SOP for Rapid Mixer Granulator

1.0 OBJECTIVE:

1.1 This document explains how to operate the Rapid Mixer Granulator safely and correctly.

1.2 We want consistent granules from every batch, every time.

1.3 Following this SOP protects product quality and keeps us in line with GMP requirements.

2.0 SCOPE:

2.1 This SOP covers the Rapid Mixer Granulator in the production department.

2.2 Use it whenever you operate, clean, or do maintenance on the RMG.

2.3 It applies to all wet granulation processes for tablets and capsules.

2.4 All operators and production staff working with the RMG must follow this procedure.

3.0 RESPONSIBILITY:

3.1 Operator: Runs the machine, monitors the process, and keeps the area clean.

3.2 Production Chemist: Supervises the granulation, verifies batch records, and handles any issues that pop up.

3.3 IPQA: Provides line clearance and checks cleaning status before the next batch.

3.4 Maintenance: Handles repairs and scheduled servicing of the equipment.

4.0 ACCOUNTABILITY:

4.1 The Production Manager owns this SOP.

4.2 Production Manager signs off on any changes to this procedure.

4.3 Production Manager ensures everyone gets trained before they use the RMG.

4.4 Any deviations must be reported to the Production Manager for review.

5.0 PROCEDURE:

5.1 Pre-Operation Checks:

5.1.1 Start by checking the area. Clean? Good. Now check the machine. You should see a “CLEANED” label attached.

5.1.2 Open the Equipment Usage Log. Write down the date, time, product name, batch number, and your name.

5.1.3 Pull off the “CLEANED” label. Put an “UNDER PROCESS” label in its place.

5.1.4 No Line Clearance Certificate, no starting. Get one from IPQA first.

5.1.5 Gather your documents—BMR, this SOP, and any checklists. Keep them within reach.

5.1.6 Look around. Anything from the previous batch still there? Remove it. Cross-contamination is a serious problem.

5.1.7 Check that the bowl, impeller, and chopper are properly installed and secured.

5.2 Precautions:

5.2.1 The lid stays closed during operation. No exceptions.

5.2.2 Safety interlocks exist for your protection. Never bypass them.

5.2.3 Thinking about modifying the machine? Stop. Get written approval first.

5.2.4 Impeller and chopper spin fast. Really fast. Never reach inside while they’re moving.

5.2.5 Before you install parts, take them apart, or clean—switch off the main power. Do this every single time.

5.2.6 Don’t disable or tamper with safety devices. They’re not optional.

5.2.7 Wipe the control panel with a soft dry cloth only. No liquids.

5.2.8 The machine gets warm during long runs. Let it cool before touching metal surfaces.

5.2.9 PPE is mandatory—gloves, safety glasses, dust mask. Wear them all.

5.2.10 Don’t overload the bowl. Respect the rated capacity or you’ll get poor granules.

5.2.11 A messy area leads to mistakes. Keep it tidy.

5.3 Safety System Checks:

5.3.1 Run these tests once a week. Document everything.

5.3.1.1 Try the main power switch. It should kill power instantly.

5.3.1.2 Hit the emergency stop button. Machine should freeze immediately.

5.3.1.3 Open the lid while it’s running. The impeller and chopper should stop right away.

5.3.1.4 Check the overload relay. Does it trip under excess load? It should.

5.3.1.5 Look at all indicator lights and alarms. Everything lit up and working?

5.4 Machine Components:

5.4.1 Mixing Bowl: This is where all the action happens. Powders go in, granules come out. It’s jacketed for temperature control if needed.

5.4.2 Impeller: The big blade at the bottom. It spins and mixes the powders together. Creates the tumbling action.

5.4.3 Chopper: Smaller blades mounted on the side wall. They spin super fast and break up lumps during wet massing.

5.4.4 Lid: Covers the bowl during operation. Has a port for adding binder solution.

5.4.5 Binder Addition Port: The opening in the lid where you pour or spray the granulating liquid.

5.4.6 Discharge Valve: Located at the bottom of the bowl. Open it to dump wet granules into a container or onto a tray.

5.4.7 Control

Panel: Houses all controls—impeller speed, chopper speed, timer, start/stop buttons, emergency stop.

5.4.8 Ampere

Meter: Shows the current draw of the impeller motor. Useful for monitoring granule formation.

5.5 Assembling:

5.5.1 Power must be off before assembly. Always.

5.5.2 Lower the mixing bowl onto the base. Make sure it sits flush and locks in place.

5.5.3 Attach the impeller to the drive shaft. Hand-tighten first, then use the tool to secure it. Give it a wiggle—no movement allowed.

5.5.4 Mount the chopper on the side shaft. Lock it tight.

5.5.5 Place the lid on top. Engage the locking clamps. All of them.

5.5.6 Check the discharge valve. Closed? Sealed properly? Good.

5.5.7 If you’re using a binder spray system, connect the nozzle and tubing now. Make sure there’s no blockage.

5.5.8 All guards in place? Lid sensor working? Double-check before moving on.

5.6 Operation:

5.6.1 Switch on the main power supply.

5.6.2 The control panel lights up. Check that all displays read correctly.

5.6.3 Load the weighed powders into the bowl as per the BMR. Don’t dump everything at once—add in portions if the batch is large.

5.6.4 Close and lock the lid securely.

5.6.5 Dry Mixing:

5.6.5.1 Set the impeller speed as per BMR. Usually low to medium speed.

5.6.5.2 Keep the chopper off during dry mixing. Or run it at low speed if the BMR says so.

5.6.5.3 Mix for the time specified in the batch record. Usually 3 to 5 minutes.

5.6.5.4 This step blends all the dry ingredients evenly.

5.6.6 Binder Addition:

5.6.6.1 Prepare the binder solution as per BMR. Strain it if needed.

5.6.6.2 With the impeller running, slowly add the binder through the port.

5.6.6.3 Pour steadily. Don’t dump it all in at once—you’ll get lumps.

5.6.6.4 If using a spray system, set the flow rate and let it do its thing.

5.6.7 Wet Massing:

5.6.7.1 Once all binder is in, bump up the impeller speed if the BMR says to.

5.6.7.2 Turn on the chopper. It breaks lumps and helps distribute moisture.

5.6.7.3 Watch the ampere meter. Current rises as granules form and get denser.

5.6.7.4 Mix until you hit the endpoint. Could be time-based, amperage-based, or visual.

5.6.7.5 Over-granulation ruins the batch. Stop when you reach the target.

5.6.8 Granule Discharge:

5.6.8.1 Stop the impeller and chopper.

5.6.8.2 Open the lid and check the granules. They should look uniform and hold together when squeezed lightly.

5.6.8.3 Place a clean container or tray under the discharge valve.

5.6.8.4 Open the discharge valve. Run the impeller at low speed to push granules out.

5.6.8.5 Scrape any material sticking to the bowl walls if needed.

5.6.9 Document everything—start time, end time, impeller speed, chopper speed, mixing times, any observations.

5.7 In-Process Checks:

5.7.1 Check the granules at stages defined in the BMR.

5.7.2 After dry mixing: look for uniform color and no visible lumps.

5.7.3 During wet massing: squeeze a small sample. It should hold shape but break apart easily.

5.7.4 Final granules: check appearance, feel, and moisture if required.

5.7.5 Record all observations on the in-process check forms.

5.7.6 Spot something off? Stop and call your supervisor right away.

5.8 Shutdown Procedure:

5.8.1 Make sure all granules are discharged from the bowl.

5.8.2 Stop the impeller and chopper completely.

5.8.3 Turn off the main power supply.

5.8.4 Transfer the wet granules to drying trays or fluid bed dryer as per BMR.

5.8.5 Fill out the BMR and Equipment Usage Log. Don’t leave blanks.

5.9 Cleaning Procedure:

5.9.1 Disconnect from power. No shortcuts here.

5.9.2 Open the lid and remove any leftover material from the bowl.

5.9.3 Detach the impeller. Remove the chopper too.

5.9.4 Wash the bowl, impeller, chopper, and lid with purified water. Scrub off sticky residue.

5.9.5 Follow up with a wash using an approved cleaning agent if specified in the cleaning SOP.

5.9.6 Rinse everything thoroughly with purified water. No soap residue allowed.

5.9.7 Wipe down with 70% IPA for sanitization.

5.9.8 Dry all parts completely before reassembly. Moisture causes rust and contamination.

5.9.9 Clean the external surfaces of the machine with a damp cloth, then dry.

5.9.10 Reassemble the impeller and chopper once everything is dry.

5.9.11 Call QA to inspect. Once approved, stick on the “CLEANED” label.

5.9.12 Log all cleaning details in the Equipment Cleaning Log.

5.10 Troubleshooting:

5.10.1 Lumpy granules: Binder added too fast? Chopper not running? Check both next time.

5.10.2 Granules too wet: Too much binder. Or mixing went too long after binder addition.

5.10.3 Granules too dry or powdery: Not enough binder. Or binder not distributed well.

5.10.4 Impeller not turning: Check power supply. Look at the overload relay. Emergency stop pressed?

5.10.5 Chopper not spinning: Same checks as impeller. Also verify the chopper is locked in correctly.

5.10.6 Discharge valve stuck: Material buildup probably. Clean it out manually.

5.10.7 Unusual noise or vibration: Stop immediately. Could be loose parts or worn bearings.

5.11 Post-Operation:

5.11.1 Batch finished? Put the “TO BE CLEANED” label on the machine.

5.11.2 Clean the RMG following Section 5.9.

5.11.3 Complete all paperwork—Equipment Usage Log, BMR, deviation reports if needed.

5.11.4 Leave the area clean and ready for the next batch.

5.12 Records:

5.12.1 Equipment Usage Log.

5.12.2 Equipment Cleaning Log.

5.12.3 Batch Manufacturing Record.

5.12.4 In-Process Check Records.

5.12.5 Deviation Reports (when applicable).

6.0 ABBREVIATIONS:

6.1 SOP: Standard Operating Procedure.

6.2 BMR: Batch Manufacturing Record.

6.3 IPQA: In Process Quality Assurance.

6.4 PPE: Personal Protective Equipment.

6.5 IPA: Isopropyl Alcohol.

6.6 RMG: Rapid Mixer Granulator.

6.7 QA: Quality Assurance.

6.8 GMP: Good Manufacturing Practice.

7.0 REFERENCES:

7.1 Manufacturer’s Equipment Manual

7.2 GMP Guidelines

7.3 Internal Quality System Documents

7.4 Cleaning Validation Protocol

8.0 REVISION HISTORY: