In a disposables implementation project, an in-depth understanding of the investment requirements, return on investment, and
associated manufacturing costs is required. Implementation strategies must be compared to determine the maximum capacity required
for the short term, and future expansion strategies; and to make cost comparisons of rival technologies.
Indirect expenditures related to operator training, validation, and utilities are usually much greater than direct equipment
costs and are considerably more difficult to measure. Industry guidelines are clearly needed as many companies are uncertain
about how to carry out an economic analysis of manufacturing options and comparative technology evaluation.
In BioPlan Associates' 2006 annual survey of biopharmaceutical manufacturing, the number one reason given for restricting
the use of single-use or disposable systems was concern about leachables and extractables, with 63% of respondents expressing
concern in this area (down from 68.9% in 2005).4
Industry end-users considering implementing a disposables manufacturing approach will evaluate various supplier validation
packages. These packages usually contain physical, chemical, and functional test results for film, filter, tubing, and connector
qualification. They also may contain extractables and leachables testing results. The packages are currently based on a variety
of industry standards, which makes comparative evaluations of validation packages more difficult. In addition, some suppliers
have more complete packages than others, so individual assessment is required. Each package should be reviewed and a risk
analysis developed with respect to product-specific studies.
Other process-specific studies that need to be carried out include:
- Integrity studies
- Aseptic simulations (media fill)
- Cleaning agent compatibility for outer surface wipedown
- Process exposure compatibility tests.
So how can end-users work their way through the variety of guidelines and standards to make an evaluation? At present, many
companies set up their own process or product specific tests, as we saw in the case of Amgen.
Bavarian Nordic based their analysis primarily on audits of suppliers (including film manufacturers), combined with supplier
validation packages and knowledge from previous use in process development and optimization. This was all combined in a risk
evaluation, which was the basis for prioritizing items for process-specific testing.
A sign of industry maturity and the drive for disposables implementation is that committees such as the Bio-Process Systems
Alliance are being set up with the aim of evaluating the guidelines already in use and making recommendations for harmonizing
the validation approaches proposed by disposable manufacturers.5
The second most common reason industry members cite for restricting use of single-use or disposable system components was
to avoid dependence on vendors—i.e., single-source issues. In the 2006 BioPlan survey, 54.5% of respondents expressed this
concern, up from 34.2% in the previous year. It is not surprising, therefore, that single-use system manufacturers are being
asked to supply far more detail around supply security. Further definitions in this area will no doubt be part of the guidelines
set up by industry standards committees.
Take home messages
Single-use systems have a key role to play in the drive for operational excellence in biotech manufacturing. This article
has set out to analyze the current status and to determine the key areas that require set up of guidelines and standards to
facilitate successful project management of single-use system implementation.
The author wishes to thank Adam Goldstein of Amgen, Karine Wassard of Bavarian Nordic, and Andrew Sinclair of Biopharm Services.
Miriam Monge is a marketing director at Stedim Biosystems, Z.I. des Paluds, Ave. de Jouques, BP 1051, 13781 Aubagne Cedex, France, +33
(0)4 42 84 56 11, fax + 33 (0)4 42 84 68 70, firstname.lastname@example.org
1. Biopharm Services, Lancer House East Street, Chesham HP5 1DG, UK: e-mail: email@example.com