RISK ASSESSMENT PROTOCOL FOR DEPYROGENATION TUNNEL
To establish documented evidence that the design of in–use “Vial Filling and rubber stoppering Machine” is in compliance with the GMP, Safety and Operational requirements identified in the Risk Assessment document.
In the project content, risk analyses are performed as basic GMP/EHS-Risk Assessment, which shall help to identify important GMP/EHS-requirements.
At the very basic stage of design, the Risk Assessment is to verify that all features are taken into consideration in User Requirement Specification to avoid the risk of failure of critical GMP and EHS parameter in the Filling Machine.
During study, all GMP and EHS parameters will be identified and assessed for the risk if not considered in the design or requirements.
The Risk Assessment report is produced to provide the documented evidence that design concepts or requirement are complete in considering all GMP and EHS risks.
Equipment Name: Filling Machine, Make: NKP, Capacity:
Output Speed
50 ml 40-50 BPM
100 ml 30-40 BPM
250 ml 20-25 BPM
500 ml 10-12 BPM
Pressure: The Filling machine is designed to provide filling machine, which is used, for the process, filling of vials, Network. All these units are briefly described as below. Vial filling & rubber stoppering machine is used for filling & stoppering of Depyrogenated vials.
Filling Machine Description: Automatic six head injectable liquid filling with rubber stoppering machine is designed to fill pre-defined amount of liquid volume into glass Bottles Followed by Stoppering operation.
Bottles are loaded onto the Infeed Turntable. Bottles from the Turntable travels towards filling station by Conveyor to fill pre-defined amount of liquid volume into glass Bottles and moves towards stoppering segment to carried out Stoppering action based upon product requirement. Bottle filling & Rubber Stoppering machine is having following Segments:
- Transport segment
- Filling Segment
- Rubber Stoppering Segment
- Control system
TRANSPORT SEGMENT:
Transport segment comprises of Infeed Turn Table equipped with Guide set, Transfer Conveyor along with guide set, Index star wheel and Outfeed guide set to transfer bottles towards outfeed bottle collection tray.
Infeed turntable feeds bottles towards filling head assembly for filling and same can be transferred for stoppering by means of Index star Wheel which placed after Filling assembly.
Index Star Wheel is programmed to hold & transfer set of 6 bottles towards stoppering station. Filled bottles are moved towards stoppering station by means of conveyor for stoppering based upon product requirement. Full-stoppered bottles are moves towards outfeed bottle collection tray unit. Whole transport segment is equipped with set of sensing devices which act upon functional operation.
FILLING SEGMENT:
Pre-Defined amount of liquid volume is filled into glass bottles by means of Peristaltic pump. Filling segment is consisting of Peristaltic pump, filling needle with pre-nitrogen purging arrangement and manifold to fill Pre-Defined volume of liquid into Bottles.
Liquid filling volume can be adjusted from peristaltic pump.
Filling head is comprising of filling nozzle with pre nitrogen purging arrangement to purge nitrogen of pre-defined volume and pressure before product filling.
Post Purging nozzle is placed before Stoppering to purge nitrogen of defined volume and pressure.
Filling segment is equipped with Set of sensing device, which prevents loss of product in case of no bottle below filling head.
Height of filling head can be adjusted manually based upon bottle height.
Pressure of the Nitrogen is controlled by set of manometers for pre & post Purging station.
RUBBER STOPPERING SEGMENT:
Machine is equipped with mechanical arm type rubber stoppering arrangement with Linear vibrator unit.
Rubber Stoppering segment consist of set of star wheel, Mechanical arm, Rubber stopper bowl and chute with vibrator. Cyst
Filled Bottles are moves towards set of star wheel of stoppering assembly where rubber stopper
from the stopper chute are picked up by arm and placed on glass bottle for Stoppering.
Vibrator frequency can be increased or decreased from the provided Pot.
Height of the Vibrator bowl can be adjusted manually
Rubber Stoppering segment is equipped with Set of Sensing device, set of measuring instruments and monitor the vacuum during process.
CONTROL PANEL:
PLC based control with colour graphics touch screen display for monitoring and control of all machine functions thus providing quick access to the machine parameters.
Speed regulation by means of a frequency control drive.
Tower Light for machine status indication.
Inching button for machine setting.
The operating panel with HMI in S.S. 304 located in front side of the machine.
Separator control module is designed for Peristaltic Pump Controlling. The electrical system is housed in a panel.
All sensing device and set of measuring instruments are controlled by PLC.
SWING CONVEYOR
Function of the conveyor is to transfer the Bottle from one equipment to another set of equipment for further course of action.
Conveyor belt is made from POM and guide assembly with housing is mounted on fixed stand. Conveyor is having Swing Movement for Man-Material Movement into Area where it is placed.
Adjustable guides are provided to set as per diameter of bottle.
Swing conveyor is equipped with Motor, gear box, Variable frequency drive, Speed pot & Actuator for operating purpose.
LAMINAR AIR FLOW
LAF generates a vertical laminar flow stream creating a sterile atmosphere in the process area according to clean- room class 100.
The unit comprises of air filtration system (Set of PRE & HEPA filter) with dynamically balanced and low noise blowers. Unit is equipped with PAO nozzle for HEPA filter integrity testing as well set of instrument to monitor differential pressure across HEPA filter.
Construction of the unit is built in S.S. 304 with provision of actuators to start/stop the LAF with lights to provide illumination inside station.
The LAF unit is supported on the frame made up of S.S. 304 of contamination control cabinet with Toughened glass doors door interlock Sensors.
Process step / influencing factor/ Component:
1.Input & Charging:
Vial size – Equipment not suitable for different size of Vials, Different Vial sizes may not be processed with same equipment – Verification shall be performed at the time of qualification activities
Transport of Vials –
Vials incorrect motion on the transport belt, Infeed guide to tunnel not properly aligned with Vial Washing machine, Vial jamming, Vial rupture, Vial cosmetic damage may take place, Functionality shall be checked at the time of qualification activities, The level of the infeed guide to tunnel shall be at the same level of Vial washing machine out feed.
Abrasion of vials due to attrition with the conveyor side walls, Damage to vials, MOC of the side walls of the conveyor shall be GMP compliant & with smooth surface finish, The suitability of the materials shall be proven by certificate/ manufacturers declarations.
No vials at infeed of tunnel, Tunnel may run without any vials, Downstream equipment functioning may be hampered, the tunnel conveyor should stop in case of minimum load at infeed.
High/ low transport belt speed, Improper Depyrogenation; damage to vials, the control system shall have suitable mechanism to ensure desirable speed is maintained, against set value with feedback of actual speed.
Frequent stopping of tunnel due to no vials at infeed, Depyrogenation process and downstream equipment functioning shall be hampered, Speed synchronization between Vial washing machine and tunnel shall be carried out and proper connectivity should be established and qualified.
Un-dried Vials enter the heating zone of tunnel directly, Vials with moisture when exposed to very high temperature may break, Functionality shall be verified during Execution of qualification studies.
2. Process:
Air Supply (Drying, Depyrogenation & Cooling zone)
Inadequate air quality, Particle laden air may enter chamber and lead to Vial contamination, Monitoring of the nonviable particle concentration in tunnel during qualification.
Choking/ Leakage in HEPA filter, non-uniform air distribution leading to improper depyrogenation , Contamination of Vials due to particle laden air, Integrity test of HEPA filters shall be performed during, Integrity testing shall also be performed at regular intervals as per SOP.
HEPA filter integrity cannot be performed, Integrity checking is a GMP requirement, Functionality shall be verified during Execution of qualification studies.
High temperature in depyrogenation zone may damage HEPA filter or affect its efficiency, Damage to HEPA filter may lead to contamination of Vials, Heater ON/ OFF action shall be interlocked with the operation of blowers to safeguard HEPA filters.
Non-unidirectional air distribution – Unidirectional airflow is requirement for Grade A classification level, Smoke study shall be carried out during qualification to demonstrate unidirectional air flow.
3. Air flow:
Inadequate air flow inside all 3 zones, Improper Vial sterilization & depyrogenation, Functionality shall be verified during execution of qualification studies.
Once through system is installed for all 3 zones i.e. entire supply air from all 3 zones is exhausted out without recirculation, Ineffective heating or Cooling in respective zone, Energy loss, Too much energy shall be consumed in heating or cooling fresh air, Functionality shall be verified during, Execution of qualification studies.
4. Air velocity:
Air velocity not adequate, Air flow will be disturbed; Unidirectional air flow shall not be maintained up to conveyor level, Adequate air velocity shall be maintained below the HEPA filters in all 3 zones, so as to maintain unidirectional air, Verification of air velocity performed during qualification.
5. Conveying:
Conveyor belt speed low/ high, Improper residence time affects the validated depyrogenation cycle, Verification of accuracy of conveyor speed during qualification.