MANAGEMENT OF ASEPTIC AREA AFTER POWER RESUME

MANAGEMENT OF ASEPTIC AREA AFTER POWER RESUMES     

PURPOSE: To establish a written procedure for the management of the filling area after power resumes.

SCOPE: This SOP shall be applicable for the management of filling area after power resumes.

REFERENCE(S) : WHO-TRS 961 (annexure: 1) & FDA and schedule M

CROSS-REFERENCE DOCUMENTS

•  Document(s) and Data Control Procedure
• Training Program for Employees
• Change Control Management
•  Preparation, review, approval, issuance & retrieval of standard operating procedure (sops)

CIP & SIP of manufacturing tank, holding tank, product line, filter assembly & FFS Machine

Cleaning & sanitization of classified/clean area

DEFINITIONS

Aseptic Area is a room or special area within the clean room designed, constructed, serviced & used to prevent microbial contamination of the product during production because it can’t support the growth of micro-organisms.

Current Good Manufacturing Practices (cGMPs): cGMPs provide for systems that assure proper design, monitoring, and control of manufacturing processes and facilities. Adherence to the cGMP regulations assures the identity, strength, quality, and purity of drug products by requiring that manufacturers of medications adequately control manufacturing operations.

ABBREVIATIONS

SVP:           Small Volume Parenteral

NA:           Not Applicable

BET:           Bacterial Endotoxin Test

SFS:           Sterile Filter Space

AHU:           Air Handling Unit

FFS:           Form Fill Seal

UPS:           Uninterrupted Power Supply

HMI:           Human Machine Interface

PLC:           Programmable Logic Control

IPA:           Isopropyl Alcohol

SIP:           Sterilization In Place

RESPONSIBILITY

The production department shall be responsible:

Initiating, preparation, review, and revision of the SOPs.

To clean & sanitation the area after power failure.

To follow the described herein SOP.

To maintain the breakdown record in the log book & BMR.

Coordinate with the engineering person regarding utilities.

To raise the incident of machine break down.

To impart in the training to maintain the clean area.

The head of the production department shall be responsible for:

Checking of the SOP for procedural, technical content, accuracy, and cGMP compliance.

To get the SOP approval from the Head of Quality Assurance or designee.

To provide training on SOP to the concerned personnel for maintenance of clean area.

To co-ordinate with engineering person for utilities & AHU failure.

To verify the breakdown record.

To ensure the compliance of SOP.

The Quality Assurance department shall be responsible for:

To check the draft SOP from technical, function, regulatory, and cGMP compliance prospective.

 To maintain the approved master copy of the SOP of all departments for document control.

To verify the area during power failure & after power resumes.

To verify the breakdown records.

To verify that all the instructions are followed properly as per the given SOP.

To ensure implementation of SOP.

To withdraw the sample & transfer it to QC.

To provide the line clearance after power resumes.

To verify the reason for the breakdown.

Head – Quality Assurance/ Designee shall be responsible for:

To approve new or revised SOP.

To verify that employees are trained to perform in clean areas.

To co-ordinate with other departments for the breakdown of incidents.

To justify the system.

To provide a final decision for the release of the product.

The engineering person shall be responsible for:

Coordinate with production person for break down.

To start the AHU & utilities.

To make an investigation of break down.

 Plant Head shall be responsible for:

To approve new or revised SOP.

To ensure the implementation of the defined system.

PROCEDURE:

SAFETY/PRECAUTION/EHS

Before entry in the filling area follow the entry exit SOP to avoid cross-contamination in the area.

During power failure don’t do any activity in the machine to avoid any mis- happening.

Follow the safety rules as per the respective SOP.

The first aid box should be kept in the production department.

ASEPTIC AREA MANAGEMENT

To maintain the aseptic area/filling area AHU system of the area should be continuously run & all the doors of the concerned area should be properly closed & positive pressure to be maintained in the area, so that outside lower class air cannot ingress into the area.

Cleaning & disinfection are to be performed at regular intervals to reduce the particles & microbial load in the aseptic area (manufacturing & filling area).

Proper gowning is to be worn during entry aseptic area & follow the clean area Behavior rule as per SOP

During processing activity in manufacturing & filling, if randomly AHU system stops due to any breakdown or power failure, the aseptic area will be contaminated due to increasing non-viable & viable particle load & product sterility can also be affected.

There are certain steps to be followed to recover the sterile/aseptic area after power failure.

IF POWER FAILS FOR LESS THAN 2 MINUTES

When power fails during processing for less than 2 minutes do not move from your places and don’t open the door of any of the rooms until power resumes.

As the power resumes, the first engineering person starts AHU of the higher class area (filling & manufacturing room) immediately & the sterile area person will wait for 15 minutes to start the activity again until the area recovers & positive pressure is attained.

Engineering persons should be trained to operate the AHU system of the most critical area or higher class first followed by the lesser class.

SFS/LFR of the FFS machine should be on the UPS supply for continuous operation during power failure also so that the filling zone should not be contaminated.

This power failure should also be covered in the process simulation study.

As the power resumes after 2 minutes of filling or manufacturing area person will sanitize

their hands with IPA 70% v/v solution & will start further remaining activity like filling or manufacturing.

IF POWER FAILURE FOR UP TO 5 MINUTES

When power failure up to 5 minutes during manufacturing & filling process time.

Immediately the ampoules exit the dynamic pass box (if open for ampoule collection outside) & don’t move from your place & don’t open the door of the manufacturing & filling room.

Wait until power resumes & as power resumes within 5 minutes first trained engineering person will start the AHU of the most critical area (filling room & manufacturing room) & then one by one start of lesser critical areas.

The sterile area person will wait for 15 minutes to maintain the positive pressure & area recovery.

As the area recovered all working person in the clean area manufacturing & filling room will sanitize their hands with IPA 70% v/v solution.

SFS/LFR of FFS machine should be on UPS supply for continuous operation during power failure also, so that the filling zone should not be contaminated.

 Spray IPA 70% v/v solution in all manufacturing & filling areas.

Start the filling & manufacturing activity.

IF POWER FAILURE OR AHU BREAK DOWN FROM 5 MINUTES TO 30 MINUTES

If power failure for more than 5 minutes & below 30 minutes close filled ampoules exit the pass box door & wait for 5 minutes for power to resume.

If the power doesn’t resume within time switch off the PLC/HMI of the machine, close all utility valves & come out from them manufacturing & filling room & sit in the exit air lock until power resumes.

As the power resumes wait for maintaining differential pressure, temperature & humidity of the area.

Clean & sanitize the area with scheduled disinfectant solution as per SOP

Sanitize the filling machine from the outside & conveyor belt with IPA 70% v/v solution.

Replace the gloves with new sterile gloves & sanitize with IPA 70% v/v solution.

Start the filling machine & all utilities & discard the initial 10 strokes of filling & run the filling.

IF POWER FAILURE OR AHU BREAK DOWN FOR MORE THAN 30 MINUTES & LESS THAN 4 HOURS

 If power failure for more than 30 minutes immediately close the filled ampoule exit pass box door.

If the power doesn’t resume within time switch off the PLC/HMI of a machine, close all utility valves,.

Close the manufacturing & holding tank tightly & assemble the mental hood on filling nozzles.

Close the solution transfer diaphragm valve of the transfer pump & tank.

Come out from the manufacturing & filling room & sit in the production office.

As the power resumes wait to maintain differential pressure, temperature & humidity of the area.

Clean & sanitize the area with scheduled disinfectant solution as per SOP

Sanitize the machine properly with IPA 70% v/v solution.

Change the gowning with another sterile gowning & replace the gloves & sanitize with IPA 70% v/v solution.

Fill the incident & CAPA & send the bulk sample from holding tank for BET and bioBurden & start machine SFS/LFR to maintain the filling zone class.

After release from BET, remove the mendral hood from filling nozzles & switch “ON” all utilities.

Separate out all initial filled units considering lot A.

Start filling machine & discard initial 15 strokes from the filling machine & collect the filled unit separately by indicating label lot B & separate finish product sample will be drawn from lot B for finish product analysis.

IF POWER FAILURE OR AHU BREAK DOWN FOR MORE THAN 4 HOURS

If power failure more than 4 hours follow the above steps

Make SIP of filling machine as per SOP

Separate out all initial filled units considering lot A.

After SIP start filling machine & discard initial 15 strokes from the filling machine & collect the filled unit separately by indicating label lot B & separate finish product sample will be drawn from lot B for finish product analysis.