Filter Validation in Sterile Manufacturing

Filter Validation in Sterile Manufacturing

Filter validation is done in sterile pharmaceutical manufacturing to ensure that filter is working properly and sterilizing the material or air.

An important aspect during the manufacture of drugs is sterile filtration. As simple as it may be to run to the nearest grocery store and grab any filters for your coffee maker, sterile pharmaceutical filters require validation to ensure the performance of the filter and quality of the end product. Typical objectives of a validation process include decreasing the risk towards the patient, ensuring sterility, reliable and reproducible results, and confirm viability for the market.

According to a document found on the Parenteral Drug Association's (PDA) website, there are eight elements which constitute the process of sterile filtration validation:

1.Fit for Use: The filter meets requirements within product and process conditions. It is currently the industry best practice to validate and design  the process around the worst 10% of filters, just to take a conservative standpoint. Along with worst-case scenario, the requirements are set by the flow rate of the process stream, the equipment used in the manufacturing process, and factors that question whether or not this filter fits in this specific process.

2.Sterilization: The sterilization method is proved effective and doesn't compromise the filter. Testing for the effectiveness of the sterilization method can be found in guidance provided by the Food and Drug Administration (FDA) involves using a representative sample, written procedures for testing, appropriate laboratory controls, and prior established sensitivity, accuracy, specificity, and reproducibility of test methods.

3.Stability: The filter is proved to not negatively affect the process stream. If the filter is somehow adding something to the stream, it isn't a filter fit for this process.

4.Binding: The filter doesn't remove important stream components. This may affect the quality and effectiveness of the end product.

5.Compatibility: The filter won't break or dissolve in the process stream, and it fits the equipment properly. It defeats the purpose of sterilization if the unfiltered stream is meandering around or breaking through the filter.

6.Extractable/Leachables: The compounds that pass through the filter are found, quantified and assessed to make sure the quality and effectiveness of the end product is maintained.

7.Retention: The filter removes bacteria from the stream per ASTM 838-15ae1, which is the most up to date standard as of October 2018. The link to the standard can be found below.

8.Integrity Testing: Retention capability of the filter is proved with non-destructive methods. 

Challenges which may be faced include limited knowledge of product formulation, small amounts of product available for testing, the membrane has been chosen while the device is not yet definitive, or the process may not be well defined yet. These challenges can be overcome by focusing on three of the above elements, namely retention, extractables and compatibility. 

Compatibility can be determined by using the wide range of compatibility data offered by the filters manufacturers. Looking at the extractable element, the filters should be certified through trustworthy sources for any possible interaction that may occur between the stream and the filter. 

Finally, regarding retention, the actual drug product should be used under conditions similar to what the normal manufacturing process would be.

In taking this information into account, the manufacturers produce high quality, commercially viable and standard and regulatory approved products.