The functional testing of the freeze-drying process and stoppering system is an essential quality assurance procedure in the pharmaceutical and biotechnology industries. This comprehensive process ensures the correct operation of freeze-drying equipment, stoppering mechanisms, and pressure equalization systems.
By verifying these functionalities, manufacturers can guarantee reliable and consistent outcomes, critical for producing stable, freeze-dried products. This article outlines the purpose, required instrumentation, acceptance criteria, and procedural steps involved in conducting these functional tests.
Purpose The purpose is to check the correct freeze drying process function, stoppering function and pressure equalization function.
Test Documents: Document name Document number Version number of pages List of parameters: 2 LOE 1982-001A-1J Pin chart Freeze drying PC1982FD, a  program Batch Report 1 Functional Specification # N/A S1982-1E
Note: If column “number of pages” is blank, the listed documents, which contribute to the determination of the test result, must be attached to the qualification binder (see B Attachments). Please mark the test documents and printouts on the first page with the “Qualification Document” stamp.
Required Instrumentation and Auxiliary Means
Type of Equipment Type, model/version number Serial Number Calibration valid until
Acceptance Criteria
- Correct function of the freeze drying process according to the pin chart.
- Correct function of the stoppering system.
- Correct pressure equalization between chamber and condenser.
 Implementation
- The functional test is based on the process flow chart (pin chart).
- Possible instructions and notes in the test documents are to be considered.
- The freeze drying unit must be switched on, and all supply media must be connected and present. No failure messages, which have an impact on the implementation, are displayed on the SCADA system.
- The tester must be appropriately assigned to the freeze drying unit and the SCADA system.
 Verification of the Freeze Drying Process
The verification of the freeze drying process takes place in accordance with the test document LOEE1507-001A-1 and the pin chart PC1507FD.
For testing of the whole freeze drying process, you have to start two freeze drying processes with different conditions, e.g., if during the first process cooling is chosen, the second process must be done with heating, and all other parameters have been set up to have the most possible variance between both processes. Please enter the general parameter and the freeze-drying recipes that are described in document LOEE1507-001A-1 and start the processes.
Compare the state of components (valves, motors, and heating elements) on the pin chart with the displayed state of components on the SCADA system. Tick off all checked states of components on the pin chart. The pin chart and batch report have to be attached to this OQ document after testing.
Acceptance criteria: Correct state of components (valves, motors, and heating elements) during the whole freeze drying process run according to the pin chart. Test result (pass / fail) Implemented (date / signature)
Verification of the Correct Function of the Stoppering System (manual)
 Lower Shelves with Push Buttons
Description:
- Press the button “Down” and keep pressing to check the lowering of the shelves
- Release the button “Down” to check the interruption of the lowering of the shelves.
- Press the button “Down” and keep pressing down to lower the shelves to their final position I (PT 2.30).
Acceptance criteria:
- The shelves move down as long as the button “Down” is pressed.
- The lowering of the shelves is interrupted
- The shelves are lowered until they reach their final positionÂ
Test result (pass / fail)
Raise Shelves with Push Buttons
| Description | Acceptance criteria | Test result |
| Press the button “Up” and keep pressing to check the raising of the shelves | The shelves move up as long as the button “Up” is pressed. | Â (passed) |
| Release the button “Up” to check the interruption of the raising of the shelves | The raising of the shelves is interrupted. | (pass) |
| Press the button “Up” and keep pressing to raise the shelves to their final position | The shelves are raised until they reach their final position. | (pass) |
Acceptance criteria: Correct function of the manual stoppering system Test result: pass/fail
Check the stoppering System (Automatic)
Start any freeze drying process with the option “Automatic Stoppering” to check the stoppering system. The test can be done together with the PIN chart verification.
| Description | Acceptance criteria | Test result (pass / fail) | Implemented (date / signature) |
| Select any freeze-drying recipe with the options “Vials” and “Automatic Stoppering.” Start the freeze-drying process. | The stoppering function is performed correctly during the freeze drying process. | Test result pass | 02/01/2025 |
Acceptance criteria: correct function of the automatic stoppering system during freeze drying.Test result found satisfactory (pass) and Implemented (date / signature) 02/01/2025
Pressure Equalization between Chamber and Condenser when P chamber < P condenser
Prepare Pressure Equalization
- Enable manual mode at the SCADA control.
- Evacuate the chamber and condenser to approximately 700 mbar.
- Vent the condenser manually to approximately 900 mbar (Pchamber < Pcondenser)
- Switch over to automatic mode at the SCADA control.
- Start a freeze-drying process with the freezing phase.
Observe the Valve Positions during Primary Drying
Observe the valve positions on the SCADA screen during the single steps of pressure equalization and confirm them in the following table.
| Step | Test result (pass / fail) | Implementation (date / signature) |
| 01) Pressure equalization through venting valves until chamber pressure = condenser pressure (+/- parameter ) according to Chart | Passed | 02/01/2024 |
| 02) Close venting valves according to the pin chart and valves are open to prepare the pressure equalization | pass | 02/01/2023 |
| 03) Open the chamber/condenser valve: Valve is opened after the waiting period, which is defined in the general parameters menu | Pass | 02/01/2025 |
Acceptance criteria: Correct pressure equalization between chamber and condenser through steps 1 to 3. And Test result  (pass / fail) and Implemented (date/signature)
For troubleshooting related to pressure deviations and venting issues, refer to our detailed guide here.
Pressure Equalization when Pcondenser < Pchamber
- Prepare Pressure Equalization
- Enable manual mode at the SCADA control.
- Evacuate the chamber and condenser to approximately 700 mbar.
- Vent the chamber manually to approximately 900 mbar (Penamber 7 Peondenser):
- Switch over to automatic mode at the SCADA control.
- Start a freeze-drying process with the freezing phase.
Observe the Valve Positions during Primary Drying
Observe the valve positions on the SCADA screen during the pressure equalization and include them in the following table.
| Step | Test (pass/fail) | Implemented (date/signature) |
| 01. Pressure equivalent through valves until chamber pressure = condenser pressure (+ parameter): Valves are opened to vent the condenser to the chamber pressure (Pchamber = condenser) | Pass | 02/01/2025 |
| 2. Open the chamber/condenser valve: Valve 5V1 is opened after the waiting period, which is defined in the general parameters menu. | Pass | 02/01/2025 |
Acceptance criteria: Correct pressure equalization between chamber and condenser through steps 1 to 2. Test Result passed and Implemented by date and sign
Conclusion
The functional test of the freeze-drying process and stoppering system is vital for maintaining operational accuracy and ensuring product integrity. By adhering to predefined acceptance criteria and systematically verifying the process flow, the test mitigates risks associated with equipment malfunctions. Proper execution of these tests guarantees optimal performance, paving the way for high-quality freeze-dried products.
Summary
This guide covers the purpose, methodology, and acceptance criteria for functional testing of freeze-drying processes, stoppering systems, and pressure equalization. It details the required documents, equipment, and step-by-step procedures, emphasizing the significance of maintaining accurate pressure balance and system functionality. Adhering to these protocols ensures equipment reliability and consistent production quality.
FAQs
1. Why is functional testing of the freeze-drying process important?
Functional testing ensures that the freeze-drying system operates correctly, minimizing risks and maintaining product quality by verifying essential components such as the stoppering system and pressure equalization.
2. What are the key acceptance criteria for these tests?
Key acceptance criteria include:
- Accurate freeze-drying process operation per the pin chart.
- Proper manual and automatic stopper functionality.
- Correct pressure equalization between the chamber and condenser.
3. What documents are required for the functional test?
Documents like the pin chart, freeze-drying recipes, and batch reports are essential, along with functional specifications and calibration certifications.
4. Can these tests be automated?
Yes, many modern systems integrate automated functionalities, such as automatic stoppering, which streamline the verification process and enhance accuracy.