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6.F Operational qualification(OQ)

Here you will find answers to the following questions:

  • What is understood by the term "OQ"?
  • What tests are carried out during OQ?
  • What documents are compiled during OQ?

 

Figure 6.F-1 Definition of OQ

Definition of OQ (EU GMP Guideline, Annex 15)

Operational qualification (OQ)

"The documented verification that the facilities, systems and equipment, as installed ormodified, perform as intended throughout the anticipated operating ranges."

Operational qualification ensures that the equipment works as planned and that its proper function is guaranteed across the entire range of process critical parameters. Operational qualification begins after successful completion of installation qualification.

To check the predetermined functionality of all components of the equipment, test procedures are developed and corresponding acceptance criteria are defined in advance. The essential elements of operational qualification are summarised in figure 6.F-2.

Figure 6.F-2 Typical elements of operational qualification

Typical elements of operational qualification

  • Execution and documentation of the calibration of quality-relevant measuring points (initial calibration) and definition of the calibration intervals
  • Checking of electromagnetic compatibility
  • Identification and checking of the functions that influence quality (risk analysis) including verification of the performance parameters prescribed in accordance with DQ
  • Identification and checking of the control of safety devices, alarms and failure messages (risk analysis)
  • CE conformity or manufacturer's declaration
  • Verification of the environmental conditions
  • Compilation of operating procedures for operating the equipment, based on the operating manual
  • Checking and, if relevant, adaptation of operating procedures for calibration and servicing of the equipment
  • Creation of a log book
  • Checking and, if necessary, adaptation of operating procedures for the cleaning or disinfection/sterilisation of the equipment

The following requirements for the execution of the function tests are considered to be indispensable:

  • Completion of initial calibration: the quality-relevant measuring points must be calibrated.
  • Use of calibrated test equipment: It must be possible to trace the equipment used for tests during the OQ to an accepted norm.
  • Completion of testing for electromagnetic compatibility (EMC)

Possible operating constraints, such as the containment of the originally intended working area, which result from the qualification, must be listed in the operating procedure. At least a draft form of the operating procedures must be available for operational qualification and upon completion of this qualification phase they should enter into force. The operating procedure then becomes a requirement for staff training and thus ultimately becomes the basis for qualified operation of a qualified piece of equipment.

Operational qualification is not usually product-specific, i.e. it extends across the entire range (working area) of the different functions of the equipment. In addition to the working area, ancillary conditions should also be tested here (e.g. the restart behaviour after switching the equipment off).

In principle, it is recommended that all qualification activities be accompanied by deviation lists. If deviations occur, they are recorded in the list and a time by which they should be eliminated and the person responsible for doing so are defined. Qualification activities are then resumed depending on the significance of the deviation that occurred, or are interrupted and only continued once the deviation has been eliminated.

Successful execution of the installation and operational qualification represents the prerequisite for technical acceptance of the equipment and should be carried out as close together as possible.

6.F.1 Examples of OQ plans

The general requirements of the qualification documentation are described in chapter 6.C Qualification documentation. There are numerous ways of structuring the individual documents. A possible systematic procedure is presented in this chapter. The forms may be used as a template for filling with the facility-specific test points. The documents are structured so that the qualification plan (list of the test points with acceptance criteria) and the test protocol (documentation of the test carried out) are summarised in a single document.

The following forms are included:

  • OQ test protocol Safety devices page 4
  • OQ test protocol Risk analysis Operating functions page 6
  • OQ qualification report page 11
  • Qualification plan Test protocol OQ 3:
    Verification of the check for the presence of screw caps page 8

6.F.1.1 Safety devices

Figure 6.F-3 OQ test protocol 1: Safety devices 

Company

OQ qualification plan
OQ test protocol 1:
Safety devices

Page x v. y

QP-0815-4721

Qualification plan for facilities and equipment for pharmaceutical products at the Ixberg site

valid from
01.10.2003

Qualification project no.

Facility/equipment

Inventory no.

Record compiled


(Date/signature)

Record approved for implementation


(Date/signature)

Test carried out


(Date/signature)

Test result approved


(Date/signature)

1. Scope

This test protocol is an integral part of the qualification plan in accordance with qualification master plan 0915 and is valid at the Ixberg site for the qualification of new and existing manufacturing and control equipment for pharmaceutical products. It does not relate to the qualification of computer systems. This document must also be used if the qualification (or parts thereof) is to be carried out by external companies or consultants.

2. Test item

Subject of the test is the safety devices and alarms of the facility to be qualified.

3. Performance of test

Practical checking of all safety devices and alarms and comparison with the requirements of the DQ. Every safety device is checked three times.

The acceptance criterion is: The alarm/safety device must be activated as soon as the specified switching/required value is reached.

4. Test list

Test feature

Switching/
required value

Actual value

Accepted
(Y/N)

Date

Signature

Emergency stop

1.

         

2.

         

3.

         

4.

         

5.

         

Alarms

1.

         

2.

         

3.

         

4.

         

5.

         

5. Test result

m Accepted

 

m  Not accepted, due to

Measures require

6.F.1.2 Risk analysis Operating functions

Figure 6.F-4 OQ test protocol 2: Risk analysis Operating functions 

Company

OQ qualification plan
OQ test protocol 2:
Risk analysis Operating functions

Page x v. y

Qualification
project no.

Facility/equipment

 

Record compiled


(Date/signature)

Record approved for implementation


(Date/signature)

Test carried out


(Date/signature)

Test result approved


(Date/signature)

1. Scope

This test protocol is an integral part of the qualification plan in accordance with qualification master plan 0915 and is valid at the Ixberg site for the qualification of new and existing manufacturing and control equipment for pharmaceutical products. It does not relate to the qualification of computer systems. This document must also be used if the qualification (or parts thereof) is to be carried out by external companies or consultants.

2. Test item

The subject of this test protocol is to identify all operating functions of the facility to be qualified that could influence the quality of the product ("critical"). Faultless operation of these critical operating functions is checked in further test protocols (OQ 3-OQ 8).

3. Performance of test

1. The functionality of the facility is visualized by a detailed flow chart (to be enclosed to this test protocol as an appendix.

2. If the facility is to be operated in different modes of operation, e.g. for different products, all modes of operation must be taken into account in the flow chart or in several flow charts.

For every operating function shown in the flow chart (e.g. stirring, temperature measurement, automat. ejection, etc.) a risk assessment must be carried out in accordance with SOP 239834. Every operating function assigned with a risk priority number of ³ 4 , is is to be considered as "quality-influencing" or "critical" operating function and must be adressed in the context of further testing.

4. Test list

Test feature

Possible failure

Failure implications

Control measure

Probability

Importance

Probability of

detection

Risk priority number RPN

Quality-relevant
operating function
(yes/no)

Operating function

4.1

               

4.2

               

4.3

               

4.4

               

4.5

               

4.6

               

5. Enclosure

(Flow charts)

6.F.1.3 Check for the presence of screw caps

Figure 6.F-5 Test protocol OQ 3: Verification of the check for the presence of screw caps 

Company

Qualification plan
Test protocol OQ 3:
Verification of the check for the presence of screw caps

Page x v. y

QP-0815-4730

Qualification plan for facilities and equipment
for pharmaceutical products at the Ixberg site

valid from
01.10.2003

Qualification
project no.

Facility/equipment

Inventory no.

Record compiled


(Date/signature)

Record approved for implementation


(Date/signature)

Test carried out


(Date/signature)

Test result approved


(Date/signature)

1. Scope

This test protocol is an integral part of the qualification plan in accordance with qualification master plan 0915 and is valid at the Ixberg site for the qualification of new and existing manufacturing and control equipment for pharmaceutical products. It does not relate to the qualification of computer systems. This document must also be used if the qualification (or parts thereof) is to be carried out by external companies or consultants.

2. Test item

Verification of the faultless operation of the check for the presence of screw caps, which was classified as critical in accordance with the risk analysis of operating functions (OQ3, Document QP 0815-4722).

3. Performance of test

The facility to be qualified is currently operated with screw caps in two different dimensions (Prod # 89-4523 and 89- 4525). The tests described below are to be carried out with both screw caps after size changeover of the corresponding components.

Test A:

1. Fill the storage container with screw caps to approx. 2/3. Ensure continuous bottle feed.

2. Start the facility (speed approx. 3,500).

3. Let the facility run for about 15 minutes without further corrective intervention. While doing so, collect the "undamaged product" and "waste" bottles separately.

4. Check the "undamaged product" for missing screw caps. Check the waste for the presence of screw caps.

Tests B and C:

Repeat points 1-4 at a higher speed (6,000 and 7,500).

Test D:

Repeat points 1-4 while the screw lid supply container is running empty.

Challenge test 1:

Set the machine speed to 3,500. Remove every second screw lid from the feed channel.

Challenge test 2:

Set the machine speed to 6,000. Insert every fifth screw lid into the feed channel upside-down.

Acceptance criteria:

1. In none of the tests should a bottle without a screw lid have entered into the "undamaged product".

2. No more than 2% of all the bottles used should be incorrectly rejected as waste (i.e. despite correctly applied screw lid).

4. Test list

Testing

Number of undamaged product items

Number of waste items

Accepted
(Y/N)

Date

Signature

with
lid

without
lid

without
lid

with
lid

A

             

B

             

C

             

D

             

Challenge test 1:

             

Challenge test 2:

             

5. Test result

m Accepted

 

m  Not accepted, due to


Measures required

6.F.1.4 OQ report

Figure 6.F-6 Qualification report OQ  

Company

Qualification report OQ

Page x v. y

QP-0815-4730

Qualification plan for facilities and equipment for pharmaceutical products at the Ixberg site

valid from
01.10.2003

Qualification project no.

Facility/equipment

Inventory no.

Record compiled


(Date/signature)

Record approved for implementation


(Date/signature)

Test carried out


(Date/signature)

Test result approved


(Date/signature)

1. Scope

This qualification report summarises the results of the OQ in accordance with qualification master plan 0915. It is valid at the Ixberg site for the qualification of new and existing manufacturing and control equipment for pharmaceutical products. It does not relate to the qualification of computer systems.

This document must also be used if the qualification (or parts thereof) is to be carried out by external companies or consultants.

2. OQ tests

Test feature

Acceptance
criterion:
OK

Date

Signature

2.1 Check for electromagnetic compatibility

     

2.2 Checking of safety devices and alarms in accordance with test protocol OQ1

     

2.3 Identification of the quality-influencing ("critical") operating functions in accordance with test protocol OQ2

     

2.4. Checking of the quality-influencing ("critical") operating functions in accordance with test protocol OQ3-7

     

2.5 Check of the environmental conditions

     

2.6 Test run of the facility (adjustment of process parameters, placebo)

     

2.7 Testing of measuring and control technology equipment

     

2.8 Testing of the automation (process control system)

     

2.9 Testing of data transfer to interfaces

     

2.10

     

2.11

     

2.12

     

2.13

     

2.14

     

3. Comments




4. Qualification result

m Accepted

 

m  Not accepted, due to



Measures required

6.F.2 Example: Fluid bed dryer

Only the measures that must be carried out (sometimes using forms) during operational qualification are listed below using a fluid bed dryer for illustration purposes. Computer validation measures are dealt with in chapter 9 Computer Validation.

Test equipment required for qualification

The test equipment required to carry out the operational qualification (OQ) must be listed (see figure 6.F-7). It must be ensured that the calibration can be traced back to certified standards, e.g. national norms, NIST (National Institute of Standards and Technology) or corresponding institutions. It must be checked that the time interval prior to recalibration has not been exceeded. Copies of the documents from the last calibration of the test equipment used must be included with the equipment/qualification documents.

Figure 6.F-7 OQ form - testing equipment

Description
of equipment

Manufacturer

Serial number

Calibration
interval

Date of last
calibration

Date/
signature

Stop watch

Solex

       

Multimeter

Fluke

       

Calibrations

The quality-relevant M&C points (measuring and control points) have been named. A copy of the compiled list can be found in the installation qualification report. The measuring circuits must be calibrated before the operational qualification is carried out. A copy of the calibration report is saved in the OQ report (see chapter 4.G Calibration).

Alarms

All alarms that indicate malfunctions in the facility must be checked by simulating the appropriate malfunctions. The type of simulation must be described in the form and documented. Care must be taken to ensure that only authorised personnel carry out these simulations.

Safety devices/locks

Figure 6.F-8 OQ form - safety

No.

Facility

Description

functioning
correctly
yes/no

Date/
signature

1

Emergency
stop button

The facility halts operation as soon as the button is pressed. All motors and pumps are switched off and the valves for utilities supply are no longer supplied with electricity.

Press the emergency stop button when the facility is in operation:

All motors stop moving.

   

The valves for the utility supply are closed.

   

All safety devices in the facility must be checked to make sure that they are functioning correctly. "Safety devices" means all equipment that protects the operator from personal injury and the facility from improper handling. The tests may be documented with the aid of the form (see figure 6.F-8).

Flow rate test

The facility is started with a flow rate of 1000 m3/h without heating output and without product (this corresponds to the minimum capacity). The air velocity is measured and recorded at three different measuring points. This measurement is then repeated with a flow rate of 3500 m3/h and 6000 m3/h. The values determined at the various measuring points are compared with one another and assessed. The test is documented using a form.

Volume flow regulation

A check must be carried out to verify that the flow rate is being controlled correctly using three different flow rates. This involves starting the facility with a flow rate of 1000 m3/h without heating output and without product. This setting is maintained for 15 minutes. The flow rate is then increased to 3500 m3/h for a further 15 minutes and then finally to 6000 m3/h for 15 minutes. During this time the control must maintain a stable value that falls within the specified range. The tolerance values are specified in a form where the results are also documented.

Spray rate

The facility is to be prepared as if a product cycle was about to be carried out. It is started with a flow rate of 2000 m3/h without heating and without product. The spray medium to be used is water. Measurements must be carried out for 10 minutes with the minimum, with 50% and with the maximum spray rates respectively. The spray quantity is determined by weighing. The trial must be carried out three times for each spray rate which must not deviate by more than ±5%. The tests are documented in a form.

Heat distribution

To check the heat distribution, the facility must be prepared as if a product cycle was about to be carried out and must be started with a flow rate of 3000 m3/h without a product load. The temperature is set at 50 °C. Following a five minute warm-up phase, the temperature is measured at five different points above the sieve screen for 10 minutes. None of the measured values may deviate by more than ±5 °C from the average value determined above the screen. The trial is repeated at 80 °C and 110 °C. The tests are documented in a form.

Temperature control

The temperature control is checked without a product with a flow rate of 5000 m3/h, at 50 °C, 80 °C and 110 °C respectively. After the five minute warm-up phase the temperature must settle down to a constant level which is maintained for 10 minutes. The same procedure is then carried out for temperatures of 80 °C and 110 °C respectively and the control checked. The deviations must not be more than ±5 °C from the preset value. The results must be documented. A printout of the plot must be included with the OQ report.

Screen masks

Checks must be carried out to verify whether the screen masks perform the functions they have been assigned. It must be ensured that the operational parameters can be modified within their assigned limits. It must be possible to save new formulations with the programmed operational parameters and retrieve data again. The temperature, humidity and pressure values displayed are checked during calibration. A hardcopy of each screen mask must be made and amended to the form.

Equipment functions

This involves testing of specific functions of the facility such as the "on/off" or "raise/lower". The decision as to which tests should be carried out is based on results from the risk analysis (see chapter 6.B.6 Risk analysis). The tests are documented in a form.

Product cycle

To check the entire sequence of functions in context, a trial run must be carried out with the product. The manufacturing instructions for the product must be used as the basis for the trial run. The final product is tested in accordance with the approved test specifications. The performance of the test and the results must be documented (see figure 6.F-9). The product cycle data may be used as well for the performance qualification and process validation.

Figure 6.F-9 OQ form - product cycle

Product cycle

Results correct:
yes/no

The product cycle was implemented in accordance with the manufacturing instructions.

 

It was possible to implement the product cycle without interruption.

 

The manufacturing steps were processed correctly.

 

The step enabling conditions were achieved and identified.

 

No process-related malfunctions occurred.

 

The preset process parameters were complied with.

 

The product was tested in accordance with existing guidelines and corresponds with the specifications.

 

Comments:

Date/signature:

Batch record

The recording of a batch starts when the process begins and ends when the container is lowered. It must be ensured that the process data entered and the measured values gathered in the batch record is reproduced correctly. To check this, the batch record for the test run described above must be additionally recorded manually in a form. Once the trial has ended, the batch record which is generated automatically is compared with the manually recorded data. There must be no deviations.

Data backup

Checks must be carried out to determine how the system responds in the event of a power/utilities failure. It must be ensured that the operating data that has accumulated up to this point is not lost in the event of a sudden power/utilities failure. The facility must also be capable of continuing with the last process status following restoration of the power/utilities and subsequent confirmation. There must be no deviations in the parameters set or the process data. The test is documented using a form.

Access protection

It must be demonstrated that unauthorised individuals cannot access the system and manipulate data. A check must be carried out to determine whether operational parameters can only be modified by authorised personnel. The test is documented using the form.

Deficiency report

Deviations identified during the operational qualification must be documented in the deficiency report. The responsible department defines corrective actions, names the departments or persons responsible, specifies deadlines, and initiates implementation of the measures. All corrective measures performed must be documented.

It must be ensured that changes made, as a result of corrective actions, are assessed and documented in accordance with the established change control procedures, and a requalification carried out as required.

Summary

During operational qualification (OQ) the functionality of the installed equipment in the intended working area is tested and documented. The risk analysis forms the basis for the scope of testing at the individual qualification steps. Deviations that occur can lead to interruption of the qualification activities. They must be eliminated and documented.
Successful execution of the IQ and OQ is the requirement for reaching the qualified status for a facility.


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