Validation and calibration of master plan

validation and calibration of master plan

1. VALIDATION AND CALIBRATION OF MASTER PLAN By B.Prinkha . M.Pharm 1 st year Modern pharmaceutics

2. CONTENT INTRODUCTION OBJECTIVE OF VALIDATION VALIDATION MASTER PLAN INTRODUCTION MEMBERS OF VMP CONTENT OF VMP CALIBRATION MASTER PLAN INTRODUCTION CALIBRATION PROCESS TIME INTERVAL OF CALIBRATION MAINTAINANCE OF RECORDS LABELLING

3. INTRODUCTION VALIDATION DEFINITION : According to FDA : “Establishing the documented evidence which provides a high degree of assurance that a specific process will consistently produce a product of predetermined specifications and quality attributes”. QUALIFICATION DEFINITION : “Documented evidence that premises, systems or equipment are able to achieve the predetermined specifications properly installed, and/or work correctly and lead to the expected results”.

4. QUALIFICATION OR VALIDATION? A system/equipment/premises must be Qualified to operate/work in a Validated process: QUALIFY: A system and/or equipment VALIDATE: A process Example: Qualify an autoclave, whereas you Validate a Sterilization process.

5. OBJECTIVES OF VALIDATION To reduces risk of regulatory non-compliance. To reduce the time to the market for the new products. To eliminate the scrap & reduces the defect cost. To reduce chances of product re-call from market. To accelerate the final release of the product batch. It requires less in-process control & end process testing. Amplified release of batch can be achieved in validation .

6. VALIDATION MASTER PLAN

7. VALIDATION MASTER PLAN(VMP) A Validation Master Plan, also referred to as "VMP", outlines the principles involved in the qualification of a facility, defining the areas and systems to be validated, and provides a written program for achieving and maintaining a qualified facility. A VMP is the foundation for the validation program and should include process validation, facility and utility qualification and validation, equipment qualification, cleaning and computer validation. It is a key document in the GMP (Good manufacturing practice) regulated pharmaceutical industry as it drives a structured approach to validation projects. Food and Drug Administration inspectors often look at VMPs during audits to see whether or not a facility's validation strategy is well thought-out and organized. A VMP should have logical reasoning for including or excluding every system associated with a validation project based on a risk assessment .

8. VALIDATION VMP Basic Risk Analysis (BRA) Detailed Risk Analysis(RA) QUALIFICATION VALIDATION OF COMPUTERIZED SYSTEM VALIDATION DESIGN QUALIFICATION(DQ) INSTALLATION QUALIFICATION(IQ) OPERATIONAL QUALIFICATION(OQ) PERFORMANCE QUALIFICATION(PQ) PROCESS VALIDATION CLEANING VALIDATION ANALYTICAL METHODS VALIDATION

9. MEMBERS OF VMP Validation manager(quality assurance department) Member from production Members of engineering Members from calibration lab Members from QC lab Members from maintenance Members from HVAC department Members from product development lab

10. CONTENT OF VMP (FACTORS TO BE CONSIDERED) Introduction Methodology Qualification Personnel Schedule Preventive maintenance Change control Procedure Documentation Appendices

11. INTRODUCTION This section is written as an introduction to the validation process and the facility, and it is intended to set the scene. The introduction of a VMP should include following details:- A description of facility, its premises and equipment, and its purpose intension and scope of validation. O ther relevant site policies and plans , like factory or corporate policy statement on GMP, QA, etc.,.

12. METHODOLOGY This section should address the predetermined requirements by identifying the standards that are to be applied to the facility. These are then used in the development of the acceptance criteria that are used to judge the validation It also involves planning and execution of documents such as, protocols, records, reports, or other. The standard will involve three elements: Regulatory and guidance documents National standards Company standards

13. QUALIFICATION This section encompasses all aspects of the design, procurement, installation, and commissioning process. The important issue is to ensure that definitions in the organization and for a specific project are consistent and cover all aspects of the validation process, and that the validation structure and organization is clear to any inspection authority.

14. Qualification Purpose Design Qualification(DQ) Design specifications to ensure that all specified design elements have been included and that the design meets the relevant regulatory and statutory requirements. Installation Qualification(IQ) Verifies that the equipment/system/process is installed correctly supplied as specified integrated into the site calibration, maintenance systems and available for use. Operational Qualification(OQ) Verifies that the equipment/system/process is operating correctly, compliant with functionality requirements and integrated into the systems and QMS. Performance Qualification(PQ) V erifies that the equipment/system/process is continuously meeting performance criteria for routine use and performing adequately for routine use in commercial production.

15. PERSONNEL The CFR 21 states “ Each person engaged in and each person responsible for supervising the manufacture, processing, packaging or holding a drug product shall have the education, training, and experience, or a combination thereof, to enable that person to perform the assigned functions.” The VMP should lay down the principles for personnel requirements. It must address the aspects like; experience of personnel (written biographies or CV), in-house training reports, etc,. Documenting the training is essential and is a requisite of the GMPs.

16. SCHEDULE This is the responsibility of Site maintenance and Operation department . This activity should be performed during the design phase, and the documentation required should be, included in the requisition. P REVENTIVE MAINTENANCE The work program is essential and should be prepared at an early stage. A good plan will contain all the necessary features which are to be considered during execution of a plan and determines the control of the project. It ensures that all the personnel involved in the VMP are not only aware of the engineering targets, but also the validation targets.

17. CHANGE CONTROL These cover engineering standards used in the project design, through to commissioning phases, and the facilities standard procedures (SOPs). PROCEDURE This section of VMP should lay down requirements for a set of procedures for change control that cover: The project through design, construction, and commissioning The ongoing change that will inevitably occur in both the process and the equipment and engineering aspects.

18. DOCUMENTATION The appendix is mostly used VMP to hold the information of type of documents and formats that will be used in the execution stage. APPENDICES This section usually used to identify the documentation that should be produced for the processing like; Engineering drawing Equipment supplier drawing and documents Factory acceptance documents IQ documents OQ documents PQ documents

19. CALIBRATION MASTER PLAN INTRODUCTION “Automatic, mechanical, or electronic equipment or other types of equipment, including computers, or related systems that will perform a function satisfactorily, may be used in the manufacture, processing, packing, and holding of a drug product. If such equipment is so used, it shall be routinely calibrated, inspected, or checked according to a written program designed to assure proper performance. Written records of those calibration checks and inspections shall be maintained.” -US Code of Federal Regulations, 21 CFR 211.68

20. CALIBRATION DEFINITION: The process of comparing the response of some instrument or system to a standard instrument or system over some measurement range. It is based on the comparison of a primary standard or instrument of known accuracy with another equipment (to be calibrated). It is used to detect, correlate, report or eliminate by adjustment of any variation in the accuracy of the equipment being calibrated. CALIBRATION MASTER PLAN: CMP is defined as a leading document in defining the requirement necessary for establishing and implementing an effective calibration control program.

21. CALIBRATION PROCESS Calibration process must be managed and executed in a professional manner . A particular place for all calibration operations to take place and keeping all instruments for calibration. A separate room is preferred: Better environmental control Better protection against unauthorized handling or use of the calibration equipment. The performance of all calibration operations is assigned as the clear responsibility of just one person. Calibration procedures, used for quality control functions, are controlled by the international standards ISO 9000.

22. CALIBRATION PROCESS MASTER INSTRUMENT LIST Serial Number Name of Instrument Location Accuracy Required Range of Measurement Calibration Done Date Due Date for Next Calibration Calibration Certificate Number & Date

23. EQUIPMENT CLASSIFICATION Critical equipment: Direct measurement that affect the final product quality. Measurement on critical process parameters in the process specification Non critical equipment: Indirect measurement that will not directly affect the final product quality Shall be maintained based on company maintenance schedule

24. VERIFICATION Applicable to equipment that cannot be calibrated (adjustment, correlation, etc) • Verification against measurement standard with correction factor documented • Actual reporting of result shall include the correction factor • Temperature correction factor “ - 2℃ ”. Measured value: 24℃ Reported value = 24℃ –2℃= 22℃

25. OUT OF CALIBRATION • Remove equipment from use • Out of Calibration Investigation to be carried out to determine the source of inaccuracy • Evaluate the impact of OOC result on the final product quality and other previously measured data • All investigation findings should be documented.

26. CALIBRATION CERTIFICATE • Name and address of contracted calibration laboratory • Name and address of client • Description and identification of item calibrated • Environment conditions when calibration was made • Date of receipt of instrument, date of calibration date of next calibration • Calibration method • Result of calibration • Signature and title of person responsible for the calibration • External calibration contract shall be awarded to Accredited by the nation institution

27. TIME INTERVAL OF CALIBRATION Depending on: Classification of Critical or non-critical Usage (light or heavy usage) Handling (light or heavy handling) Manufacturer’s recommendation Reference to NIST or accreditation body guideline for a specific measurement system

28. MAINTANANCE OF RECORD OF CALIBRATION Records will be maintained for all the calibrations done It should be according to the cGMP The individual calibration history files will be prepared and maintained for each instrument The records will be maintained and stored in the metrology or QA department

29. LABELLING All calibrated equipment's are labelled or coded to indicate its status Labels should be design and made of material suitable to working environment Following declarations are to be made after calibration “calibrated” “calibration required” The label should contain Date of last calibration Date of recalibration Person responsible for calibration Calibration certificate number.