Economics of adopting single-use bioprocess containers in Asian manufacturing scenario -Swapnil...

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21-Apr-08 S.Ballal, Intas Biopharmaceuticals Ltd. India 1 of 25

Economics of adopting single-usebioprocess 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, Interferon2b, 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 validationrequirement

Speed of deployment and batchchangeover

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:1-4lead 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 ofbiosimilars

Divisions of existing pharmaceuticalcompanies or state funded willing

to make capital investments

Many have similar developmentpipeline- do not risk outsourcing to

other manufacturers

Very few startups with new biologicalcandidates



Other Differentiating Factors of Asia

Need for affordable therapy highly cost sensitive

Availability of skilled manpower at significantly lowersalaries

50-80% lower

Overall lower cost of manufacturing set up : lowerconstruction, land cost and taxes compared todeveloped countries



How does it relate to Adoption ofSingle Use Disposables in Asia ?

Using Bioprocess Container as a model toAnalyze



Steel Fabrication in Asia

Labor part: 30-60% of SS vesselcost in US/ EU

Skilled labor cost 50-80% lower in

most part of Asia

Experienced in GMP manufacturing dueto strong pharma manufacturing

background

Availability of customized steel vesselsat significant lower prices

Similar cost benefits in WFI plant, Cleanutility piping etc.



Capital CostSS Bioprocess Container

200-

500 L buffer preparation

Stainless Steel 316 L tank

Jacketed pressure vessel withCIP/SIP pressure rating, magneticagitator, pH & temperature control

Customized PLC control

GMP documentation

Price in India-

$50-70,000

Price in US/Europe 1.5

3 X



Capital Cost Single UseBioprocess 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 facilitysize

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 regulatoryexpectation decreasing over the years

Cleaning validation on 23rd

place-Total

GMP deficiencies ranking by EMEAbetween 1995-2005 (3)

1.3% deficiency attributed cleaningvalidation

Only 1 out of 193 critical deficiencycited 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 Steamin Place annual validation and paper work

Sampling & Testing cost TOC, Microbial load & productspecific 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 SystemsVendor 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

Labor

34%

Material

13%Indirect material17%

Consumables

17%

Capital19%

waste

management

0%

Labor

37%

Material12%

Indirectmaterial

15%

Consumables

8%

Capital

28%

waste

management

0%

DISPOSABLECONCEPT PLANT

TRADITIONALPLANT

Traditional Disposables ConceptLabor 200.1 154.4Material 61.5 57.0Indirect material 82.2 74.2Consumables 40.8 76.3

Capital 149.1 83.7

Total 534.0 445.6Savings 00% 17%

-Adapted from: A. Sinclair and M. Monge, BioProcess International 3(9):S51-55 (October 2005)


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Cost of Goods Comparison: Asia

Labor

15%

Material

18%

Indirect

material24%

Consumables

12%

Capital

31%

TRADITIONALPLANT -ASIA Labor

12%

Material

18%

Indirect

material

23%

Consumables

25%

Capital

22%

DISPOSABLE CONCEPTPLANT-ASIA

Traditional Disposables Concept

Labor 50.0 38.6Material 61.5 57.0Indirect material 82.2 74.2Consumables 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 forDisposable plant in Asia

Total 339 317

Savings 00% 6.4%


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COG Comparison Asia: With 30% Import duties on ConsumablesWithout Capital Charges


Labor 50.0 38.6Material 61.5 57.0

Indirect material 82.2 74.2Consumables 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 costWithout Capital Charges

Single use product will be more attractive in Asia atmuch lower costs than present

Cost reduction by:

Offering significant lower pricing for Asia

Manufacture locally : lower cost & no import duties


Labor 50.0 38.6Material 61.5 57.0Indirect material 82.2 74.2

Consumables 28.6 53.4- Considering 30% cost reduction and no Import duties

Total 222 223

Savings 0.4% --


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Adopting Single Use in Asia

Areas Most Benefited byadopting Single use containers

Vaccines & Blood derived

Product : Safety

Contract Manufacturer: Highgrowth area

but would

reduce cost advantage

Facilities with clean utilitiescapacity limitation

Finished dose manufacturing

multi product lines,

should shift from syringe pump based filling to peristalticpump


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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 usechoose 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 foryour 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 thanSingle 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.. sheoutsourced herself


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21-Apr-08 S Ballal Intas Biopharmaceuticals Ltd India 25 of 25

References:

1.

Quantitative Economic Evaluation of Single Use Disposables inBioprocessing: 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 20043.

Good Manufacturing Practice: An analysis of regulatory inspection findings inthe 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 International3(9):S51-55(October 2005)

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

Acknowledgements:

Economics of adopting single-use bioprocess containers in Asian manufacturing scenario -Swapnil...

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