SOP for Millrock Bench-Top Freeze Dryer

OBJECTIVE

This SOP describes the procedure for the operation of the Millrock Bench-Top Freeze-Dryer.

SCOPE

Freeze Drying, or lyophilization as it is referred to in the Pharmaceutical and Diagnostic industries, is a dehydration technique, which enables liquid or slurry products, which have previously been frozen to be dried under a vacuum. The applications of freeze-drying are numerous, such as

1. Preservation of temperature-sensitive products, particularly those of biological origins, such as enzymes, blood plasma, vaccines, etc.
2. To achieve a chemical balance, such as for biological reagents.
3. To provide a practical solution for certain delivery problems, for example, the packaging of constituents that cannot be mixed in the liquid state, but which are solidified in successive stages and then freeze-dried.
4. To implement an important stage of a product (such as concentration).
5. To improve storage life and improve marketing of the pharmaceutical product.

RESPONSIBILITIES

• It is the responsibility of the QC Analyst to ensure adherence to this procedure.
• It is the responsibility of the QC Manager to follow the instructions of this procedure.

DEFINITIONS

• Biological materials typically must be dried to stabilize them for storage, preservation, or shipping. Many times, drying causes damage and some loss of cellular or protein activity.
• Lyophilization, called freeze-drying, is a method of sample preservation that significantly reduces damage to biological samples.

PRECAUTIONS

• Wear Appropriate Eye Protection At All Times When Working With Or Anywhere Near A Lyophilizer.
• For Medical Emergencies, Fires, Or Explosions, Call the emergency number Immediately And Report The Details Of The Incident.
• If solvents are part of the product being freeze-dried, they may be flammable or hazardous. Proper precautions should be taken.
• Acids and bases may cause damage to the stainless steel and vacuum pump.
• If the gas ballast is left open for extended periods, the oil can be pumped out the exhaust, causing the pump to fail.
• Do not fill the chamber above the vacuum port as water will enter the vacuum tubing and drain into the vacuum pump.
• Do not chip the ice from the condenser or chamber If acid or base products are collected, immediately neutralize and dispose of them properly.

ALSO READ: SOP for the Performance Verification of an LC-MS system

PROCEDURE

Inspection of glassware & seals

NOTE: Use only glassware designed for the lyophilizer!!

• The lyophilizer, when in good working order, should have a pressure of 5-50 milliterr (normal atmospheric pressure is 760 torr), as indicated on the LED screen. (If the pressure is outside of this range, contact one of the people listed above.) This means that all glassware attached and under vacuum on the lyophilizer represents a significant implosion hazard.
• All glassware used on the lyophilizer must be free of any visible defect (cracks, chips, or scratches), no matter how seemingly minor. Any glassware that is defective in this way must not be used under any circumstances. If such glassware is found, it should be discarded. The seals themselves are somewhat more forgiving, in that a defective seal reduces the vacuum. However, defective seals should still be removed from service.
• A greater risk is present in seals that connect two pieces of glass. All seals of this type place rubber between joined pieces of glass. If these seals are used improperly, the glass pieces come into contact and scratch each other during installation. These scratches compromise the integrity of the glass thus creating a potentially serious implosion hazard. Install any seals of this type carefully to avoid this; if you are uncertain of how to do this do not proceed until you have received further training from one of the contact people given above.
• Most vacuum pumps are supplied with a gas ballast adjustment. It is recommended that the gas ballast be closed during the operation of the Freeze Dryer.

• Push the RUN button 2X

1. The first time you press the run button the displays a reminder to check the system.
2. The second press activates the freeze-drying run.
3. The Condenser will get below -40°C (CTVAC) within 10min (CTtim).
4. After 10 minutes of operation, the vacuum pump will start.
5. A vacuum will go to 500mT(VACRDY) within 10min(VACtim):
6. If NO - an alarm will sound and “VACU > 500mT, after 10min” will flash on the lower part of the screen.
7. If YES – then “READY FOR FREEZE DRYING” will flash at the top of the screen.

Adding product to the manifold for freeze-drying

• Make sure that the product is frozen in the flask before attaching it to the freeze dryer.
• When a freezing product is in flasks, the flask should be tilted on its side.
• If the flask is not tilted the expansion of freezing will break the flask.
• Attach the flask to the vacuum valve using a ¾” to ½” adapter.
• Make sure that the adapter is greased.
• Slowly open the valve to apply a vacuum to the flask.
• Wait for the “READY FOR FREEZE-DRYING” indication before adding additional products.

Removing products from the system

• To remove the product from the system, you must remove the vacuum in the flask/vial/container (without removing the vacuum in the freeze dryer). Simply turn the valve stem past closed to release the vacuum. The vacuum is released through a small opening in the valve stem.

Defrost

• When a sufficient amount of material accumulates on the condenser, the frozen material will obstruct the vapor flow. At this point, the system must be defrosted.
• Remove any unfinished product and keep it frozen. The Opti-dry offers hot gas defrost to speed up the defrosting process.

1. Add approximately 1 liter of warm water to the condensing chamber, making sure not to fill above the vacuum port at the rear of the chamber.
2. Press the “DEFROST” button.

• The compressors will direct hot gas to the condenser coil until it reaches +40°C then cycle off. If the presence of cold water is detected the controller will repeat the process until all ice is melted.

ABBREVIATION

QC: Quality Control

ANNEXURE

Nil

REVISION HISTORY

Nil

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