Handling of Out Of Trend (OOT)

1.0 OBJECTIVE :

To lay down a procedure for handling of Out Of Trend.

2.0 SCOPE :

This procedure is applicable for handling of out of trend results in all parameters excluding microbiological data.

3.0 RESPONSIBILITY :

Production Executive / IPQA Officer: Compile the data on various process parameters from BMRs, BPRs, analyze and conclude from the results obtained.

QC Head: Compilation of analytical data, analyze and conclude from the results obtained.

4.0 ACCOUNTABILITY:

Q.A. Head and QC Head

5.0 PROCEDURE :

5.1 OOT identification and investigation shall be applicable to annual trending, routine production and Stability study batches.

5.2 All the abnormal results which are out of in-house specification shall constitute the OOT. OOT shall be identified and investigated for critical test parameters like assay, content uniformity, impurities and dissolution for following alert limits:

Any abnormal results are outside the trends.

The result is outside ± 5% of the initial result (stability batches).

The result is outside ± 3% of the label claim (routine production batches).

5.3 OOT alerts shall be classified as

5.4 Analytical alert: Observed when a single result is abnormal but within specification limits (i.e. outside normal Analytical or sampling variation and normal change over time)

5.5 Process control alert: Observed when a succession of data points shows an a typical pattern possibly caused by changes in the laboratory or manufacturing process.

5.6 Compliance alert: Is the potential for OOT results to occur before the expiry date of the product within the stability study on the same product.

OOT identified shall be presented during annual product review for the respective product.

5.7 On observing OOT results analyst shall report to his/her supervisor. QC Head shall investigate cause for OOT results based on investigation.

5.8 Any observed OOT shall be intimated by concerned department to Q.A. Head and this investigation shall be recorded with annual product review.

5.9 An out of trend result can be due to

Assignable cause

Non-Assignable cause

5.10 Assignable cause for OOT results can be due to laboratory error.

5.11 Laboratory errors occur when an analyst makes a mistake in following the method of analysis uses incorrect working standard or wrongly calculation of data.

5.12 To confirm an error is a laboratory error an investigation shall be carried out as per Annexure No. 01 Out of Trend Investigation Report.

5.13 If the investigation reveals that the OOT is due to laboratory error, then the sample shall be re-tested as per respective STP.

5.14 Repeat analysis shall be done in duplicate each by the original analyst (say A) and another analyst (say B) after taking the required corrective actions as applicable.

5.15 If on repeat analysis the results obtained are as per expected trend then the original testing results shall be invalidated and the repeat test results shall be reported.

5.16 When a laboratory error is not identified (non assignable cause) then a repeat testing shall be planned in duplicate each by two different analysts (say B) and (say C). If the repeat analysis results are within trend then the average of retest results shall be reported.

5.17 If repeat analysis results obtained are still out of trend then initial OOT results shall be reported. Repeated results shall be identified as confirmatory results.

5.18 If OOT is confirmed, further trend of data shall be compared with the OOT values.

5.19 Various process parameters which shall be recorded for establishing the trend and / or verification of designed parameters are as under:

Tablets: Dry mixing time, Assay of active ingredient which is checked, Drying time, LOD, Friability, Hardness, DT, Dissolution, Assay values for finished product, Content uniformity.

Capsules: Mixing time, Assay of active ingredient, DT, Dissolution, Assay values for finished product, Content uniformity and Yield.

5.20 Minimum 10 batches in a year or all the batches.

5.21 RSD shall be calculated and shall not deviate by more than 3% for various parameters.

5.22 Any physical parameter which appears to be deviating more, frequency for IPQA check for such parameter can be increased.

5.23 Based on the observed trend analysis, if any change is to be incorporated, it shall be executed as per SOP for Change Control.

6.0 ABBREVIATIONS:

Abbreviation Expanded form

SOP Standard Operating Procedure

OOT Out of Trend

STP Standard Test Procedure

QA Quality Assurance

QC Quality Control