In the field of pharmaceutical manufacturing, producing a high-quality product is not related to how well you design and install equipment but it’s also about consistent operation under actual working conditions. This consistency is what both regulatory agencies and patients require.
Performance Qualification (PQ) is the last step of the qualification lifecycle and is the most important because it verifies that all of the equipment, utilities, systems, etc. will operate effectively and consistently in real-time production or in a simulated environment.
PQ therefore serves as evidence of product performance when it answers the key question, “Will this system provide consistent and compliant output while operating in the routine manner of manufacturing?” PQ provides evidence of both the technical performance of the system and the operational assurance that the system operates as anticipated in the context of GMP and user expectations.
The order of qualifications generally follows this flow:
1. Design Qualification (DQ) – Determines the appropriateness of the design.
2. Installation Qualification (IQ) – Confirms that the system was installed properly.
3. Operational Qualification (OQ) – Tests the capability of the equipment at specified operation conditions.
4. Performance Qualification (PQ) – Verifies the steady-state operational capability of the equipment under actual operating conditions.
PQ is the last step to verify the system prior to releasing for GMP manufacturing.
Annex 15 of the European Union GMP documents state the following regarding Performance Qualification: “Performance qualification provides evidence that the system consistently and reproducibly delivers a product as defined in the approved process method and the associated product specifications.”
Annex 4 of the World Health Organization (WHO) Technical Report Series (TRS) No. 937 states: “Performance Qualification confirms that an equipment or system operates consistently and reproduces the defined limits when the equipment or system is used in the intended manufacturing process.”
Section 211.110(b) of the Federal Drug Administration (FDA) Code of Federal Regulations Title 21 (21CFR) states: "An establishment’s control procedure must monitor the manufacturing process output and validate the effect of variations in in-process material and drug product characteristics on the effectiveness of the finished drug product."
Performance qualification, therefore, serves as regulatory proof that the equipment or system can consistently reproduce an approved drug product before it is marketed.
The PQ protocol includes but is not limited to:
1. The Objective and Scope of the qualification.
2. Identification of equipment and systems being qualified.
3. Documents referenced (URS, DQ and IQ and OQ).
4. Definition of test parameters including sampling plan.
5. Identification of instruments used for testing and calibration references.
6. Format of data records and reporting of results.
7. Deviation & CAPA procedures.
8. QA review structure for production qualification protocols.
The PQ protocol must be approved by the quality assurance (QA) department before conducting the PQ tests.
Download Performance Qualification Sample Protocol
Typical activities associated with testing include:
- operating three batches of production or simulated production consecutively;
- monitoring key process parameters including temperature, pressure, flow rate, speed and time;
- collecting samples and testing outputs to ensure continuous format consistency and compliance;
- evaluating control system responses and alarms during operations;
- evaluating process reproducibility among multiple runs.
The execution stage verifies the performance consistency of an equipment and its ability to control processes.
- Batches
- Locations of equipment (e.g. top, middle and bottom of trays)
- Time intervals
For example:
- Performance qualification of tablet coating machines consists of taking samples from multiple pans and time intervals
- In purified water generation system evaluating samples from the various user points to guarantee consistent water quality.
All performance qualification sample's analytical results are evaluated using pre-established statistical acceptance criteria to determine if there is sufficient reproducibility of the sample.
For example:
For every deviation documented the following must be included:
F. Compilation of PQ Report
The PQ report is a comprehensive record of all test results, observations, deviations and conclusions.
The PQ report will contain:
2. Production: Responsible for operating the system and providing input for the process
3. Engineering: Responsible for supporting operational checks and maintenance of the system
4. Quality Control: Responsible for sampling and testing
5. Quality Assurance (QA): Approve protocols, monitor testing and review reports
1. Heating Ventilation Air Conditioning (HVAC) system will be tested for air velocity, HEPA filter integrity, differential and for long-lasting stability of the temperature and humidity during production.
2. Water Systems will be subject to PQ tests that include the presence of microbes, chemicals and total organic carbon (TOC) at multiple locations (user points) and across timeframes that extend over a period longer than a production cycle.
3. Autoclaves will undergo biological and thermal mapping studies to confirm that sterilization has taken place after usage of the equipment.
4. Production equipment is evaluated for uniformity, efficiency and reproducibility over multiple production uses.
- Sample plans that are inadequate.
- Inadequate batch runs.
- Variable testing conditions
- Acceptance criteria not well defined.
- Slowness to close out deviations.
- No use of statistical analysis.
Each of these may impact the quality of qualification results and attract auditor attention.
2. Simulate Actual Conditions: Generate dynamic type testing instead of static type testing.
3. Use Prequalified Instruments: Only use instruments that have been calibrated to record data.
4. Clearly Define Acceptance Criteria: Eliminate the use of vague acceptance criteria.
5. Ensure QA Oversight: Involve QA in the early process to ensure documentation is in place & prevent quality gaps.
6. Use Statistical Analysis: The goal is to show reproducibility, not simply compliance with established standards.
7. Document Everything: In a GMP facility, if it is not documented, it did not occur.
The OQ stage provides evidence that the equipment is operating as expected.
The PQ stage confirms that the output produced by the equipment meets specified requirements like repeatable, reproducible and consistent.
Completing all three validation stages (IQ, OQ, PQ) assures that the equipment has been validated per GMP.
Performance qualification provides ultimate assurance that the pharmaceutical system will consistently execute as intended through its design specifications to produce products of expected quality and ensure patient safety.
The PQ process also provides documentation of how the equipment should operate and as a result, the user has confidence that it will operate properly, provide consistent and reliable performances in actual manufacturing conditions.
The PQ process, when done correctly ensures that all pharmaceutical systems are ready for operation and that the quality assurance is always in place and there are no inconsistencies in quality from production to distribution.
Performance Qualification (PQ) is the last step of the qualification lifecycle and is the most important because it verifies that all of the equipment, utilities, systems, etc. will operate effectively and consistently in real-time production or in a simulated environment.
Understanding Performance Qualification (PQ)
PQ, which stands for Performance Qualification, is a verification process and procedure for systems and equipment to verify that they perform according to the intended purpose when implemented under routine operating conditions and without fail according to the established specifications.PQ therefore serves as evidence of product performance when it answers the key question, “Will this system provide consistent and compliant output while operating in the routine manner of manufacturing?” PQ provides evidence of both the technical performance of the system and the operational assurance that the system operates as anticipated in the context of GMP and user expectations.
The Purpose of Performance Qualification
The primary reason for the performance qualification (PQ) process is to confirm that all forms of equipment and systems are:- Consistently and reliably operating over a period of time.
- Delivering quality outputs that meet specifications and standards required by both processes and products.
- Capable of functioning properly within a variety of normal, worst-case and long-term operating conditions.
- Preserving data traceability and data integrity through the use of a performance record.
When is Performance Qualification Performed?
Performance Qualification takes place after Operational Qualification (OQ) has been completed successfully and all materials are ready to be produced in full-scale.The order of qualifications generally follows this flow:
1. Design Qualification (DQ) – Determines the appropriateness of the design.
2. Installation Qualification (IQ) – Confirms that the system was installed properly.
3. Operational Qualification (OQ) – Tests the capability of the equipment at specified operation conditions.
4. Performance Qualification (PQ) – Verifies the steady-state operational capability of the equipment under actual operating conditions.
PQ is the last step to verify the system prior to releasing for GMP manufacturing.
Regulatory Expectations for Performance Qualification
Performance Qualification (PQ) is a necessary step for validation of equipment and system according to the requirements of all major regulatory agencies and the Good Manufacturing Practice (GMP) guidelines.Annex 15 of the European Union GMP documents state the following regarding Performance Qualification: “Performance qualification provides evidence that the system consistently and reproducibly delivers a product as defined in the approved process method and the associated product specifications.”
Annex 4 of the World Health Organization (WHO) Technical Report Series (TRS) No. 937 states: “Performance Qualification confirms that an equipment or system operates consistently and reproduces the defined limits when the equipment or system is used in the intended manufacturing process.”
Section 211.110(b) of the Federal Drug Administration (FDA) Code of Federal Regulations Title 21 (21CFR) states: "An establishment’s control procedure must monitor the manufacturing process output and validate the effect of variations in in-process material and drug product characteristics on the effectiveness of the finished drug product."
Performance qualification, therefore, serves as regulatory proof that the equipment or system can consistently reproduce an approved drug product before it is marketed.
Scope of Performance Qualification
The performance qualification (PQ) applies to all GMP critical systems and equipment including:- Manufacturing equipment like granulators, tablet presses, reactors, filling lines and autoclaves.
- Utilities like HVAC systems, purified water system, WFI systems and compressed air.
- Analytical instruments like HPLC, dissolution testers and particle size analyzers.
- Computerized systems like manufacturing execution systems (MES), supervisory control and data acquisition (SCADA) systems, laboratory information management systems (LIMS) and data management systems.
Performance Qualification (PQ) Process
The performance qualification (PQ) process is a formalized, written method for determining whether or not a system will perform consistently under actual production conditions.A. Preparation of the PQ Protocol
The PQ protocol defines the strategy for testing, who is responsible for what, what criteria must be met in order for the test results to be accepted as valid and how the items tested will be documented.The PQ protocol includes but is not limited to:
1. The Objective and Scope of the qualification.
2. Identification of equipment and systems being qualified.
3. Documents referenced (URS, DQ and IQ and OQ).
4. Definition of test parameters including sampling plan.
5. Identification of instruments used for testing and calibration references.
6. Format of data records and reporting of results.
7. Deviation & CAPA procedures.
8. QA review structure for production qualification protocols.
The PQ protocol must be approved by the quality assurance (QA) department before conducting the PQ tests.
Download Performance Qualification Sample Protocol
B. Execution of PQ Tests
The PQ testing phase consists of operations and manipulation of equipment or systems in actual production or simulated production environments.Typical activities associated with testing include:
- operating three batches of production or simulated production consecutively;
- monitoring key process parameters including temperature, pressure, flow rate, speed and time;
- collecting samples and testing outputs to ensure continuous format consistency and compliance;
- evaluating control system responses and alarms during operations;
- evaluating process reproducibility among multiple runs.
The execution stage verifies the performance consistency of an equipment and its ability to control processes.
C. Sampling and Data Analysis
During performance qualification (PQ), samples are taken at predetermined intervals in order to clearly demonstrate consistent results across the following:- Batches
- Locations of equipment (e.g. top, middle and bottom of trays)
- Time intervals
For example:
- Performance qualification of tablet coating machines consists of taking samples from multiple pans and time intervals
- In purified water generation system evaluating samples from the various user points to guarantee consistent water quality.
All performance qualification sample's analytical results are evaluated using pre-established statistical acceptance criteria to determine if there is sufficient reproducibility of the sample.
D. Verification of Critical Parameters
Each equipment or system has critical parameters that directly affect product quality. Verification of these critical parameters must occur to ensure that all parameters remain within their validated or established ranges.For example:
- The validated range for sterilizers and reactors is determined by temperature and pressure.
- The validated range for HVAC systems is airflow and particulate levels.
- The validated range for purified water systems is pH and conductivity levels.
- The validated range for mixers and blenders is speed and torque.
E. Handling of Deviations
Any unexpected findings, non-conforming (out of specification) data or interruptions in the process that occur will be classified and documented as a deviation.For every deviation documented the following must be included:
- Detailed description of the nonconformance.
- Perform a root cause analysis.
- Corrective and preventive action (CAPA).
- Impact on qualification outcome.
F. Compilation of PQ Report
The PQ report is a comprehensive record of all test results, observations, deviations and conclusions.
The PQ report will contain:
- Summary of test results vs acceptance criteria
- Graphs and tables of data showing parameter trends
- The summary of deviations and closure of CAPA actions
- QA review and approval by QA manager
Roles and Responsibilities in Performance Qualification
1. Validation Team: Responsible for writing & executing the PQ Protocol & analyzing data2. Production: Responsible for operating the system and providing input for the process
3. Engineering: Responsible for supporting operational checks and maintenance of the system
4. Quality Control: Responsible for sampling and testing
5. Quality Assurance (QA): Approve protocols, monitor testing and review reports
Performance Qualification in Utilities and Systems
Each system type requires Performance Qualification (PQ) based on how that system operates.1. Heating Ventilation Air Conditioning (HVAC) system will be tested for air velocity, HEPA filter integrity, differential and for long-lasting stability of the temperature and humidity during production.
2. Water Systems will be subject to PQ tests that include the presence of microbes, chemicals and total organic carbon (TOC) at multiple locations (user points) and across timeframes that extend over a period longer than a production cycle.
3. Autoclaves will undergo biological and thermal mapping studies to confirm that sterilization has taken place after usage of the equipment.
4. Production equipment is evaluated for uniformity, efficiency and reproducibility over multiple production uses.
Common Challenges During Performance Qualification
Experienced teams also experience PQ difficulties, including:- Sample plans that are inadequate.
- Inadequate batch runs.
- Variable testing conditions
- Acceptance criteria not well defined.
- Slowness to close out deviations.
- No use of statistical analysis.
Each of these may impact the quality of qualification results and attract auditor attention.
Best Practices for Successful Performance Qualification
1. Risk Assessment-Based PQ: List out all the parameters that will impact product quality in order of criticality.2. Simulate Actual Conditions: Generate dynamic type testing instead of static type testing.
3. Use Prequalified Instruments: Only use instruments that have been calibrated to record data.
4. Clearly Define Acceptance Criteria: Eliminate the use of vague acceptance criteria.
5. Ensure QA Oversight: Involve QA in the early process to ensure documentation is in place & prevent quality gaps.
6. Use Statistical Analysis: The goal is to show reproducibility, not simply compliance with established standards.
7. Document Everything: In a GMP facility, if it is not documented, it did not occur.
Relationship between IQ, OQ and PQ
By confirming that the equipment was installed correctly, IQ is the stage during which we verify that the equipment is functioning correctly.The OQ stage provides evidence that the equipment is operating as expected.
The PQ stage confirms that the output produced by the equipment meets specified requirements like repeatable, reproducible and consistent.
Completing all three validation stages (IQ, OQ, PQ) assures that the equipment has been validated per GMP.
Documentation in Performance Qualification
The complete set of documents contained within the PQ Dossier:- Protocol and report associated with the PQ.
- Calibration certificates.
- Process data sheets associated with the process.
- Sample testing and sampling records.
- Deviation reports and corrective and preventive action reports (CAPA Reports).
- QA approval documentation.
Performance qualification provides ultimate assurance that the pharmaceutical system will consistently execute as intended through its design specifications to produce products of expected quality and ensure patient safety.
The PQ process also provides documentation of how the equipment should operate and as a result, the user has confidence that it will operate properly, provide consistent and reliable performances in actual manufacturing conditions.
The PQ process, when done correctly ensures that all pharmaceutical systems are ready for operation and that the quality assurance is always in place and there are no inconsistencies in quality from production to distribution.
Frequently Asked Questions on Performance Qualification
Q1. What is Performance Qualification (PQ)?
Answer: Performance Qualification (PQ) is a method to attest to the equipment or systems' ability to operate properly and consistently under the conditions of an actual production facility.Q2. Why is PQ important in pharmaceuticals?
Answer: PQ is important in the pharmaceutical industry because PQ provides assurance of reproducibility, data integrity and compliance with the expectations of Good Manufacturing Practice (GMP) as it relates to reliability of manufacturing.Q3. When is PQ performed?
Answer: PQ is performed once OQ has been completed and prior to using the equipment or systems in a routine GMP manner.Q4. What is the difference between OQ and PQ?
Answer: The difference between OQ and PQ is that OQ tests the operational functions of equipment or systems, while PQ demonstrates the ability of the equipment or systems to consistently perform during the course of actual operation.Q5. How many batches are used in PQ?
Answer: In order to demonstrate reproducibility in PQ, it is common to require at least three consecutive batches to demonstrate the equipment or system's ability to operate properly.Q6. What documents are required for PQ?
Answer: For PQ, the following documents need to be available: PQ protocol, PQ report, sampling data, calibration certificates and records of deviations.Q7. Who performs PQ in pharmaceuticals?
Answer: PQ in pharmaceuticals is performed by a validation team and supported by the quality assurance (QA), production and engineering departments.Q8. What happens after PQ approval?
Answer: Upon PQ approval, the equipment or system shall be approved for use in a routine GMP manufacturing environment.
Get ready to use editable Validation Protocols in MS-Word FormatView List
Dear Sir
ReplyDeleteThis blog is very useful and really educated. And I will be more thankful if you can can share PQ protocol sample/template for HVAC and incubator...please send it to:gunawanta.g@supratechnic.co.id
Thankyou
Three reactors are used for same purpose (Hydrolysis). Can I use single Performance Qualification Protocol for the re-qualification of the three reactors? Please suggest.
ReplyDeleteYou you can use same for all but make separate copy for each with their equipment id.
DeleteThank you Sir.
DeleteDear Sir,
ReplyDeleteYour information is very informative and useful for me. Can I ask if you can share some information related to IQ,OQ and PQ for balances using in GMP area, from small scale to large scall. Thanks a lot for your sharing and appreciate for your reply.