Documente Academic
Documente Profesional
Documente Cultură
Report 9215
June 2006
www.drugandmarket.com
One Research Drive, Suite 400A Westborough, MA 01581
Phone: +1 (508) 616-5500 Fax: +1 (508) 616-5544
D&MD Publications
One Research Drive
Suite 400A
Westborough, MA 01581
Phone: +1 (508) 616-5500
Fax: +1 (508) 616-5544
http: / / www.drugandmarket.com
An informa publication.
ISBN: 1-57936-360-1
Published in the U.S.A.
Biodisposables
Table
of
Contents
11
21
31
Scaling Up Logistics............................................................................................32
Comparison and Validation of Disposable Bioreactor Systems. ..............................33
Growing Cells in BagsWave Cellbags Characteristics........................................38
Factors that Amplify the Bioreactors Yield........................................................ 310
Wave Biotech Bioreactor Case Histories.............................................................. 311
CatchMabs Tsunami Bioreactor. ........................................................................ 316
Osmoteks LifeReactor. ..................................................................................... 319
Cellexus Biosystems. ........................................................................................ 320
Disposable Bioreactor Flasks, Bottles, and Other Containers.............................. 322
Integra Biosciences CELLine Biodisposable Flask .................................................. 323
FiberCell Systems FiberCell Hollow Fiber Bioreactor .............................................. 326
Hollow Fiber Bioreactor Applications:................................................................... 327
Synthecons Rotary Cell Culture System. .............................................................. 329
Fluorometrixs Cellstation .................................................................................. 330
Cellons RollerCell............................................................................................. 331
Integra Biosciences Cellroll................................................................................ 332
2006
Biodisposables
41
Biodisposables
51
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Biodisposables
Table
of
Exhibits
Exhibit 2.1
Exhibit 2.2
Exhibit 2.3
Exhibit 2.4
Exhibit 2.5
Exhibit 2.6
Cost of Goods Cap-Ex, Materials, and Labor in a Disposable Module Plant .....221
Exhibit 2.7
Exhibit 2.8
Exhibit 2.9
Exhibit 3.2
Exhibit 3.3
Exhibit 3.4
Exhibit 3.5
Exhibit 3.6
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Biodisposables
Exhibit 3.7
Exhibit 3.8
Exhibit 3.9
Exhibit 3.10 Comparison of Batch and Perfusion Modes for MAb Production in the .
Wave Bioreactor (System 20/50EH).......................................................315
Exhibit 3.11 Comparisons of Batch and Perfusion MAb Production with 2L Cellbag...........315
Exhibit 3.12 Tsunami Multiple Wave Agitated Culture System. .......................................316
Exhibit 3.13 Excellerex Disposable Bioreactors............................................................317
Exhibit 3.14 AppliFlex Disposable Cell Culture Bag System.............................................319
Exhibit 3.15 LifeReactor Plant Cell Bag Culture System. ...............................................320
Exhibit 3.16 Cellexus Biosystems Optimized Cell Growing Chamber.................................321
Exhibit 3.17 Bags are more Stable than Bottles..........................................................322
Exhibit 3.18 Integra CELLine Disposable Bioreactor Flask..............................................323
Exhibit 3.19 Cost and Yield for Monoclonal Production in CELLine and Other Systems. ......324
Exhibit 3.20 Comparisons of CellLine, Roller Bottle Grown, and Bioreactor. .....................325
Exhibit 3.21 FiberCell Module and Flowpath Assembly with Medium Reservoir Bottle.........328
Exhibit 3.22 Rotary Perfusion RCCS-D and -4D Disposable Bioreactors...........................329
Exhibit 3.23 Cellstation High-throughput Bioreactor with Disposable Culture Vessels. ........331
Exhibit 3.24 RollerCell40 Automated Bottle System.....................................................332
Exhibit 3.25 Cornings CellCube System....................................................................333
Exhibit 3.26 Growth of Cells under Different Seeding Densities in the CellCube System......334
Exhibit 3.27 Flexel 3D Bag Bioreactor Harvesting System.............................................336
Exhibit 3.28 Composition of Flexel 3D Bags ...............................................................337
Exhibit 3.29 Xcellerex Disposable Bags and Mixing Systems..........................................338
Exhibit 4.1
Exhibit 4.2
Exhibit 4.3
2006
Biodisposables
Exhibit 4.4
Exhibit 4.5
Exhibit 4.6
Exhibit 4.7
Exhibit 4.8
Exhibit 4.9
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Biodisposables
Exhibit 5.2
Exhibit 5.3
Exhibit 5.4
Exhibit 5.5
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Biodisposables
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2006
Biodisposables
and
Future
Biodisposables
products are supplied pre-sterilized to eliminate the need for steam-in-place (SIP) or autoclaving.
Opening a package and plugging a single-use device or multi-component disposable system
into a product train offers a simplification to process development staff that otherwise must
develop extensive cleaning protocols. The result is not only labor savings, but also a shift in
facility design toward fewer cleanrooms and reduced environmental monitoring requirements.
With single-use operations, applications no longer need to be physically segregated. Instead,
they can be performed side by side as closed-loop systems. This allows for the more efficient
use of facility space, especially for CMOs and biotech start-ups.
Even as disposable systems seal off processes from contamination, their translucency provides
operators with visibility into manufacturing operations. Users can observe flow and fluid levels
as well as spot fluid discoloration and air pockets immediately. Single-use processes also allow
for a high degree of modularity in that capacity can be built out gradually in phases as demand
increases. Within conventional facilities, not only do hard-piped systems need to be factored
into the initial facility design, but also oversized utility systems are specified in anticipation
of future needs. Retrofitting is significantly easier with disposables than with fixed equipment
since disposable components are inherently modular.
Disposables can also simplify transfer of the drug production processes to other manufacturing
sites, such as CMOs, or other facilities within a company. Also, without the need for significant
capital investment in hard-piped systems, single-use technologies have allowed biotech startups to manufacture their products in-house. This option provides these companies with more
control over the development process and enables production to be accelerated as needed.
Previously, outsourcing production was the only economical option. This new flexibility enables
companies to better manage their own manufacturing expenses and investments during later
development stages, when greater drug supply requirements for advanced clinical trials can still
carry considerable risk of product failure.
The FDA has been a major proponent of disposables technology. Considering that validation
accounts for 1020% of the cost of a new plant, disposables provide the industry with practical
solutions to alleviate the challenges and costs associated with cleaning operations. Singleuse (disposable) manufacturing technology can be particularly useful in clinical phases of
development, when a company may handle a variety of drugs each year with limited quantities
required. The burden of conducting necessary changeovers and associated validation studies
when using stainless steel equipment reduces available production time in a multi-product
facility. Disposables may be substituted in numerous unit operations in a biological production
process such as production (bioreactors), mixing, product transfer, connection/disconnection,
filtration, chromatography, centrifugation, storage, sampling, and filling.
Exhibit 5.1 provides design consideration steps when considering the use of disposables in a
single or in multiple biomanufacturing unit operations.
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