Aseptic area start up procedure after shut down

This Document describes (Standard Operating procedure) SOP for aseptic area start up procedure after shut down

SOP for Aseptic area start up procedure after shut down

I. Purpose & Scope:

  • The Purpose of this SOP is to lay down the procedure for aseptic area start up procedure after shut down.
  • This procedure is applicable production Department personnel for aseptic area start up procedure after shut down.

II. Responsibilities:

  •  All production personnel’s shall be responsible to follow and implement this SOP.

III . Introduction and Procedural Part :

Definition :

Major shut down:

  • The activities which have major impact on the quality of aseptic area environment includes activities such as
  • Civil works in the area.
  • Major maintenance activity
  • HVAC shut down
  • After long shut down of areas

Minor shut down:

  •  The activities which have low impact on quality of the aseptic area environment includes activities such as
  • HVAC shut down for more than 10 minutes
  • Preventive maintenance activity.
  • Minor modifications in the area

Procedure for Aseptic area start up procedure after shut down :

Restart After Major Shut Down :

HVAC Shut Down for more than 8 hours :

  • In case of power failure, all equipments shall be resumed within 10 minutes by power back up through Diesel Generator.
  • In case of HVAC failure, during filling, all the vials shall be filled & sealed immediately which are on the conveyor.
  • Filling shall be stopped until the HVAC is restarted.
  • All the sterile powder lying on the hopper inside LAF shall be covered immediately.
  • All the bungs and vials shall be removed from the areas and shall be processed after resume HVAC.
  • The batch shall be stand cancelled if no vials are filled for that Batch Number.
  • In such cases batch shall be filled with different batch number with additional testing and sterility test after sanitization of area & fumigation of the areas.

Preventive Maintenance Activity :

  • Preventive maintenance of activity shall be planned during non routine days of production.
  • In case of preventive maintenance of Machine during production run, ensure that sanitization & fogging is done before start of activity in classified areas.
  • In case of shut down of Autoclave, refer respective SOP.
  • In case of Tunnel shut down during operation, all the vials shall be removed, washed and depyrogenated after maintenance and cleaning activity.
  • In case of vial washing shut down, restart the machine after ensuring proper functioning of nozzles and physical parameters for the machine changeover such as 10 ml vial or 20 ml vials.
  • Ensure that vial washing machine is cleaned as per respective SOP
  • In case of filling & sealing machine shut down due to major maintenance during batch, all the vials on the conveyor belt shall be discarded.
  • Line clearance shall be followed before start up the activity.
  • Deviation shall be filled in case of major maintenance during batch as per respective SOP and shall be resumed after appropriate impact assessment by QA.
  • For restart after major shut down through cleaning of floors, walls, and ceiling, doors, and window panels by mopping with 0.2 micron filtered Water for Injection and 70 % IPA.
  • LAF are under UPS. In case of Breakdown of LAF, due to mechanical failure, alarm will be annunciated. The activity shall be stopped immediately.
  • All the vials & sterile powder under LAF shall be discarded.
  • Area shall be resumed after sanitization of area.
  • All the vials shall be washed & depyrogenated as per respective SOP
  • Extended surface monitoring & environmental monitoring shall be carried out by raising appropriate action by raising deviation.

Restart after Long Shut Down :

  • Instruct engineering personnel to start AHU, ensure that LAF ‘s are “ON”
  • Allow area to be purged for at least 1 hour.
  • Re-clean and sanitize the areas as per SOP ensuring that the floors, walls, and ceiling are cleaned and sanitized.
  • Clean all the equipments present in the area thoroughly externally and internally as per their respective SOP’s, if required.
  • Non Viable Monitoring shall be performed at rest before start up in the respective areas.
  • Area clearance shall be taken to start up the activity based on the impact assessment by QA.
  • Perform fogging (fumigation) once in day continuously for three days in all core areas of Grade C, B & A areas.
  • Sanitize Purified water Generation and distribution system and WFI distribution system prior to start of the activity.
  • Garments shall be prepared and Autoclaved for area cleaning.
  • Daily cleaning shall be performed as per respective SOP
  • Perform microbial environmental monitoring for consecutive 5 days to start up the activity.
  • The final approval to start the area should be given by QA after reviewing all the data and ensuring compliance to the requirements.

Restart after minor shut Down :

Break down of HVAC more than 10 Minutes :

  • In case of Break down due to power failure, follow respective SOP
  • Raise deviation if directly impacts on the product such as failure of HVAC for more than 10 minutes.
  • If motor or belt is out of order replace the same with spare capacity.
  • In case of other maintenance, inform production & QA for further advice on batch.
  • Follow steps as per the above steps which are provided for shut down for more than 8 hours till the resume of breakdown.
  • Fumigate the areas as per respective SOP
  • Restart activity if LAF is operational after removal of vials & plugs from the areas.
  • Sanitize the areas as per respective SOP.
  • Based on the risk assessment, additional monitoring of environment and assessment of batch with sterility assurance shall be performed.
  • All modification of the areas shall be performed through change control.
  • In case of minor preventive maintenance, do not touch the open vials.
  • Ensure that no hands should fall above depyrogenated vials and sterile rubber lugs.
  • Sanitize the machine and accessories with 70 % IPA.
  • Record the details on the Batch Manufacturing record.
  • Collect the first filled vials after maintenance for sterility tests.


Annexure -I

                                                                      Approval for area Shut Down



Sr. No. Shut Down Check Points Status
1 Machine parts are cleaned, sanitized and kept in designated areas. Yes/No/NA
2 Vial Washing machine purified water loop (SS external pipe) is disconnected and assembly removed & dried. Yes/No/NA
3 Filter connection removed & dried. Yes/No/NA
4 All dynamic pass boxes are switched off except decartoning pass box. Yes/No/NA
5 All fly O Cide are kept “ON”. Yes/No/NA
6 All garments are removed and kept in designated areas. Yes/No/NA
7 Wash area is cleaned & sanitized. Yes/No/NA
8 All tubes are removed & dried and kept sealed. Yes/No/NA
9 All areas are cleaned, area sanitization & fogging performed in Grade A/B/C/D area respectively. Yes/No/NA
10 All previous disinfectants are discarded. Yes/No/NA
1 PW& WFI jacketed storage tanks empty & loop water is drained out. Yes/No/NA
2 All solutions from tanks are drained and kept dried. Yes/No/NA
3 All water filters are removed and dried. Yes/No/NA
4 MCDP valves are open and drained. Yes/No/NA
5 All AHU of sterile area are shut down as per SOP. Yes/No/NA
6 Boiler steam valve is closed for Cephalosporin Block. Yes/No/NA
7 Compressed air line is closed for Cephalosporin Block. Yes/No/NA
8 Nitrogen line main Header valve is closed. Yes/No/NA






Performed By:     __________________ & ________________________                                                                                                                



Approved By:  ______________________



Annexure -II

Page No.: 1 of 2                                                                                                                                   

Approval for area Start-UP 



  • Plant was completely shut down from ­­­­­­­­­­­­_______________.
  • To perform _____________________________ following action plan followed.
  • AHU, DPB & LAF were continuously ON from _________________.
  • Purified water loop and WFI loop sanitized periodically.
  • Start up activities has been carried out such as cleaning, fogging before start up of the activities.
  • Non viable monitoring performed before start up.
Shut Down Period Start Up  Planned Activity Action Plan
____________ to _____________ __________ onwards ________ 1.     Sanitization of purified water storage and distribution loop was carried out on _________________.

2.     Sanitization of WFI storage and distribution loop was carried out on _________________.

3.     Area cleaning, Disinfection and fogging of the area were adequate and found satisfactory.

4.     Environmental monitoring started from _________________.

5.     pH and Conductivity test results of purified water and WFI was reviewed for the period from ______________ to _____________ and found satisfactory.

6.     Environmental monitoring and microbiological results of Purified water and WFI for _____________ was found satisfactory. Environmental monitoring from ______________ to __________ has been carried out and 1st day results found satisfactory.





Page No.: 2 of 2                                                                                                                                    




Based on the sanitization data, pressure differential and humidity data,

___________ activity can be carried out on _________________.


Department Name Signature/Date
Prepared By Production Injection
Reviewed By Production Injection
Reviewed By Microbiology
Reviewed By Quality Control
Reviewed By Engineering
Reviewed By QA
Approved By QA

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