The main concerns of regulators when it comes to sterile filtration depend on which regulator is consulted. Critical regulators
very much stress the benefits of heat sterilisation versus sterilised filtration, a known fact acknowledged by everyone who has any scientific sense. Having said that, it would be
an advantage if regulators, in contrast, acknowledged the fact that there are drug products that cannot be heat sterilised;
in these instances, filtration is the best option.
In addition, when will regulators acknowledge the thousands of process validations performed by the industry with sterilising grade filters, the billions of
litres filtered and the decades of experience? If similar scepticism were attached to flying, planes probably would only be
used for short distance flights. The regulatory promotion of redundant filtration, pre-use integrity testing or the use of
a tighter pore size should be left to the end user, as the decision to use either or all of the aforementioned is an economic
decision after the filtration process has been properly validated.
The requested process validation (by all regulators) of sterilising grade filters is necessary and welcomed by filter manufacturers
and end users alike. The stated tasks required during process validation are of help to any validation exercise and create
a robust performance analysis of a sterilising grade filter. However, it would be good if regulators relied on their stated
requirements when the industry performs the requested tasks and documents the outcome and reliability.
Optimising and improving current processes
The sterilising filtration of biopharmaceuticals generally means that a high value, low volume fluid is filtered. As such,
oversized filtration systems, redundant filtration systems and, in single-use instances, tubing length, all contribute to
excessive hold-up volume, i.e., valuable product losses. Therefore, the size and design of filter systems should not be neglected
because these can impact the production process.
Again, unspecific adsorption, which is often neglected, should be tested very early in the drug development process to understand
which filter membrane polymer is optimal for a particular fluid or application. Yields are very much influenced by unspecific
adsorption and can vary greatly between membrane polymers. Total throughput — the volume that can be filtered through a specified
filter device — also has an influence on yield. In some application, yield can drop dramatically when the filter starts blocking.
This drop-off has to be determined in small-scale studies utilising flat disc filter composites — so-called indicator trials.
When a filter needs to be scaled to production requirements, however, indicator trials are not sufficient and verification
trials with small scale pleated devices should be used. The data of these trials are commonly reliable to scale the filter
appropriately; again, the goal is not only to find a filter system that is able to process the entire volume, but also not
to over-size. High flow rate is the desired parameter in some applications, but flow rate cannot be tested with 47 mm disc
filters because the results would be meaningless. The flow dynamics and the filtration area within a 10 in. element requires
testing in high flow applications. The interaction between the filter adapter and housing recess, as well as pipe work, the
filter pleat behaviour under pressure and possible compression, can only be tested when the actual filter element is used.
In essence, a filter system can be compared to a well-defined recipe; too much as well as not enough can spoil it. Similarly,
too much filtration area is as undesirable as too little.
Maik W. Jornitz is Senior Vice President, Marketing, at Sartorius-Stedim North America, Inc. firstname.lastname@example.org