B.Sc. Chemistry/Entomology, ACSM-CPT, Competitive Bodybuilder

OOS OOT

Comparison of results vs. a predetermined specs criteria.

Comparison of many historical data values vs. time.

e.g.: specs limit for assay 98.0-105.0%w/w of LC.Result: a particular batch has 97.2% w/w.

e.g.: same one.

Result: 98.8% w/w, although the results are within the specs, analyst should compare results w/z previous batch trend. If the average value of the trend as 99% w/w, then the batch 98.8% is OOT.

OOS

No

Release

Yes

Calculations ok?

No

Correction of calculation

Yes Analysis ok?

No

Retest n=3

Yes

Testing Protocol

Retest n≥3 ResampleFurther Investigation

Investigation Concluded

Yes

Analytical error

Sample errorProduct failure

Unknown failure

Investigation report

CAPA

No

Go to testing protocol

Lab Analysis

Satisfactory OOS results

Phase I Investigation

Phase II Investigation

Concluding the

investigation

Review Production

Additional lab testing

Reporting testing results

Averaging Outlier test

No obvious error

revealed

OOS observed during the analysis of:

Stability study Finished API

Intermediates Excipients

Raw material In-Process

Packaging material

OOS is due to

Lab error

Method analysisNon calibrated

instruments

Calculation error Analyst error

Instrument failure

Process related

Quality of raw material

Ambient environment

In-process control during manufacturing

Deviation from validated procedure

Sample homogeneity

Sampling errorPooling of

sample

Handling of sample

OOS causes

OOS investigation CDER/FDA

Phase-I investigation (Lab investigation) Phase-II investigation (Manufacturing)

Analyst observed OOS result.

Verify calculations, if the results are the same. QC supervisor shall be informed.

Log OOS.

Start Phase-I.

Review documents, instruments, RS, reagents.

Ambient Temp., storage conditions.

If there’s no abnormality observed, then report results as valid OOS and report to QA officer.

Repeat the analysis n=3 if the QA officer permits, with different analyst.

If results complies, then invalidate OOS and release batch. If not report to QA and continue OOS investigation.

Begins if an error assignable to the testing lab can’t be identified in phase-I.

Recommended by QA.

Production personnel should investigate raw material.

Process parameters.

Calibration and PM of equipment.

Contamination investigation.

Ambient environment check.

If there is no assignable cause observed, then report to QA.

QA, QC and production will evaluate the situation. The QA may request resampling.

QC shall analyze the sample as per SOP. Report results (pass/fail).

Define CAPA & release batch

Reject batch & transfer to R&D

Pass

Fail

Responsibilities

Analyst Supervisor

Verify paperwork is in order & matches label info.

Verify proper test method is used.

Retain original test prep until data and results have been checked.

Discontinue testing and notify supervisor if a problem is suspected.

Ensure each analyst is properly trained.

Ensure proper sample management within the lab.

Notify the QAU when an OOS result arises.

Ensure documentation and implementationof the retesting protocol.

Ensure investigation is conducted within the specified timeframes.

http://www.fda.gov/downloads/Drugs/.../Guidances/ucm070287.pdf

http://images.alfresco.advanstar.com/alfresco_images/pharma/2014/08/22/c1ccdea4-5bc5-4960-9617-7ce7a7d9943e/article-6989.pdf