• Author / Uploaded
• venki_bee

Citation preview

Operational Qualification Protocol for the Capsule Filling Machine Protocol No. EQNational Institute of Health Operational Qualification Protocol Equipment:

Protocol #:

Date:

Capsule Filling Machine

Facility: National Institute of Health

16 March, 2010

Location: Building 10 Room 1N249 Bethesda, MD 20892

Revision: Original

Title: Operational Qualification Protocol for the Capsule Filling Machine. Objective: The objective of this protocol is to document the satisfactory operation of the Capsule Filling Machine used for manufacturing at National Institute of Health Written By: Michael Molloy Title: Consultant

Approved By: ______________________ Title: _____________________________

Signature: Signature: Date: Date: Approved By: ______________________

Approved By: ______________________

Title: _____________________________

Title: _____________________________

Signature:

Signature:

Date:

Date:

Approved By: ______________________

Quality Assurance Approved By: ______________________

Title: _____________________________

Title: _____________________________

Signature:

Signature:

Date:

Date:

Qualification Process Solutions, Inc. DOCUMENT NUMBER REVISION NUMBER 1

PROPRIETARY INFORMATION: Unauthorized Duplication Is Prohibited DATE: 3/16/10

Author: Michael Molloy ______________________

PAGE: 1 of 36

Revision DATE: N/A

Operational Qualification EQUIPMENT NAME: Capsule Filling Machine

OPERATIONAL QUALIFICATION FOR THE

Capsule Filling Machine INSTALLED AT

NATIONAL INSTITUTE OF HEALTH BUILDING 10 ROOM 1N249 BETHESDA, MD 20892

QUALIFICATION PROCESS SOLUTIONS 13406 BLYTHENIA RD PHOENIX, MD 21131

DOC. # OPERATIONAL QUALIFICATION PROTOCOL Capsule Filling Machine National Institute of Health, Building 10 Room 1n249 Bethesda MD 20892

Page 2 of 36

TABLE OF CONTENTS 16 March, 2010....................................................................................................................................................2 Quality Assurance...................................................................................................................................2 1.0Purpose..............................................................................................................................................3 2.0Scope..................................................................................................................................................3 3.0Equipment Description.......................................................................................................................3 4.0Responsibilities..................................................................................................................................4 5.0Reference Documents........................................................................................................................4 6.0Definitions.........................................................................................................................................5 7.0Test Function Number One: OQ Signature Verification List (Attachment #1).................................5 8.0Test Function Number Two: Test Equipment (Attachment #2).........................................................5 9.0Test Function Number Three: Procedure List (Attachment #3).........................................................6 10.0Test Function Number Four: Training Verification (Attachment #4)..............................................6 11.0Test Function Number Five: Operator Controls and Indicators (Attachment #5)............................6 12.0Test Function Number Six: Functional Verification (Attachment #6).............................................7 13.0Test Function Number Seven: Alarms, Safeties and Interlocks (Attachment #7)............................7 14.0Test Function Number Eight: Sequence of Operations (Attachment #8).........................................7 15.0Test Function Number Nine: Maximum / Minimum Values (Attachment #9)................................7 16.0Deviation Reporting Log (Attachment #10).....................................................................................8 17.0Operational Qualification Protocol Review (Attachment #11).........................................................8 18.0Summary Report Requirements ......................................................................................................8 19.0Attachment List .............................................................................................................................10 Attachment #1 OQ Signature Verification List.....................................................................................11 Attachment #2 Test Equipment.............................................................................................................12 Attachment #3 Procedure List...............................................................................................................13 Attachment #4 Training Verification...................................................................................................14 Attachment #5 Operator Controls and Indicators.................................................................................15 Attachment #6 Functional Verification.................................................................................................19 Attachment #6 Functional Verification.................................................................................................20 Attachment #6 Functional Verification.................................................................................................21 Attachment #6 Functional Verification.................................................................................................22 Attachment #6 Functional Verification.................................................................................................23 Attachment #7 Alarms, Safeties and Interlocks.....................................................................................25 Attachment #8 Sequence of Operation..................................................................................................31 Attachment #8 Sequence of Operation..................................................................................................32 Attachment #9 Maximum / Minimum Values.......................................................................................33 Attachment #10 Deviation Reporting Log............................................................................................34 Attachment #11 Operational Qualification Protocol Review................................................................36

DOC. # OPERATIONAL QUALIFICATION PROTOCOL Capsule Filling Machine National Institute of Health, Building 10 Room 1n249 Bethesda MD 20892

Page 3 of 36 1.0

Purpose The objective of this protocol is to verify that the Capsule Filling Machine, described in Section 3.0, operates in accordance to manufacturers’ specification, and in accordance with Current Good Manufacturing Practices (cGMP’s).

2.0

Scope This Operational Qualification pertains to the verification of the operation of the equipment described in Section 3.0 of this protocol installed in the National Institute of Health, Building 10 room 1N249, Bethesda MD, 20892. This protocol is specific to the Capsule Filling Machine and related instrumentation and equipment. This protocol is specific to the Capsule Filling System, and related instrumentation and equipment, and does not address other facility, or facility related equipment and systems.

3.0

Equipment Description The Capsule Filling Machine (Model : Zanasi 6F serial 35XXX) is a hard gelatine capsule filler, which is designed for filling liquids, powders, granular product, pellets and tablets. The filler is designed to accommodate capsules size 0,1,2,3 and 4. The output of the filler is adjustable with a maximum production rate of 6000-6120 capsules/hr dependant upon process selection. The filler is an alternate movement capsule filling machine provided with a rotary stage that provides clockwise axis centered slip stick motion to transport capsules thru 8 process stages. The stages are: 1) 2) 3) 4) 5) 6) 7) 8)

Capsule feed (w/relative automatic selection via optional unit) Capsule orientation , positioning and opening (equipped w/ 8 stages) Capsule separation pre-filling Capsule product filling Unopened capsule selection (Automatic) Capsule alignment and closure Capsule ejection Capsule selection (automatic empty and partial fill segregation)

The capsule filling machine is comprised of the following major elements: 1) 2) 3) 4) 5) 6) 7) 8) 9) 10) 11) 12) 13)

Base Motorization Moving Parts Protective hood Electric cabinet and control panel Size-change parts for process changeover Manual controls Powder feed unit Powder layer and leveling control Pellet or tablet dosing unit Powder or pellet dosing unit Defective capsule selection unit Capsule closing unit

DOC. # OPERATIONAL QUALIFICATION PROTOCOL Capsule Filling Machine National Institute of Health, Building 10 Room 1n249 Bethesda MD 20892

Page 4 of 36 14) 15) 16) 17) 18)

Capsule selection unit Liquid dosing unit Central stage Emergency stop push button Electric extension plug

The following general parameters apply to the Zanasi 6F 1) 2) 3) 4) 4.0

5.0

Dimension: 2000mm W x 1670 mm H x 2140 mm L Weight 1050 kg Power 480 V – 1.5 kw Air

Responsibilities 4.1

Qualification Process Solutions, LLC. 4.1.1 It is the responsibility of QPS to write this protocol. 4.1.2 It is the responsibility of QPS to execute this protocol.

4.2

National Institutes of Health (SI) 4.2.1 Following the execution, NIH will approve the final report associated with this protocol, indicating the executed protocol was completed correctly and all acceptance criteria were met.

Reference Documents 5.1 5.2 5.3 5.4 5.5 5.6 5.7 5.8 5.9 5.10 5.11 5.12 5.13 5.14 5.15 5.16 5.17 5.18 5.19 5.20 5.21 5.22

Drawing: Drawing: Drawing: Drawing: Drawing: Drawing: Drawing: Drawing: Drawing: Drawing: Drawing: Drawing: Drawing: Drawing: Drawing: Drawing: Drawing: Drawing: Drawing: Drawing: Drawing: Drawing:

400024-00 4400d010-37 4401d011-28 4402d012-11 4403d013-15 4404d014-05 4405d015-11 4407d017-01 4408d018-07 4409d019-11 4410d020-11 4411d021-11 4005d002-03 4002d004-07 4004d004-05 4008d004-05 4009d004-11 4402d028-03 4410d090-12 4005d141-06 4005d142-06 4005d143-06

Capsule Filling Machine Assembly Base Machine Kinematic Motion Unit Powder Unit Manual Return Unit Plate Unit Capsule Feeding and Opening Unit Powder Feeding Unit Compression/Powder Ejection Unit Reject Sorting Unit and Closing Counterplate Capsule Ejection Unit Cleaning Unit Components Added to Basic Machine Components Added to Basic Machine Components Added to Basic Machine Components Added to Basic Machine Components Added to Basic Machine Components Added to Rotary Tank Capsule Chute without SPC Powder/Pellet Capsule Equipment Unit F1 Powder/Pellet Capsule Equipment Unit F2 Powder/Pellet Capsule Equipment Unit F3

DOC. # OPERATIONAL QUALIFICATION PROTOCOL Capsule Filling Machine National Institute of Health, Building 10 Room 1n249 Bethesda MD 20892

Page 5 of 36 5.23 5.24 5.25 5.26 5.27 5.28 5.29 5.30 5.31 5.32 5.33 5.34 5.35 5.36 5.37

6.0

7.0

Definitions 6.1

Critical Instrumentation – Critical instruments are defined as those whose performance will affect the operation of the system and/or the quality attributes of the processed materials. Critical instruments are calibrated and certified using standards that are traceable to NIST (National Institutes of Standards and Testing).

6.2

Non-Critical Instrumentation – Instrumentation provided for indication or convenience purposes only.

Test Function Number One: OQ Signature Verification List (Attachment #1) 7.1 7.2 7.3

8.0

Drawing: 4005d144-06 Powder/Pellet Capsule Equipment Unit F4 Drawing: 4005d146-06 Powder/Pellet Capsule Equipment Unit F0 Drawing: 4019d151-03 Powder Dosing Equipment F1 Drawing: 4019d152-03 Powder Dosing Equipment F2 Drawing: 4019d153-03 Powder Dosing Equipment F3 Drawing: 4019d154-03 Powder Dosing Equipment F4 Drawing: 4019d156-03 Powder Dosing Equipment F0 Drawing: 4440d363-02 Added Components without Weight Unit Drawing: 4428d364-37 Safety Hood Drawing: IE 44.68 Electrical Schematic Document: IE 44.68 Electrical Spare Part List Document: F-S22V1 Program Listing Drawing: 440C033 Compressed Air Plant Drawing: 440C039-01 Aspiration Air Plant Document: 35071M04 Installation & Operation Manual for the Capsule Filling Machine including: Maintenance Safety Notices CE Conformity Documents Test Reports and Equipment Certs

Objective To identify and document all personnel involved in executing this protocol. Procedure Verify that each person who executes this protocol signs Attachment #1. Each person must be identified by name, title, company, signature, initials and date on the attached form. Acceptance Criteria Signatures from all personnel involved in execution of this protocol shall be present.

Test Function Number Two: Test Equipment (Attachment #2) 8.1 8.2

Objective To verify and document all test equipment Procedure 8.2.1 Complete a list of all the instruments required for conducting OQ testing.

DOC. # OPERATIONAL QUALIFICATION PROTOCOL Capsule Filling Machine National Institute of Health, Building 10 Room 1n249 Bethesda MD 20892

Page 6 of 36 8.2.2

8.3

9.0

Test Function Number Three: Procedure List (Attachment #3) 9.1 9.2

9.3 10.0

Objective To verify the operating Standard Operating Procedures (SOP’s) provide adequate direction and control over the operation of the equipment. Procedure 9.2.1 Verify that the operational SOP provides personnel adequate direction and control over the operation of the equipment. (The SOP’s used for execution may be in draft form.) 9.2.2 Complete the applicable attachment with a list of all applicable SOP’s. 9.2.3 Redline the SOP’s with an operator and validation personnel. Attach the redline copy to this qualification protocol. Acceptance Criteria All associated SOP’s for operation and execution shall be reviewed and documented.

Test Function Number Four: Training Verification (Attachment #4) 10.1 10.2

10.3

11.0

Verify that the test equipment/instruments are calibrated and the reference standards are traceable to National Institute for Standards and Technology (NIST) or other approved standard. 8.2.3 Complete the applicable attachment, indicating the equipment description, ID/serial number, calibration date, re-calibration date Acceptance Criteria All equipment required for execution shall be calibrated with copies of calibration records attached.

Objective To document applicable personnel have received the required training for operation of the equipment. Procedure 10.2.1 Document all personnel executing this protocol that have been trained on the approved/draft SOP for the equipment. 10.2.2 List all SOP’s used during the execution of this protocol 10.2.3 Complete required training forms in accordance with NIH’s training requirements. Acceptance Criteria Training shall be performed on all SOP’s used during the execution of this qualification protocol.

Test Function Number Five: Operator Controls and Indicators (Attachment #5) 11.1 11.2

11.3

Objective To verify the controls and indicators operate as specified by manufacturer recommendations. Procedure 11.2.1 Manually operate the control switches listed in the applicable attachment. 11.2.2 Visually verify and document the actual responses. 11.2.3 Document any discrepancies in Attachment #10, Deviation Reporting Log. If any variances/deviations are present, complete the appropriate deviation/variance form. Acceptance Criteria All operator controls and indicators tested shall conform to the expected response.

DOC. # OPERATIONAL QUALIFICATION PROTOCOL Capsule Filling Machine National Institute of Health, Building 10 Room 1n249 Bethesda MD 20892

Page 7 of 36

12.0

Test Function Number Six: Functional Verification (Attachment #6) 12.1 12.2

12.3 13.0

Test Function Number Seven: Alarms, Safeties and Interlocks (Attachment #7) 13.1 13.2

13.3 14.0

Objective To verify and document the operation and functionality of the alarms, safeties and interlocks. Procedure 13.2.1 Follow the procedures in the applicable attachments. 13.2.2 Visually verify and document the actual responses as pass or fail against the expected results. 13.2.3 Document all operational parameters used during execution. 13.2.4 Document any discrepancies in Attachment #10, Deviation Reporting Log. If any variances/deviations are present, complete the appropriate deviation/variance form. Acceptance Criteria All safeties and interlock requirements must conform to the expected responses.

Test Function Number Eight: Sequence of Operations (Attachment #8) 14.1 14.2

14.3 15.0

Objective To verify and document the operation and functionality of the equipment. Procedure 12.2.1 Follow the procedures in the applicable attachments. 12.2.2 Visually verify and document the actual responses as pass or fail against the expected results. 12.2.3 Document all operational parameters used during execution. 12.2.4 Document any discrepancies in Attachment #10, Deviation Reporting Log. If any variances/deviations are present, complete the appropriate deviation/variance form. Acceptance Criteria All functional requirements must conform to the expected responses.

Objective To verify and document the operational sequence of the system. Procedure 14.2.1 Execute the procedures in the order listed. 14.2.2 Observe the expected operations and write “Pass” if the results were as expected, and “Fail” if the expected operation did not take place. 14.2.3 Document any discrepancies in Attachment #10, Deviation Reporting Log. If any variances/deviations are present, complete the appropriate deviation/variance form. Acceptance Criteria The operating sequence occurs as expected.

Test Function Number Nine: Maximum / Minimum Values (Attachment #9) 15.1 15.2

Objective To verify the maximum and minimum allowable values of changeable setpoints. Procedure

DOC. # OPERATIONAL QUALIFICATION PROTOCOL Capsule Filling Machine National Institute of Health, Building 10 Room 1n249 Bethesda MD 20892

Page 8 of 36

15.3 16.0

17.0

Deviation Reporting Log (Attachment #10) 16.1

Objective: To document any deviation to the stated test procedure or acceptance criteria, and to evaluate the deviation relative to acceptability of the qualification study.

16.2

Procedure: 16.2.1 Document all deviations found during execution using the Deviation Report Form that is with the Deviation Reporting Log. Make copies of the form for each logged Deviation. 16.2.2 Deviations caused by Out of Specification (OOS) Conditions. If during the evaluation of equipment parameters against specifications, the equipment fails to meet predetermined acceptance criteria, a formal deviation report investigates the cause. In these cases, the cause must be known prior to continuing the protocol execution since a true failure in equipment performance is likely to affect the completion of the protocol. The protocol deviation report determines 1) if the acceptance criteria are correct and current with user requirements and manufacturer's ratings, or 2) if there is an immediate and obvious explanation for the failure. If a true failure is documented, then appropriate root cause analysis and corrective actions ensue and are agreed to between the protocol executors and the department owners and QA. The protocol deviation report documents the conclusion to this investigation and any appropriate retesting and an impact assessment on the portions of the protocol executed prior to the documented failure. 16.2.3 Completed Deviation Report Forms are submitted to QA for signature acceptance.

Operational Qualification Protocol Review (Attachment #11) 17.1 17.2

18.0

15.2.1 Display the changeable setpoint on the applicable attachment and test maximum and minimum values. 15.2.2 Visually verify and document the actual results of the functions that appear on the operator interface. 15.2.3 Document any discrepancies in Attachment #10, Deviation Reporting Log. If any variances/deviations are present, complete the appropriate deviation/variance form. Acceptance Criteria The actual results of the changeable setpoint limits shall conform to the expected responses.

Objective To document that this protocol has been reviewed for completeness as per Qualification Process Solutions, LLC Requirements. Procedure Complete attachment with name, title, signature and date.

Summary Report Requirements 18.1 18.2

Objective To provide an overview of the test results during the execution of this operational qualification. Procedure 18.2.1 Generate a final summary on completion of this protocol execution. 18.2.1.1 Compile a summary of the results obtained.

DOC. # OPERATIONAL QUALIFICATION PROTOCOL Capsule Filling Machine National Institute of Health, Building 10 Room 1n249 Bethesda MD 20892

Page 9 of 36 18.2.1.2

Generate a conclusion, based on these results, of the acceptability of the qualification results. 18.2.1.3 Include a statement of conformance to the specified acceptance criteria, evaluated in conjunction with the approved deviations and corrective actions taken. 18.2.1.4 Determination of acceptability of the protocol, as executed. 18.2.2 Attach the completed, executed and approved protocol to the final report. 18.2.3 Attached copies of all completed, approved Deviation Report and Corrective Action Forms, where necessary.

DOC. # OPERATIONAL QUALIFICATION PROTOCOL Capsule Filling Machine National Institute of Health, Building 10 Room 1n249 Bethesda MD 20892

Page 10 of 36 19.0

Attachment List

16 March, 2010....................................................................................................................................................2 Quality Assurance...................................................................................................................................2 1.0Purpose..............................................................................................................................................3 2.0Scope..................................................................................................................................................3 3.0Equipment Description.......................................................................................................................3 4.0Responsibilities..................................................................................................................................4 5.0Reference Documents........................................................................................................................4 6.0Definitions.........................................................................................................................................5 7.0Test Function Number One: OQ Signature Verification List (Attachment #1).................................5 8.0Test Function Number Two: Test Equipment (Attachment #2).........................................................5 9.0Test Function Number Three: Procedure List (Attachment #3).........................................................6 10.0Test Function Number Four: Training Verification (Attachment #4)..............................................6 11.0Test Function Number Five: Operator Controls and Indicators (Attachment #5)............................6 12.0Test Function Number Six: Functional Verification (Attachment #6).............................................7 13.0Test Function Number Seven: Alarms, Safeties and Interlocks (Attachment #7)............................7 14.0Test Function Number Eight: Sequence of Operations (Attachment #8).........................................7 15.0Test Function Number Nine: Maximum / Minimum Values (Attachment #9)................................7 16.0Deviation Reporting Log (Attachment #10).....................................................................................8 17.0Operational Qualification Protocol Review (Attachment #11).........................................................8 18.0Summary Report Requirements ......................................................................................................8 19.0Attachment List .............................................................................................................................10 Attachment #1 OQ Signature Verification List.....................................................................................11 Attachment #2 Test Equipment.............................................................................................................12 Attachment #3 Procedure List...............................................................................................................13 Attachment #4 Training Verification...................................................................................................14 Attachment #5 Operator Controls and Indicators.................................................................................15 Attachment #6 Functional Verification.................................................................................................19 Attachment #6 Functional Verification.................................................................................................20 Attachment #6 Functional Verification.................................................................................................21 Attachment #6 Functional Verification.................................................................................................22 Attachment #6 Functional Verification.................................................................................................23 Attachment #7 Alarms, Safeties and Interlocks.....................................................................................25 Attachment #8 Sequence of Operation..................................................................................................31 Attachment #8 Sequence of Operation..................................................................................................32 Attachment #9 Maximum / Minimum Values.......................................................................................33 Attachment #10 Deviation Reporting Log............................................................................................34 Attachment #11 Operational Qualification Protocol Review................................................................36

DOC. # OPERATIONAL QUALIFICATION PROTOCOL Capsule Filling Machine National Institute of Health, Building 10 Room 1n249 Bethesda MD 20892

Page 11 of 36 Attachment #1 OQ Signature Verification List This section identifies the personnel conducting the Operational Qualification. Each person who will be executing this protocol shall complete an entry on the page. Print Name

Title

Department/ Company Name

Signature

Initials

Date

Comments: ________________________________________________________________________ __________________________________________________________________________________ __________________________________________________________________________________ __________________________________________________________________________________ Acceptance Criteria: Signatures from all personnel involved in execution of this protocol shall be present. Meets Acceptance Criteria? ( ) Yes ( ) No Reviewed by: __________________________________

Date: __________

DOC. # OPERATIONAL QUALIFICATION PROTOCOL Capsule Filling Machine National Institute of Health, Building 10 Room 1n249 Bethesda MD 20892

Page 12 of 36 Attachment #2 Test Equipment This attachment identifies the instruments, equipment, and materials that are not part of the equipment or system being qualified, but are used in this qualification. Equipment Description

Manufacturer

ID#

Serial #

Certified/ Calibrated

Cal. Date

Cal Due Date

Initials/ Date

Yes/No Yes/No Yes/No Yes/No Yes/No Yes/No Yes/No Yes/No Yes/No

Comments: ______________________________________________________________________________ _______________________________________________________________________________________ _______________________________________________________________________________________ _______________________________________________________________________________________ Acceptance Criteria: All test equipment required for execution shall be calibrated with copies of calibration records attached. Meets Acceptance Criteria? ( ) Yes ( ) No Reviewed by: _____________________________________

Date: __________

DOC. # OPERATIONAL QUALIFICATION PROTOCOL Capsule Filling Machine National Institute of Health, Building 10 Room 1n249 Bethesda MD 20892

Page 13 of 36 Attachment #3 Procedure List List the Standard Operating Procedures (SOP) that are required for execution of this protocol. SOP Number

SOP Revision #

Effective Date

Procedure Title

Original

Operation of the Capsule Filling Machine

Original

Maintenance of the Capsule Filling Machine

Initials/Date

Comments: ________________________________________________________________________ __________________________________________________________________________________ __________________________________________________________________________________ __________________________________________________________________________________ Acceptance Criteria: A list of written procedures that are used to operate the equipment is provided above. If procedures are in draft form, attach a copy to the executed protocol. Meets Acceptance Criteria? ( ) Yes ( ) No Reviewed by: __________________________________

Date: __________

DOC. # OPERATIONAL QUALIFICATION PROTOCOL Capsule Filling Machine National Institute of Health, Building 10 Room 1n249 Bethesda MD 20892

Page 14 of 36 Attachment #4 Training Verification List the Standard Operating Procedures (SOP) used to train personnel for operating the equipment. SOP #

Procedure Title Operation of the Capsule Filling Machine Maintenance of the Capsule Filling Machine

Training Documented (Y/N)

Initials/Date

Yes/No Yes/No

Comments: ________________________________________________________________________ __________________________________________________________________________________ __________________________________________________________________________________ __________________________________________________________________________________ Acceptance Criteria: A list of written procedures that are used to train personnel to operate the equipment is provided above. Meets Acceptance Criteria? ( ) Yes ( ) No Reviewed by: __________________________________

Date: __________

DOC. # OPERATIONAL QUALIFICATION PROTOCOL Capsule Filling Machine National Institute of Health, Building 10 Room 1n249 Bethesda MD 20892

Page 15 of 36 Attachment #5 Operator Controls and Indicators Press the control keys to verify that the equipment/system operations function as indicated. Note: document any failing results. Device

Expected Results

Actual Results

Pass/Fail

CONTROL PANEL SWITCHES and INDICATORS Emergency Stop Button. Control Panel

Places equipment in safe mode when pressed. Red

LED A.C. Power On

Indicates AC Power is on. LED Green.

LED Feed Logic Control LED Breakers Tripped LED Handwheel Engaged LED No Compressed Air Vacuum Pump Off Pushbutton. Vacuum Pump Engaged Lamp Vacuum Pump On Pushbutton. LED No Powder LED No Capsules LED No Pellets Machine Motor Speed Reg. Potentiometer.

Indicates Feed Logic is enabled. LED Green Indicates breakers have tripped. LED Red Indicates manual hand wheel is engaged. LED Red Indicates compressed air is not available. LED Red Shuts down vacuum pump when pressed. Red Indicates vacuum pump is operating. Lamp Green Starts vacuum pump when pressed. Indicates no powder. LED Red Indicates no capsules LED Red Indicates no Pellets LED Red Rotating clockwise /counterclockwise increases/decreases motor speed

_________ equipment in safe mode when pressed. Red Indicates AC Power ________ on. LED Green. Indicates Feed Logic ________ enabled. LED Green Indicates breakers ________ tripped. LED Red Indicates manual hand wheel _________ engaged. LED Red Indicates compressed air ____________ available. LED Red ___________ down vacuum pump when pressed. Red Indicates vacuum pump __________ operating. Lamp Green _________ vacuum pump when pressed. _________ no powder. LED Red _________ no capsules LED Red _________ no Pellets LED Red Rotating clockwise /counterclockwise __________/ __________ motor speed

Pass/Fail Pass/Fail Pass/Fail Pass/Fail Pass/Fail Pass/Fail Pass/Fail

Pass/Fail Pass/Fail Pass/Fail Pass/Fail Pass/Fail

Pass/Fail

Initials/Date

DOC. # OPERATIONAL QUALIFICATION PROTOCOL Capsule Filling Machine National Institute of Health, Building 10 Room 1n249 Bethesda MD 20892

Page 16 of 36

Indicates powder mixer on. LED Green

__________ the machine normally. Red ____________ the machine normally ___________ machine operating. Lamp Green ___________ no tablets LED Red __________ powder mixer is selected. LED Green __________ either Manual or Auto Control _________ powder mixer on. LED Green

Powder Loading Enable Selector

Enables Powder Loading

____________ Powder Loading

LED Max. Jog Runtime

Indicates JOG has exceeded Runtime. LED Red

LED Tablet Unit Enabled

Indicates Tablet Unit Enabled. LED Green.

Indicates JOG _________exceeded Runtime. LED Red ____________ Tablet Unit Enabled. LED Green.

Tablet Unit Enable Selector

Enables Tablet Selector

____________ Tablet Selector

Pass/Fail

Production Counter

Displays production counts

____________ production counts

Pass/Fail

Hour Counter

Logs run time when machine is operating.

Hour Counter

Logs run time when machine is operating.

Hourly Production Counter

Logs run time when machine is operating

Machine Stop Pushbutton

Stops the machine normally. Red

Machine Start Pushbutton

Starts the machine normally Indicates machine operating. Lamp Green Indicates no tablets LED Red Indicates powder mixer is selected. LED Green

Lamp Machine Running LED No Tablets LED Powder Mixer (MAN/AUTO) On Powder Mixer MAN/AUTO Selector LED Powder Mixer Enabled

Selects either Manual or Auto Control

___________ run time when machine is operating. ___________ run time when machine is operating. ______________ run time when machine is operating

Pass/Fail Pass/Fail Pass/Fail Pass/Fail Pass/Fail Pass/Fail Pass/Fail Pass/Fail

Pass/Fail

Pass/Fail

Pass/Fail

Pass/Fail

Pass/Fail

DOC. # OPERATIONAL QUALIFICATION PROTOCOL Capsule Filling Machine National Institute of Health, Building 10 Room 1n249 Bethesda MD 20892

Page 17 of 36

Hour Counter

Logs run time when machine is operating.

______________ run time when machine is operating.

Pass/Fail

Engage/Disengage Guards Selector

Engages / disengages guards

_____________ / _____________ guards

Pass/Fail

Guards Disengaged LED

Guards disabled LED Red

Guards ___________ LED Red

Pass/Fail

REAR PANEL SWITCHES and INDICATORS Emergency Stop Button. Machine rear panel

Places equipment in safe mode when pressed.

Manual Control Handwheel

Engages/Disengages Mechanical Components

_____________ equipment in safe mode when pressed. _____________/ _____________ Mechanical Components

Pass/Fail

Pass/Fail

SIDE PANEL SWITCHES and INDICATORS Reset Capsules Produced

Resets the capsule counter

___________ the capsule counter

Pass/Fail

ELECTRICAL PANEL (Inside Door) SWITCHES and INDICATORS Vacuum Bowl ON/OFF Selector

Enable/disable Vacuum Bowl

Pellet Unit 1 ON/OFF

Enable/disable Pellet Unit 1

Pellet Unit 2 ON/OFF

Enable/disable Pellet Unit 2

_____________/ _____________ Vacuum Bowl _____________/ _____________ Pellet Unit 1 _____________/ _____________ Pellet Unit 2

Pass/Fail Pass/Fail Pass/Fail

Comments: ________________________________________________________________________

DOC. # OPERATIONAL QUALIFICATION PROTOCOL Capsule Filling Machine National Institute of Health, Building 10 Room 1n249 Bethesda MD 20892

Page 18 of 36

__________________________________________________________________________________ __________________________________________________________________________________ __________________________________________________________________________________ Acceptance Criteria: The actual results are the same as the expected results or explained. Meets Acceptance Criteria? ( ) Yes ( ) No Reviewed by: __________________________________

Date: __________

DOC. # OPERATIONAL QUALIFICATION PROTOCOL Capsule Filling Machine National Institute of Health, Building 10 Room 1n249 Bethesda MD 20892

Page 19 of 36 Attachment #6 Functional Verification Verify that the equipment/system operations function as indicated. Input Address I 00.00

I 00.01

Input Test Description Machine Start Push Button Energized(SB 5.17) Machine Start Push Button Not Energized (SB 5.17) Handwheel Detector Sensor Energized(BI 8.3) Handwheel Detector Sensor not Energized (BI 8.3)

I 00.02

I 00.03

I 00.04

I 00.05

I 00.06

Jog Button energized (XC5.15) Jog Button de-energized (XC5.15) Machine Start Relay Energized (KA8.6) Machine Start Relay De-energized (KA8.6) Guard MicroSwitch Switch Energized (A 4A.9) Guard MicroSwitch Switch De-energized(A 4A.9) Mixer Auto/Manual Switch energized (SA7.2) Mixer Auto/Manual Switch de-energized (SA7.2)

Expected Results

Performed By/Date

Lamp HL5.6 Green Machine starts Lamp HL5.6 off Machine stops LED E RED Machine won’t start LED E off Machine will start Machine starts, after 20 sec LED Z Red Machine stops LED B Green LED B off LED G off Machine will start LED G RED Machine wont start LED T Green LED T off

Emergency Push Button Button energized (SE 4A.4)

ESTOP Button RED, Machine stopped

Emergency Push Button Button de-energized (SE 4A.4)

ESTOP Button off

Test Power Up the Equipment. Manually actuate the I/O by either simulating a condition or forcing a condition to activate the output. Verify the system I/O act accordingly.

Pass/ Fail

Expected Result I/O operates as expected

Pass/Fail

Initial/Date

DOC. # OPERATIONAL QUALIFICATION PROTOCOL Capsule Filling Machine National Institute of Health, Building 10 Room 1n249 Bethesda MD 20892

Page 20 of 36 Attachment #6 Functional Verification Verify that the equipment/system operations function as indicated. Input Address I 00.07

I 00.08

I 00.09

I 00.10

I 00.11

I 01.00

I 01.01

Input Test Description Powder Min. Level Detector 2 Sensor energized (BC8.10) Powder Min. Level Detector 2 Sensor de-energized (BC8.10) Locked Inverter Signal energized (AR1.14) Locked Inverter Signal de-energized (AR1.14) Powder Charging Auto Switch energized (SA7.14) Powder Charging Auto Switch de-energized (SA7.14) Powder Charging Manual Switch energized (SA7.14) Powder Charging Manual Switch de-energized (SA7.14) Powder Min. Level Detector 4 Sensor energized (BC8.14) Powder Min. Level Detector 4 Sensor de-energized (BC8.14) Stop Phase Sensor Energized (BI8.15) Stop Phase Sensor Energized De-energized (BI8.15) Capsule Minimum Level Sensor Energized (BC8.16) Capsule Minimum Level Sensor Energized Not Energized (BC8.16)

I 01.02

JOG start Relay energized (KA5.13) JOG start Relay de-enegized (KA5.13)

Expected Results

Pass/ Fail

Performed By/Date

LED L Red LED L off LED D flashing RED LED D off LED V Green LED V off LED X Green LED X off LED L Red LED L off LED D flashing RED LED D off LED M flashing RED, after 1 min. steady RED LED M off Machine starts while jog is pressed Machine stops when jog is released

Guards Control LED G RED Key Switch energized (SA5.12) Guards Control LED G off Key Switch de-energized (SA5.12) Test Expected Result Power Up the Equipment. Manually actuate the I/O by either simulating a condition or I/O operates as forcing a condition to activate the output. expected Verify the system I/O act accordingly. I 01.03

Pass/Fail

Initial/Date

DOC. # OPERATIONAL QUALIFICATION PROTOCOL Capsule Filling Machine National Institute of Health, Building 10 Room 1n249 Bethesda MD 20892

Page 21 of 36 Attachment #6 Functional Verification Verify that the equipment/system operations function as indicated. Input Address I 01.04

Input Test Description Program Stop On (SB5.17D1) Program Stop Off (SB5.17D1)

I 01.05

I 01.06

I 01.07

I 01.08

I 01.09

Machine motor brake control Relay energized (AR1.14) Machine motor brake control Relay de-energized (AR1.14) Mixer On/Off Switch energized (KT10.15) Mixer On/Off Switch de-energized (KT10.15) Pellet Group 1 Selector Switch On (SA9.5) Pellet Group 1 Selector Switch Off (SA9.5) Pellet Group 2 Selector Switch On (SA9.6) Pellet Group 2 Selector Switch Off (SA9.6) Pellet Group Sensor On (SA9.6)

Pellet Group Sensor Off (SA9.6) Motor Overload I 01.10 Cutout energized (QM7.11) Motor Overload Cutout de-energized (QM7.11) Air Pressure I 01.11 Sensor energized (SP9.9) Air Pressure Sensor de-energized (SP9.9) Test Power Up the Equipment. Manually actuate the I/O by either simulating a condition or forcing a condition to activate the output. Verify the system I/O act accordingly.

Expected Results

Pass/ Fail

Performed By/Date

Program initiated machine stop Machine enabled normal Machine brake engaged Machine brake disengaged LED T Green LED T off Pellet Group 1 enabled. Pellet Group 1 disabled. Pellet Group 2 enabled. Pellet Group 2 disabled. LED N Red no pellets LED N off LED D Red Machine stops LED D off LED F off LED F Red Expected Result I/O operates as expected

Pass/Fail

Initial/Date

DOC. # OPERATIONAL QUALIFICATION PROTOCOL Capsule Filling Machine National Institute of Health, Building 10 Room 1n249 Bethesda MD 20892

Page 22 of 36 Attachment #6 Functional Verification Verify that the equipment/system operations function as indicated. Output Address

Output Test Description

Expected Results

Pass/ Fail

Mixer starts when bit is enabled. Machine stops O10.01 Machine Stop (KA10.12) when bit is enabled. Machine starts O10.02 Remote Machine Start (KA10.13) when bit is enabled. Mixer is on when bit is enabled. O10.04 Mixer ON/OFF (KT10.15) Mixer is off when bit is not enabled. Test Expected Result Pass/Fail Power Up the Equipment. Manually actuate the I/O by either simulating a condition or I/O operates as forcing a condition to activate the output. expected Verify the system I/O act accordingly. O10.00

Performed By/Date

Mixer Start (KA10.11)

Initial/Date

DOC. # OPERATIONAL QUALIFICATION PROTOCOL Capsule Filling Machine National Institute of Health, Building 10 Room 1n249 Bethesda MD 20892

Page 23 of 36 Attachment #6 Functional Verification Verify that the equipment/system operations function as indicated. Procedure Machine Start/Stop Sequence

Expected Result

1. With no dosing unit installed start pumps/aspirator. Press machine start pushbutton on control panel. 2. While running push machine stop pushbutton. 3. With unit running verify proper operation of the emergency stops provided on the machine and the control panel. Capsule Feed System

1. Machine starts and LED R illuminates green.

1. Manually fill hopper with capsules. No dosing units installed. Start pumps/aspirator. Initiate machine start. 2. Verify capsule minimum level operates correctly by positioning sensor to simulate no capsules. 3. Verify operation of the Sort/Unopened capsule system. Manually insert 4 unopened capsules in the feed channels. Operate the machine 4. Adjust machine speed to 6000 Caps/hr

1. Capsules flow into the machine is initiated until stop pushbutton is pressed.

2. Machine stops

Pass/Fail

Pass/Fail

3. Machine stops immediately

2. LED M is lit.

Pass/Fail

3. Closed capsules will be ejected into the unopened capsule container. 4. Verify machine is at minimum feed of 6000 caps/hr

Powder Feed System 1. Load upper powder hopper ¾ full. Turn the manual feed selector on the control panel. 2. With tube full of powder calibrate capacitive sensor per IMA 35064M04 (Instruction manual) 3. Utilize “Jog” to start and stop machine until product bowl is filled.. 4. Place feed selector in “auto” and observe powder coming out of dosators and a “tablet falls into capsule bottom. Adjust dosators in accordance with IMA 35064M04 (Instruction manual). 5. Adjust powder layer in accordance with IMA 35064M04 (Instruction manual).

1. Observe powder flow into lower powder hopper via plexiglass fill tube 2. Observe indicator light on capacitive sensor turns on. Pass/Fail 3. Observe product bowl. 4. Confirm proper compactness and verify dosator piston projects .5mm from dosating unit. 5. Observe powder layer for proper height and homogeneity.

Initials/Date

DOC. # OPERATIONAL QUALIFICATION PROTOCOL Capsule Filling Machine National Institute of Health, Building 10 Room 1n249 Bethesda MD 20892

Page 24 of 36 Pellet System 1. Install pellet unit 2 in the powder dosing unit station in accordance with IMA 35064M04 (Instruction manual). With the main switch on, use key lock and open the door guard and place selector switch C to on. 2. After filling the hopper with product adjust the sensitivity of the pellet level sensors in accordance with IMA 35064M04 (Instruction manual).

1. Observe pellets filling dosators.

Pass/Fail 2. Observe no pellets LED N is Red when pellets are below this sensor.

Comments: _______________________________________________________________________ Acceptance Criteria: The actual results are the same as the expected results or explained. Meets Acceptance Criteria? ( ) Yes ( ) No Reviewed by: __________________________________

Date: __________

DOC. # OPERATIONAL QUALIFICATION PROTOCOL Capsule Filling Machine National Institute of Health, Building 10 Room 1n249 Bethesda MD 20892

Page 25 of 36 Attachment #7 Alarms, Safeties and Interlocks Verify that the alarms, safeties and interlocks function as indicated. Procedure

Expected Result

Pass/Fail

Initials/Date

Expected Result

Pass/Fail

Initials/Date

Machine stops operations

Pass/Fail

CONTROL PANEL

Procedure EMERGENCY STOP

Push an emergency stop button while the machine is running. LOW VOLTAGE Fault LED B

DOC. # OPERATIONAL QUALIFICATION PROTOCOL Capsule Filling Machine National Institute of Health, Building 10 Room 1n249 Bethesda MD 20892

Page 26 of 36 When machine is powered on LED B is green. Remove fuse from LV circuit .Low voltage transformer faults and LED B is off.

Low voltage fault LED indicates off

Pass/Fail

DC Power fault LED C indicates off.

Pass/Fail

Machine inverter fault LED indicates flashing RED

Pass/Fail

Motor Overlaod fault LED indicates steady RED

Pass/Fail

DC POWER SUPPLY FAULT LED B AND LED C

When machine is powered on LED B and LED C are green. Remove fuse in DC PS circuit. DC power supply faults LED B is Green and LED C is off. MACHINE INVERTER FAULT LED D

While operating and inverter faults LED D is on Remove fuse in Inverter circuit. MOTOR OVERLOAD FAULT LED D

While operating and motor overloads LED D is on Remove fuse in motor circuit.

DOC. # OPERATIONAL QUALIFICATION PROTOCOL Capsule Filling Machine National Institute of Health, Building 10 Room 1n249 Bethesda MD 20892

Page 27 of 36

HANDWHELL ENGAGED ALARM LED E

With handwheel engaged LED E is on. Machine will not start

Handwheel engaged alarm LED E RED

Pass/Fail

Machine stops operations. LED F RED

Pass/Fail

No powder LED indicates RED

Pass/Fail

LOW PRESSURE ALARM LED F

Adjust the main regulator to cut off the air supply while the machine is running.. POWDER MIXER EXCEEDS LIMITS ALARM LED L

While operating powder mixer motor de-energize the motor. When stop limit (pre-set) is exceeded No Powder alarm is enabled. INSUFFICIENT CAPSULE LEVEL ALARM LED M

DOC. # OPERATIONAL QUALIFICATION PROTOCOL Capsule Filling Machine National Institute of Health, Building 10 Room 1n249 Bethesda MD 20892

Page 28 of 36

With no or low capsule level and machine running LED will flash.

Insufficient capsule level LED M flashing RED

Pass/Fail

Insufficient capsule level Timeout LED M steady RED

Pass/Fail

Insufficient pellet level LED N flashing RED

Pass/Fail

Insufficient pellet level Timeout LED N steady RED

Pass/Fail

INSUFFICIENT CAPSULE LEVEL TIMEOUT ALARM LED M

When capsule level is low for more than one minute machine stops and alarm LED changes from flashing to steady. INSUFFICIENT PELLET LEVEL ALARM LED N

With no or low pellet level and machine running LED will flash. INSUFFICIENT PELLET LEVEL TIMEOUT ALARM LED N

When pellet level is low for more than one minute machine stops and alarm LED changes from flashing to steady.

DOC. # OPERATIONAL QUALIFICATION PROTOCOL Capsule Filling Machine National Institute of Health, Building 10 Room 1n249 Bethesda MD 20892

Page 29 of 36

INSUFFICIENT TABLET LEVEL ALARM LED S

With no or low tablet level and machine running LED will flash.

Insufficient tablet level LED S flashing RED

Pass/Fail

Powder Loading LED X steady GREEN

Pass/Fail

Maximum JOG time reached LED Z RED

Pass/Fail

POWDER LOADING MANUAL ALARM LED X

Placing powder Loading in manual causes LED to be on. MAXIMUN JOG RUNTIME ALARM LED Z

Operate jog beyond 20 sec will cause LED Z to be on.

DOC. # OPERATIONAL QUALIFICATION PROTOCOL Capsule Filling Machine National Institute of Health, Building 10 Room 1n249 Bethesda MD 20892

Page 30 of 36

GUARDS DISABLED ALARM LED G

Disable Guards with keylock switch F. LED G is on.

Guards Disabled. LED G RED

Pass/Fail

Guards Opened. LED G RED

Pass/Fail

Tablet Unit On LED A GREEN

Pass/Fail

GUARDS OPENED ALARM LED G

With machine running guards are opened. LED G is on. TABLET UNIT RUNNING ALARM LED A

Turning on tablet unit causes LED A to be on.

Comments: _______________________________________________________________________ Acceptance Criteria: The actual results are the same as the expected results or explained. Meets Acceptance Criteria? ( ) Yes ( ) No Reviewed by: __________________________________

Date: __________

DOC. # OPERATIONAL QUALIFICATION PROTOCOL Capsule Filling Machine National Institute of Health, Building 10 Room 1n249 Bethesda MD 20892

Page 31 of 36

Attachment #8 Sequence of Operation Setup equipment to run with the appropriate operational parameters for a typical Production Cycle. Run equipment. Inspect cycle run data and verify it meets acceptance criteria. Verify the sequence of operation of the pre-programmed cycle in Attachment #9. Sequence

Procedure

Expected Results

Pass/Fail

Initials/Date

Power Up and System Operation 1 2 3 4 5 6 7 8 9 10 11 12

Ensure that the machine is connected to a 115VAC power supply and compressed air supply. Turn the main power switch to the "on" position. Manually load capsules into the capsule hopper Turn on suction system Manually insert capsules into load position Load the upper product hopper ¾ full with powder product Load lower product hopper by placing selector to manual Put power loading into automatic Press machine start (pushbutton Q) to begin filling operation. Operate at slow speed. Press machine stop (pushbutton P) to stop filling operation. Operate at slow speed. Conduct weight checks of filled capsules. Restart machine and begin production.

Machine is connected to a 115VAC power supply and compressed air. The machine homes and the HMI boots. Machine is ready for Auto Mode operations. Machine ready for capsule insertion Capsules ready for fill Powder ready for manual fill Lower hopper filled with powder Machine ready for filling

Pass/Fail Pass/Fail Pass/Fail Pass/Fail Pass/Fail Pass/Fail Pass/Fail

Machine automatically fills capsules.

Pass/Fail

Machine stops

Pass/Fail

Capsules are within limits Verify fill and feed rates for 10 minutes

Pass/Fail Pass/Fail

Comments: ________________________________________________________________________ Acceptance Criteria: The actual results are the same as the expected results or explained. Meets Acceptance Criteria? ( ) Yes ( ) No Reviewed by: __________________________________

Date: __________

DOC. # OPERATIONAL QUALIFICATION PROTOCOL Capsule Filling Machine National Institute of Health, Building 10 Room 1n249 Bethesda MD 20892

Page 32 of 36

Attachment #8 Sequence of Operation Setup equipment to run with the appropriate operational parameters for a typical Production Cycle. Run equipment. Inspect cycle run data and verify it meets acceptance criteria. Verify the sequence of operation of the pre-programmed cycle in Attachment #9. Sequence

Procedure

Expected Results

Pass/Fail

Power Up and System Operation - Continued Repeat sequence of Verify Handwheel Engaged 13 operations with handwheel in LED E is on RED. manual mode. Repeat sequence of Verify Max. Jog Runtime LED Z 14 operations using Jog mode illuminates after 20 sec. for 20 seconds. Power Off Stop machine operations by 15 Machine operations stop. pressing pushbutton P Press each emergency stop 16 Machine immediately stops while machine is running Turn machine off with main 17 AC power LED B is off. power switch

Initials/Date

Pass/Fail Pass/Fail

Pass/Fail Pass/Fail Pass/Fail

Comments: ________________________________________________________________________ Acceptance Criteria: The actual results are the same as the expected results or explained. Meets Acceptance Criteria? ( ) Yes ( ) No Reviewed by: __________________________________

Date: __________

DOC. # OPERATIONAL QUALIFICATION PROTOCOL Capsule Filling Machine National Institute of Health, Building 10 Room 1n249 Bethesda MD 20892

Page 33 of 36 Attachment #9 Maximum / Minimum Values Change the system setpoints and verify the maximum and minimum values allowed. Note: document any failing results. Setpoint Machine Speed

Minimum

Maximum

Pass/Fail

6000 cap/hr

12000 cap/hr

Pass/Fail

Initials/Date

Comments: ________________________________________________________________________ __________________________________________________________________________________ __________________________________________________________________________________ __________________________________________________________________________________ Acceptance Criteria: The actual results are the same as the expected results or explained. Meets Acceptance Criteria? ( ) Yes ( ) No Reviewed by: __________________________________

Date: __________

DOC. # OPERATIONAL QUALIFICATION PROTOCOL Capsule Filling Machine National Institute of Health, Building 10 Room 1n249 Bethesda MD 20892

Page 34 of 36 Attachment #10 Deviation Reporting Log Document all deviations found during execution. Note: Make additional copies of this attachment as necessary. DEVIATION LOG Deviation Number

Description

Resolved (Y/N)

Initials & Date

Yes / No

Yes / No

Yes / No

Comments: _______________________________________________________________________ _________________________________________________________________________________ _________________________________________________________________________________ Acceptance Criteria: A list of deviations resulting from the execution of this protocol shall be recorded. Meets Acceptance Criteria? ( ) Yes ( ) No Reviewed by: __________________________

Date: ____________

DOC. # OPERATIONAL QUALIFICATION PROTOCOL Capsule Filling Machine National Institute of Health, Building 10 Room 1n249 Bethesda MD 20892

Page 35 of 36 Protocol Deviation Report (Template) Protocol #

Protocol Section

Date Encountered:

Page

Executor/Discovered By

Step

Description of Deviation

Investigation / Findings

Statement of Impact

Resolution

Approvals Role Executor Reviewer NIH QA Officer

Name (Print)

Signature

Date

DOC. # OPERATIONAL QUALIFICATION PROTOCOL Capsule Filling Machine National Institute of Health, Building 10 Room 1n249 Bethesda MD 20892

Page 36 of 36 Attachment #11 Operational Qualification Protocol Review Qualification Process Solutions, LLC signature below verifies this Operational Qualification protocol has been reviewed, for completeness and for accuracy of calculations. A separate final report will be written and attached to this protocol. The final report will discuss any deviations, conclusions, and/or recommendations resulting from the execution of the protocol.

Name (print):_____________________________________ Company (print): __________________________________ Title: ____________________________________________ Signature: ________________________________________

Date: _____________________