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1. CASE STUDY
withdrawal of
animal-de rived peptone
GOAL
To understand the impact of shortage or withdrawal of
a key raw material on the supply chain network.
• Analysis of a long-range plan incorporating titer improvements based
on the use of a raw material, animal-derived peptone
• Quantified effect of a disruption in peptone supply to plant capacities
and the entire production network
• Compared facility loading and product shortages caused by peptone
withdrawal to the ‘business-as-usual’ scenario.
high level
summary
The production of biopharmaceuticals currently relies on a number of
compounds that are not fully characterized, and are sourced from a single
biopharmaceutical manufacturer. Peptones are one such substance used by
most biopharmaceutical manufacturers, as it has been shown to increase
production titers when added to media. Despite the availability of plant-based
and other peptone substitutes, animal-derived peptones are still most
commonly used in the industry since they maximize cell production. The high
product titers using animal-derived peptones are used to shorten campaign
lengths, making existing facilities more productive. The graph below shows
historical titers for new molecular entities for a number of companies from
1985 to 2009.
TITER (mg/L)
PEPTONE-BASED NME TITERS
0
1985 1990 1995 2000 2005 2010 2015
YEAR
4500
4000
3500
3000
2500
2000
1500
1000
500
WITHDRAWAL
OF PEPTONE
POST-PEPTONE
NME TITERS
While peptones can markedly improve titer, they are typically provided
by a single manufacturer and are not well characterized, with higher
contamination risks. Bioproduction Group’s brief was to determine the
impact to the network of removing one key peptone raw material from
the market. The effect on titers for new products (after the withdrawal of
peptone) is shown on the graph above. It was projected that removing this
product would not allow titer increases above the 1-2 grams / liter range seen
in current mammalian cell culture processes. As such, new molecular entities
(NMEs) would have to be produced at far lower titers than supply chain
planners expected.
THE BRI EF
© Bioproduction Group. All Rights Reserved. 1

2. How We Did It
“The impacts of the
withdrawal of a crucial
raw material are especially
important in biotech”
Rick Johnston, Principal
RESULTS
MOR E INFORM ATION
BIOPRODUCTION GROUP
CONTACT@BIO-G.COM
www.bio-g.com
Bioproduction Group’s key insight was that titer reductions translated to
increased campaign lengths in production facilities, since less material was
produced per batch. Bio-G used simulation analysis to quickly model the
effect of peptone withdrawal across all products and plants in the network.
“The impacts of the withdrawal of a crucial raw material are especially
important in biotech”, says Principal Rick Johnston. “Simulation technology
provides a fast and effective analysis platform to quantify the impact of raw
material shortages.”
Realizing that it was not sufficient to just look at one product or plant in the
Network, Bioproduction Group modeled the effect of increased cell culture
durations across the entire stream of commercial, clinical, and projected
material in a 10 year horizon for all products and plants. The result: a highly
accurate model of the long-range supply plan showing the effect of peptone
withdrawal on facility utilizations and eventually supply continuity.
Bio-G’s Network Simulation engine suggested a significant increase in facility
utilizations that ultimately affected the ability of the manufacturer to meet
demand. The graph below shows the increased risk of stockout over a 5 year
horizon, across all products. A dramatically increased risk in the 2011-2012
timeline occurred once existing manufacturing capacity was exhausted. This
analysis allowed the manufacturer to justify efforts to remove animal-derived
peptones from their cell-culture development, as well as source backup
manufacturers in the case of short-term outage for existing processes.
PROBABILITY OF STOCKOUT IN ONE OR MORE PRODUCTS (%)
PEPTONE WITHDRAWAL
2009 2010 2011 2012 2013 2014
YEAR
INCREASED RISK OF STOCKOUT
(PEPTONE WITHDRAWAL)
BASELINE RISK OF STOCKOUT
(NO PEPTONE WITHDRAWAL)
10
8
6
4
2
0
© Bioproduction Group. All Rights Reserved. 2