Filter qualification typically involves demonstrating bacterial retention of a filter under process simulated conditions.
A crucial first step in this is in the hands of the filter vendor, who is responsible for producing a ‘fit for purpose’ filter such as those in Parker's PROPOR membrane filter range. Supporting data which demonstrates filter performance under standardized test conditions should then be presented in a validation guide.
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Expectations of the filter vendor
- The material of construction needs to be consistent and defined. There is no point in validating a filter if the material is not consistent across all products.
- The performance limits of the filter – encompassing temperature, chemical compatibility, pressure and bacterial retention – should be defined and published in the validation guide.
- The validation guide must explain how to correctly sterilize the filter by steam or irradiation.
Biopharmaceutical manufacturer's responsibility
- The biopharmaceutical manufacturer must prove that when operated within the published performance limits, the process will not alter the filter performance. Among the elements to consider are:
- Will differences in temperature alter the filter’s pore size and shape so potentially making it easier for bacteria to pass and therefore affect microbial retention?
- Could the presence of certain solvents affect microbial retention by altering the pore size or shape?
- How will the filter deal with adjuvants? These are notoriously difficult to filter because they somehow change the filter membrane’s properties making it easier for bacteria to pass through. Although it has never been conclusively proved, there is a theory that adjuvants lower the surface tension of a membrane by acting as a surfactant. In effect, this lubricates the membrane.
A destructive test – bacterial retention performed during validation – should be carried out and this is typically undertaken by the filter manufacturer.
In addition, a non-destructive filter integrity test should be performed by both the end user and the manufacturer. This will be in the form of either a bubble point test or a diffusion test and will link to the work carried out in the destructive test.
Process qualification must be carried out to prove the filter works in the customer process and with the fluid stream.
You can access guidance on process qualification in PDA Technical Report 26 and in ISO 13408-2:2018.
To carry out effective process qualification, it is best to start at a small scale, develop the process and then test it. Testing should then be carried out at the largest scale possible – so with the largest batch size, at the highest pressure and across the longest process time. If the feed stream is variable, then this should be taken into account. However, typically at this stage the feed stream is fairly well defined: the volume may change but the constituents of the feed stream will be the same.
In order to carry out effective filter qualification, you need to show that the combination of a defined, consistent filter membrane, used to filter a particular and controlled feed stream, under defined conditions of temperature, time and pressure, will retain bacteria.
This post was contributed by Paul Hymus, product manager (filtration), Parker Bioscience Filtration, United Kingdom
Parker Bioscience Filtration specializes in automating and controlling single-use bioprocesses. By integrating sensory and automation technology into a process, a manufacturer can control the fluid more effectively ensuring the quality of the final product. Visit www.parker.com/bioscience to find out more.