3.ICH &WHO Guidelines for Calibration And Validation of Equipments.pptx

Modern pharmaceutics

1. ICH &WHO Guidelines for Calibration And Validation of Equipments 11/9/2016 1 pt&v seminor . by krishna kanth Dept.of Quality Assurance

2. WHO Guidelines for caliberation and validation of equipments 11/9/2016 pt&v seminor . by krishna kanth Dept.of Quality Assurance 2

3. Calibration Definition: Calibration is the determination of the accuracy of an instrument, usually by measurement of its variation from a standard, to ascertain necessary correction factors. Its the periodic assessment of a piece of test equipment or system. It involves the act of adjusting equipment so that it performs in accordance with an established standard or specification based upon International Standards which are traceable and within specified accuracy and precision. 11/9/2016 3 pt&v seminor . by krishna kanth Dept.of Quality Assurance

4. Instrument calibrations are required at intervals based on the criticality of the instruments, instrument capability , and instrument calibration history . before using new test equipment after relocation or major maintenance at regular intervals (“every 6 months”) following the repair of the instrument. within the OQ process, the calibration of measuring and controlling devices checked. 11/9/2016 pt&v seminor . by krishna kanth Dept.of Quality Assurance 4

5. All equipment used to perform calibrations will be calibrated to standards traceable to the National Institute of Standards and Technology ( NIST ) or other proved standards and maintain the following: Standards Instrument numbering system Instrument calibration files 11/9/2016 pt&v seminor . by krishna kanth Dept.of Quality Assurance 5

6. Validation Master plan 11/9/2016 pt&v seminor . by krishna kanth Dept.of Quality Assurance 6

7. TYPES OF INSTRUMENTATION CALIBERATION Critical instruments includes: temperature controlling Resistance Temp. Detectors (RTD), tank level sensors, chart recorders that provide documents for batch records, resistivity meters and controls, and flow meters used to control resin bed regeneration. 11/9/2016 pt&v seminor . by krishna kanth Dept.of Quality Assurance 7

8. B. Non-critical instruments such as instrument air regulator gauges, or redundant pressure or temperature instruments, do not need rigorous calibration schedules. However, non-critical instruments must still be identified and logged into a calibration program. There must be a clear identification on such an instrument that it is not used for process control. 11/9/2016 pt&v seminor . by krishna kanth Dept.of Quality Assurance 8

9. CALIBERATION REQUIREMENTS . Procedures must be available( SOP ) for the calibration of these instruments, which include the method of calibration, the range and accuracy of the instruments, An appropriate schedule for performing these calibrations. Records of these calibrations must be kept to comply with the GMPs. Instrument identification numbers and a sticker indicating date of calibration and The date of next calibration must be clearly visible on all critical instruments. 11/9/2016 pt&v seminor . by krishna kanth Dept.of Quality Assurance 9

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11. Validation Definition: Establishing documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality attributes. 11/9/2016 11 pt&v seminor . by krishna kanth Dept.of Quality Assurance

12. Validaton and caliberation includes following steps. It is a regulatory requirement for pharmaceutical companies. It includes: Design qualification Installation qualification Operation qualification Performance qualification 11/9/2016 pt&v seminor . by krishna kanth Dept.of Quality Assurance 12

13. All SOPs for operation, maintenance and calibration should be prepared during qualification Training provided and records maintained Design qualification : Provides documented evidence that the design specifications were met. 2. Installation qualification : Provides documented evidence that the installation was complete and satisfactory During IQ: Purchase specifications, drawings, manuals, spare parts lists and vendor details should be verified Control and measuring devices should be calibrated 11/9/2016 13 pt&v seminor . by krishna kanth Dept.of Quality Assurance

14. 3. Operational qualification : Provides documented evidence that utilities, systems or equipment and all its components operate in accordance with operational specifications Demonstrate satisfactory operation over the normal operating range as well as at the limits of its operating conditions (including worst case conditions) Operation controls, alarms, switches, displays and other operational components should be tested. 4. Performance qualification : Provides documented evidence that utilities, systems or equipment and all its components can consistently perform in accordance with the specifications under routine use Test results collected over a suitable period of time to prove consistency 11/9/2016 14 pt&v seminor . by krishna kanth Dept.of Quality Assurance

15. Revalidation Processes and procedures - to ensure that they remain capable of achieving the intended results Periodic revalidation, as well as revalidation after changes In accordance with a defined schedule Frequency and extent determined using a risk-based approach together with a review of historical data. Periodic revalidation To assess process changes that may occur gradually over a period of time, or because of wear of equipment Consideration given to: master formulae and specifications SOPs records (e.g. of calibration, maintenance and cleaning) analytical methods 11/9/2016 15 pt&v seminor . by krishna kanth Dept.of Quality Assurance

16. Changes requiring revalidation should be defined in the validation plan and may include: - changes in starting materials -change of starting material manufacturer - transfer of processes to a different site - changes of primary packaging material - changes in the manufacturing process -changes in the equipment - production area and support system changes -appearance of negative quality trends -appearance of new findings based on current knowledge - support system changes - e.g. including physical properties, such as density, viscosity or particle size distribution that may affect the process or product e.g. change of facilities and installations which influence the process e.g. substituting plastic for glass e.g. mixing times or drying temperatures e.g. addition of automatic detection systems, installation of new equipment, major revisions to machinery or apparatus and breakdowns e.g. rearrangement of areas, or a new water treatment method e.g. new technology 11/9/2016 16 pt&v seminor . by krishna kanth Dept.of Quality Assurance

17. Revalidation after change (continuation) Changes of equipment which involve the replacement of equipment on a “like-for-like” basis would not normally require a revalidation For example, installation of a new centrifugal pump to replace an older model would not necessarily require revalidation Change control SOP followed - as changes may have an impact on a qualified utility, system or piece of equipment, and a validated process and/or procedure Describe the actions to be taken, including the need for and extent of qualification or validation Changes should be formally requested, documented and approved before implementation Records should be maintained 11/9/2016 17 pt&v seminor . by krishna kanth Dept.of Quality Assurance

18. Personnel Demonstrate that personnel are appropriately qualified, where relevant These include for example: laboratory analysts; personnel following critical procedures; personnel doing data entry in computerized systems; and risk assessors. 11/9/2016 18 pt&v seminor . by krishna kanth Dept.of Quality Assurance

19. ICH Guidelines for Caliberation and Validation of HPLC RUNNING A FLOW STABILITY TEST: . The flow stability test is a common test of the pump’s performance. The pump must be running, or be in a READY state for this test to be initiated, and the flow rate must be greater than 0 ml/min. If you need the flow rate, edit the flow setting from the Status Menu, then proceed with the steps below. 1. When the status Screen shows READY, press (MENU) and select/TESTS. 2. Select/Diagnostics/from the Tests Menu. 3. The cursor should be on / Flow Stability/Press (ENTER). 11/9/2016 19 pt&v seminor . by krishna kanth Dept.of Quality Assurance

20. 4. After a short time, the flow stability rating followed by a numerical value will appear. STABLE flow corresponds to a reading between 0 and 25, ACCEPTABLE is between 26 and 90, and UNSTABLE is a value greater than 90. 5. The calibration menu contains a flow calibration “test”, the flow calibration can be run in one of three modes. FLOW CALIBRATION : The flow calibration asks the pump to perform some internal calculations based on user measured values. This is a passive test but it uses the (RUN) key. Unless run incorrectly, this test will not interfere with pump operation. Select /Flow Calibration / to access the flow calibration menus. 11/9/2016 20 pt&v seminor . by krishna kanth Dept.of Quality Assurance

21. Column oven temperature check: Set the column oven temperature to 25, 30, 35, 40, 45°C. Allow the system to attain set temperature. Keep one calibrated working thermometer in column oven and allow it to attain thermal equilibrium. Ensure that mercury bulb of the thermometer is not touching to any portion of the compartment. Read the temperature of the thermometer immediately after taking out. Acceptable range for column oven is ± 2°C of the set temperature.   11/9/2016 21 pt&v seminor . by krishna kanth Dept.of Quality Assurance

22. Auto sampler Injection Linearity.   Freshly prepare the Benzophenone solution 0.10 mg/ml in methanol and inject 5μl, 10 μl , 15 μl , 20 μl and 25 μl in duplicate. From the data plot a graph of injection volume verses area response, calculate the Correlation co-efficient Acceptance Criteria: Correlation co-efficient should be not less than 0.99 11/9/2016 22 pt&v seminor . by krishna kanth Dept.of Quality Assurance

23. Validation of HPLC In this approach, the three critical components for a HPLC method (sample preparation, HPLC analysis and standardization) will first be investigated individually. Step 1: Define method objectives and understand the chemistry (10%) Determine the goals for method development (e.g., what is the intended use of the method?), and to understand the chemistry of the analytes and the drug product.   Step 2: Initial HPLC conditions (20%) Develop preliminary HPLC conditions to achieve minimally acceptable separations. These HPLC conditions will be used for all subsequent method development experiments.   11/9/2016 23 pt&v seminor . by krishna kanth Dept.of Quality Assurance

24. Step 3 : Sample preparation procedure (10%) . Develop a suitable sample preparation scheme for the drug product   Step 4 : Standardization (10%). Determine the appropriate standardization method and the use of relative response factors in calculations.  Step 5: Final method optimization/robustness (20%) . Identify the “weaknesses” of the method and optimize the method through experimental design. Understand the method performance with different conditions, different instrument set ups and different samples.   Step 6 : Method validation (30%) . Complete method validation according to ICH guidelines 11/9/2016 24 pt&v seminor . by krishna kanth Dept.of Quality Assurance

25. Resolution (Rs) A stability indicating method must resolve all significant degradation products from each other. Typically the minimum requirement for baseline resolution is 1.5. This limit is valid only for 2 Gaussian-shape peaks of equal size. In actual method development, Rs = 2.0 should be used as a minimum to account for day to day variability, non-ideal peak shapes and differences in peak sizes. 11/9/2016 25 pt&v seminor . by krishna kanth Dept.of Quality Assurance

26. Limit of Quantitation (LOQ) The desired method LOQ is related to the ICH reporting limits. If the corresponding ICH reporting limit is 0.1%, the method LOQ should be 0.05% or less to ensure the results are accurate up to one decimal place. However, it is of little value to develop a method with an LOQ much below this level in standard practice because when the method is too sensitive, method precision and accuracy are compromised.   11/9/2016 26 pt&v seminor . by krishna kanth Dept.of Quality Assurance

27. Precision, Accuracy Expectations for precision and accuracy should be determined on a case by case basis. For a typical related substance method, the RSD of 6 replicates should be less than 10%. Accuracy should be within 70 % to 130% of theory at the LOQ level.   Analysis time A run time of about 5-10 minutes per injection is sufficient in most routine related substance analyses. Unless the method is intended to support a high-volume assay, shortening the run time further is not recommended as it may compromise the method performance in other aspects ( e.g.,specificity , precision and accuracy.) 11/9/2016 27 pt&v seminor . by krishna kanth Dept.of Quality Assurance

28. REFERENCE : A WHO guide to good manufacturing practice (GMP) requirements .Part 2: Validation. By; Gillian Chaloner -Larsson, Ph.D , GCL Bioconsult , Ottawa. Pharmaceutical Validation Plan, 3 rd Edition, By: Syed Imitiaz Ali, Pg no. 83 and 157 Validation of Pharmaceutical processes,3 rd Edition, Edited By: James Agallocco , Pg no. 99-108 http://www.reagecon.com/techpapers/calibrationvalidation.pdf 11/9/2016 28 pt&v seminor . by krishna kanth Dept.of Quality Assurance