Economics of adopting single-use

bioprocess containers in Asian

manufacturing scenario

Swapnil Ballal,
Head, Biopharmaceutical Bulk Manufacturing
Intas Biopharmaceuticals Ltd. India

Biomanufacturing Asia 2008

Singapore 15-16 April

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 About Intas Biopharmaceuticals
• 1st and only EU-GMP approved
Biotechnology Facility in India
• Manufacturer of G-CSF, Interferon
α2b, Erythropoietin and PEG-GCSF
• First PEG-GCSF in the World after
innovator
• Part of the $250 Million Intas group

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 World of Single Use Products

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 Single Use – Advantages
• Lower Capital Investment

• Cost saving in Cleaning and Sterilization

• Elimination of cleaning validation

requirement

• Speed of deployment and batch

changeover

• Flexibility of scales

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Key Drivers of Single Use Technology
• Increasing number of bio-
molecules in clinicals - Phase I & II
GMP requirement
• Startups to mid sized firms:1-4
lead molecules
• Innovators reduce investments–
Outsource clinical production
• CMOs: Fast turnaround, flexibility. Limit allied activities
like changeover and cleaning validation

• CMOs adopt disposables: low capital investment, higher

operating cost- borne by client

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 Asian Biotechnology Scenario
• Major manufacturers are of
biosimilars
• Divisions of existing pharmaceutical
companies or state funded – willing
to make capital investments
• Many have similar development
pipeline- do not risk outsourcing to
other manufacturers
• Very few startups with new biological
candidates

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Other Differentiating Factors of Asia
• Need for affordable therapy –highly cost sensitive

• Availability of skilled manpower at significantly lower

salaries – 50-80% lower

• Overall lower cost of manufacturing set up : lower

construction, land cost and taxes compared to
developed countries

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 How does it relate to Adoption of
Single Use Disposables in Asia ?

Using Bioprocess Container as a model to

Analyze

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 Steel Fabrication in Asia
• Labor part: 30-60% of SS vessel
cost in US/ EU
• Skilled labor cost 50-80% lower in
most part of Asia

• Experienced in GMP manufacturing due

to strong pharma manufacturing
background
• Availability of customized steel vessels
at significant lower prices
• Similar cost benefits in WFI plant, Clean
utility piping etc.

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 Capital Cost–SS Bioprocess Container
• 200- 500 L buffer preparation
Stainless Steel 316 L tank

• Jacketed pressure vessel with

CIP/SIP pressure rating, magnetic
agitator, pH & temperature control
• Customized PLC control

• GMP documentation
• Price in India- $50-70,000

• Price in US/Europe 1.5 – 3 X

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 Capital Cost – Single Use
Bioprocess Container (BPC)
• Complete 200 L buffer preparation setup made in US/EU
– Steel Holding tank
– Magnetic stirrer
– Tubing welder & sealer

• List price $65,000-$90,000 based on configuration

• Without temperature control, pH & conductivity

measurement: additional cost

• Excludes applicable custom duties

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 Overall Capital Investment
• A. Sinclair & M. Monge – Adopting single use
technology reduces capital costs directly & indirectly
• Reduce capital cost by 20- 40% depending upon
extent of adoption(1)
– Reduced overall utility sizing, piping and facility
size
• Capital cost in Asia lower by 30%
• Cost of disposables same – since they are made in
EU/US

Capital required similar between traditional plants &

those with Single use in Asia

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 Operating Cost Differences
• Fixed steel tank: Cost of CIP and SIP
• Requires volumes of high quality water
• Cost of generation of PW/WFI: $ 6-10/1000 L(2)
• Considering un optimized CIP cycle
– 1000 L water for 200 L tank:
Cost/run – $ 10
• 200 L buffer bag: $ 250
• Sterile connections : $ 10-50/connection
Material Expense
5 buffers/ day for 150 days

Fixed Tank Single use BPC

$7,500 $187,000

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 Cleaning Validation
• Gap between practice and regulatory
expectation decreasing over the years

• Cleaning validation on 23rd place-Total

GMP deficiencies ranking by EMEA
between 1995-2005 (3)

• 1.3% deficiency attributed cleaning

validation

• Only 1 out of 193 critical deficiency

cited during the period

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 Cost of Cleaning Validation
• Manpower cost

• Operational delay- line clearance

• Ongoing cost requirement for Clean In Place and Steam

in Place annual validation and paper work
• Sampling & Testing cost –TOC, Microbial load & product
specific testing

Cleaning validation set up will anyway be required

Major equipment are still not single use !

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 Additional Validation for Single
Use Systems
Vendor Support and Data availability Critical
• Vendor supported data
– Extractables
– Sterilization validation:- third party executed! Audit ?
– Leak testing
• Product & Process specific testing (4)
- Leachable testing - Compatibility testing
- Short term stability testing - Endotoxin
Product & Process Specific
Bag Material & Chemistry Specific
Manufacturer Specific

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 Cost of Goods Comparison:
US/EU Traditional Disposables Concept
Labor 200.1 154.4
Material 61.5 57.0
Indirect material 82.2 74.2
Consumables 40.8 76.3
Capital 149.1 83.7
Total 534.0 445.6
Savings 00% 17%
- Adapted from : A. Sinclair and M. Monge, BioProcess International 3(9):S51-55 (October 2005)

TRADITIONAL waste DISPOSABLE

management waste
PLANT 0% CONCEPT PLANT management
0%
Capital
19%
Capital
28%
Labor
Labor
34%
37%

Consumables
17%

Consumables
8%

Material
Indirect Material Indirect material 13%
material 12% 17%
15%

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 Cost of Goods Comparison: Asia
Traditional Disposables Concept
Labor 50.0 38.6
Material 61.5 57.0
Indirect material 82.2 74.2
Consumables 40.8 76.3
Capital 104.4 71.1
- Considering Asian labor cost in Asia 25% of US/EU
- Considering 30% lower capital for traditional & 15% lower capital for
Disposable plant in Asia
Total 339 317

Savings 00% 6.4%

TRADITIONAL DISPOSABLE CONCEPT

PLANT -ASIA Labor PLANT-ASIA Labor
15% Capital 12%
22%
Capital
31%

Material
18%
Material
18%

Consumables
Consumables 25%
12% Indirect
Indirect material
material 23%
24%

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 COG Comparison –Asia:
With 30% Import duties on Consumables
Without Capital Charges

Traditional Disposables Concept

Labor 50.0 38.6
Material 61.5 57.0
Indirect material 82.2 74.2
Consumables 53.0 99.1
- Considering 30% Import duties on Consumables
Total 246.8 269

Savings 8.5% --

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 COG Comparison –Asia:
With reduced disposable cost
Without Capital Charges

Traditional Disposables Concept

Labor 50.0 38.6
Material 61.5 57.0
Indirect material 82.2 74.2
Consumables 28.6 53.4
- Considering 30% cost reduction and no Import duties
Total 222 223

Savings 0.4% --

• Single use product will be more attractive in Asia at

much lower costs than present

• Cost reduction by:

– Offering significant lower pricing for Asia
– Manufacture locally : lower cost & no import duties

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 Adopting Single Use in Asia
Areas Most Benefited by
adopting Single use containers
– Vaccines & Blood derived
Product : Safety
– Contract Manufacturer: High
growth area – but would
reduce cost advantage
– Facilities with clean utilities
capacity limitation
– Finished dose manufacturing – multi product lines,
should shift from syringe pump based filling to peristaltic
pump

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 Hybrid Systems:
Flexibility on demand
Design new plants for traditional system
– Utilities available; choice of using
fixed tanks when required
– Depending upon product type use
choose single use / tank
– Non product contact can be steel:
E.g. Buffer Prep
– Live Biological can be single use
– Product requiring more batches can be with fixed:
others on single use

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 Take Home Message For
End User In Asia
• Single use products may not be an obvious choice for
your manufacturing set up

• Stainless Steel was and will widely be in use- do not

eliminate it as an option

• Operating Cost of Fixed tanks would be lower than

Single Use

• Critically analyze your applications and cost benefits of

both the options before committing

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 Message for Single Use
Manufacturers

“Janet was always ahead of the curve….. she

outsourced herself”

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References:
1. Quantitative Economic Evaluation of Single Use Disposables in
Bioprocessing: Sinclair A, Monge M, Pharmaceutical Engineering, 2002, Vol.
22,3, 20-34
2. Design Economics for USP Purified Water Systems, Andrew Collentro,
MECO, Inc. Pharmaceutical Processing, Dec 2004
3. Good Manufacturing Practice: An analysis of regulatory inspection findings in
the centralised procedure, EMEA/INS/GMP/23022/2007, January 2007
4. Implementation and Validation of Single Use Systems : Ian Sellick & Joe
Dallapiazza, Pall Life Science, 2007
5. Andrew Sinclair and Miriam Monge: BioProcess International 3(9):S51-55
(October 2005)

Acknowledgements:
• M. Kodilkar, Intas Biopharmaceuticals
• Vishal Wagh, Director Marketing , adam fabriwerk, Mumbai India
• Sartorius –Stedim, Millipore, Bioprocess Intl. & GE Healthcare Websites
• Jill Tan & Sarah Lee, Terrapin Singapore

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