This guide explains the Rapid Mixer Granulator PQ process in a practical and easy-to-follow manner. It covers qualification responsibilities, prerequisites, equipment operation, placebo and drug-product trials, sampling locations, mixing uniformity, acceptance criteria, deviations, change control, corrective actions and final qualification reporting.
What is Rapid Mixer Granulator PQ?
Performance Qualification (PQ) of a Rapid Mixer Granulator is documented evidence that the equipment can consistently perform its intended function throughout the established operating range.
The purpose of the study is not simply to confirm that the machine operates. The study also demonstrates that the RMG can produce the expected mixing and granulation performance under defined operating conditions.
The supplied protocol describes PQ as a means of demonstrating reproducibility and consistent performance of the RMG within its operating range and according to specified requirements and cGMP expectations.
During PQ, the performance of the equipment is evaluated using defined checks, observations and analytical results. The results are then compared with predetermined acceptance criteria.
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Objective of Rapid Mixer Granulator PQ
The main objective of RMG Performance Qualification is to provide documented evidence that the Rapid Mixer Granulator and its associated systems perform as intended.
The qualification study is designed to:
- Demonstrate reproducible and consistent performance of the RMG.
- Verify the established operating range.
- Document the performance of the equipment at defined operating conditions.
- Evaluate the equipment under appropriate operating conditions.
- Confirm that the RMG performance is suitable for the process for which it is intended.
- Record the results of performance tests and in-process checks.
- Establish documented evidence supporting consistent equipment performance.
The supplied document specifically identifies reproducibility, consistent performance across the operating range and documentation of operational performance as key objectives of the qualification.
Scope of Rapid Mixer Granulator PQ
This qualification protocol applies to the Performance Qualification of the Rapid Mixer Granulator used for pharmaceutical manufacturing.
The protocol covers:
- Qualification responsibilities.
- RMG process description.
- Qualification prerequisites.
- Required supporting documents.
- Calibration status of instruments.
- Product and batch information.
- Performance evaluation using placebo formulation.
- Performance evaluation using drug products.
- Sampling plan.
- Mixing uniformity analysis.
- Acceptance criteria.
- Deviation handling.
- Change control.
- Corrective actions.
- Summary and conclusion.
- Final approval of the qualification report.
The supplied document defines the scope around the RMG PQ activity and includes the procedures, responsibilities, documentation, acceptance criteria, change control and qualification requirements.
Qualification Team and Responsibilities
RMG Performance Qualification is a cross-functional activity. The supplied protocol identifies the following departments as part of the qualification team:
- Quality Assurance
- Production
- Quality Control
- Engineering
Each department has a specific role during preparation, execution, review and approval of the qualification activity.
| DEPARTMENT | RESPONSIBILITIES |
| Quality Assurance | Initiation, Review, Approval and Compilation of the Performance Qualification Protocol cum Report. Review of Performance Qualification Protocol cum Report after Execution. Coordination with Production and Engineering to carryout Performance Qualification. Monitoring of Performance Qualification Activity. Post approval of Performance Qualification Protocol cum Report after Execution. Approve any change control generated during the Performance Qualification Study. |
| Production | Review & Pre Approval of Performance Qualification Protocol cum Report. To coordinate & support for execution of Qualification Study as per Protocol. Post approval of Performance Qualification Protocol cum Report after Execution. |
| Quality Control | Review & Pre Approval of Performance Qualification Protocol cum Report. Analytical Support (Microbiological Testing/ Analysis). Post approval of Performance Qualification Protocol cum Report after Execution. |
| Engineering | Review & Pre Approval of Performance Qualification Protocol cum Report. Coordination, execution and technical support in Rapid Mixer Granulator Performance Qualification Activity. Responsible for Trouble shooting (if occurs during execution). Review of Performance Qualification Protocol cum Report after Execution. |
RMG Process Description – Rapid Mixer Granulator PQ
A Rapid Mixer Granulator is used for mixing dry powders or powder blends and for granulating material using a granulating agent and high shear forces.
The RMG described in the supplied document consists of a product bowl with a lid and ports for material and paste addition. The equipment includes a bottom-mounted impeller and a chopper. The discharge assembly is pneumatically operated.
The basic process can be divided into the following stages:
- Charging
- Dry mixing
- Binder addition
- Wet mixing/granulation
- Discharging
Charging and Dry Mixing
Pre-weighed raw materials are charged into the RMG bowl through the charging port located on the top of the bowl.
The material may be transferred using the applicable material-handling arrangement, such as an IPC bin or paste kettle.
The main impeller and chopper are operated according to the defined process parameters. The supplied document describes operation at slow and fast speeds through the PLC, with the process duration controlled through a timer.
During dry mixing, the objective is to achieve a uniform distribution of the powder throughout the bowl.
Wet Mixing and Granulation
After dry mixing, the binder solution is added to the material according to the approved process requirements.
The main impeller and chopper operate together to promote proper wet mixing and granule formation. The process is carried out for the specified time and monitored through the equipment operating panel.
The supplied protocol notes that the ampere load displayed on the operating panel is monitored during this operation.
Important observations during this stage include:
- Uniformity of the wet mass.
- Granule formation.
- Absence of dry powder lumps.
- Consistency of the material at different sampling locations.
Discharging
After completion of the granulation process, the material is discharged from the RMG through the pneumatically operated discharge assembly.
The discharge operation should be observed during PQ to confirm that the product is discharged efficiently and that no abnormality affecting the operation is observed.
Acceptance Criteria for Rapid Mixer Granulator PQ
The qualification is considered acceptable when the specified conditions and checks are successfully completed and the optimum operating conditions have been established, including appropriate simulation of worst-case conditions where applicable.
Any failure against a defined acceptance criterion should be documented and assessed. Depending on the outcome of the assessment, the equipment or affected component may require rejection, replacement or rectification.
The supplied document specifically requires deviations from acceptance criteria to be reported and evaluated.
When is Requalification of RMG Required?
Requalification should be considered when changes or events may affect the established performance of the equipment.
The supplied protocol identifies the following situations:
Equipment Modification
Requalification may be required when modifications or replacement of spare parts have a direct impact on RMG performance.
Major Repair
Requalification may be required after major repair or modification of the RMG.
Equipment Relocation
Requalification is applicable when the RMG is transferred from one location to another within the same premises.
Process Trend Variation
If product trend data indicate variation in a previously established process, parameters associated with RMG performance may need to be evaluated.
Periodic Qualification
Periodic qualification may also be performed according to the site’s established qualification program.
These conditions are specifically included in the supplied document’s requalification criteria.
Prerequisites Before Rapid Mixer Granulator PQ
Before beginning the PQ activity, all required supporting documents and records should be checked.
The supplied protocol identifies the following documents for verification:
| S. No. | Document |
| 1 | DQ Protocol cum Report |
| 2 | IQ Protocol cum Report |
| 3 | OQ Protocol cum Report |
| 4 | SOP for Operation and Cleaning of Rapid Mixer Granulator |
| 5 | SOP for Preventive Maintenance of Rapid Mixer Granulator |
The availability status should be documented and checked by Engineering and verified by Quality Assurance.
Calibration Status of Instruments
Before executing the qualification, instruments used for measurements and evaluation should have their calibration status verified.
The qualification document provides fields for recording:
- Instrument name.
- Purpose.
- Instrument identification number.
- Calibration date.
- Calibration due date.
- Engineering verification.
- Quality Assurance verification.
This ensures that measurements generated during qualification can be associated with instruments having documented calibration status.
Test Product and Batch Information
The qualification protocol requires the relevant product or placebo batch information to be recorded before execution.
The required information includes:
- Product name.
- Batch number.
- Batch size.
- Manufacturing date.
- Expiry date.
- Placebo formulation, where applicable.
- Drug product information.
The supplied document specifically provides a section for recording product and batch information before qualification activities.
Performance Evaluation Using Placebo Formulation
The placebo study is used to verify equipment performance within the operating range established during Operational Qualification.
It also helps establish the performance-based operating range for the PQ activity.
The supplied protocol identifies the following checks:
Power Consumption
- Impeller ampere load with product.
- Chopper ampere load with product.
Dry Mixing
- Appearance of dry mix at different locations.
Wet Mixing/Granulation
- Appearance of wet mix.
- Uniformity of cohesive wet mass.
- Granule formation.
- Presence of dry powder lumps.
- Product discharge function.
These checks are included in the source document’s placebo performance evaluation section.
Procedure for Placebo Performance Evaluation
The general procedure described in the supplied protocol is:
- Load the sifted raw material into the RMG bowl.
- Perform dry mixing according to the parameters and instructions specified in the applicable BMR.
- Visually check the powder mixing inside the bowl.
- After completion of the specified dry mixing time, collect samples from different locations.
- Examine the samples for uniformity of appearance.
- Add the binder solution to the RMG.
- Perform wet mixing for the specified time.
- Collect samples from different locations.
- Examine the wet mass for uniform consistency.
- Check for the presence of dry powder lumps.
Placebo Acceptance Criteria
The supplied protocol establishes the following basic acceptance requirements:
- Power consumption should remain within the equipment specification.
- Dry mixed material should be uniform.
- Wet mixed material should be uniform.
- Dry powder lumps should not be present in the wet mixed samples.
Rapid Mixer Granulator PQ– Sampling Plan
The supplied protocol specifies a total of 10 samples for the stated sampling plan.
The sampling arrangement is:
| Sampling Area | Sample Locations |
| Upper layer | U1, U2, U3 |
| Middle layer | M1, M2, M3 |
| Bottom layer | L1, L2, L3 |
| Composite | 1 composite sample |
| Total | 10 samples |
Each sample is specified as three times the average weight in the supplied document.
Performance Evaluation Using Drug Products
After the equipment performance is evaluated using the placebo formulation, performance evaluation using drug products is carried out according to the approved qualification plan.
The purpose is to verify that the RMG performs consistently within the established operating range and that the predefined product-related acceptance criteria are achieved.
The source document identifies the following objectives:
- Verify RMG performance within the established operating range.
- Generate documented evidence of consistent performance.
- Confirm that test parameters meet predefined acceptance criteria for the granulated product.
Checks During Drug Product Evaluation– Rapid Mixer Granulator PQ
The following checks are included in the supplied protocol:
Dry Mixing
- Appearance of dry mix at different locations.
Wet Mixing/Granulation
- Appearance of wet mix.
- Uniformity of cohesive wet mass.
- Granule formation.
- Presence of dry powder lumps.
- Product discharge function.
Mixing Uniformity Analysis
Mixing uniformity is an important part of the RMG performance evaluation.
The supplied report provides a results table for different sampling locations and includes:
- U1
- U2
- U3
- M1
- M2
- M3
- L1
- L2
- L3
- Average value
- Composite sample
- % RSD
The results can be documented separately for the placebo batch and the three drug-product batches identified in the qualification report.
Mixing Uniformity Sampling Locations
The sampling locations are distributed throughout the RMG bowl to provide representation from different areas.
Upper Layer
- U1
- U2
- U3
Middle Layer
- M1
- M2
- M3
Lower Layer
- L1
- L2
- L3
Additional Results
- Average value
- Composite sample
- % RSD
This arrangement allows the qualification team to evaluate whether the material is adequately mixed throughout the sampling locations defined in the protocol.
Deviation During RMG Qualification
Any deviation or modification identified during Performance Qualification should be documented.
The supplied document states that deviations or equipment modifications should be handled according to the applicable change control procedure. An assessment should be performed when changes or modifications are proposed.
A deviation record should include appropriate information such as:
- Serial number.
- Specification or requirement.
- Description of deviation.
- Review/check.
- Verification.
- Final assessment.
Change Control
Changes associated with the equipment or qualification activity should be controlled through the approved change control system.
The supplied document specifies that change control should be authorized and approved before corrective actions are undertaken and that the change control should be recorded.
A change control record may include:
- Change control title.
- Change control number.
- Description of proposed change.
- Review.
- Verification.
- Approval.
Corrective Action
When a deviation or qualification failure requires corrective action, the action should be documented against the approved change control or applicable procedure.
The supplied report provides a corrective-action section covering:
- Deviation.
- Corrective action.
- Action taken by vendor.
- Checked by.
- Verified by.
The actual corrective action should always be based on the investigation and approved assessment rather than being predefined without evaluating the cause.
Summary of Rapid Mixer Granulator PQ
After completion of the qualification activities, the results should be summarized.
The final summary should clearly state:
- Qualification activities performed.
- Batches or placebo runs evaluated.
- Major observations.
- Analytical results.
- Deviations, if any.
- Change controls, if any.
- Whether acceptance criteria were achieved.
The supplied protocol includes separate sections for Summary, Conclusion and Recommendation following completion of the PQ activity.
Conclusion of RMG PQ
The conclusion should clearly state whether the Rapid Mixer Granulator demonstrated satisfactory performance under the conditions evaluated.
The conclusion should be based on the actual documented results and approved acceptance criteria.
A typical conclusion section should address:
- Whether the equipment performed as intended.
- Whether the operating range was successfully evaluated.
- Whether mixing and granulation results met the defined criteria.
- Whether any unresolved deviation remains.
- Whether the equipment can proceed according to the site’s approved qualification status.
The supplied document leaves dedicated fields for recording the final conclusion and recommendation after execution.
Protocol Post-Approval
Following completion and review of the qualification report, the final documentation is approved by the responsible departments.
The supplied document provides approval fields for:
- Engineering Head
- Quality Control Head
- Quality Assurance Head
The approval section includes department, name, signature and date.
Rapid Mixer Granulator PQ Checklist
Before closing the qualification, verify that the following records are complete:
Approved PQ protocol available.
DQ completed and available.
IQ completed and available.
OQ completed and available.
Equipment SOP available.
Cleaning procedure available.
Preventive maintenance SOP available.
Calibration status verified.
Product/batch details recorded.
Placebo evaluation completed, where applicable.
Drug-product evaluation completed.
Sampling performed according to approved plan.
Mixing uniformity results reviewed.
In-process observations documented.
Acceptance criteria evaluated.
Deviations documented, where applicable.
Change controls documented, where applicable.
Corrective actions documented, where applicable.
Final summary completed.
Final conclusion completed.
Recommendation recorded.
QA approval completed.
QC approval completed.
Engineering approval completed.
Frequently Asked Questions About Rapid Mixer Granulator PQ
What is RMG Performance Qualification?
RMG Performance Qualification is a documented study used to demonstrate that a Rapid Mixer Granulator performs consistently and reproducibly within its established operating range.
Why is RMG PQ performed?
RMG PQ is performed to provide documented evidence that the equipment can perform its intended mixing and granulation functions consistently under defined conditions.
What is checked during RMG PQ?
The supplied protocol includes checks such as impeller and chopper ampere load, dry-mix appearance, wet-mix appearance, wet-mass uniformity, granule formation, dry powder lumps and discharge performance.
How many samples are specified in the supplied RMG PQ protocol?
The supplied protocol specifies 10 samples: three from the upper layer, three from the middle layer, three from the bottom layer and one composite sample.
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