Biomedical Engineering Reference
In-Depth Information
needs to be revalidated. Minor assay modifications may be made without revalidation
if these changes do not alter the fundamental properties of the assay. A full revalida-
tion is required for (1) A change in matrix/or species. i.e., dog plasma to rat plasma,
(2) a change in anticoagulant, i.e., Na
2
EDTA to Na-Heparin, or Na
2
EDTA to
K
3
EDTA, (3) a change of internal standard, i.e., from structure analog to stable
isotope labeled analog, or from D
4
-labeled IS to D
5
-labeled IS, and (4) a change of
extraction procedure or LC condition or MS condition.
6
Regulated Sample Analysis
Regulated bioanalytical sample analysis must be conducted according to Sample
Analysis (SA) SOP which is typically written following FDA guidance and white
papers. The SA SOP describes procedures for bioanalysis performed in support of
submissions to regulatory agencies. A validated method has to be used and analysis
will be conducted by scientists who have been certified on the assay. Similarly as
formal MV, a Principle Investigator (PI) or Study Director (SD) is assigned for
assuring that the validated method is approved, that sufficient stability is estab-
lished, and adequate for the analysis of study samples, and that the execution of the
sample analysis follows SOP and meets FDA guidance. A Study Protocol (SP) is
written and approved prior to sample analysis in which the criteria for data accep-
tance and criteria for reanalysis of samples are outlined. Any planned deviation
must be documented in protocol or amendment
a priori
and approved by PI and
Laboratory Director (LD). The following sections detail the chronicle of the study
samples from sample receiving to data reporting in a GLP bioanalytical laboratory.
6.1
Sample Accession and Storage
Biological samples typically arrive in bioanalytical laboratory in secured boxes with
dry ice or ice pack. Formal sample accession is the process of inspecting sample
physically and registering into a LIMS (Laboratory information management sys-
tem). The initial physical examinations of the samples include any missing vial,
leakage, broken tubes, or thawing. The verification of documentation of the samples
includes the number of the samples, subject ID, time point, period, group number,
dose information et al. Any discrepancies and irregularities need to be documented
and the Study Director and testing facility need to be notified immediately. After
accession, samples are stored in secured environment designated by the protocol.
Refrigerator or freezer for sample storage is typically monitored by a temperature
monitoring software. Matrix STD and QC samples have to be stored in the same
condition and, at least one set of high and low QC should be stored in the same
storage unit along with study samples.
