Filter validation: Aspects to be considered

 

Just like other processes in the pharmaceutical industry, the filtration process needs to be validated. It must be demonstrated that the product filters perform their intended purpose adequately. A sterile filtration should result in a sterile filtrate. The technical report 26 „Sterilizing Filtration of Liquids“ of the PDA (Parenteral Drug Association) describes the basic requirements for the validation of product filters for sterile filtration of liquids. The following table gives an overview over the validation aspects / studies recommended by the PDA:

 

Filter user (= pharmaceutical company)

Filter supplier
Bacterial retention in water - R, D
Bacterial retention in product V* -
Chemical compatibility V D
Extractables V D
Leachables E -
Sterilization method V D
Filter integrity with water V R, D
Filter integrity with product V -
Toxicity - D
Bacterial endotoxins V R, D
Partikel release E D
Fiber release E D
TOC and conductivity E D
D = Part of the supplier's filter validation documentation 
R = Part of the release criteria for each filter batch
E = Evaluate the necessity for testing
V = Process specific validation
V* = Performance also allowed with small filter discs

During this, it must be differentiated between studies performed with the product (primarily by the filter users themselves) and non-product-specific studies, where the filter supplier is generally able to provide information. Many filter suppliers offer a detailed filter validation documentation that can include bacterial retention in water, filter integrity, applicable sterilization methods and requirements, chemical compatibility, partly extractable substances (extractables), toxicity studies, bacterial endotoxins, the release of particles and fibers, conductivity, total organic carbon (TOC) as well as oxidable substances and information about materials of animal origin ( keyword: transmissible spongiform encephalopathies, TSE). A lot of the described studies are performed according to the corresponding compendial methods and comply with the requirements for (sterile) water for injection purposes.

 In conclusion, the filter user needs to implement the following studies with the product:

  • Bacterial retention, and viability test before
  • Filter integrity
  • Extractable substances (leachables, extractables if necessary)
  • Examination of the product-specific adsorption to the filter membrane (as part of the chemical compatibility)
  • Release of particles from the filter membrane during product contact
  • Multiple filtration if necessary

Some of these studies are performed in-house during development, for others a collaboration with the filter supplier is advisable, for examples by commissioning an associated contract laboratory.

 

Cookies make it easier for us to provide you with our services. With the usage of our services you permit us to use cookies.