how much hydrolysis to perform? a. Need to characterize peptide, amino acid, vitamin, mineral composition; b. Lot to lot variability; c. Other unique bioactivity (antioxidant, antimicrobial, anti-nutritional or growth inhibitory factors) 4. Deep, experimental characterization in different cell types from different species is needed. ● Results, protocols, & methods should be published openly to prevent duplication ● Lots of opportunity for collaborative, public-private work Source: Yamanaka, 2023 Protocol for optimizing microalgae hydrolysis
  • 31. 31 Amino acids from hydrolysates? For cultivated meat, can hydrolysates from plants, microalgae, or other organisms be used as the primary source of amino acids? To be determined…
  • 32. 1. Source lower cost ingredients ($/L) a. Pharma-grade → food-grade and feed-grade ingredients b. New sources for recombinant proteins and amino acids 2. Use less media (g/kg) a. Formulation discovery: metabolic modeling and engineering to create cultivated meat with low feed conversion ratios and to inform media formulations and the future supply chain 3. Scale the new supply chain Steps to reduce cell culture media costs
  • 33. Feed conversion: why $/L is not the correct long-term metric Data source: Table 1, Sinke et al, 2023. Most of cell culture media volume and weight is water. Measuring costs on a volumetric basis says little about the amount of actual ingredients in the media or how efficiently those ingredients are being converted into meat. The question to ask is: what amount (mass) of media ingredients is necessary to produce 1kg of cultivated meat in your production process?
  • 34. The importance of feed conversion A minimum of ~600-800 g of solids per kg of meat (70% of meat is water) was determined (needs further experimental validation). The baseline scenario results in a feed conversion nearly 3x as efficient as chicken production. If feed conversion is inefficient (high medium scenario), the costs would increase dramatically and the carbon footprint would increase by 73 to 241% compared to baseline, depending on where and how renewable energy is used in the supply chain. The medium (in this study) includes: ● 75% of amino acids derived from soy hydrolysate ● 25% of amino acids from fermentation and chemical synthesis ● Glucose from corn ● Recombinant proteins and growth factors produced via microbial fermentation. Data source: Table 1, Sinke et al, 2023.
  • 35. 35 Raw material estimates from multiple studies Data source: Table D.9, Sinke et al, 2023. A large research gap is that more real-world data points from different cells and species, and different cellular stages (proliferation, differentiation) are needed to estimate the amount of raw materials needed. Note that including hydrolysates will result in higher overall amounts of amino acids compared to solely sourcing them from fermentation processes because some amino acids will be in overabundance. But the cost savings justify these higher amounts.
  • 36. 36 Cell metabolism is central to achieving cost and environmental goals Source: Humbird, 2021. Assumes a cell is 15% lipid, 10% carbohydrate, 5% RNA/DNA, and 70% protein. Hypothetical wild-type metabolism 0.147 glucose + 0.378 O2 + 0.007Arg + 0.004Cys + 0.022Gln + 0.003His + 0.007Ile + 0.010Lys + 0.002Met + 0.005Phe + 0.009Thr + 0.002Trp + 0.005Tyr +0.010Val +0.013Ala + 0.006Asn + 0.008Asp + 0.011Gly + 0.011Leu + 0.007Pro + 0.010Ser → 1DCM + 0.005Glu + 0.070 NH3 + 0.474 Lac + 0.435 CO2 + 0.495 H2 0 Hypothetical “enhanced” metabolism 0.147 glucose + 0.378 O2 + 0.007Arg + 0.004Cys + 0.022Gln + 0.003His + 0.007Ile + 0.010Lys + 0.002Met + 0.005Phe + 0.009Thr + 0.002Trp + 0.005Tyr +0.010Val +0.013Ala + 0.006Asn + 0.008Asp + 0.011Gly + 0.011Leu + 0.007Pro + 0.010Ser → 1DCM + 0.005Glu + 0.004 NH3 + 0.041 Lac + 0.455 CO2 + 0.613 H2 0 Efficient metabolism means better feed conversion and less waste. But it also translates to creating fewer toxic metabolic byproducts (i.e., ammonia and lactate). Stoichiometric/mass balance equations need to be validated based on real biomass compositional measurements from animal cells used in cultivated meat production. This is a current data gap that is critical for informing techno-economic and environmental impact models.
  • 37. Case study: media formulation optimization Source: Lyra-Leite, 2023 Off-the-shelf media formulations are not tailor-made. They often contain ingredients that are unnecessary or in overabundance, leading to waste. Number of ingredients reduced from 52 to 39. Concentration of several ingredients such as amino acids and vitamins were reduced. Fewer ingredients = lower costs. DMEM/F12 BMEM Very labor intensive. Other machine learning and high dimensional design-of-experiments techniques will also be valuable in formulation optimization (Cosenza).
  • 38. 38 Metabolic modeling to optimize feed conversion Source: Romero & Boyle, 2023; more explained in GFI’s solutions database. The diverse array of species, cell types, and dynamic cellular states (e.g., proliferation, differentiation) necessitates many custom media formulations catered to individual metabolisms or metabolic states. The creation and validation of genome-scale metabolic models can accelerate formulation discovery and optimize feed conversion in a hypothesis-driven manner.
  • 39. Recycling and valorization Ammonia is the metabolite of highest concern because it becomes toxic at relatively low concentrations (3-5 mM). ● There is a large incentive to lower ammonia production via cell engineering (e.g., glutamine synthetase) or change in media composition (e.g., avoid feeding glutamine). ● Limiting ammonia production increases productivity and lowers costs. Lactate is the metabolite produced in the highest quantity. ● How tractable is it to valorize lactate, creating a co-product, revenue stream, and carbon footprint offset? ● Toxicity of lactate is less of an issue compared to ammonia: less research on how to stop its production, more research on what we do with it? More on recycling: Yang, 2023 Recycling water, growth factors, amino acids, or other metabolites may also be performed, influencing cost and environmental impact of production. ● More research needed to uncover what other inhibitory metabolites may exist.
  • 40. 1. Source lower cost ingredients ($/L) a. Pharma-grade → food-grade and feed-grade ingredients b. New sources for recombinant proteins and amino acids 2. Use less media (g/kg) a. Formulation discovery: metabolic modeling and engineering to create cultivated meat with low feed conversion ratios and to inform media formulations and the future supply chain 3. Scale the new supply chain (see slides 70-71) Steps to reduce cell culture media costs
  • 41. Summary 1. There is a clear path for the steps to take and major R&D areas of focus to significantly reduce the costs of cell culture media. a. The major buckets are (1) sourcing lower cost ingredients and (2) optimizing formulations for efficient feed conversion. 2. Many pathways to sourcing lower cost ingredients are already known. a. Many solutions can be used throughout the entire industry. b. Several examples in the literature already demonstrate tractable approaches. c. Sourcing lower cost ingredients already gets you to >99% cost reduction compared to pharma-grade media. 3. Formulation discovery, understanding metabolism, and using media efficiently with low feed conversion rates will require more R&D time and effort compared to sourcing lower cost ingredients. a. Solutions will need to be uniquely tailored to each cell line. b. This research is just beginning.
  • 42. Two major buckets drive cultivated meat production cost Cell culture media Infrastructure Growth factors Amino acids Buildings Bioreactors Labor Utilities Other media components, equipment, consumables
  • 43. Infrastructure 1. Infrastructure buildout requirements and current status in scaling to meet market growth estimates 2. Production facility cost estimates 3. Bioreactor types, costs, considerations, and metrics
  • 44. By 2030, McKinsey estimates that under high growth scenarios, cultivated meat could account for up to 2.1 million metric tons (MMT), making it a $25B market. This is ~0.56% of global meat demand (assuming 375 MMT, excluding seafood by 2030). Cultivated meat growth estimates Source: McKinsey, 2021
  • 45. A significant amount of new infrastructure will be needed “Building the infrastructure to make more meat requires a significant amount of capital. The kind of infrastructure we need is not available on the planet.” - Josh Tetrick CEO, Eat Just Size range of current global pharmaceutical capacity = 10 million liters of capacity to to Capacity range needed for 1.5 MMT of cultivated meat (~0.4% of 2030 market) is about 22x that of the current global pharmaceutical industry Source: McKinsey, 2021
  • 46. Capacity gap estimations Source: Ark Biotech, the bioreactor gap Capacity calculations based on expected yield of 8.2 kg/L/year, which assumes 50% of cultivated meat is produced with an optimized fed-batch process, and 50% is produced with an optimized continuous process. Global meat consumption could be satisfied with 60 billion liters* of bioreactor capacity, which could fit in the size of lower Manhattan * Assumes more efficient production with Ark’s bioreactors
  • 47. Scale up terminology and current status Source: Harsini and Swartz, 2024; GFI facility and capacity tracker. The largest known installed bioreactors are 6,000L (GOOD Meat, Singapore) and 10,000L (OMeat, U.S.), although there is no confirmation that these reactors are currently operational. The largest known bioreactors in operation within the cultivated meat industry are 2,000L (several companies). There are at least 35 facilities that have been built or announced around the world. ● The vast majority are pre-pilot or pilot scale facilities. ● A few facilities (including those currently under construction) could be considered industrial scale. A proposed guide for aligning on scale up terminology.
  • 48. Cultivated meat industry growth estimates: how are we tracking? Source: Harsini & Swartz, 2024. * Assumes 100% cultivated meat production, not incorporation into hybrid products. 1 Based on red meat (beef, mutton, pork) production across 800 federally-regulated slaughterhouses. Key considerations: commission time of facilities (difference between reactor capacity and actual production), cultivated meat or hybrid products, actual success in scaling, financing availability and overall de-risking of business models, regulatory challenges or bans Survey data: ~25k tons expected from 19 companies by 2026. Multiply by 5 to account for ~100 B2C companies. = A very rough estimate of ~125k tons* of CM production by the end of 2026 (~4 U.S. slaughterhouses1 worth of production). Currently tracking toward the low growth estimate from McKinsey. Disclaimer: Caution is advised when interpreting the figures presented, as they are based on a subset of 19 responses, not representative of all CM companies, and do not fully reflect the industry. Scaling challenges and optimistic projections can lead to varying production capacity estimations. Technological advancements and process refinements may accelerate industry growth. The projections do not account for potential innovations or new industry players, which could greatly influence future production capacity. The higher and lower bounds in the figure refer to the ranges of options selected by companies. "Max capacity" refers to maximum production capacity, and "estimated production" refers to expected production amount. Estimated cultivated meat production by end of 2026 (19 respondents)
  • 49. Infrastructure 1. Infrastructure buildout requirements and current status in scaling to meet market growth estimates 2. Production facility cost estimates 3. Bioreactor types, costs, considerations, and metrics
  • 50. Estimates for new facility CAPEX: example 1 Facility 1 Facility 2 Source: Humbird, 2021 The total capital investment for a facility with ~7,000 tons of annual production capacity is $325M (facility 1)* to $663M (facility 2)* . *Facility 1 uses 20kL bioreactors operating under fed-batch mode. Facility 2 incorporates a 2kL perfusion system.
  • 51. The total capital investment of a 10,000 ton annual production facility is $450M (-20% to +40%). Source: CE Delft Techno-Economic Assessment (2021) Webinar: The costs and environmental impacts of cultivated meat Policy recommendations Technical recommendations Estimates for new facility CAPEX: example 2
  • 52. Summary estimates for new facility CAPEX Study Negulescu, 2023 Negulescu, 2023 Negulescu, 2023 Vergeer, 2021 Humbird, 2021 Humbird, 2021 Largest proliferation vessel 42 kL stirred-tank reactor 211 kL stirred-tank reactor 262 kL air-lift reactor 10 kL stirred-tank reactor + 2 kL perfusion system for differentiation 20 kL stirred-tank reactor 2 kL stirred-tank perfusion reactor Annual production capacity 4,000 tons 20,000 tons 25,000 tons 10,000 tons 6,800 tons 6,900 tons CAPEX per facility $438M $1,172M $366M $450M $325M $663M Capital cost per ton ~$109,000 ~$58,000 ~$14,000 ~$45,000 ~$46,000 ~$94,000 *Each study uses different assumptions and in some cases different bioreactor types or modes of operation that can affect overall capital costs. These numbers therefore are not necessarily directly comparable but can be used to provide a sense of expectations for CAPEX costs. Capital cost per ton is to get a sense of differences from a normalized value (does not account for amortization).
  • 53. Size (sq. ft.) 187,000 200,000 Capacity Up to 13,600 tons At least 10,000 tons Reactor size Up to 100,000 L Not stated Investment amount $140M investment (~$10,000/ton)* $123M investment (~$12,000/ton)* Real-world production facility announcements *it is not stated exactly what is accounted for by these investment totals. It is possible that future investments will be needed to outfit the facility with the necessary equipment to achieve the stated maximum capacities or operational efficiencies. Source Source
  • 54. Ballpark estimates for the cost of new infrastructure = 10,000 tons annual capacity = ~$300M? = 150 facilities = 1.5M tons annual capacity = 0.4% of 2030 market = $45B? ● There is high variability in the estimated costs of facilities capable of producing thousands of tons of cultivated meat. ● Facility costs may vary significantly by region and this has yet to be modeled. ● More data and studies are needed before higher confidence predictions on anticipated costs of new infrastructure can be made.
  • 55. Infrastructure 1. Infrastructure buildout requirements and current status in scaling to meet market growth estimates 2. Production facility cost estimates 3. Bioreactor types, costs, considerations, and metrics
  • 56. The cultivated meat industry uses diverse bioreactor types Nearly all TEA studies performed to date focus on the cost of production using stirred-tank bioreactors. This does not capture the diversity of approaches being pursued. Different bioreactors may have different roles in proliferation and differentiation. Different bioreactors can have different components (e.g., impellers) that influence material and utilities costs. Different bioreactors occupy different amounts of space in a facility, influencing overall design facility footprint, or shipping and assembly. Production in different bioreactor types will have different techno-economic outcomes. Source: Harsini & Swartz, 2024.
  • 57. Source: Negulescu, 2023; Humbird, 2021 1 Total direct cost, 2 Single equipment purchase cost Humbird: Estimated cost of a 20 m3 stirred-tank bioreactor made of pharma-grade 316L stainless steel: $1.5M1 Negulescu: Estimated cost of a 42 m3 stirred-tank bioreactor made of food-grade 304 stainless steel: $904k2 Negulescu: Estimated cost of a 211 m3 stirred-tank bioreactor made of food-grade 304 stainless steel: $2.38M2 Negulescu: Estimated cost of a 262 m3 air-lift bioreactor made of food-grade 304 stainless steel: $313k2 Bioreactors: type, size, and material influences cost
  • 58. Use of food-grade steel alloys in the cultivated meat industry The material makeup of the 316 stainless steel alloy makes it more durable but also more expensive (~40% higher). Some cultivated meat companies are already using the 304 stainless steel alloy, which is more commonly used in food production. Adoption of 304 stainless steel or other more affordable materials1 will be important to track as the cultivated meat industry scales. Source: Harsini & Swartz, 2024. 1 Read how sterility controls may influence the types of materials that can be used for bioreactors.
  • 59. Assumes: 50K MT annual output, fed-batch process reaching 20M cells/mL and no differentiation step; bioreactors <250K L fabricated in shop with others fabricated in field; 15-year depreciation period with no salvage value; bioreactor volumes are nominal with 80% working volume. Source: Ark Biotech TEA Economies of scale are real. Why? As the scale of the reactor increases, production becomes more efficient. ● (1) fewer reactors (including seed train vessels and parts) are needed for the same production output, (2) fewer personnel and utilities are needed to operate the equipment, and (3) the cost contribution of maintenance and depreciation decreases.
  • 60. 60 Influence of bioreactor size on cost contribution Source: Negulescu, 2023. This figure assumes a fixed media cost. With less equipment, total costs become more dependent on cell culture media.
  • 61. Anticipated bioreactor size in future facilities Some companies in the cultivated meat industry expect to use bioreactors >50,000L. The first successful cultivated meat production runs in bioreactors larger than 25,000L (the largest reactors used in biopharma) could be a significant de-risking event for the industry. Source: Harsini & Swartz, 2024.
  • 62. Scaling up vs. scaling out: balancing risk With larger size comes larger risk, but potentially larger rewards (i.e., lower COGS). ● Technical risk: animal cells have never been grown at such large scales. ● Operational risk: larger vessels increase production time and reactor surface area, which could increases opportunity for contamination and loss of batches. Different philosophies: Some believe that scaling out at a certain “sweet spot” will enable them to achieve favorable cost profiles for their products, balancing risk vs. reward. Others believe continuing to scale up is the most prudent path forward. Where companies decide to stop scaling up and instead scaling out will dependent on many factors such as the process and product. Additional TEAs are needed to evaluate this under different scenarios (different bioreactors, different scales, different process designs, etc). scale up scale out
  • 63. Contamination prevention If pharmaceutical clean rooms are assumed, the costs of the facility as it increases in size outpace any efficiencies gained from scaling (Humbird). Cultivated meat manufacturers will need to be able to grow cells in environments with lower clean room classifications, potentially exposing them to higher rates of contamination and loss of batches. Different philosophies: Skeptics believe that growing cells at large scale in a non-pharmaceutical environment is a dead end. Others believe it not a big hurdle, it’s just never needed to be done before. Other potential solutions: food-safe antimicrobial peptides as a second layer of defense.
  • 64. Bioreactors: mode of operation Source: Harsini & Swartz, 2024. Fed-batch is currently the most frequent mode of operation used for production. However, companies throughout the cultivated meat industry are exploring all types of operation modes for running production processes.
  • 65. Bioreactors: mode of operation Source: Ark Biotech TEA Many companies are developing continuous or perfusion processes. But this may have operational limitations at increasingly larger bioreactor scales or higher media costs.
  • 66. Bioreactors: cell density Source: Ark Biotech TEA Note: it is recommended to measure and report cell density in grams per liter. This normalizes for differences in cells per mL measurements that are dependent on cell size. Cell density (g/L) is one of the most important cost variables and metrics to track. But context matters: achievable cell densities will vary based on the mode of operation and the type of bioreactor used.
  • 67. Bioreactors: cell density Source: Humbird, 2021; Pasitka, 2023 The Humbird report says perfusion would max out at 195 g/L, given certain constraints and perfusion rates. A study by Believer Meats in Nature Food reports very high densities of 360 g/L at small scale. But the high perfusion rates (VVD) implies a large amount of media being exchanged. If these rates are not lowered, media costs at scale would be very high. Cell density as a singular metric does not tell the full story. Context matters.
  • 68. Process intensification lowers CAPEX by reducing the number of bioreactors and the number of buildings Source: CE Delft Techno-Economic Assessment (2021) Webinar: The costs and environmental impacts of cultivated meat More efficient production processes (e.g, faster cell doubling times, increased cell densities, reduced media costs) means fewer bioreactors needed in the facility and fewer personnel to operate and maintain the equipment, reducing overall cost burden. STAFF 200 130 CAPEX $450M $250M
  • 69. Closing thoughts 1. Scaling the supply chain, interventions, and other factors 2. Where are we and what’s next?
  • 70. Scaling the supply chain The supply chain for media, bioreactors, and other equipment will need to be reshaped to fit the needs of the cultivated meat industry. Significant investments will also be needed by suppliers to acquire land, build production facilities, source energy and raw materials, and hire labor to run new facilities for inputs and equipment. None of this happens overnight. Suppliers will need to scale alongside the growth of the cultivated meat industry. This will inherently limit how fast certain costs can be reduced. Higher demand Lower costs, better products Scaled production CapEx Longer term, lower cost, non-VC capital. Government support: loan guarantees, tax credits, grants, procurement contracts Source: discussions with Zak Weston (BERA partners)
  • 71. Supply chain interventions: learnings from past market-shaping work Pooled procurement: Creating buyer consortiums for media, media inputs (e.g., growth factors), and high-cost equipment (e.g., bioreactors) to combine purchasing power, provide predictable demand to suppliers, and lower costs. Coordinated ordering: Multiple buyers use group-negotiated prices and terms derived from information sharing and joint market research to optimize purchasing strategies. Variant optimization and standardization: Standardized medium formulations, input and equipment specifications, and purchasing terms. Interventions taken to rapidly scale supply chains and lower costs for vaccines and other medicines can be applied to the cultivated meat industry. Source: Zak Weston; Parmaksiz, 2022; USAID Market Shaping Primer, 2014.
  • 72. Learning rates Could learning curves for bioreactors be analogous to what learning curves for batteries enabled for electric vehicle competitiveness? Modularity and low design complexity for equipment and processes can help ensure that robust manufacturing learning curves emerge Source: Malhotra & Schmidt, 2020.
  • 73. Ample opportunities for learning rates to emerge Cultivated meat differs from biofuels — it does not need to directly compete with commodities from the get-go. Meat prices span two orders of magnitude. The premium and specialty meat market is ~6 million tons annually. Solar gained scaling foothold in the high-priced satellite industry in space, then learning rates took over on Earth. From its current point, cultivated meat will take ~13-15 doublings in capacity just to fulfill the premium/specialty meat demand.
  • 74. Cultivated meat companies do not need to limit themselves to just selling meat Cultivated meat companies can license or sell media formulations, cell lines, or other process and equipment-related IP. It is possible that other co-products could be valorized to provide a meaningful revenue stream for companies.
  • 75. Closing thoughts 1. Scaling the supply chain, interventions, and other factors 2. Where are we and what’s next?
  • 76. 76 Summary of select scenarios from select TEAs Scale of reactor (L x 1000)
  • 77. 77 Summary of select TEAs ● Contrary to some opinions, scenarios in multiple cultivated meat TEAs suggest cost competitiveness could be achieved. ○ Many of these scenarios are at very large scales or have favorable assumptions. ● Need for more TEAs: ○ There is a large need for TEAs to reflect the diversity of manufacturing approaches being taken in the industry. Knowledge gaps include TEAs with other bioreactor types (hollow fiber, air lift, fixed bed), modes of operation, the influence of accounting for mass gain during differentiation, and hybrid products. ○ Most TEAs don’t include all of the production steps (e.g., stop at cell harvest) or analyze profitability and payback time in detail. Scale of reactor (L x 1000)
  • 78. 78 Predictions by some cultivated meat companies outpace most TEA outlooks “Our TEA results show for the first time that a credible path to sub $7 per kg on beef production at the first commercial factory,” he writes, “and can reach sub $5/kg beef at the second commercial scale facility.” - Deniz Kent, CEO Prolific Machines Fast Company, 2023 “We can achieve price parity today if we operate at scale, without relying on future innovations. And we can do that with the 10,000-liter bioreactors we’re planning in our pilot plant, whereas others require really large bioreactors that haven’t been validated.” - Ali Khademhosseini, CEO Omeat AgFunder, 2023 Achieving price parity in the short-term is not predicted by existing public cost models. Can this actually be achieved? “We believe we can do profitable production from 2,000-liter reactors for premium species [such as eel and grouper], and we as we go to larger volumes, 10,000-liters makes sense.” - Mihir Pershad, CEO Umami Bioworks AgFunder, 2023 *BlueNalu plans to use eight 100,000L bioreactors in their future facility Food Dive, 2022 Profitability is usually mentioned in the context of high-priced conventional meat or seafood products
  • 79. 79 Where do we stand? As of now, we do not actually know the cost of cultivated meat production today or in the future. There are many production scenarios and approaches — a single number cannot be given. Additional studies are needed to get higher confidence in the expected range. It is critical to provide the context for the product (chicken vs. foie gras) and whether it’s a hybrid (100% vs. 5%) when discussing how cultivated meat costs compare to conventional meat. Taking the current knowledge of costs and expected progress: ● If pursuing a high-end product type (e.g., foie gras, tuna toro), then a 100% cultivated meat product (or similarly high inclusion rates) can be a tractable approach to cost-competitiveness. ● If pursuing commodity meats (e.g., chicken, pork, beef, certain seafoods), then hybrid products at low inclusion rates offer the most tractable way to approach cost-competitiveness. However, the timeline is uncertain and success will depend on many of the variables discussed in this presentation.