The main advantage of terminal sterilization versus filtration is the reduced risk of a nonsterile product release to the end user.  There are a few different views on what the SAL is of product sterilized by the filtration method, the most common agreed upon being 10-4 SAL, and even that cannot be validated in the truest sense of the word.  However, sometimes the effect of terminal sterilization on a drug ingredient or API is detrimental and, therefore, terminal sterilization is not an option.

The main commercial terminal sterilization methods (EtO and Radiation)  do provide a validated SAL of 10-6.  And an ISO standard for each of these methods of terminal sterilization has been published for many years, both of which are listed as “accepted” standards by FDA.

It should be noted that for most pharmaceutical products, radiation provides the best method for delivering terminal sterilization, mainly owing to the high heat and introduction of moisture required of the EtO sterilization process.  Regarding costs, the costs associated with validating and maintaining the validation of a terminally sterilized process are also very inexpensive, as compared to filtration sterilization and the dreaded media fill testing. For example, a typical radiation sterilization validation costs at most $5000 initially and around $2000 quarterly for subsequent dose audits that are required to maintain the SAL validation (this includes cost of sterilization, bioburden testing, sterility testing.) There are also new methods of radiation validation that only use 10 to 30 product units, versus 100 - 200 units required of some of the methods used in the past. In addition, the latest ISO standard for radiation (ISO 11137-2) defines dose-setting methods designed specifically for low bioburden products, such as pharmaceuticals, so that a lower minimum dose can be used in order to obtain an SAL of 10-6.

Another suggestion, if one is still uncomfortable with the whole thought of terminal sterilization or your product is degraded by EtO or Radiation,  is not to exclude the use of terminal sterilization of the key components prior to filtration, e.g., packaging materials, vials, lyophilized ingredients, etc.).  Once again terminally sterilizing even just the key or some components prior to the filtration process can even further reduce the risk of producing a nonsterile product.

To gain more information about a respective terminal sterilization method, I suggest you obtain the ISO standard that addresses the type of sterilization.  Each of these standards can be purchased at www.aami.org, Radiation Sterilization (ISO 11137 parts 1 - 2), EO Sterilization (ISO 11135).