Pharmaceutical validation QA I Year.pptx
- 1. Presented by Manohar S Kasdekar P R Pote Patil College Of Pharmacy, Amravati Guided by Dr. Dipti Ruikar Mam
- 2. The process validation was developed in the 20th century in order to improve the quality of pharmaceutical products. Validation is a systematic process that involves gathering and analysing data to establish documented evidence that systems, instruments, processes, and facilities do what they are intended to do. Validation can help organizations increase productivity, reduce costs, and ensure consistent operations.
- 3. Validation Validation is a systematic approach to collecting and analysing sufficient data to give reasonable assurance and documented evidence that a process or an analytical method will, when operated within specified parameters, consistently produce results within predetermined specifications.. https://www.totalpharmaceuticaltopics.com/2020/08/process-validation-study- types-of.html?m=1#google_vignette
- 4. Qualification Qualification is described as the action of proving that any premises, systems and items of equipment work correctly and actually lead to the expected results. https://www.icqconsultants.com/services/qualification/
- 5. calibration Calibration is a process or action that compares the measurement values of a measuring device or equipment against a reference standard and certifies the measurement accuracy. https://www.inspiredpharma.com/2017/09/12/gmp- measuring-instrument-calibration/
- 6. 1.2 Scope of Calibration To determine the accuracy, precision, and deviation of the measurements produced by all the instruments To establish the reliability of the instrument being used and whether it can be trusted to deliver repeatable results each time. To make sure that the readings of equipment/instrument are consistent and correct every single time
- 7. 1.3 Frequency Of Calibration Calibration frequency is the time interval between recalibrating an instrument or device. It’s also known as a calibration interval or due date Calibration interval may be based on calendar. The frequency of calibration depends on following factors a) What is level of accuracy desired? b) What is the recommendation of manufacturer? The interval between calibration varies as: I) Weakly II) Monthly or bi-monthly III) Annually or semi-annually IV) After every heavy usage of equipment or instrument.
- 8. 1.4 Importance of calibration Calibration is responsible for defining the accuracy of any measurement and its quality that is recorded by any instrument. It helps in improving accuracy of the instrument. Calibration helps in quantifying and controlling errors Finally in a single word, it allows pharmaceutical companies to have confidence in their results.
- 9. 1.5 Difference Between Calibration and Validation
- 10. 1.6 Calibration of weight and measures. Although analytical weights are made to a high degree of precision, their weight may alter with time. Therefore weights must be checked or calibrated from time to time. It should be noted that as a rule the relative rather than the absolute precision of the weights is important. https://m.indiamart.com/proddetail/standard-calibration-weights-sets- 22235249897.html
- 11. ISO definition: Validation is the confirmation by examination and the provision of objective evidence that the particular requirements for a specific intended use are fulfilled. 2.1 Scope of validation Validation requires an appropriate and sufficient infrastructure including: • organization, documentation, personnel and finances • Personnel with appropriate qualifications and experience • Extensive preparation and planning before validation is performed • A specific programme for validation activities in place
- 12. 2.3 Organization: The organization must have clearly defined areas of responsibility and authority. The structure must be tailored to meet the requirements in the specific organization, and these will vary from company to company. A defined structure exists, is accepted, and is in operation.
- 14. 2.4 Validation Master Plan (VMP) • VMP is a general document that summarizes validation policy and all the intended validation qualification activities, together with a description of the facility and organizational structure. The present EANM guidance covers the qualification and validation aspects intertwined with the preparation of small- scale radiopharmaceuticals. It concerns the preparation of radiopharmaceuticals which are not intended for commercial purposes or distribution. https://pharmaanalytica.com/regulatoryaffairs.html
- 15. To this regard, the overall validation activities should be described in a general document, usually known as Validation Master Plan (VMP). VMP should include: i) A general validation policy, with a description of the intended working methodology, and factors that may affect the quality of the intended radiopharmaceutical(s); ii) A description of the facility, with a detailed description of the critical points. iii) A description of the radiopharmaceutical preparation process (es); iv) The general policy related to process validation. v) A list of the quality control equipment to be qualified, including the extent of qualification required. vi) Cleaning validation of premises and equipment.
- 16. 2.5 Types of Validation Validations are of different types which are given below: 1) Process Validation 2) Analytical Method Validation 3) Cleaning Validation 4) Computerized System Validation 1)Process Validation: The manufacturing process should be flexible with some restrictions during the process of manufacture of the product. The achievement of the alluring qualities should be ensured with the prevention of essential properties. For achieving these, process validation is performed
- 17. Types of Process validation
- 18. 2) Analytical Validation “The process by, which it is established, by laboratory studies, that the performance characteristics of the method meet the requirements for the intended analytical application”. Accuracy: The accuracy of an analytical method is the extent to which test results generated by the method and the true value agree. Accuracy can also be described as the closeness of agreement between the value that is adopted, either as a conventional, true, or accepted reference value, and the value found. Precision: Precision provides an indication of random errors and can be broken down into repeatability and intermediate precision. This procedure should only be performed when the entire analytical method procedure is finalized.
- 19. Specificity: “The ability to assess unequivocally the analyte in the presence of components that may be expected to be present, such as impurities degradation products and matrix components.” Linearity : The linearity of an analytical procedure is its ability (within a given range) to obtain test results which are directly proportional to the concentration (amount) of analyte in the sample. It may be directly demonstrated on the analyte, or on spiked samples using at least five concentrations over the whole working range.
- 20. Repeatability :- In addition to the system precision, this short-term variability includes the contributions from the sample preparation, such as weighing, aliquoting, dilution, extraction, homogenization, and etc. Therefore, it is essential to apply the whole analytical procedure (as described in the control test), rather merely to injecting the same sample solution six times. This is also the reason for using authentic samples because only then can the analytical procedure be performed exactly as in the routine application. Intermediate precision. Intermediate precision includes the influence of additional random effects according to the intended use of the procedure in the same laboratory and can be regarded as an (initial) estimate for the long-term variability. Relevant factors, such as operator, instrument, and days should be varied. Intermediate precision is obtained from several independent series of applications of the (whole) analytical procedure to (preferably) authentic, identical samples.
- 21. Reproducibility represents the precision obtained between different laboratories. The objective is to verify that the method will provide the same results in different laboratories. The reproducibility of an analytical method is determined by analyzing aliquots from homogeneous lots in different laboratories with different analysts, and by using operational and environmental conditions that may differ from, but they are still within, the specified parameters of the method (inter laboratory tests). Validation of reproducibility is important whether the method is to be used in different laboratories. The main factors affecting the reproducibility are: Reproducibility Differences in room temperature and humidity. Operators with different experience and thoroughness. Equipment with different characteristics, e.g., delay volume of an HPLC system. Variations in material and instrument conditions, e.g., HPLC, composition of mobile phase, pH, and flow rate of mobile phase. Variation in experimental details not specified by the method. Equipment and consumables of different ages. Columns from different suppliers or different batches.
- 22. Robustness:- Robustness tests examine the effect that operational parameters have on the analysis results. For the determination of robustness, a number of method parameters are varied within a realistic range, and the quantitative influence of the variables is determined. If the influence of the parameter is within a previously specified tolerance, the parameter is said to be within the robustness of the method range. Obtaining data on these effects helps to assess whether a method needs to be revalidated, for instance, when one or more parameters are changed to compensate the column performance over time. In the ICH document, it is recommended to consider the evaluation of robustness of the method during the development phase, and any results that are critical for the method should be documented. In summary, an analyst must have a critical look at three different types of parameters when robustness and ruggedness are investigated: Internal parameters (e.g., temperature, pH, and etc., in the case of HPLC). External parameters (e.g., different analysts, instruments, laboratories, and etc.). Basic parameters (e.g., stability of test solutions and etc.).
- 23. 3) Cleaning Validation “A process of documenting sufficient evidence to give reasonable assurance, given the current state of Science and Technology, that the cleaning process under consideration does, and / or will do, what it purpose to do.” Objectives To minimize cross contamination. To determine efficiency of cleaning process. To do troubleshooting in case problem identified in the cleaning process and give suggestions to improve the process.
- 24. 4) Computer System Validation Computerized system validation (CSV) is a documented process that ensures a computer system meets its intended use and performs as designed. CSV is a critical process in the pharmaceutical industry to ensure that computerized systems used for manufacturing, testing, and quality control comply with regulatory requirements. Ex. Empower 3 software
- 25. 2.5 STREAMLINING VALIDATION OPERATIONS Set of strategies, mostly risk and science based, to transform or standardize validation activities and documentation. • Typically reduces resources such as time, personnel, and cost. • The practice enhances reliability, cost, and quality of the product.
- 26. Advantages of validation: Optimized processes. Assured quality of products. Reduced cost of maintaining quality. Reduced complaints, rejections, batch failure, mix-ups, and cross-contamination. Faster scale-up from pilot level to the manufacturing level. Better compliance with regulatory requirements
- 27. Reference 1)Huber, L., 2007. Validation and qualification in analytical laboratories. CrC Press. 2)Alexeyev, V., 2000. Quantitative analysis: a textbook. 3) CR Journals (Page 48–58) 2020. All Rights Reserved 4)World Health Organization, 2009. Forty-third report of the WHO Expert Committee on specifications for pharmaceutical preparations.