Fully Disposable Manufacturing Concepts for Clinical and Commercial Manufacturing and Ballroom Concepts

  • Berthold BoedekerEmail author
  • Adam Goldstein
  • Ekta Mahajan
Part of the Advances in Biochemical Engineering/Biotechnology book series (ABE, volume 165)


The availability and use of pre-sterilized disposables has greatly changed the methods used in biopharmaceuticals development and production, particularly from mammalian cell culture. Nowadays, almost all process steps from cell expansion, fermentation, cell removal, and purification to formulation and storage of drug substances can be carried out in disposables, although there are still limitations with single-use technologies, particularly in the areas of pretesting and quality control of disposables, bag and connections standardization and qualification, extractables and leachables (E/L) validation, and dependency on individual vendors. The current status of single-use technologies is summarized for all process unit operations using a standard mAb process as an example. In addition, current pros and cons of using disposables are addressed in a comparative way, including quality control and E/L validation.

The continuing progress in developing single-use technologies has an important impact on manufacturing facilities, resulting in much faster, less expensive and simpler plant design, start-up, and operation, because cell culture process steps are no longer performed in hard-piped unit operations. This leads to simpler operations in a lab-like environment. Overall it enriches the current landscape of available facilities from standard hard-piped to hard-piped/disposables hybrid to completely single-use-based production plants using the current segregation and containment concept. At the top, disposables in combination with completely and functionally closed systems facilitate a new, revolutionary design of ballroom facilities without or with much less segregation, which enables us to perform good manufacturing practice manufacturing of different products simultaneously in unclassified but controlled areas.

Finally, single-use processing in lab-like shell facilities is a big enabler of transferring and establishing production in emergent countries, and this is described in more detail in 7.

Graphical Abstract


Ballroom facilities Disposables Disposables-based manufacturing E/L Facility of the future Monoclonal antibodies (mAbs) Single-use bioreactors (SUBs) Single-use equipment Single-use systems 


  1. 1.
    Mahajan E, Dent K, Chan E, Hudson T (2014) UNICAN: dual capability in single use bioreactors, Cell Culture Engineering XIV, April 2014, Quebec, CanadaGoogle Scholar
  2. 2.
    Gikanga B et al. (2015) Mixing monoclonal antibody formulations using bottom-mounted mixers: impact of mechanism and design on drug product quality. PDA J Pharma Sci Technol 69:284–296CrossRefGoogle Scholar
  3. 3.
    Goldstein A (2015) Pharmaceutical engineering, vol 35. ISPE, BethesdaGoogle Scholar
  4. 4.
    Samavedam R, Goldstein A, Schieche D (2006) Implementation of disposables: validation and other considerations. Am Pharm Rev 9(5):46–51Google Scholar
  5. 5.
    Goldstein A, Pohlscheidt M (2012) Disposable freeze systems in the pharmaceutical industry. Am Pharm Rev 15, 53–58Google Scholar
  6. 6.
    Boedeker B (2012) Improving biologic manufacturing operations and plant design through single-use technologies applications. Pharm Outsourcing 13:12–17Google Scholar
  7. 7.
    Boedeker B (2013) Assessing possibilities and preventing the risk of using disposables. BioPharma Asia Vol 2(2) March/April 2013, 38–45Google Scholar
  8. 8.
    Leveen L (2009) Single use technology and its carbon and water footprints, part 2. Am Pharm Rev 13:50–56Google Scholar
  9. 9.
    Ding W et al. (2014) Standardized extractables testing protocol for single use systems in biomanufacturing. Pharm Eng 34(6), 1–11Google Scholar
  10. 10.
    Boedeker B (2014) Facility of the future: effect of disposables and continuous processing on plant design. BioPharma Asia Vol 4(3) May/June 2014, 24–27Google Scholar
  11. 11.
    Chalk S et al. (2011) Challenging the cleanroom paradigm for biopharmaceutical manufacturing of bulk drug substance. BioPharm Int Aug 2011:1–13Google Scholar
  12. 12.
    Mahajan E (2011) Microline: a fully disposable manufacturing facility. In: ISPE Annual Conference, Nov 2011Google Scholar
  13. 13.
    Hudson T (2014) Evaluating where single-use technology provides the most value for a company with well established manufacturing infrastructure. 247th ACS National Meeting and Exposition, March 16–20, 2014, Dallas, Texas Chemistry and Materials for EnergyGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Berthold Boedeker
    • 1
    Email author
  • Adam Goldstein
    • 2
  • Ekta Mahajan
    • 3
  1. 1.Pharmaceuticals, Biological DevelopmentBayer AGWuppertalGermany
  2. 2.Global Manufacturing SciencesRoche/GenentechSouth San FranciscoUSA
  3. 3.Pharma Technology DevelopmentRoche/GenentechSouth San FranciscoUSA

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