At the end of February, I attended the ISPE Tampa Conference in Florida, where I spoke at an aseptic processing seminar about
sterilizing filtration. One of the hot topics discussed is related to European GMP Annex 1 recommendations, which call for
integrity testing of sterilized filters prior to use and double filtration schemes to enhance sterilization assurance. These
recommendations can lead to complex systems and procedures, but are possible when using properly designed single-use systems
(as opposed to stainless steel systems). One concern, however, is that the EMA cites a potential subtle change in membrane
retention properties that might occur with exposure to moist heat (steam sterilization), but could also potentially be resolved
by filter plugging during the process.
With single-use filtration systems, sterilization is most commonly performed with gamma irradiation, which does not introduce
heat and has not been associated with changes to membrane filter porosity or bacterial retention property (so long as the
filter materials are gamma compatible and validated for gamma irradiation stability). Single-use filtration systems are typically
supplied presterilized, so that a poststerilization integrity test is the only pre-use test a user can apply. Even without
the hypothesized potential changes in membrane flow path and retention property caused by moist-heat sterilization conditions,
it can still be economically prudent to conduct a pre-use (poststerilization) integrity test in many single-use filtration
processes. This step ensures that the filter has not been damaged during shipment and handling. Such damage is not repairable
by plugging and is a more valid reason to conduct pre-use integrity testing of the sterilized filter, especially where a drug
product is sterile filtered through single (nonredundant) filtration schemes and filled into multiple final containers, or
that cannot otherwise be refiltered in the event of post-use filter integrity failure. When designing single-use single or
double filtration systems, it is important to consider how the filters will be initially wetted, how they will be tested,
and whether or how to displace the wetting liquid before product introduction. Approved system design should be discussed
with the filter supplier, system-design engineer, and system integrator.
In March, I finished my single-use tour by chairing the second annual IBC Biomanufacturing and SingleUse Systems Asia Conference,
which took place in Shanghai. Last year, the event was held in Seoul, South Korea. I was immediately struck by the progress
in appreciation for the benefits of single-use manufacturing by many of the Chinese participants. Single-use manufacturing
has been a difficult concept for many Chinese biopharmaceutical manufacturers to accept because they have historically been
focused on minimizing cost per batch, rather than the degree of cleaning and cleaning validation required in the West, or
other beneficial aspects of single-use systems, such as reduced carbon footprint. At this meeting, participants heard case
studies and considerations for single-use technologies from companies across Asia, including Simcere Pharmaceuticals, Shanghai
Kanda Biotech, Wison, and Autekbio, all based in China; Novartis and Green Cross, based in Korea; Innobioventures, based in
Malaysia; as well as from Piramal Healthcare and Intas Biopharmaceuticals, both based in India. In Asia, much of the biopharmceutical
focus is on the development of biosimilars. Although the cost of single-use technologies versus cleanable and reusable stainless
steel is still an issue for many process developers in Asia, disposable bioreactors and single-use tangential flow filtration
are now being seen as potential ways to accelerate biosimilar development.
For those involved in or considering single-use processes, two upcoming US conferences may be of interest. The PDA Single-Use
Workshop, taking place June 22–23 in Bethesda, Maryland, will include details about PDA's technical report on single-use technologies
using quality-by-design principles. Workshop attendees will have the opportunity to preview and discuss the draft report during
the workshop so that industry input can be incorporated into the final version, which will be published by PDA in fall 2011.
http://www.pda.org/ for details.
The Bio-Process Systems Alliance International Single-use Summit, to be held July 27–30 in Washington, DC, is meant for biopharmaceutical
business leaders and will focus on the impact of single-use manufacturing on the future of healthcare and biopharmaceuticals.
The meeting will feature speakers from PricewaterhouseCoopers, Venable LLP, and FDA, as well as international single-use end-users
and leading suppliers. See
http://www.bpsalliance.org/ for details.
Jerold Martin is senior vice-president of Global Scientific Affairs at Pall Life Sciences, Port Washington, NY, and chairman of the Board
and Technology Committee at Bio-Process Systems Alliance, tel. 516.801.9086, firstname.lastname@example.org