Validation of cone blender, mixer granulator and tablet compression machine.
- 1. Validation of cone blender, mixer granulator and tablet compression machine Presented by Ms. Mayuri Ghavate (M.Pharm Pharmaceutics)
- 2. MAIN TOPICS POINTS TO TALK ABOUT To understand validation of equipments. Validation of powder blenders mixers granulators tablet compression machine
- 3. Validation is the process of establishing documentary evidence demonstrating that a procedure, process, or activity carried out in testing and then production maintains the desired level of compliance at all stage. The validation concept was first proposed by the Food and Drug Administration (FDA) in the mid-1970s to improve the quality of pharmaceutical products
- 4. EQUIPMENT VALIDATION The process of equipment validation is based on the principle that equipment must be designed, constructed, maintained, and adapted to perform the operations which are to be carried out. Equipment validation is Vital for- • Safety. • Fewer interruptions of work. • Reduction of variation in results. • Greater confidence in the reliability of results.
- 5. PHASESOF EQUIPMENT VALIDATION 1.Design Qualification • User requirement specification • Functional specification • Operational specification • Vendor specification 2. Installation Qualification • Arrival Qualification • Installation of hardware and software Pre- Validation Phase Process Validation Phase 1.Operational Qualification • Testing of Operational functions. • Testing of Security function 2. Performance Qualification • On-going performance testing • Testing for specified applications 3. Revalidation Validation Maintenance Phase routine servicing and necessary repairs.
- 6. It is the responsibility of the production manager and technical services manager to follow the procedure. The quality assurance manager is responsible for SOPcompliance. PROCEDUREFORQUALIFICATION OFEQUIPMENT
- 7. Types of the powder blenders 1.V cone blenders 2. Double cone blenders 3. Drum mixer 4. Ribbon blenders 5. Conical screw mixer 6. Tumble blender Validation of Blenders
- 8. CONE BLENDER Cone Blender is an efficient and versatile machine for mixing of dry powders and granules homogeneously. All the contact parts are made of stainless steel. The effective volume for optimum homogeneity is between 35-70% of gross volume. Why is the validation of Cone blender essential? The mixing of the API and excipients is the critical step in the solid dosage form preparations that affect the content uniformity at great extent.
- 9. URSfor the powder Blender Operating criteria must be adequate Spares should be available Easy maintenance Equipment should not disseminate dust Low cost Non reactive surface Capacity
- 10. INSTALLATION QUALIFICATION Details of the Equipment Equipment name, made by & model No. Shall be noted down. Location for the installation equipment shall be checked. Utilities required shall be listed down. Any deviation observed while following above procedure should be inform ed for corrective action.
- 11. Operational qualification After completions of successful installation qualification initiate the actual operation of to ensure that machine is operating within specification. Check the operation qualification parameters against their specifications. Document the deviation details. The Quality head and the department head shall decide whether deviation is acceptable or not.
- 12. Variable and Monitoring VARIABLES RPM MIXING TIME MIXING LOAD MONITORING BLEND UNIFORMITY
- 13. BLEND UNIFORMITY This parameter is perhaps the most important to measure. It is not easy, to define as it is both a physical (size, shape), and chemical (composition) property.
- 14. Performance qualification Load the materials to be mixed in the cone. Start the mixer and rotate it for the time as mentioned in the BMR. After completion of mixing switch OFF the mixer and separate out the sample. Collect the sample as per sampling procedure. Send the samples to Quality control dept. for content uniformity, bulk density and sieve analysis. V cone blender Double cone blender
- 15. Latest advancements in the Blend analysis 1.NIR spectroscopy 2.Raman spectroscopy 3.Microscopic FTIR mapping
- 16. In evaluating a mixing process it is important to consider the worst case in all measurable parameters. These include maximum and minimum mixer load, maximum and minimum speed (rpm), maximum and minimum mixing time.
- 17. Revalidation Qualification: Re-validation process is carried out in pharmaceutical industry at periodic intervals and it is mandatory especially when the company made any change in the formulas, procedures, manufacturing systems, packaging, and support system such as electricity/ power supply, water supply, and steam. Revalidation criteria Location of the equipment is changed. There is change of spare/ parts that have a direct effect on the performance of the equipment At normal revalidation schedule.
- 18. Granulation, the process of particle enlargement by agglomeration technique, is one of the most significant unit operations in the production of pharmaceutical dosage forms, mostly tablets and capsules. Granulation process transforms fine powders into free- flowing, dust-free granules that are easy to compress. Granulation process can be divided into two types: wet granulation that utilize a liquid in the process and dry granulation that requires no liquid GRANULATORS:
- 19. Dry granulator Roller Compactor: are used to force fine powders between two counter rotating rolls and presses the raw materials into a solid compact (flakes, sheets, strips). Polygran roller compactor
- 20. Process Qualification Variables Compaction Pressure i.e. compaction force per cm of roll width. Speed of feeding screws Roll Speed Monitoring Drug distribution and size
- 22. WET GRANULATOR Wet granulation is a process that involves combining different particles of powder together using liquid solutions and adhesives. RAPID MIXERGRANULATOR -Homogenous mixing of dry & wet powders, deaglomeration of wet mass and fast dispersion of binding agent.
- 23. The installation must meet the manufacturer's specified guidelines, along with design changes at installation. Also the supporting electrical utilities must meet all electrical codes. Equipment identification: Record the equipment identification number, with equipment manufacturer, purchase order, model number, and equipment number. Required Documentation: The manufacturers operation and maintenance manual and SOPs that coverthe set up. Utility requirements Power, Water, Compressed air, spraying, impeller movement, pneumatic discharge port. Installation Qualification:
- 24. Operational Qualification: Regulators, discharge port opening, spraying button. Calibration requirements for temp, timer, pressure gauges, ammeter. Equipment control functions: Impeller, timer, bowl on/off & slow/fast buttons. Emergency, discharge port on/off Alarm, wash down walls on/off.
- 25. Process Qualification Variables Mixing speed, Amount of granulating fluid, Feed rate granulation time, Load. Monitoring Drug distribution, water content, size
- 26. TABLETCOMPRESSION MACHINE A 45-STATION TABLETPRESSThe press is automatic, high speed rotary press. A motor drives the press at speeds that vary from 410 to 1630 tablets per minute (rpm). The material being tableted is fed from a hopper by gravity through the feed frame into dies. Regulating the weight adjusting cam controls the weight of material in each tablet can be adjusted. (Fluid pack Tablet compression Machine Acura brand)
- 27. The supporting electrical utilities must meet all electrical codes.The information required for an IQ evaluation is equipment identification required documentation equipment utility requirements major component specifications component material, lubricants equipment safety features. INSTALLATION QUALIFICATION
- 28. competitive, w s Operational Qualification: An OQ evaluation should establish that the equipment can operate within specified tolerances and limits. The mechanical ranges of the tablet press are challenged, along with the basic tablet press operations. Information required for the OQ evaluation is: calibration of the instruments used to control the tablet press equipment control functions (switches and push buttons) equipment operation ( c a m tracks, upper punches, lower punches, feed frames, take off bars, rotor head direction, tablet press speed). A) Cam Tracks Test Install the punches and verify that the cams are contacting the punch head angles on the both the sides of the double-sided cams. Verify that the punches are contacting one side of the single-sided came through a full cam track, upper and lower. C) Lower Punch Test A dial indicator test is required. Measure the height of the lower punch above the die with a dial indicator and record the results and the instrument used to measure the height B) Upper Punch Test A verniercaliper is required for this test, which is performed as follows: Attach a piece of tape to mark the depth of penetration of an upper punch when it is set to a standard depth. Remove the upper punch and use a calibrated vernier calliper to measure the depth of penetration into the die. Record the results and instrument used to measure the depth D) Feed Frame Test Feeler gauge test: Measure the clearance between the feed frame and the motor head with a feeler gauge and record the results and the instrument used to measure the clearance. E) Take Off Bar Test The objective of the take-off bar test is to verify that the take-off bars do not make contact with the lower punches. Turn the tablet press by hand and verify that the takeoff bars do not make contact with the lower punches. G) Tablet Press Speed The objective of the speed test is to verify that the measured speeds are within ± 10% of the manufacturer's specification of a minimum of 9 rpm and a maximum of 36 rpm
- 30. Acceptance Criteria: Average weight variation of the tablet should not be m ore than ± 2% of target weight and individual weight variation should not be m ore than ±5% of target weight. Hardness of the tablets should not be less than 2.0kg/cm2. Friability should not be more than 1%. Relative standard Deviation between the results of any test param eters should not be more then 5%.
- 31. Subpart D – Equipment Section 211.67Equipment Cleaning and Maintenance Cleaning and maintenance activities are to prevent malfunctions which could lead to contamination of a drug product Written procedures for cleaning and maintenance of equipment should be established and followed Records SHALLbe kept for cleaning, sanitizing, maintenance and inspection
- 32. Increased throughput Reduction in rejections and reworking Reduction in utility costs Avoidance of capital expenditures Fewer complaints about process-related failures Reduced testing in-process and in finished goods More rapid and reliable start-up of new equipment Easier scale-up from development work Easier maintenance of equipment Improved employee awareness of processes More rapid automation Application of Validation of equipments
- 33. Validation is an important process to ensure the safety, reproducibility and purity of a substance. Equipment Validation helps in obtaining reproducible results as well as optimisation. Equipment validation mainly operates in 4 parts DESIGN VALIDATION, INSTALLATION VALIDATION, OPERATIONAL VALIDATION and PERFORMANCE VALIDATION. SUMMARY
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