Analysis and Testing Flashcards
How long should test reagents be kept for?
All solutions and reagents should be retained until all data has been second person verified as being within the defined acceptance criteria
How many samples for disso testing and what are the A/C
6
Each unit is not less than Q + 5 %.
How many samples for disso stage 2 and what are the A/C
6 to give 12
Average of 12 units (S1 + S2) is equal to or greater than Q, and no unit is less than Q − 15 %
How many samples for disso stage 3 and what are the A/C
12 to give 24
Average of 24 units (S1 + S2 + S3) is equal to or greater than Q, not more than 2 units are less than Q − 15 per cent, and no is less than Q − 25 per cent.
When is OOS testing not applicable
IPC or where looking to adjust a process based on the results
What is an OOT result
- Is generally a stability result that does not follow the expected trend, either in comparison with other stability batches or with respect to previous results collected during a stability study. However the trends of starting materials and in-process samples may also yield out of trend data.
- The result is not necessarily OOS but does not look like a typical data point.
- Should be considered for environmental trend analysis such as for viable and non viable data (action limit or warning limit trends)
What is an Atypical / Aberrant / Anomalous Result
- Results that are still within specification but are unexpected, questionable, irregular, deviant or abnormal. Examples would be chromatograms that show unexpected peaks, unexpected results for stability test point, etc.
What are 1a investigation examples
Calculation error –
analyst and supervisor to review, both initial and date correction.
Power outage –
analyst and supervisor document the event, annotate “power failure; analysis to be repeated” on all associated analytical documentation.
Equipment failure –
analyst and supervisor document the event, annotate “equipment failure; analysis to be repeated” cross reference the maintenance record.
Testing errors –
for example, spilling of the sample solution, incomplete transfer of a sample; the analyst must document immediately.
for microbiology it could be growth on a plate not in the test sample area, negative or positive controls failing.
Incorrect Instrument Parameters –
for example setting the detector at the wrong wavelength, analyst and supervisor document the event, annotate “incorrect instrument parameter”; analysis to be repeated” on all associated analytical documentation .
What is expected of a 1a investigation
It is expected that these issues are trended even if a laboratory investigation lb or ll was not raised.
What is the analyst and supervisor stage 1b investggiation limited to?
The Analyst and Supervisor investigation should be restricted to data / equipment / analysis review only
Done against a checklist
What should be on the lab investigation Ib checklist
The checklist may not be all-inclusive, but should be a good guideline to cover the pertinent areas that need to be covered in any laboratory investigation:-
- Correct test methodology followed e.g.. Version number.
- Correct sample(s) taken/tested (check labels was it taken from correct place).
- Sample Integrity maintained, correct container and chain of custody (was there an unusual event or problem).
- How were sample containers stored prior to use
- Correct sampling procedure followed e.g. version number
- Assessment of the possibility that the sample contamination has occurred during the testing/ re-testing procedure (e.g. sample left open to air or unattended).
- All equipment used in the testing is within calibration date.
- Review equipment log books.
- Appropriate standards used in the analysis.
- Standard(s) and/or control(s) performed as expected.
- System suitability conditions met (those before analysis and during analysis).
- Correct and clean glassware used.
- Correct pipette / volumetric flasks volumes used.
- Correct specification applied.
- Media/Reagents prepared according to procedure.
- Items were within expiry date
- A visual examination (solid and solution) reveals normal or abnormal appearance
- Data acceptance criteria met
- The analyst is trained on the method.
- Interview analyst to assess knowledge of the correct procedure.
- Examination of the raw data, including chromatograms and spectra; any anomalous or suspect peaks or data.
- Any previous issues with this assay.
- Other potentially interfering testing/activities occurring at the time of the test.
- Any issues with environmental temperature/humidity within the area whilst the test was conducted.
- Review of other data for other batches performed within the same analysis set.
- Consideration of any other OOS results obtained on the batch of material under test.
- Assessment of method validation.
What are the extra 1b things micro test checklists need?
Additional considerations for microbiological analysis:
- Are the isolates located as expected – on glove dab marks, SAS ‘dimples’, filter membrane etc.
- Was the sample media integral – i.e. no cracks in plates.
- Was there contamination present in other tests (or related tests) performed at the same time, including environmental controls.
- Were negative and positive controls satisfactory.
- Were the correct media/reagents used.
- Were the samples integral (not leaking)
- Were the samples stored correctly (refrigerated)
- Were the samples held for the correct time before being tested.
- Was the media/reagent stored correctly before use
- Were the incubation conditions satisfactory.
- Take photographs to document the samples at time of reading (include plates, gram stains and any thing else that may be relevant).
When should the contract giver/MAH/QP be informed of OOS
Generally at 1b but could be II dependent on TA
When should hypothesis testing be started
Should be started as part of Phase Ia and continue into Phase II if no assignable cause found.
1a hypothesis testing can include the original working stock solutions but should not include another preparation from the original sample
What are the zone 1 stability conditions
21 / 45 RH ±2° / 5%
What are the zone II stability conditions
25 / 60 ±2° / 5%
What are the zone III stability conditions
30 / 35 ±2° / 5%
