Sterility Test Failure Investigation

(Ref. MICLAB 060)

Form 680 Issue date:

Table Contents 1. Purpose of report 2. Batch Details 3. Batch Manufacturing review and Sterility testing 4. Summary of Conclusions found 5. Possible causes 6. Corrective action 7. Preventative action 8. Disposition of filling room 9. Documentation Approval of Investigation

DR____________

1 Purpose of report The purpose of this document is to provide a summary report of the incident investigation conducted into:

2 Batch Details Product Name Date of Manufacturing Product Code Container and size Terminally sterilized Y/N Sterility Test Details Date Test room Time of test session Validated test method Date of results Contaminant/s type

Batch # Filling Room # Filling Machine Autoclave Cycle

Technician Number of products tested Session number that day Tested to Specification Test session results Negative control result

File Location:

Date Printed:

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Sterility Test Failure Investigation

(Ref. MICLAB 060)

Form 680 Issue date:

3 Batch review from manufacturing and testing.

Product Manufacturing Review

REVIEW AREA
Dispensing results:

DETAILS & Results Batch # Materials code Validated test method Results of tests Autoclave Cycle# Date Result Time of collection Sample port results Time of collection Validated test method Results of tests Validated test method Results of tests Finished product Water used for manufacture of batch Line # Date Result Vessel # Date Result Holding Tank # Date Result Bioburden reduction filter # Exacta # Date Results

REVIEWED BY

Review of raw materials used for the manufacture Dispensing of the raw materials Sterilization cycles for components

Sign: Date: Review Attached: Yes/No Sign: Date: Review Attached: Yes/No Sign: Date: Review Attached: Yes/No

Solution Preparation results:

Distilled water used for manufacturing Review Bulk solution Bioburden Review of Filled Container Bioburden Review of Bacterial Endotoxin results

Sign: Date: Review Attached: Yes/No

Sign: Date: Review Attached: Yes/No Sign: Date: Review Attached: Yes/No Sign: Date: Review Attached: Yes/No

Line steaming results Vessel steaming results Holding tank results

Sign: Date: Review Attached: Yes/No Sign: Date: Review Attached: Yes/No Sign: Date: Review Attached: Yes/No

Filtering review

Sign: Date: Review Attached: Yes/No

Filling Machine results: Environmental monitoring results

Filling machine Viable

File Location:

Surface plates machine

Sign: Date: Review Attached: Yes/No

Date Printed:

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Sterility Test Failure Investigation

(Ref. MICLAB 060)

Form 680 Issue date:

Filling Machine non viable particulates Manufacturing room Viable Air Manufacturing room Viable Surface Manufacturing room Non- Viable particulates Fallout Plates for Batch Review of Prepared plate media
Filling Machine results:

Sterile filling zone, date when last conducted Air L/F Air Filling Room Air Corridor Surface floor Surface wall Filling room, date when last conducted Date Start time of exposure End time of exposure Shift Result Type of Media Batch # Expiry Date

Sign: Date: Review Attached: Yes/No Sign: Date: Review Attached: Yes/No Sign: Date: Review Attached: Yes/No Sign: Date: Review Attached: Yes/No

Sign: Date: Review Attached: Yes/No

Sign: Date: Review Attached: Yes/No

Setting up Procedures Machine steaming results Error log report Filtering review Manufacturing instruction sheet review Interventions Stoppages Reject rate Maintenance log review Product values Pressure testing calibrations Differential pressure excursion review Air shower system Waste tanks Machine # Date Result Report Date Result Sterilisation filter # Date Results

Sign: Date: Review Attached: Yes/No Sign: Date: Review Attached: Yes/No Sign: Date: Review Attached: Yes/No Sign: Date: Review Attached: Yes/No

Sign: Date: Review Attached: Yes/No

Sign: Date: Review Sign: Date: Review Sign: Date: Review Sign: Date: Review Sign: Date: Review Sign: Date: Review

Attached: Yes/No Attached: Yes/No Attached: Yes/No Attached: Yes/No Attached: Yes/No Attached: Yes/No

File Location:

Date Printed:

Page 3 of 9

Sterility Test Failure Investigation

(Ref. MICLAB 060)

Form 680 Issue date:

Filling Process All shifts Cleaning review Disinfectants Chilled water review Product line integrity Work orders Run Sheet Sterile Log Book
Sterile Operator Review

Sign: Date: Review Sign: Date: Review Sign: Date: Review Sign: Date: Review Sign: Date: Review Sign: Date: Review Sign: Date: Review Sign: Date: Review Sign: Date: Review

Attached: Yes/No Attached: Yes/No Attached: Yes/No Attached: Yes/No Attached: Yes/No Attached: Yes/No Attached: Yes/No Attached: Yes/No Attached: Yes/No

Name Name and Number of Operators & Location of working Location

Sign: Date: Review Attached: Yes/No

Interview of Operator Name: for any excursion of procedures: Date Name Training records Training Record Gowning validations Operators Finger Dabs Operators Uniform Name Results Name Results

Sign: Date: Review Attached: Yes/No Sign: Date: Review Attached: Yes/No Sign: Date: Review Attached: Yes/No Sign: Date: Review Attached: Yes/No

Packing Line:

Autoclave cycle finished product

Issues on Inspection / Finishing line

Autoclave # Cycle # Result

Sign: Date: Review Attached: Yes/No Sign: Date: Review Attached: Yes/No

File Location:

Date Printed:

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Sterility Test Failure Investigation

(Ref. MICLAB 060)

Form 680 Issue date:

QA Review Manufacturing:

Product Review of past 12 months of results Deviation Reports Review Similar incidents Change control history review Audit of security card swipe Review of Media run reports past 12 months Summary

Sign: Date: Review Attached: Yes/No Sign: Date: Review Sign: Date: Review Sign: Date: Review Sign: Date: Review

Attached: Yes/No Attached: Yes/No Attached: Yes/No Attached: Yes/No

Sign: Date: Review Attached: Yes/No

Micro. Lab. to place a HOLD on adjacent & subsequent batches until establishing a cause which will eliminate their risk of contamination and also;
Date done: Notify QA Manager

Batches on HOLD (Q) Batch # Code

Product & %

Container Size

File Location:

Date Printed:

Page 5 of 9

Sterility Test Failure Investigation

(Ref. MICLAB 060)

Form 680 Issue date:

Sterility Testing Review REVIEW AREA DETAILS Results of known sterile controls Level of false positives in routine testing (previous 12 months) Level false positives in known sterile controls previous 12 months) Review of sampling procedures Review of handling procedures Review of swab method Review of certificate for Steritest unit Review of autoclave cycle for sterility test equipment Media used in sterility test Validation of HEPAs Validation of Laminar Flow unit Review of sterility test session, other batches Training records for sterility technician EM results for the sterility test room Viable EM results for the sterility test room Viable EM results for the sterility test room Non- Viable Review of Prepared plate media LAF Fallout Plate for Session

REVIEWED BY
Sign: Date: Review Attached: Yes/No Sign: Date: Review Attached: Yes/No

Sign: Date: Review Attached: Yes/No Sign: Date: Review Attached: Yes/No Sign: Date: Review Attached: Yes/No Sign: Date: Review Attached: Yes/No Sign: Date: Review Attached: Yes/No Sign: Date: Review Attached: Yes/No Sign: Date: Review Attached: Yes/No Sign: Date: Review Attached: Yes/No Sign: Date: Review Attached: Yes/No Sign: Date: Review Attached: Yes/No Sign: Date: Review Attached: Yes/No

Air L/F Air Sterility Test room Air Change room Surface plates LAF Surface floor Sterility test Room Surface floor Change room Sterility test room Change room Type of Media Batch # Expiry Date

Sign: Date: Review Attached: Yes/No Sign: Date: Review Attached: Yes/No Sign: Date: Review Attached: Yes/No Sign: Date: Review Attached: Yes/No Sign: Date: Review Attached: Yes/No

File Location:

Date Printed:

Page 6 of 9

Sterility Test Failure Investigation

(Ref. MICLAB 060)

Form 680 Issue date:

Sterility Technician Finger Dabs Sterility Technician Uniform Differential pressure excursion review Audit of security card swipe Cleaning review Disinfectants for cleaning Interview of Technician Sterility Log Book Comparison of Isolates Date of Streaking all Isolates:_________________ Technician:________________________________ Source of Isolate Product Finger Dab Plate Uniform Plate Laminar Flow Contact plate Laminar Flow Air Sample Fallout Plate
File Location: Date Printed:

Sign: Date: Review Attached: Yes/No Sign: Date: Review Attached: Yes/No Sign: Date: Review Attached: Yes/No Sign: Date: Review Attached: Yes/No Sign: Date: Review Attached: Yes/No Sign: Date: Review Attached: Yes/No Sign: Date: Review Attached: Yes/No Sign: Date: Review Attached: Yes/No

No. of Colonies N/A

Colony Morphology

Microscopic Appearance

Page 7 of 9

Sterility Test Failure Investigation

(Ref. MICLAB 060)

Form 680 Issue date:

IPA Exp. Date: Bucket 1 Bucket 2

N/A

N/A 4. Summary of Conclusions found

5. Possible cause/ Root Cause

6. Corrective action Task

Responsible

Date Completed

7 Disposition of filling room/batch

8. Documentation Approval of Investigation Prepared by Signature Date

Page 8 of 9

File Location:

Date Printed:

Sterility Test Failure Investigation

(Ref. MICLAB 060)

Form 680 Issue date:

Reviewed by 1 Reviewed by 2 Approved by Quality Assurance Manager

Signature Signature Signature

Date Date Date

Glossary: EM L/F Fallout plates Environmental Monitoring Laminar Flow Also known as Settle Plates

File Location:

Date Printed:

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