Sterilizing Filtration of Adjuvanted Vaccines: Ensuring Successful Filter Qualification - Filterability and bacterial retention must be verified very early in process development to ensure successful

ADVERTISEMENT

Sterilizing Filtration of Adjuvanted Vaccines: Ensuring Successful Filter Qualification
Filterability and bacterial retention must be verified very early in process development to ensure successful sterilizing filtration validation.


BioPharm International Supplements


Achieving Successful Sterilizing Grade Filter Qualification


Table 3. Summary of the results of metadata analysis. Risk is qualitatively defined here as the likelihood of an occurrence of bacterial penetration during retention validation challenge.
A review of field and laboratory bacterial retention validation data for a variety of fluids and challenge conditions suggests that low surface tension fluids, such as many adjuvants and adjuvanted vaccines, present a higher risk of the occurrence of a bacterial penetration event during sterilizing filter validation (Table 3). Among the classified solutions examined, liposome solutions represent the highest risk, followed by lipid and finally surfactant solutions. B. diminuta bacteria loading above 1 x 108 CFU/cm2 (>10 times the minimum required challenge density) increases the chance of a penetrative event, as does a loading rate of greater than 1 x 105 CFU/min. For liposome, lipid, and surfactant solutions, bacterial challenge using constant flow may present a higher risk and we would hence recommend conducting validation studies and operating processes of low surface tension adjuvants and adjuvanted vaccines at constant pressure.

The analysis discussed herein, along with published work by other filter manufacturers, strongly suggests that although bacterial retention by sterilizing grade filters is most commonly achieved by size exclusion, it occasionally can be strongly influenced by the nature of some feed solutions (surface tension, particle size), processing conditions (constant pressure versus constant flow, temperature, operating pressure), membrane structure, and bacterial challenge test conditions (bacterial challenge load, loading rate). Based on the reviewed data, clearly no single membrane is successful in all applications.

For the successful sterilizing filtration of adjuvants and adjuvanted vaccines, we recommend filter users consider the risk of reduced bacterial retention very early in the process, i.e., when designing the formulation, the filtration operating conditions and sequence, and when drafting the sterilizing filtration validation bacterial challenge test protocol. Several membrane candidates for bacterial retention should be tested along with filterability studies, to arrive at the candidate offering both complete bacterial retention and providing the highest filtration capacity for superior process economy. Because of the impact of operating conditions on bacterial retention, it is important to maintain process consistency during scale-up and to design the process with the end in mind.


blog comments powered by Disqus

ADVERTISEMENT

ADVERTISEMENT

Pfizer to Acquire Vaccines from Baxter
July 30, 2014
GSK Submits EU Regulatory Filing for Malaria Vaccine Candidate
July 29, 2014
Bristol-Myers Squibb and Ono Pharmaceutical Collaborate on Immunotherapies
July 28, 2014
FDA Accepts First Biosimilar Filing
July 24, 2014
Compounding Pharmacy Issues Recall, But Challenges FDA Decision
July 22, 2014
Author Guidelines
Source: BioPharm International Supplements,
Click here