Examples of Types of PTM Modification Validations

whole kit  

Stability study of frozen and refrigerated product; growth  curve analysis, shelf‐life data and lot‐to‐lot; real‐time  stability data; testing on several instruments.   Depending upon the change and the technology, specific  details will need to be reviewed by the AOAC volunteer  expert.  Lot‐to‐lot comparison testing of 1 lots from previous  manufacturing facility and 3 lots from the new  manufacturing facility. One target strain at 10XLOD  tested using 10 replicate samples with fractional recovery  results.  Comparison of QA/QC data has been used when old lots  are no longer available. 

Software changes 

Manufacturing location changes 

Changes in raw agar ingredients 

Inclusivity/exclusivity 

Table 1 details a summary of level 2 method modifications and the data requirements to  substantiate the changes. For most level 2 modifications a matrix comparison study is required,  some inclusivity/exclusivity testing and possible robustness testing. For manufacturing location  changes a lot‐to‐lot comparison testing scheme is used with lots from the previous  manufacturing site to those lots from the current site. However, in instances where there are  no available kits produced at the previous manufacturing site AOACRI has accepted QA/QC  comparison data from kits produced at the new manufacturing site compared to QA/QC data  from the previous manufacturing site.  Level 3 modifications are major changes to the test method, components and/or workflow.  Internal and independent study data are required to substantiate the method modification  changes. 

Table 2. Level 3 Method Modification Examples and Data Requirements  Method Modification  Data Requirement 

Inclusivity/exclusivity, matrix comparison for subset of  claimed matrices, robustness testing and an  independent laboratory study. 

Changes in enrichment media, extraction  buffer, temperature and/or times.  Matrix extensions where the number of  matrices being added is exceeds the  independent laboratory testing threshold  of 1 matrix independently tested for every  5 claimed matrices in the original  validation claim.  

Matrix comparisons for all matrices being added and an  independent laboratory study for 1 matrix for every 5  matrices in the total claim.