Mississippi Administrative Code › Title 15 - Mississippi Department of Health › Part 22 - Medical Cannabis Program › Subpart 5 - Product Testing and Safety › Section 15-22-5.11 - Cannabis Testing Entity Quality Control Samples

Current through June 25, 2024
5.11.1
				The cannabis testing entity shall use Quality Control samples (QC) and adhere
				to good, approved laboratory practice ("GLP") in the performance of each
				analysis according to the specifications of this Part.
5.11.2 The cannabis testing entity shall
				analyze QC samples in the same manner as the cannabis testing entity analyzes
				cannabis and cannabis products samples.
5.11.3 The cannabis testing entity shall use
				at least one negative control, one positive control, and one cannabis testing
				entity replicate sample in each analytical batch for each target organism
				during microbial testing. If one of the controls produces unexpected results,
				the samples shall be re- prepped and reanalyzed with a new set of
				controls.
5.11.4 If the result of
				the microbial analyses is outside the specified acceptance criteria in Appendix
				A, Table 2, the cannabis testing entity shall determine the cause and take
				steps to remedy the problem until the result is within the specified acceptance
				criteria.
Microbiology
Culture Methods - Qualitative and Quantitative
The quality control (QC) samples that are required for
				  culturing of cannabis and cannabis products using qualitative and quantitative
				  methods are included in Appendix A, Table 2.
Molecular Assays/Methods
The QC samples that are required for molecular (i.e.,
				  polymerase chain reaction (PCR), gel electrophoresis and probe-based qPCR with
				  or without melting curve analyses) analysis of cannabis and cannabis products
				  are listed in Appendix A, Table 3.
PCR positive DNA controls are used to verify that the PCR
				  master mix and reagents were prepared correctly to produce amplification of the
				  target nucleic acid. This type of positive control is analyzed with each PCR
				  run.
A PCR run is defined as a group of samples that are analyzed
				  at the same time under the same amplification conditions, using the same PCR
				  master mix, and in the same thermocycler. A PCR run may contain more than one
				  extracted sample batches.
A PCR run with multiple assays must have a DNA positive
				  control for each assay.
Inhibition controls are used to verify that interfering
				  constituents from a cannabis form, which may be carried over during isolation
				  of nucleic acids or organisms during sample processing, do not inhibit the PCR.
				  Because cannabis forms are constantly changing, inhibition positive controls
				  must be performed in every extracted sample.
PCR DNA negative controls are used to verify that the PCR
				  master mix and reagents were prepared correctly to produce amplification of the
				  target nucleic acid. This type of negative control is analyzed with each PCR
				  run. A PCR run is defined as a group of samples that are analyzed at the same
				  time under the same amplification conditions, using the same PCR master mix,
				  and in the same thermocycler. A PCR run may contain more than one extracted
				  sample batches.
A PCR run with multiple assays must have a DNA negative
				  control for each assay to verify that the amplification conditions are working
				  properly.
No template controls are used to verify no contaminating
				  nucleic acid has been introduced into the master mix. These controls are
				  prepared when template is added to the master mix. They are prepared as
				  separate PCR reactions to which aliquots of molecular-grade water or buffer are
				  added to the master mix in place of target nucleic acid or sample. A negative
				  result with this control indicates that the master mix and final processing
				  reagents are not contaminated. This type of negative control is analyzed with
				  each PCR run. A PCR run is defined as a group of samples that are analyzed at
				  the same time under the same amplification conditions, using the same PCR
				  master mix, and in the same thermocycler. A PCR run may contain more than one
				  extracted sample batch. A PCR run with multiple assays must have not template
				  controls for each assay to verify that the sterility of the assays.
One duplicate sample is required per run. A duplicate sample
				  is subjected to all of the same steps as the original sample. For qualitative
				  analyses, if the duplicate sample does not equal the sample result, the sample
				  and its duplicate must be reanalyzed. Consideration should also be given to
				  possibility of re-preparing and reanalyzing all associated samples. For
				  quantitative analyses, if the RPD of the sample and duplicate is greater than
				  100, the parent sample and duplicate sample must be reanalyzed. Consideration
				  should also be given to possibility of re-preparing and reanalyzing all
				  associated samples. When data are accepted, the result for the sample portion
				  designated as the "original sample" is reported.
5.11.5 Chemistry - Analytical, Organic and
				Inorganic (Metals).
Quality control must be performed for each analytical,
				  organic and metal chemistry method.
Each cannabis testing entity shall maintain sufficient raw
				  data records to ensure the QC was performed at the frequency specified.
'Bracketing' of QC samples, rotating from across the
				  calibration curve range, is required.
QC samples must follow the first twenty (20) samples after an
				  initial calibration, every twenty (20) samples thereafter, and at the end of
				  testing samples. This would also apply to a continuing calibration.
Initial Calibration
A. Samples results must be associated with an
				acceptable initial calibration. If the initial calibration is not acceptable,
				corrective actions must be performed and all associated samples
				re-analyzed.
B. No sample results
				are to be reported nor data qualified for a failed initial
				calibration.
C. Samples must be
				analyzed under an initial calibration that was performed no more than one month
				prior.
D. The following items are
				required elements of an initial calibration:
1. The details of the initial calibration
				procedures including calculations, integrations, acceptance criteria, and
				associated statistics must be included or referenced in the method SOP. When
				initial calibration procedures are referenced in the method SOP, then the
				referenced material must be retained by the cannabis testing entity and be
				available for review;
2. Sufficient
				raw data records must be retained to permit reconstruction of the initial
				calibration (e.g., calibration date, method, instrument, analysis date, each
				analyte name, and analyst or technician's initials or signature; concentration
				and response, calibration curve or response factor; or unique equation or
				coefficient used to reduce instrument responses to concentration);
3. The cannabis testing entity must use the
				most recent initial calibration analyzed prior to the analytical
				batch;
4. Standards used for
				calibration must be traceable to an international or national standard, when
				commercially available; and
5. The
				cannabis testing entity must have a written procedure addressing removal and
				replacement of calibration standards.
E. The lowest calibration standard must be at
				or below the lowest concentration for which quantitative data are to be
				reported without qualification.
F.
				The highest calibration standard shall be at or above the highest concentration
				for quantitative data are to be reported without qualification.
G. Sample results must be quantitated from
				the initial calibration and may not be quantitated from any continuing
				calibration verification.
H.
				Criteria for the acceptance of an initial calibration must be established
				including any calculations (e.g., relative error, relative standard deviation).
1. R2 >= 0.990, and
2. Curve recovery of ±20% (and
				±30% for the lowest point) for all points must be maintained.
I. The cannabis testing entity
				must use and document a measure of relative error in the calibration as
				specified in the method SOP.
Initial Calibration Verification
A. All initial calibrations must be verified
				with a standard obtained from a second manufacturer or a separate lot prepared
				independently by the same manufacturer.
B. Initial calibration verification is
				performed by analyzing a test solution of known analyte concentration(s) after
				initial calibration and prior to sample analysis.
C. In general, the check must be ± 20%
				(± 30% for the lowest point) of the known value. Some individual methods
				may require tighter tolerances (±10% of the known value).
Continuing Calibration Verification
A. The validity of the initial calibration
				must be verified prior to sample analyses by a continuing calibration
				verification with each analytical batch.
B. A CCV is performed by analyzing a test
				solution of known analyte concentration(s) prior to sample testing on each
				testing day and continued periodically during the analytical batch run, no less
				frequently than once after each set of 20 samples, and at the end of each
				run.
C. The CCV must be a standard
				that is from the same vendor/lot that is used for the calibration
				curve.
D. In general, the check
				must be ± 20% (and ± 30% for the lowest point) of the known
				value.
E. Calibration must be
				verified for each compound, element, or other discrete chemical analyte, except
				for multi-component analytes where a representative chemical, related substance
				or mixture can be used.
F.
				Instrument continuing calibration verification must be performed at the
				beginning and end of each analytical batch, and at the frequency defined in the
				method.
G. Sufficient raw data
				records must be retained to permit reconstruction of the continuing instrument
				calibration verification (e.g., method, instrument, analysis date, each analyte
				name, concentration and response, calibration curve or response factor, or
				unique equations or coefficients used to convert instrument responses into
				concentrations).
H. Continuing
				calibration verification records must explicitly connect the continuing
				calibration verification data to the initial calibration.
I. If the continuing instrument calibration
				verification results obtained are outside the established acceptance criteria,
				the following steps must be taken:
1. If a
				cause for the calibration verification failure is identified that impacts only
				the calibration verification sample (e.g., a missed autosampler injection),
				then analysis may proceed if a second calibration verification sample is
				analyzed immediately and the result is within acceptance criteria. Samples
				analyzed previously must be considered valid if bracketed by a passing
				calibration verification sample. The cause for the failure of the first
				calibration verification result must be documented; and
2. If the cause for the calibration
				verification failure is not identifiable or has impacted other samples, then
				corrective action must be performed and documented. Prior to analyzing samples,
				the cannabis testing entity must demonstrate acceptable performance after
				corrective action with calibration verification or a new initial calibration
				must be performed. Samples analyzed prior to the calibration verification
				failure must be reanalyzed.
J. Data associated with an unacceptable
				calibration verification must not be reported with a qualifier. Qualifying the
				data is not an acceptable approach.
Low Level Continuing Calibration
				  Verification
A. A LLCCV will
				be run at the end of each analytical batch.
B. The measured value must be within ±
				30 % of the prepared value.
C. The
				cannabis testing facility entity shall prepare and analyze at least one of each
				of the following QC samples for each analytical batch:
1. Negative Control, Method Blank;
				and
2. Positive Control, Laboratory
				Control Sample (LCS);
3. Matrix
				spike sample;
4. Duplicate matrix
				spike sample; and
5. Duplicate
				sample.
D. The required
				QC is summarized in Appendix 2, Table 4.
Negative Control - Method Blank (MB)
A. A method blank must be analyzed at a
				minimum of one (1) per preparation batch.
B. The MB must be processed along with and
				under the same conditions as the associated samples to include all steps of the
				preparation and analytical procedure.
C. The MB is used to assess the samples in
				the preparation batch for possible contamination during the preparation and
				processing steps.
D. The measured
				concentration of each analyte in the MB or LRB must be < LOQ or
				MRL.
E. Procedures must be in place
				to determine if a MB or LRB is contaminated. While the goal is to have no
				detectable contaminants, each method blank must be critically evaluated as to
				the nature of the interference and the effect on the analysis of each sample
				within the batch.
F. The source of
				contamination must be investigated and measures taken to minimize or eliminate
				the problem and affected samples reprocessed if the concentration of a targeted
				analyte in the blank is at or above the LOQ, if the blank contamination
				otherwise affects the sample results as per the method requirements or the
				individual project data quality objectives, and a blank is determined to be
				contaminated. Samples associated with a contaminated blank must be evaluated as
				to the best corrective action for the samples (e.g., reprocessing or data
				qualifying codes). In all cases, the corrective action must be
				documented.
G. Any affected samples
				associated with a contaminated MB or LRB must be reprocessed for
				analysis.
Positive Control - Laboratory Control Sample
				  (LCS)
A. The LCS is used to
				evaluate the performance of the total analytical system, including all
				preparation and analysis steps.
B.
				The LCS must be carried through the entire sample preparation process and
				analyzed.
C. The LCS must be spiked
				with all target analytes at a mid-level concentration in the curve.
D. The LCS must be analyzed at a minimum of
				one (1) per preparation batch.
E.
				The LCS is a quality system matrix, known to be free of analytes of interest,
				spiked with known concentrations of analytes that are within the calibration
				range.
1. A laboratory control sample (LCS)
				may be used in place of a continuing calibration verification (CCV) (but not as
				a replacement for a failing CCV) for methods where the calibration goes through
				the same process as the LCS. Note that the more stringent acceptance criteria
				must be met.
2. The matrix spike
				may be used in place of this control as long as the acceptance criteria are as
				stringent as for the LCS.
3. The
				lab may use commercially available or pre-prepared standards (separate from
				calibrators) for QC.
F.
				All analyte concentrations must be within the calibration range of the
				methods.
G. The individual LCS must
				be compared to the acceptance criteria stated in the standard operating
				procedure. The results of the individual batch LCS are calculated in percent
				recovery or other appropriate statistical technique that allows comparison to
				established acceptance criteria. The cannabis testing entity must document the
				calculation.
H. When the acceptance
				criteria for the positive control are exceeded, those sample results must be
				investigated, and a corrective action implemented.
Matrix Spikes and Matrix Spike
				  Duplicates
A. Analyze an
				actual sample with a known amount of standard added (matrix spike. MS). A
				second portion of the actual sample used to prepare the MS that is spiked and
				processed in the same manner as the MS (matrix spike duplicate, MSD).
1. For potency testing, a "representative
				matrix" may be used to prepare the MS/MSD.
2. MS/ MSD shall be spiked at a midlevel
				concentration with the target analytes.
B. Calculate the relative percent difference
				(RPD) between first sample and replicate. The calculations must be documented,
				and the target value must be close to the first value and have a RPD of less
				than 20%.
C. Matrix-specific QC
				samples indicate the effect of the sample matrix on the precision and accuracy
				of the results generated using the selected method. The information from these
				controls is sample/matrix specific and would not normally be used to determine
				the validity of the entire batch.
D. For methods that include one (1) to twenty
				(20) targets, spike all components.
E. For methods with more than twenty (20)
				targets, randomly spike at least sixteen (16) components.
Sample Duplicate
A. Analyze the same sample twice, using two
				separate preparations. The sample should be chosen at random and run together
				on the same analytical run.
B.
				Calculate the relative percent difference (RPD) between first sample and
				replicate. Calculations must be documented, and the target value must be close
				to the first value and have a RPD of less than twenty percent (20%).
Variability may be introduced during sample preparation. To
				  account for this, if more than one staff member is prepping samples, each staff
				  must also prepare and analyze a sample matrix duplicate for each set of
				  prepared samples.