SPADA Draft Documents

be established via production records and orthogonal testing. It may also be desirable to use 46 application-oriented testing to ensure study-specific similarities between the cultures. 47 ( f ) Propagation history describes a test culture’s step-by-step derivation from the index 48 culture via a series of production records. These data are an essential part of the culture 49 verification process because a culture’s propagation history is impossible to recover through 50 empirical means. Furthermore, production and handling details provide important clues to the 51 health and disposition of the culture that may not be evident through empirical observations, 52 including potential changes in the genetic makeup. 53 ( g ) Orthogonal testing is the use of functionally independent assays to verify the genotypic 54 and phenotypic relatedness of test and index cultures. Orthogonal testing is important for 55 identifying genetic or physical changes that might have resulted from laboratory handling and 56 could impact the validity of an extensible study. 57 ( h ) Application-oriented testing is designed to assess the relationship between the test and 58 index cultures with respect to the specific genotypic or phenotypic phenomena being evaluated 59 in the extensible study. For example, if the study relates to microbial virulence, some effort 60 should be made to show that the virulence of the test strain resembles that of the index strain. 61 ( i ) Culture verification statements provide a convenient mechanism for documenting the 62 relatedness of microbial cultures used in extensible studies. 63

3.0 Roles and Responsibilities

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An extensible study’s sponsor, culture producer, and performer have distinct roles and 65 responsibilities with respect to the culture verification process. Each of these roles and their 66 associated responsibilities are described below and can be filled by the same or different 67 organizations. 68

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