Capsule Filling Machine: 16 March, 2010

Operational Qualification Protocol
for the Capsule Filling Machine
Protocol No. EQ-
National Institute of Health

Operational Qualification Protocol
Equipment: Protocol #: Date:

Capsule Filling Machine 16 March, 2010
Facility: Location: Revision:

National Institute of Health Building 10 Room 1N249 Original
Bethesda, MD 20892
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 Approved By: ______________________

Title: Consultant
Title: _____________________________
Signature:
Signature:
Date:
Date:
Approved By: ______________________ Approved By: ______________________
Title: _____________________________ Title: _____________________________
Signature: Signature:
Date: Date:
Quality Assurance
Approved By: ______________________ Approved By: ______________________
Title: _____________________________ Title: _____________________________
Signature: Signature:
Date: Date:
Qualification
Process PROPRIETARY INFORMATION:
Solutions, Inc. Unauthorized Duplication Is Prohibited
DOCUMENT NUMBER
DATE: 3/16/10 PAGE: 1 of 36
REVISION NUMBER 1
Author: Michael Molloy ______________________ 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
National Institute of Health, Building 10 Room 1n249
Bethesda MD 20892
Page 2 of 36
TABLE OF CONTENTS
1.0 Purpose3
2.0 Scope 3
3.0 Equipment Description 3
4.0 Responsibilities 4
5.0 Reference Documents 4
6.0 Definitions 5
7.0 Test Function Number One: OQ Signature Verification List (Attachment #1) 5
8.0 Test Function Number Two: Test Equipment (Attachment #2) 5
9.0 Test Function Number Three: Procedure List (Attachment #3) 6
10.0 Test Function Number Four: Training Verification (Attachment #4) 6
11.0 Test Function Number Five: Operator Controls and Indicators (Attachment #5) 6
12.0 Test Function Number Six: Functional Verification (Attachment #6) 7
13.0 Test Function Number Seven: Alarms, Safeties and Interlocks (Attachment #7) 7
14.0 Test Function Number Eight: Sequence of Operations (Attachment #8) 7
15.0 Test Function Number Nine: Maximum / Minimum Values (Attachment #9) 7
16.0 Deviation Reporting Log (Attachment #10) 8
17.0 Operational Qualification Protocol Review (Attachment #11) 8
18.0 Summary Report Requirements 8
19.0 Attachment List10
DOC. #
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) Capsule feed (w/relative automatic selection via optional unit)

2) Capsule orientation , positioning and opening (equipped w/ 8 stages)
3) Capsule separation pre-filling
4) Capsule product filling
5) Unopened capsule selection (Automatic)
6) Capsule alignment and closure
7) Capsule ejection
8) Capsule selection (automatic empty and partial fill segregation)
The capsule filling machine is comprised of the following major elements:
1) Base
2) Motorization
3) Moving Parts
4) Protective hood
5) Electric cabinet and control panel
6) Size-change parts for process changeover
7) Manual controls
8) Powder feed unit
9) Powder layer and leveling control
10) Pellet or tablet dosing unit
11) Powder or pellet dosing unit
12) Defective capsule selection unit
13) Capsule closing unit
DOC. #
Bethesda MD 20892
Page 4 of 36
14) Capsule selection unit

15) Liquid dosing unit
16) Central stage
17) Emergency stop push button
18) Electric extension plug
The following general parameters apply to the Zanasi 6F
1) Dimension: 2000mm W x 1670 mm H x 2140 mm L

2) Weight 1050 kg
3) Power 480 V – 1.5 kw
4) Air
4.0 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.
5.0 Reference Documents

5.1 Drawing: 400024-00 Capsule Filling Machine Assembly
5.2 Drawing: 4400d010-37 Base Machine
5.3 Drawing: 4401d011-28 Kinematic Motion Unit
5.4 Drawing: 4402d012-11 Powder Unit
5.5 Drawing: 4403d013-15 Manual Return Unit
5.6 Drawing: 4404d014-05 Plate Unit
5.7 Drawing: 4405d015-11 Capsule Feeding and Opening Unit
5.8 Drawing: 4407d017-01 Powder Feeding Unit
5.9 Drawing: 4408d018-07 Compression/Powder Ejection Unit
5.10 Drawing: 4409d019-11 Reject Sorting Unit and Closing Counterplate
5.11 Drawing: 4410d020-11 Capsule Ejection Unit
5.12 Drawing: 4411d021-11 Cleaning Unit
5.13 Drawing: 4005d002-03 Components Added to Basic Machine
5.18 Drawing: 4402d028-03 Components Added to Rotary Tank
5.19 Drawing: 4410d090-12 Capsule Chute without SPC
5.20 Drawing: 4005d141-06 Powder/Pellet Capsule Equipment Unit F1
DOC. #
Bethesda MD 20892
Page 5 of 36

5.25 Drawing: 4019d151-03 Powder Dosing Equipment F1
5.30 Drawing: 4440d363-02 Added Components without Weight Unit
5.31 Drawing: 4428d364-37 Safety Hood
5.32 Drawing: IE 44.68 Electrical Schematic
5.33 Document: IE 44.68 Electrical Spare Part List
5.34 Document: F-S22V1 Program Listing
5.35 Drawing: 440C033 Compressed Air Plant
5.36 Drawing: 440C039-01 Aspiration Air Plant
5.37 Document: 35071M04 Installation & Operation Manual for the Capsule Filling Machine
including:
Maintenance
Safety Notices
CE Conformity Documents
Test Reports and Equipment Certs
6.0 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.
7.0 Test Function Number One: OQ Signature Verification List (Attachment #1)
7.1 Objective
To identify and document all personnel involved in executing this protocol.
7.2 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.
7.3 Acceptance Criteria
Signatures from all personnel involved in execution of this protocol shall be present.
8.0 Test Function Number Two: Test Equipment (Attachment #2)

8.1 Objective
To verify and document all test equipment
8.2 Procedure
8.2.1 Complete a list of all the instruments required for conducting OQ testing.
DOC. #
Bethesda MD 20892
Page 6 of 36
8.2.2 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
All equipment required for execution shall be calibrated with copies of calibration records
attached.
9.0 Test Function Number Three: Procedure List (Attachment #3)

9.1 Objective
To verify the operating Standard Operating Procedures (SOP’s) provide adequate direction and
control over the operation of the equipment.
9.2 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.
All associated SOP’s for operation and execution shall be reviewed and documented.
10.0 Test Function Number Four: Training Verification (Attachment #4)

10.1 Objective
To document applicable personnel have received the required training for operation of the
equipment.
10.2 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.
Training shall be performed on all SOP’s used during the execution of this qualification
protocol.
11.0 Test Function Number Five: Operator Controls and Indicators (Attachment #5)
11.1 Objective
To verify the controls and indicators operate as specified by manufacturer recommendations.
11.2 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.
All operator controls and indicators tested shall conform to the expected response.
DOC. #
Bethesda MD 20892
Page 7 of 36
12.0 Test Function Number Six: Functional Verification (Attachment #6)

12.1 Objective
To verify and document the operation and functionality of the equipment.
12.2 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.
All functional requirements must conform to the expected responses.
13.0 Test Function Number Seven: Alarms, Safeties and Interlocks (Attachment #7)
13.1 Objective
To verify and document the operation and functionality of the alarms, safeties and interlocks.
13.2 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.
All safeties and interlock requirements must conform to the expected responses.
14.0 Test Function Number Eight: Sequence of Operations (Attachment #8)
14.1 Objective
To verify and document the operational sequence of the system.
14.2 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.
The operating sequence occurs as expected.
15.0 Test Function Number Nine: Maximum / Minimum Values (Attachment #9)
15.1 Objective
To verify the maximum and minimum allowable values of changeable setpoints.
15.2 Procedure
15.2.1 Display the changeable setpoint on the applicable attachment and test maximum and
minimum values.
DOC. #
Bethesda MD 20892
Page 8 of 36
15.2.2 Visually verify and document the actual results of the functions that appear on the
operator interface.
The actual results of the changeable setpoint limits shall conform to the expected responses.
16.0 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.
17.0 Operational Qualification Protocol Review (Attachment #11)

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

18.1 Objective
To provide an overview of the test results during the execution of this operational
qualification.
18.2 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.
18.2.1.2 Generate a conclusion, based on these results, of the acceptability of the
qualification results.
DOC. #
Bethesda MD 20892
Page 9 of 36
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. #
Bethesda MD 20892
Page 10 of 36
19.0 Attachment List

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 #7 Alarms, Safeties and Interlocks 25
Attachment #8 Sequence of Operation 31
Attachment #9 Maximum / Minimum Values 33
Attachment #10 Deviation Reporting Log 34
Attachment #11 Operational Qualification Protocol Review 36
DOC. #
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.
Department/
Print Name Title Signature Initials Date
Company Name
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. #
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 Certified/ Cal. Cal Initials/

Manufacturer ID# Serial #
Description Calibrated Date Due Date 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.
Reviewed by: _____________________________________ Date: __________

DOC. #
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 SOP Effective

Procedure Title Initials/Date
Number Revision # Date
Original Operation of the Capsule Filling Machine
Original Maintenance of the Capsule Filling Machine
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.
Reviewed by: __________________________________ Date: __________

DOC. #
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.
Training
SOP # Procedure Title Documented Initials/Date
(Y/N)
Operation of the Capsule Filling
Yes/No
Machine
Maintenance of the Capsule Filling
Yes/No
Machine
Comments: ________________________________________________________________________
__________________________________________________________________________________
__________________________________________________________________________________
__________________________________________________________________________________
Acceptance Criteria: A list of written procedures that are used to train personnel to operate the
equipment is provided above.
Reviewed by: __________________________________ Date: __________

DOC. #
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 Initials/Date

CONTROL PANEL SWITCHES and INDICATORS
Emergency Stop Places equipment in _________ equipment
Button. Control safe mode when in safe mode when Pass/Fail
Panel pressed. Red pressed. Red
Indicates AC Power
LED A.C. Power Indicates AC Power
________ on. LED Pass/Fail
On is on. LED Green.
Green.
Indicates Feed Logic Indicates Feed Logic
LED Feed Logic
is enabled. LED ________ enabled. Pass/Fail
Control
Green LED Green
Indicates breakers Indicates breakers
LED Breakers
have tripped. LED ________ tripped. Pass/Fail
Tripped
Red LED Red
Indicates manual Indicates manual hand
LED Handwheel
hand wheel is wheel _________ Pass/Fail
Engaged
engaged. LED Red engaged. LED Red
Indicates compressed Indicates compressed
LED No
air is not available. air ____________ Pass/Fail
Compressed Air
LED Red available. LED Red
Shuts down vacuum ___________ down
Vacuum Pump Off
pump when pressed. vacuum pump when Pass/Fail
Pushbutton.
Red pressed. Red
Indicates vacuum
Indicates vacuum
Vacuum Pump pump __________
pump is operating. Pass/Fail
Engaged Lamp operating. Lamp
Lamp Green
Green
Vacuum Pump On Starts vacuum pump _________ vacuum
Pass/Fail
Pushbutton. when pressed. pump when pressed.
Indicates no powder. _________ no
LED No Powder Pass/Fail
LED Red powder. LED Red
Indicates no capsules _________ no
LED No Capsules Pass/Fail
LED Red capsules LED Red
Indicates no Pellets _________ no Pellets
LED No Pellets Pass/Fail
LED Red LED Red
Rotating clockwise
Rotating clockwise
Machine Motor /counterclockwise
/counterclockwise
Speed Reg. __________/ Pass/Fail
increases/decreases
Potentiometer. __________ motor
motor speed
speed
Machine Stop Stops the machine __________ the Pass/Fail
DOC. #
Bethesda MD 20892
Page 16 of 36
machine normally.
Pushbutton normally. Red
Red
Machine Start Starts the machine ____________ the
Pass/Fail
Pushbutton normally machine normally
Indicates machine ___________ machine
Lamp Machine
operating. Lamp operating. Lamp Pass/Fail
Running
Green Green
Indicates no tablets ___________ no
LED No Tablets Pass/Fail
LED Red tablets LED Red
Indicates powder __________ powder
LED Powder Mixer
mixer is selected. mixer is selected. LED Pass/Fail
(MAN/AUTO) On
LED Green Green
Powder Mixer __________ either
Selects either Manual
MAN/AUTO Manual or Auto Pass/Fail
or Auto Control
Selector Control
LED Powder Mixer Indicates powder _________ powder
Pass/Fail
Enabled mixer on. LED Green mixer on. LED Green
Powder Loading Enables Powder ____________
Pass/Fail
Enable Selector Loading Powder Loading
Indicates JOG has Indicates JOG

LED Max. Jog
exceeded Runtime. _________exceeded Pass/Fail
Runtime
LED Red Runtime. LED Red
____________ Tablet
LED Tablet Unit Indicates Tablet Unit
Unit Enabled. LED Pass/Fail
Enabled Enabled. LED Green.
Green.
Tablet Unit Enable Enables Tablet ____________ Tablet

Pass/Fail
Selector Selector Selector
Displays production ____________

Production Counter Pass/Fail
counts production counts
___________ run time

Logs run time when
Hour Counter when machine is Pass/Fail
machine is operating.
operating.
___________ run time
Logs run time when
Hour Counter when machine is Pass/Fail
operating.
______________ run
Hourly Production Logs run time when
time when machine is Pass/Fail
Counter machine is operating
operating
DOC. #
Bethesda MD 20892
Page 17 of 36
______________ run
Logs run time when
Hour Counter time when machine is Pass/Fail
operating.
_____________ /
Engage/Disengage Engages / disengages
_____________ Pass/Fail
Guards Selector guards
guards
Guards Disengaged Guards disabled LED Guards ___________

Pass/Fail
LED Red LED Red
REAR PANEL SWITCHES and INDICATORS

Emergency Stop Places equipment in _____________
Button. Machine safe mode when equipment in safe Pass/Fail
rear panel pressed. mode when pressed.
_____________/
Engages/Disengages
Manual Control _____________
Mechanical Pass/Fail
Handwheel Mechanical
Components
Components
SIDE PANEL SWITCHES and INDICATORS
Reset Capsules Resets the capsule ___________ the

Pass/Fail
Produced counter capsule counter
ELECTRICAL PANEL (Inside Door) SWITCHES and INDICATORS

_____________/
Vacuum Bowl Enable/disable
_____________ Pass/Fail
ON/OFF Selector Vacuum Bowl
Vacuum Bowl
_____________/
Pellet Unit 1 Enable/disable Pellet
_____________ Pellet Pass/Fail
ON/OFF Unit 1
Unit 1
_____________/
Pellet Unit 2 Enable/disable Pellet
_____________ Pellet Pass/Fail
ON/OFF Unit 2
Unit 2
Comments: ________________________________________________________________________
DOC. #
Bethesda MD 20892
Page 18 of 36
__________________________________________________________________________________
__________________________________________________________________________________
__________________________________________________________________________________
Acceptance Criteria: The actual results are the same as the expected results or explained.
Reviewed by: __________________________________ Date: __________

DOC. #
Bethesda MD 20892
Page 19 of 36
Attachment #6 Functional Verification
Verify that the equipment/system operations function as indicated.
Input Pass/ Performed

Input Test Description Expected Results
Address Fail By/Date
Machine Start Lamp HL5.6 Green
I 00.00 Push Button Energized(SB 5.17) Machine starts
Machine Start Lamp HL5.6 off
Push Button Not Energized (SB 5.17) Machine stops
LED E RED
Handwheel Detector
I 00.01 Sensor Energized(BI 8.3)
Machine won’t
start
Handwheel Detector LED E off
Sensor not Energized (BI 8.3) Machine will start
Machine starts,
I 00.02 Jog Button energized (XC5.15) after 20 sec LED Z
Red
Jog Button de-energized (XC5.15) Machine stops
Machine Start
I 00.03 Relay Energized (KA8.6)
LED B Green
Machine Start
Relay De-energized (KA8.6)
LED B off
Guard MicroSwitch LED G off
I 00.04 Switch Energized (A 4A.9) Machine will start
Guard MicroSwitch LED G RED
Switch De-energized(A 4A.9) Machine wont start
Mixer Auto/Manual
I 00.05 Switch energized (SA7.2)
LED T Green
Mixer Auto/Manual
Switch de-energized (SA7.2)
LED T off
ESTOP Button
Emergency Push Button
I 00.06 Button energized (SE 4A.4)
RED, Machine
stopped
Emergency Push Button
ESTOP Button off
Button de-energized (SE 4A.4)
Test Expected Result Pass/Fail Initial/Date
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.
DOC. #
Bethesda MD 20892
Page 20 of 36
Input Input Test Description Expected Results Pass/ Performed

Powder Min. Level Detector 2
I 00.07 LED L Red
Sensor energized (BC8.10)
LED L off
Sensor de-energized (BC8.10)
Locked Inverter LED D flashing
I 00.08 Signal energized (AR1.14) RED
Locked Inverter
LED D off
Signal de-energized (AR1.14)
Powder Charging Auto
I 00.09 LED V Green
Switch energized (SA7.14)
Powder Charging Auto
LED V off
Powder Charging Manual
I 00.10 LED X Green
Switch energized (SA7.14)
Powder Charging Manual
LED X off
I 00.11 LED L Red
Sensor energized (BC8.14)
LED L off
Sensor de-energized (BC8.14)
Stop Phase LED D flashing
I 01.00 Sensor Energized (BI8.15) RED
Stop Phase
LED D off
Sensor Energized De-energized (BI8.15)
LED M flashing
Capsule Minimum Level
I 01.01 Sensor Energized (BC8.16)
RED, after 1 min.
steady RED
Capsule Minimum Level LED M off
Sensor Energized Not Energized (BC8.16)
JOG start Machine starts
I 01.02
Relay energized (KA5.13) while jog is pressed
Machine stops
JOG start
when jog is
Relay de-enegized (KA5.13)
released
Guards Control
I 01.03 LED G RED
Key Switch energized (SA5.12)
Guards Control
LED G off
Key Switch de-energized (SA5.12)
the I/O by either simulating a condition or I/O operates as
forcing a condition to activate the output. expected
DOC. #
Bethesda MD 20892
Page 21 of 36
Input Input Test Description Expected Results Pass/ Performed

Program initiated
I 01.04 Program Stop On (SB5.17D1)
machine stop
Machine enabled
Program Stop Off (SB5.17D1)
normal
Machine motor brake control Machine brake
I 01.05
Relay energized (AR1.14) engaged
Machine motor brake control Machine brake dis-
Relay de-energized (AR1.14) engaged
I 01.06 Mixer On/Off LED T Green
Switch energized (KT10.15)
Mixer On/Off LED T off
Switch de-energized (KT10.15)
I 01.07 Pellet Group 1 Pellet Group 1
Selector Switch On (SA9.5) enabled.
Pellet Group 1 Pellet Group 1 dis-
Selector Switch Off (SA9.5) abled.
I 01.08 Pellet Group 2 Pellet Group 2
Selector Switch On (SA9.6) enabled.
Pellet Group 2 Pellet Group 2 dis-
Selector Switch Off (SA9.6) abled.
LED N Red no
I 01.09 Pellet Group Sensor On (SA9.6)
pellets
Pellet Group Sensor Off (SA9.6) LED N off
Motor Overload LED D Red
I 01.10
Cutout energized (QM7.11) Machine stops
Motor Overload
LED D off
Cutout de-energized (QM7.11)
Air Pressure
I 01.11 LED F off
Sensor energized (SP9.9)
Air Pressure
LED F Red
Sensor de-energized (SP9.9)
I/O operates as
expected
DOC. #
Bethesda MD 20892
Page 22 of 36
Output Pass/ Performed

Output Test Description Expected Results By/Date
Address Fail
Mixer starts
O10.00 Mixer Start (KA10.11) 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.
I/O operates as
expected
DOC. #
Bethesda MD 20892
Page 23 of 36
Procedure Expected Result Pass/Fail Initials/Date

Machine Start/Stop Sequence
1. With no dosing unit installed start 1. Machine starts and LED R

pumps/aspirator. Press machine start illuminates green.
pushbutton on control panel.
Pass/Fail
2. While running push machine stop 2. Machine stops
pushbutton.
3. With unit running verify proper 3. Machine stops immediately
operation of the emergency stops provided
on the machine and the control panel.
Capsule Feed System
1. Manually fill hopper with capsules. No 1. Capsules flow into the machine
dosing units installed. Start is initiated until stop pushbutton is
pumps/aspirator. Initiate machine start. pressed.
2. Verify capsule minimum level operates
correctly by positioning sensor to simulate 2. LED M is lit.
Pass/Fail
no capsules.
3. Verify operation of the Sort/Unopened 3. Closed capsules will be ejected
capsule system. Manually insert 4 into the unopened capsule
unopened capsules in the feed channels. container.
Operate the machine
4. Adjust machine speed to 6000 Caps/hr 4. Verify machine is at minimum
feed of 6000 caps/hr
Powder Feed System
1. Load upper powder hopper ¾ full. Turn 1. Observe powder flow into lower
the manual feed selector on the control powder hopper via plexiglass fill
panel. tube
2. With tube full of powder calibrate
capacitive sensor per IMA 35064M04 2. Observe indicator light on
(Instruction manual) capacitive sensor turns on.
3. Utilize “Jog” to start and stop machine Pass/Fail
until product bowl is filled.. 3. Observe product bowl.
4. Place feed selector in “auto” and
observe powder coming out of dosators 4. Confirm proper compactness and
and a “tablet falls into capsule bottom. verify dosator piston projects .5mm
Adjust dosators in accordance with IMA from dosating unit.
35064M04 (Instruction manual).
5. Adjust powder layer in accordance with 5. Observe powder layer for proper
IMA 35064M04 (Instruction manual). height and homogeneity.
DOC. #
Bethesda MD 20892
Page 24 of 36
Pellet System
1. Install pellet unit 2 in the powder 1. Observe pellets filling dosators.

dosing unit station in accordance with
IMA 35064M04 (Instruction manual).
With the main switch on, use key lock
Pass/Fail
and open the door guard and place
selector switch C to on.
2. After filling the hopper with product 2. Observe no pellets LED N is Red
adjust the sensitivity of the pellet level when pellets are below this sensor.
sensors in accordance with IMA
35064M04 (Instruction manual).
Comments: _______________________________________________________________________
Reviewed by: __________________________________ Date: __________

DOC. #
Bethesda MD 20892
Page 25 of 36
Attachment #7 Alarms, Safeties and Interlocks
Verify that the alarms, safeties and interlocks function as indicated.
CONTROL PANEL
EMERGENCY
STOP
Push an emergency stop button while

Machine stops operations Pass/Fail
the machine is running.
LOW VOLTAGE
Fault LED B
DOC. #
Bethesda MD 20892
Page 26 of 36
When machine is powered on LED

B is green. Remove fuse from LV
Low voltage fault LED indicates off Pass/Fail
circuit .Low voltage transformer
faults and LED B is off.
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 DC Power fault LED C indicates off. Pass/Fail
supply faults LED B is Green and
LED C is off.
MACHINE
INVERTER FAULT
LED D
While operating and inverter faults

Machine inverter fault LED indicates
LED D is on Remove fuse in Pass/Fail
flashing RED
Inverter circuit.
MOTOR
OVERLOAD
FAULT LED D
While operating and motor overloads

Motor Overlaod fault LED indicates
LED D is on Remove fuse in motor Pass/Fail
steady RED
circuit.
DOC. #
Bethesda MD 20892
Page 27 of 36
HANDWHELL
ENGAGED
ALARM LED E
With handwheel engaged LED E is

Handwheel engaged alarm LED E RED Pass/Fail
on. Machine will not start
LOW PRESSURE
ALARM LED F
Adjust the main regulator to cut off

the air supply while the machine is Machine stops operations. LED F RED Pass/Fail
running..
POWDER MIXER
EXCEEDS LIMITS
ALARM LED L
While operating powder mixer motor

de-energize the motor. When stop
No powder LED indicates RED Pass/Fail
limit (pre-set) is exceeded No
Powder alarm is enabled.
INSUFFICIENT
CAPSULE LEVEL
ALARM LED M
DOC. #
Bethesda MD 20892
Page 28 of 36
With no or low capsule level and

Insufficient capsule level LED M flashing
machine running LED will flash. Pass/Fail
RED
INSUFFICIENT
CAPSULE LEVEL
TIMEOUT ALARM
LED M
When capsule level is low for more

than one minute machine stops and Insufficient capsule level Timeout LED M
Pass/Fail
alarm LED changes from flashing to steady RED
steady.
INSUFFICIENT
PELLET LEVEL
ALARM LED N
With no or low pellet level and Insufficient pellet level LED N flashing
Pass/Fail
machine running LED will flash. RED
INSUFFICIENT
PELLET LEVEL
TIMEOUT ALARM
LED N
When pellet level is low for more

than one minute machine stops and Insufficient pellet level Timeout LED N
Pass/Fail
alarm LED changes from flashing to steady RED
steady.
DOC. #
Bethesda MD 20892
Page 29 of 36
INSUFFICIENT
TABLET LEVEL
ALARM LED S
With no or low tablet level and Insufficient tablet level LED S flashing
Pass/Fail
machine running LED will flash. RED
POWDER
LOADING
MANUAL ALARM
LED X
Placing powder Loading in manual

Powder Loading LED X steady GREEN Pass/Fail
causes LED to be on.
MAXIMUN JOG
RUNTIME ALARM
LED Z
Operate jog beyond 20 sec will cause

Maximum JOG time reached LED Z RED Pass/Fail
LED Z to be on.
DOC. #
Bethesda MD 20892
Page 30 of 36
GUARDS
DISABLED
ALARM LED G
Disable Guards with keylock switch

Guards Disabled. LED G RED Pass/Fail
F. LED G is on.
GUARDS OPENED
ALARM LED G
With machine running guards are

Guards Opened. LED G RED Pass/Fail
opened. LED G is on.
TABLET UNIT
RUNNING
ALARM LED A
Turning on tablet unit causes LED

Tablet Unit On LED A GREEN Pass/Fail
A to be on.
Comments: _______________________________________________________________________
Reviewed by: __________________________________ Date: __________

DOC. #
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
Machine is connected
Ensure that the machine is connected
to a 115VAC power
1 to a 115VAC power supply and Pass/Fail
supply and compressed
compressed air supply.
air.
Turn the main power switch to the The machine homes
2 Pass/Fail
"on" position. and the HMI boots.
Manually load capsules into the Machine is ready for
3 Pass/Fail
capsule hopper Auto Mode operations.
Machine ready for
4 Turn on suction system Pass/Fail
capsule insertion
Manually insert capsules into load
5 Capsules ready for fill Pass/Fail
position
Load the upper product hopper ¾ Powder ready for
6 Pass/Fail
full with powder product manual fill
Load lower product hopper by Lower hopper filled
7 Pass/Fail
placing selector to manual with powder
Machine ready for
8 Put power loading into automatic
filling
Press machine start (pushbutton Q)
Machine automatically
9 to begin filling operation. Operate at Pass/Fail
fills capsules.
slow speed.
Press machine stop (pushbutton P) to
10 stop filling operation. Operate at Machine stops Pass/Fail
slow speed.
Conduct weight checks of filled Capsules are within
11 Pass/Fail
capsules. limits
Restart machine and begin Verify fill and feed
12 Pass/Fail
production. rates for 10 minutes
Comments: ________________________________________________________________________
Reviewed by: __________________________________ Date: __________

DOC. #
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 Initials/Date

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

DOC. #
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 Minimum Maximum Pass/Fail Initials/Date
Machine Speed 6000 cap/hr 12000 cap/hr Pass/Fail
Comments: ________________________________________________________________________
__________________________________________________________________________________
__________________________________________________________________________________
__________________________________________________________________________________
Reviewed by: __________________________________ Date: __________

DOC. #
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
Description Resolved (Y/N) Initials & Date
Number
Yes / No
Yes / No
Yes / No
Comments: _______________________________________________________________________
_________________________________________________________________________________
_________________________________________________________________________________
Acceptance Criteria: A list of deviations resulting from the execution of this protocol shall be recorded.
Reviewed by: __________________________ Date: ____________

DOC. #
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 Name (Print) Signature Date
Executor
Reviewer
NIH QA Officer
DOC. #
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: _____________________

Capsule Filling Machine: 16 March, 2010

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Capsule Filling Machine: 16 March, 2010

Uploaded by

Copyright:

Available Formats

Operational Qualification Protocol

for the Capsule Filling Machine

Protocol No. EQ-

National Institute of Health

Equipment: Protocol #: Date:

Facility: Location: Revision:

Written By: Michael Molloy Approved By: ______________________

Approved By: ______________________ Approved By: ______________________

Title: _____________________________ Title: _____________________________

Title: _____________________________ Title: _____________________________

EQUIPMENT NAME: Capsule Filling Machine

Capsule Filling Machine

NATIONAL INSTITUTE OF HEALTH

QUALIFICATION PROCESS SOLUTIONS

3.0 Equipment Description

1) Capsule feed (w/relative automatic selection via optional unit)

The capsule filling machine is comprised of the following major elements:

14) Capsule selection unit

The following general parameters apply to the Zanasi 6F

1) Dimension: 2000mm W x 1670 mm H x 2140 mm L

4.2 National Institutes of Health (SI)

5.0 Reference Documents

5.23 Drawing: 4005d144-06 Powder/Pellet Capsule Equipment Unit F4

6.2 Non-Critical Instrumentation – Instrumentation provided for indication or convenience

8.0 Test Function Number Two: Test Equipment (Attachment #2)

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

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

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

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

16.0 Deviation Reporting Log (Attachment #10)

17.0 Operational Qualification Protocol Review (Attachment #11)

18.0 Summary Report Requirements

18.2.1.3 Include a statement of conformance to the specified acceptance criteria,

19.0 Attachment List

Attachment #1 OQ Signature Verification List

Meets Acceptance Criteria? ( ) Yes ( ) No

Reviewed by: __________________________________ Date: __________

Attachment #2 Test Equipment

Equipment Certified/ Cal. Cal Initials/

Meets Acceptance Criteria? ( ) Yes ( ) No

Reviewed by: _____________________________________ Date: __________

Attachment #3 Procedure List

SOP SOP Effective

Meets Acceptance Criteria? ( ) Yes ( ) No

Reviewed by: __________________________________ Date: __________

Attachment #4 Training Verification

Meets Acceptance Criteria? ( ) Yes ( ) No

Reviewed by: __________________________________ Date: __________

Attachment #5 Operator Controls and Indicators

Device Expected Results Actual Results Pass/Fail Initials/Date

Indicates JOG has Indicates JOG

Tablet Unit Enable Enables Tablet ____________ Tablet

Displays production ____________

___________ run time

Guards Disengaged Guards disabled LED Guards ___________

REAR PANEL SWITCHES and INDICATORS

Reset Capsules Resets the capsule ___________ the

ELECTRICAL PANEL (Inside Door) SWITCHES and INDICATORS

Meets Acceptance Criteria? ( ) Yes ( ) No

Reviewed by: __________________________________ Date: __________

Attachment #6 Functional Verification

Verify that the equipment/system operations function as indicated.

Input Pass/ Performed

Approved By: Approved By:

Title: _ Title: _

Title: _ Title: _

Reviewed by: ________________________ Date:

Reviewed by: ___________________________ Date:

Reviewed by: ________________________ Date:

Reviewed by: ________________________ Date:

Reviewed by: ________________________ Date:

Reviewed by: ________________________ Date:

Reviewed by: ________________________ Date:

Reviewed by: ________________________ Date:

Reviewed by: ________________________ Date:

Reviewed by: ________________________ Date:

Reviewed by: ______________ Date:

Signature: ____________________ Date: _