SOP FOR INVESTIGATION OF MEDIA FILL FAILURE
PURPOSE: To lay down a procedure for Media fill failure Investigation.
SCOPE: This Standard Operating Procedure is applicable for Media fill failure Investigation.
RESPONSIBILITY:
Preparation of SOP: Officer QA Department
Checking and Review of the SOP: Executive QA Department
Approval of SOP: Executive QA Department
Authorization of SOP: Head QA/Designee
Concern person from the department where contamination observed is responsible for intimation of media fills failure to QA.
Head – QA/ Designee shall inform to all departments about media fill failure and subsequently organize a team for investigation.
Concern department head/ designee is responsible to provide all necessary support to investigation team during investigation.
Head QA/ Designee is responsible to make final conclusion and to ensure the implementation of necessary Corrective and preventive action.
Head QA is responsible for overall compliance of this SOP.
ACCOUNTABILITY: The accountability of implementation and compliance of the SOP is Head Quality Assurance.
PROCEDURE: Concern person from the department where contamination is observed shall inform the media Fills failure to QA.
Head QA/Designee shall immediately organize a team to precede the media fill failure investigation and team names shall be mentioned in SOP.
Investigation team shall give the request to documentation cell-QA for issuance of investigation form; media fill failure report and other format as required.
Documentation cell QA shall issue the investigation checklist & media fill failure report to investigation team with reference number, allotted.
QA department shall allocate reference number to the Media fill failure, as per instruction given below.
Number shall be given as MFF XXYY, Where
MFF stands for Media Fill Failure.
XX stands for the year
YY stands for the media fill failure number which starts from 01.
e.g. First media fill failure in year 2025 shall be numbered as MFF2501.
Investigation team shall mention the media fill failure description and immediate action on failure.
Investigation team shall initiate the investigation as per checklist.
After completion of investigation as per investigation checklist, report shall be prepared by investigation team as per SOP.
If no root cause is found, then investigation team shall denote extended investigation is required and subsequently further investigation shall be started as per SOP.
All-encompassing brainstorming session on the Ishikawa fish bone diagram can be used during investigation as shown in SOP, but this is not limited for investigation.
Extended investigation shall be carried out as per following sequence:
Phase 1- Laboratory Investigation:
During this investigation phase at quality control end, through review shall be carried out by investigation team including but not limited to media preparation, Sampling and microbiology related activities, training and expertise of analysts, trends of environmental monitoring of related areas, environmental isolates, personal qualification data, any other reason to all concerned person’s involved in sampling and Environment monitoring etc.
Co-relation of identified isolate from the contaminated vials to any other Contamination observed on surfaces, environment, personnel etc.
Detailed conclusion report shall be prepared for investigation and if root cause found which is laboratory related then necessary CAPA shall be initiated.
If no laboratory related cause was found which lead to failure of media fill then further Phase 2 investigation shall be carried out.
Phase 2- manufacturing Investigation:
Complete manufacturing: filtration and filling process and equipment’s /instruments involved shall be reviewed thoroughly for their qualifications, validations and calibrations.
All entry- exit procedures, cleaning procedures shall be reviewed.
The persons involved in related activities like aseptic connections, cleaning, sterilization shall be evaluated for all prospective.
All related record of disinfectant preparation, cleaning, sterilization, differential pressure etc. shall be reviewed.
Trends of environment monitoring of all the areas shall be reviewed.
Water and utilities used and their analysis results for all user points related to process shall be reviewed.
Detailed conclusion report shall be prepared for investigation.
After completion of extended investigation, media fill failure investigation report shall be prepared. report shall include but not limited to below details,
- Batch details.
- Date of incubation.
- Failure observed on.
- of contaminated vials.
- Details of primary packaging material used.
- Immediate action taken after reporting of failure.
Detailed Phase 1 investigation i.e. laboratory investigation at quality control end and Conclusion.
If required further Phase 2 investigation – Process related deformities and conclusion.
Suggested CAPA for implementation.
The effectiveness of corrective measures shall be verified separately prior to conducting additional run of media fill.
Conclusion shall be written in investigation report indicating root cause of failure.
Necessary CAPA, if required shall be suggested by investigation team with co-ordination to Head-QA and same shall be marked in investigation report.
Implemented and effectiveness of CAPA shall be accessed by concern department with co-ordination to QA department prior to conducting next media fill run.
After necessary CAPA implementation the investigation shall be closed and contaminated vials shall be destructed after authorization from Head QA/Designee.
REFERENCE:
Standard Operating Procedure for Standard Operating Procedure.
PIC/S recommendation on the “Validation of Aseptic Process”, January 2011.
PDA Technical Report No. 22 (Revised 2011), Process Simulation for Aseptically Filled Products