Validation of equipment copy
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The document discusses various aspects of process validation for pharmaceutical products. It defines process validation as a documented program that provides a high degree of assurance a specific process will consistently produce a product meeting its predetermined specifications. It outlines the key stages of process validation including process design, process qualification, and continued process verification. The document also discusses validation of different dosage forms including solids, liquids, semisolids, and parenterals. It covers validation of various processes involved such as mixing, granulation, filling, and inspection. Validation of equipment and facilities is also summarized.
Validation of equipment copy
- 1. 1 Sneha A. Chavan M- Pharmacy 1st Year, I Semester
- 2. USFDA, 1987 A Documented programme, which provides a high degree of assurance that a specific process will consistently produce, a product meeting its pre-determined specifications and quality attributes. validation is scientific study of process : 1. To prove that process is consistently doing what it is suppose to do (i.e., the process is under control) 2. To determine the process variables and acceptable limits for these variables, and to set up appropriate in – process controls. 2
- 3. Reduction of quality cost ( less reject, rework, wastage and so on) Assurance of quality Safety Government regulation Validation is necessary part of a quality assurance program and is fundamental to efficient production operation. 3
- 4. 4 Stage 1 – Process Design: The commercial process is defined during this stage based on knowledge gained through development and scale- up activities. Stage 2 – Process Qualification: During this stage, the process design is confirmed as being capable of reproducible commercial manufacturing. Stage 3 – Continued Process Verification: Ongoing assurance is gained during routine production that the process remains in a state of control. Stages Of Process Validation
- 5. A Documented programme which provides a high assurance that a specific process will consistently produce a product, meeting its pre-determined specification and quality attributes. 5
- 6. Validation team consist of following departments • Involve with new or modified equipment or facilities 2.Engineering • Whose process require validation3. Production • Concerning change control4. Maintainance • Involve with the testing laboratories5. Quality Control • Involve with GMP compliance6. Quality Assurance • Involve with new product development and new product improvement 1.Research operation 6 Team Work
- 7. Totally new processes. New equipment. Process where the end product test is poor and unreliable indicator of product quality. 7
- 8. Validation Programme 8 Define objective Type of validation Type of process Define the process ( chart or flow diagram of the process) Defination of process output ( in terms of potency or yield) Analysis of process ( critical process and variables) Control limits of critical variables Preparation of validation protocol ( details about facilities, sampling, test to perform, methods used ) Organizing for validation ( define responsibilities of each department) Planning validation trial Validation trials ( supervision, administration, documentation) Validation finding ( data, summery, analysis, conclusion) Final report and recommendations ( process validated further trials)
- 10. 10 PROSPECTIVE VALIDATION CONCURRENT VALIDATION RETROSPECTIVE VALIDATION REVALIDATION Establishing documented evidence prior to process implementation that a system does what it proposed to do based on preplanned protocols Monitoring of critical processing steps and end product testing of current production, to show that the manufacturing process is in a state of control. Validation of facilities, processes, and process controls is possible using historical data to provide the necessary documentary evidence that the process is doing what it is believed to do. It means repeating the original validation effort or any part of it, and includes investigative review of existing performance data. Process for a new formula (or within a new facility) must be validated before routine pharmaceutical production commences. This is conducted in a product already distributed based on accumulated data of production, testing and control. maintain the validated status of mfg processes
- 11. Reason For Revalidation 11 Changes in the starting material(s) Change of formulae. Changes in the packaging material. Changes in the process. Changes in equipment. Changes in the production area and support system. Unexpected changes.
- 12. 12 Additionally, the following points should be checked at the time of a scheduled revalidation: Have any changes in master formula and methods, batch size, etc., occurred? If so, has their impact on the product been assessed ? Have calibrations been made in accordance with the established programme and time schedule ? Have the standard operating procedures (SOPs) been properly updated ? Have the SOPs been implemented ? Have the cleaning and hygiene programme been carried out ? Have any changes been made in the analytical control methods ? Cont…
- 13. VALIDATION OF SOLID DOSAGE FORM 13
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- 15. Both Active Pharmaceutical Ingredients (APIs) And Excipients Product Variation Or Deviation From Specification. Stability Of The Product. Compatible With The Other Ingredients The individual supplier’s conformance to regulatory requirements in terms of facilities, personnel, operating procedures, and controls. water content, residue on ignition, and heavy metals, should also be monitored 15 Validation Of Raw Material
- 16. Cont… Manufactured in different grades and by different companies. Differences in the chemical composition, crystallinity, and particle size/size distribution between different lots. Besides differences can be seen with the same company using different manufacturing sites, raw materials, and/or manufacturing processes. Differences in particle size distribution between lots can result in: (1) the initial mix not actually being uniform (2) materials segregating during compression. A smaller particle size – more binder solution - granules having greater strength - decrease the tablet dissolution rate. 16
- 17. 17 on-site inspection of the supplier to review the vendor’s manufacturing operations and control procedures If it is in acceptable range of specifications and stability, it should be used to manufacture a batch of the final dosage form Assessme nt of raw material stability Performing checks on several batches (at least three) from the primary supplier as well as the alternate supplier. Validation Of Raw Materials - Steps
- 18. A wet granulation formulation may require two mixing/ blending steps: (1) prior to granulating to have a uniform drug/excipient mixture, and (2) after milling the dried granulation to add other excipients, such as the lubricant. Factors in creating a uniform mix or blend: 1. Bulk density 2. Particle shape 3. Particle size distribution 4. Surface area 18 Validation Of Mixing / Blending
- 19. Cont…. 19 Mixing or blending technique Mixing or blending speed Mixing or blending time Drug uniformity Excipient uniformity Equipment capacity/load:
- 20. Validation Of Granulation type of wet granulation technique Will it be low shear (e.g., Hobart), high shear (e.g., Diosna, GEI-Collette) OR fluid bed (e.g., Glatt, Fluid Air)? Each technique will produce granules with different physical properties and will require monitoring of different processing parameters. Wet granulation parameters to be considered during development and validation are: Binder addition Binder concentration Amount of binder solution/granulating solvent Binder solution / granulating solvent addition rate Mixing time Granulation end point 20
- 21. Validation of liquid dosage form 21
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- 25. Validation Parameter For Semisolid Dosage Form 25 Addition of wax depend on its melting point Mixing speed Mixing time Temperature Cooling time Homogenizing speed Homogenizing time Filling machine speed Product temperature to aid product flow and maintain product consistency before and during filling and packaging operations
- 26. Validation of Parenteral Dosage form 26
- 27. Filling System currently used in parenteral filling include 1.Positive displacement volumetric liquid filler 2.Time –Pressure Filling 3.Weight Dosing Filling 27
- 28. Validation condition 1. viscosity 2. Type of product e.g., (Non-aqueous product, suspension) 3. Design of filling needles for high-speed filling equipment. 4. Filling system 5. Fill volume accuracy 6. Fill the product without splashing, foaming or damaging the container 7. Factor affecting fill volume accuracy are a) Machine speed ( depend on machine design) b) Delivery system pressure 28
- 29. Inspection performed by three technique Visual inspection with manual handling Visual inspection with automated handling Automated inspection 29 Validation of inspection
- 30. Validation Condition Trained visual inspector monitored by an in-process testing group Operating speed of presentation device based on normal defect level present in those operation. If defect level higher than normal, so machine can be slowed to allow removal of all defective units. excessive spin rate will create bubble, which will result in false reject An insufficient spin rate may not adequate suspend particles in liquid. Variability in light intensity will cause signal fluctuation that will interpreted as reject by detection device. 30
- 32. Equipment qualification Equipment qualification phase of certification involves the assessment of the equipment that will involved in the certification against the purchase specifications or any other equipment requirement that exit. 32
- 33. Parts of Equipment Validation Equipment Validation Installation Qualification (IQ) Operational Qualification (OQ) Performance Qualification (PQ) Design Qualification (DQ) 33
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- 36. 36 Design qualification (DQ) defines the functional and operational specifications of the instrument and details for the conscious decisions in the selection of the supplier Installation qualification(IQ) establishes that the instrument is received as designed and specified, that it is properly installed in the selected environment, and that this environment is suitable for the operation and use of the instrument Operational qualification (OQ) is the process of demonstrating that an instrument will function according to its operational specification in the selected environment Performance Qualification (PQ) is the process of demonstrating that an instrument consistently performs according to a specification appropriate for its routine use
- 37. Validation of Mixer/granulator a. Method of mixing (e.g., planetary, pneumatic)? b. Is the equipment capable of providing low and/or high shear to the material? c. Can the mixing be varied (e.g., changing the rpm of the impeller)? d. Does the mixer/granulator have a monitoring system (e.g., end point detection) or can it accommodate one? e. What is the working load range and capacity of the equipment? f. How is material charged and discharged from the unit? Is it manual, semi automated, or automated? g. Are there options to introduce the granulating fluid (e.g., dump, meter, or spray)? 37
- 38. 38 a. What is the operating principle of the dryer (e.g., direct heating—fluid bed, indirect conduction—tray, or indirect radiant—microwave)? b. Will the wet material be static (e.g., tray) or fluid (e.g., fluid bed)? c. What is the working load range and capacity of the equipment? d. What is the heating range and airflow capabilities of the equipment? e. What is the heat distribution of the unit? Are there any hot and/ or cold spots? f. Temperature Validation Of Dryer
- 39. Validation Parameters For Tablet Coater 39 Tablet properties Equipment type Coater load Pan Speed Spray Guns Application/Spray rate Degree of Atomization & Spray Pattern Tablet flow Inlet/outlet temperature and airflow Coating solution Coating weight Residual solvent level
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- 41. Seminar Open For Discussion 41