CRITICAL ASPECT ANALYTICAL TEST REVIEW

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1 CRITICAL ASPECT ANALYTICAL TEST REVIEW Jakarta 14 December 2017 Speaker: HERU PURNOMO, ST

2 QC WORK FLOW Start Sample Received (In-Process & Finished Good) Testing Review Lab Result Yes No Non Conformance or Out of Specification Investigation Meet Specification Submission Lab Record to QA BATCH DISPOSITION Stop Connecting Pharmaceutical Knowledge ispe.org 2

3 Analytical Test Result Analytical Worksheet Analytical Report Certificate of Analysis (CoA) Internal document to be used by the analyst for recording information about the sample, the test procedure, calculations and the results of testing. It is to be complemented by the raw data obtained in the analysis The analytical test report is a compilation of the results and states the conclusions of the examination of a sample The list of test procedures applied to a particular sample with the results obtained and the acceptance criteria applied. It indicates whether or not the sample complies with the specification Connecting Pharmaceutical Knowledge ispe.org 3

4 Certificate of Analysis (CoA) A specification is defined as a list of tests, references to analytical procedures, and appropriate acceptance criteria that are numerical limits, ranges, or other criteria for the tests described It establishes the set of criteria to which a drug substance or drug product should conform to be considered acceptable for its intended use. Conformance to specifications means that the drug substance and/or drug product, when tested according to the listed analytical procedures, will meet the listed acceptance criteria Connecting Pharmaceutical Knowledge ispe.org 4

5 Review of Analytical Test Result Written procedure should be in place when reviewing analytical result with the following information: Provide general guideline for checking of analytical raw data, worksheet and associated document in QC Lab Applies to GMP analytical raw data in physical chemical, microbiology and raw material Preparation steps, observation and calculation step should be documented and show on the worksheet, these associated documentations have to be reviewed for completeness and accuracy as well The date of execution and analyst / chemist / microbiologist who perform the testing is to be identified on worksheet All printout of raw data should be attached to the analytical worksheet. Printout must signed or initialled across the edge of attachment Connecting Pharmaceutical Knowledge ispe.org 5

6 HPLC / GC Chromatographic Test The following review for chromatographic data should be done for completeness and accuracy: 1. Program setup: Flow rate, detector wavelength, column temperature, mobile phase (e.g. isocratic / gradient) & composition, need wash / seal wash setup 2. Sequence Setup Injection Volume, Column ID, Sample Type, Sample Description, Sample Weight, Reference accuracy weight 3. Integration Setup SST Setup, Reference Standard Weight Entry, retention setup and allowable window, proper integration peak 4. Chromatogram Examine the blank chromatogram and note any extra peaks, particularly those that co-eluate with any peak interest 5. Audit trail Check data integrity of sequence by verifying the audit trail for any unauthorized changes Connecting Pharmaceutical Knowledge ispe.org 6

7 HPLC / GC Chromatographic Test (cont) 6. Check the expiry of standard and test mix, use in the analysis, against the relevant reference material certificate or preparation. Ensure they are within the expiry date and preparation correct 7. Check that specified system suitability result are met against the relevant testing method 8. Check the accuracy of all values that are manually calculated Connecting Pharmaceutical Knowledge ispe.org 7

8 Dissolution Check should be carried out on both the dissolution procedure and method analysis: 1. Dissolution medium used and the operating temperature 2. Type of Aparatus 3. Preparation standard and sample 4. Sampling procedure and technique (e.g. intervals, filtration, handling of samples, dilution) 5. Calculations 6. The blank and standard solution spectra or chromatograms supporting the dissolution test should either be available electronically or documented in lab worksheet Connecting Pharmaceutical Knowledge ispe.org 8

9 Microbiological Testing for Water, Environment Monitoring (EM), Microbial Limit Test (MLT) 1. Check that the analytical worksheet and SOP used were correct and the sampling points were accurately recorded. Check the presence and accuracy of the following minimum information: Date of sampling / performed date of testing Date of reading plate / result recording date Indicate the lot reference and expiry date of media used and verified that the lot reference used is within expiry date at point of usage Date and temperature of incubation Equipment ID and ensure equipment are still within their qualification / calibration status at point of usage Test result of negative or positive control which was carried out in accordance to the test method Water sampling point (for microbiological testing for water) / legend (for environment monitoring) Initial of analyst & reviewer and date 2. Check the result against the acceptance criteria in the relevant test procedure Connecting Pharmaceutical Knowledge ispe.org 9

10 Other Tests Hard copy, generated from test (for example: UV, infrared absorption) should bear the following information: Initial / name of analyst Sample Identity Instrument Number Spectrum (where applicable) Testing date Instrument Parameter (where applicable) Result / data obtained Connecting Pharmaceutical Knowledge ispe.org 10

11 Tolerance Limit & Specification Check If the test method requires tolerance limit check for the replicate runs, check the replicate value against the pre-defined tolerance limit in the test method Check the reported results against specification and trend limit (if any) The review period of a GMP analytical result should be recorded in a timely manner (e.g. 24 working hours from the test completion date) Connecting Pharmaceutical Knowledge ispe.org 11

12 Trend Rule Violation Out of Trend There are three (3) trend rule violations: 1. Result out of trend limits 2. Nine (9) or more consecutive data points shifted above or below the center line 3. Six (6) or more data points consecutively increasing or decreasing Connecting Pharmaceutical Knowledge ispe.org 12

13 OUT OF TREND (OOT) - NELSON TEST Rule # 1 Any point outside control limit Rule # 2 9 consecutive point on same side centreline Rule # 3 6 consecutive point decreasing or increasing Connecting Pharmaceutical Knowledge ispe.org 13

14 What is an Audit Trail? 1. Systematic story of the data from creation, through interpretation and final assessment and report 2. Each functional area that have GxP computer systems need to perform audit trail 3. The information should be recorded in Audit Trail: Date and Time Name of person making change Original Change and value Reason of change made Invalid attempts to log on the system If audit trail procedure is not available, the company has no possibility to detect violations to data integrity executed by site Operators due to errors / malfeasances, unintended or deliberate Connecting Pharmaceutical Knowledge ispe.org 14

15 Regulatory Guidance for Audit Trail Review Connecting Pharmaceutical Knowledge ispe.org 15

16 Audit Trail Review Evaluation of process risk associated to the system intended use An assessment must be performed for each system in order to identify the most adequate method Connecting Pharmaceutical Knowledge ispe.org 16

17 Audit Trail Review Risk class identification to define critical point: Frequency of audit trail Sampling Plan: The number of record to be reviewed Connecting Pharmaceutical Knowledge ispe.org 17

18 Audit Trail Review Create form to define the verification to be executed and the relevant acceptance criteria Connecting Pharmaceutical Knowledge ispe.org 18

19 Common Question During Inspection Is the audit trail activated? SOP? Record of review? How to prevent or detect any deletion of modification of audit trail data? Training staff? Is predicate rule principle followed for changed? Preserve of original data Corrected data Date of correction Name of person who correction the data Justification comment for correction What if there is no audit trail function? Can you prove data manipulation did not occur? Connecting Pharmaceutical Knowledge ispe.org 19

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22 QA Responsibility Do I need to review Analytical test result? System & Facility Create robust procedure to review analytical test result Qualified personnel Allocate budget to reduce potential data integrity issue Culture Develop management practises and supervision to encourage reporting problem Identify root causes without finger pointing Confident Random check based on risk assessment approach Connecting Pharmaceutical Knowledge ispe.org 22

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Inspection of Quality Control Laboratories

Inspection of Quality Control Laboratories PQP Manufacturer's Meeting April 4-5 th 2011, Geneva, Switzerland Stephanie Croft, M.Sc. Technical Officer (Inspector), WHO Prequalification of Medicines Programme