Information

Guidances

PDA Technical Report #26, 2008:
Probably the most thorough and detailed document for liquid sterilizing grade filtration. Validation requirements are described in detail and the report gives practical description of what requires to be done and why. The report is not meant as a guidance but as an educational tool. However, since the report is as thorough, it is used by everybody including regulators.

Other PDA Technical Reports are:
TR #15 Validation of Tangential Flow Filtration in Biopharmaceutical Applications
TR #40 Sterilizing Filtration of Gases
TR #41 Virus Filtration
TR #45 Filtration of Liquids Using Cellulose-Based Depth Filters

FDA Aseptic Processing Guidance, 2004:
The aseptic guidance succeeding the 1987 guidance. Multiple topics are described and a must read for aseptic processing guidance. The guidance also describes filter process validation activities.

FDA Changes to NDA/ANDA, 2004:
A good guidance to check since it creates a view of post approval change perspectives of what are moderate or major changes considered.

EC GMP Guidance, Annex 1, 2008:
Again a must read document. It has a distinct prejudice against filtration, which is unfortunate since aseptic processing will increase with increasing biotech drug applikations. It would be good to realize that sterilzing grade filtration is more robust than described as this technology has evolved over the last years. Paragraph 113 promotes prefiltration integrity testing of a sterilized filter, which from a risk management standpoint includes a higher risk level than not testing the filter.

EMEA CPMP/QWP/486/95, 1996:
The document includes the controversial 10cfu/100ml prefiltration bioburden limit. It describes that when the bioburden of 10cfu/100ml is exceeded, one has to use another filter to reduce the bioburden below the set limit. However, sterilizing grade filters are validated to remove 10 to 7 Brevundimonas diminuta per square centimeter, by far higher than the limit specified by the guidance document.
 
ISO 13408 Part 2, 2003:
The document describes filtration processes and validation needs of sterilizing grade filters.

PQRI PAC, 2007:
Post approval changes are reviewed under risk management

Warning Letters:
Learn from the warning letter database within the FDA web site. These warning letters, as unfortunate as these are, create always a good learning tool and creates a glimpse of what is of importance and where can it go wrong.