In-life phase

After completion of the in-life phase (i.e., the period during which live animals are used) of any study, significant additional effort is still required to complete the research. This effort includes the following. 

Typically, a PK study is composed of three phases, namely the in-life phase, bioanalysis, and data analysis. The in-life phase includes administering the compound to animals or humans and collecting samples from an appropriate matrix of interest such as blood or urine at predetermined time intervals for bioanalysis. The bioanalytical phase involves analysis of a drug and/or its metabohte(s) concentration in blood, plasma, serum, or urine. This analysis typically involves sample extraction and detection of analytes via LC-MS/MS. The third phase is data analysis using noncompartmental or compartmental PK computational methods. 

This function, as has already been stated, is an independent review. The responsibilities here start with a review of the study plan and continue through the review of the study in the in-life phase, data audits, and the final study report audit. 

Additional language in the preamble (TJ 15) to the GLP revisions of 1987 (4) as well as enforcement policies of individual the FDA investigators have broadly interpreted the requirement to include the current status of each study on the master schedule. According to this view, the master schedule should include such study events as test article-mixture preparation, test system dosing, and in-life observation. Because such detailed information is usually available in other study documentation (e.g., protocol, study schedules), most laboratories limit a description of current status to broad categories such as in-life phase, study terminated, report preparation, and report issuance. ... 

Another point to be made is connected with activities associated to the main study performance. The termination of the toxicokinetic part of a chronic toxicity or carcinogenicity study will obviously be delayed with respect to the experimental end of the in-life phase of the main study, if blood samples from the last treatment day are to be analysed. Should the study plan assign the end of the analytical determinations as the experimental end date, or should stiU the necropsy determine this date In analogy to the field studies, where analysis of the samples will constitute, scientifically speaking, the main... 

Evaluation Clinical signs of toxicity during in-life phase including general health, body... 

Study dates Dates when the study is scheduled to be initiated, when the in-life phase is to be completed, and when the draft final report will be available for review... 

Moribund or found dead animals Statements on how animals found moribund or dead during the in-life phase will be handled... 

This effect was discovered during assay development when very basic experiments were conducted to determine background effects in potential matrices for safety studies. The significant differences in dose response for these curves would be expected to impact assay sensitivity. Equally important is the fact that, without further refinement of the method to reduce this matrix effect, accurate quantification of drug in-study samples can only be assured when samples are collected with the same anticoagulant in the matrix as that used to prepare the standard curve. Whenever possible, experiments to evaluate the effect of the matrix on the assay should be conducted before the in-life phase of the study begins. 

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