Checklist for investigation of out of specification
- Is performance against written procedure carried out?
- Are the cleaned sampling equipments used?
- Are the cleaned containers used for collection of samples?
- Is the sample integrity maintained until testing?
- Is composite sample prepared correctly?
- Is correct weighing from correct portion of sample done?
- Is clean and dried apparatus used?
- Are the samples completely transferred?
- Is the sample properly shaken, sonicated or heated / warmed as per specification?
- Are the sample dilutions correctly performed as per specification?
- Are the samples filtered/ centrifuged/membrane filtered properly before introduction into instrument or analysis by classical method?
- Are the samples correctly transferred to auto sampler devices and correctly labelled for traceability?
- Are samples / standards correctly prepared for each tests as per specification?
- Are cleaned glassware’s and correct equipment’s used to prepare the sample for analysis?
- Are samples / standards preparations stored under correct environment / time before analysis?
- Are analysis performed on calibrated instrument?
- Is there any possible contamination from syringe or auto sampler carryover?
- Is instrumental setting done as per specification?
- Are the details of method of analysis followed as per specification?
- Is sequence of samples on instrument correct?
- Is the correct column used as per specification?
- Are the correct general analytical method followed for testing?
- Are instruments used as per written procedure (SOP)?
- Is instrument No. identified in test data sheet?
- Are the relevant training records of the analyst available?
- Is there any power supply fluctuation?
- Were there problems during analysis like improper flow or generation of bubbles during HPLC analysis or did one of the paddles fall off during dissolution or was the sample extraction during analysis was incomplete?
- Is authorised data sheet used?
- Are all the relevant entries in test data sheet filled with correct transcription of raw data?
- Are correct calculations done as per specification / General analytical method?
- Is the interpretation of results of test done correctly?
- Is the data collation from instrument in sequential order?
- Are the formulae use to calculate the results correct?
DATA EVALUTION / REVIEW:
- Is each test in Test Data Sheet /Specification checked for correlation?
- Are all signatures / dates / weighments available with report?
- Are all general analytical method numbers / instruments code entered in Test Data Sheet?
- Are all charts / spectra /Instrumental recordings available with the report?
- Is there evidence of who checked the report, and when with signature and date?
The following steps should be taken as part of the supervisor’s assessment:
- Discuss the test method with the analyst; confirm analyst knowledge of and performance of the correct procedure.
- Examine the raw data obtained in the analysis, including chromatograms and spectra, and identify anomalous or suspect information.
- Verify that the calculations used to convert raw data values into a final test result are scientifically sound, appropriate, and correct. also determine if unauthorized or unvalidated changes have been made to automated calculation methods.
- Confirm the performance of the instruments.
- Determine that appropriate reference standards, solvents, reagents, and other solutions were used and that they met quality control specifications.
- Evaluate the performance of the test method to ensure that it is performing according to the standard expected based on method validation data and historical data.
- Fully document and preserve records of this laboratory assessment.
- The assignment of a cause for OOS results will be greatly facilitated if the retained sample preparations are examined promptly. Hypotheses regarding what might have happened (e.g.dilution error, instrument malfunction) should be tested.
- Examination of the retained solutions should be performed as part of the laboratory investigation.
Mr. Shiv Kumar is the Author and founder of pharmaceutical guidance, he is a pharmaceutical Professional from India having more than 14 years of rich experience in pharmaceutical field.
During his career, he work in quality assurance department with multinational company’s i.e Zydus Cadila Ltd, Unichem Laboratories Ltd, Indoco remedies Ltd, Panacea Biotec Ltd, Nectar life Science Ltd. During his experience, he face may regulatory Audit i.e. USFDA, MHRA, ANVISA, MCC, TGA, EU –GMP, WHO –Geneva, ISO 9001-2008 and many ROW Regularities Audit i.e.Uganda,Kenya, Tanzania, Zimbabwe. He is currently leading a regulatory pharmaceutical company as a head Quality. You can join him by Email, Facebook, Google+, Twitter and YouTube