Pharmaceutical validation , Types of validation
- 1. Pharmaceutical validation RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES. KARNATAKA, BANGALORE.
- 2. Contents Introduction scope of validation merits of validation validation and calibration of master plan ICH &WHO guidelines for calibration and validation of equipment Definition of validation Importance of validating dosage form Validation of specific dosage form Types of validation Government regulation Manufacturing process model URS,DQ,IQ,OQ & PQ of facilities.
- 3. INTRODUCTION TO PHARMACEUTICAL VALIDATION Quality is the primordial intention to any industry and its products manufactured. Multiple views on obtaining such quality are the current interest in the pharmaceutical industry. Acquainted with a practice that puts us in common and routine convention ensured to deliver a quality that sounds globally in terms of a spoken quality is on the dais of pharmaceutical arena. Validation is the mean of catering enormous benefits to even more than the acceptable quality level which in the global standard scale. Lending importance to validation is increasingly profound in recent years. Validation is the art of designing and practicing the designed steps alongside with the documentation. Validation and quality assurance will go hand in hand, ensuring the through quality for the products.
- 4. WHAT IS VALIDATION Validation is defined as “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 the process of evaluating products or analytical methods to ensure compliance with products or cleaning method requirements TERMS & DEFINITION As per WHO: Validation means providing documented evidence that any procedure, process, activity or system actually leads to the expected results. As per ICH: Validation of analytical method is the process by which it is established by laboratory studies, which the performance characteristics of the method meet the requirements for predetermined standard. As per FDA: validation is establishing documented evidence, which provides a high degree of assurance that a specific process will produce a product meeting its pre determined specification & quality attributes.
- 5. Validation of Specific Dosage Form Validating a specific dosage form, whether it’s a tablet, capsule, liquid formulation, or any other form, is crucial to ensure its safety, efficacy, and consistency. The validation process for a dosage form typically involves several key steps: 1. Formulation Development: The first step is to develop a formulation that meets the required specifications for the dosage form. This includes selecting appropriate ingredients, determining their proportions, and optimizing the manufacturing process. 2. Analytical Method Development: Validating a dosage form requires reliable analytical methods to assess its quality attributes. This involves developing and validating analytical methods for testing parameters such as potency, purity, dissolution rate, and stability 3. Process Validation: Process validation ensures that the manufacturing process consistently produces dosage forms of the desired quality. It involves establishing process parameters, conducting process qualification studies, and monitoring process performance over time. 4. Stability Studies: Stability studies assess the shelf-life and stability of the dosage form under various storage conditions. These studies help determine
- 6. appropriate storage conditions, shelf-life expiration dates, and packaging requirements. 5. Quality Control Testing: Quality control testing involves routine testing of finished dosage forms to ensure they meet predefined specifications for identity, strength, purity, and quality. This includes testing for physical characteristics, such as appearance and uniformity, as well as chemical and microbiological attributes. 6. Documentation and Reporting: Throughout the validation process, detailed documentation is maintained to provide evidence of compliance with regulatory requirements and internal quality standards. This documentation includes validation protocols, reports, batch records, and standard operating procedures. 7. Regulatory Compliance: Validation of a dosage form must comply with regulatory requirements set forth by health authorities such as the FDA (Food and Drug Administration) in the United States or the EMA (European Medicines Agency) in Europe. This may involve submitting validation data as part of a regulatory filing for marketing approval. By following a systematic approach to validation, pharmaceutical companies can ensure the quality, safety, and efficacy of their dosage forms, ultimately benefiting patients and healthcare providers.
- 7. THE MAJOR TYPES OF VALIDATION: ▫️ Process validation. ▫️ Cleaning validation. ▫️ Equipment validation. ▫️ Validation of analytical methods.
- 8. Process validation: ► Process validation is the means of ensuring and providing documentary evidence that processes are capable of repeatedly and reliably producing a finished product of the required quality. ▸ pre-requisites for process validation: qualification of manufacturing equipment and instruments as well as the formulation, this involve compatibility of active ingredients and recipients and of final product and packaging materials. Critical services (water, air, nitrogen, power supply). Equipment cleaning and motivation of personnel.
- 9. ➤ TYPES OF PROCESS VALIDATION: (a) PROSPECTIVE VALIDATION. (b) CONCURRENT VALIDATION. (C) RETROSPECTIVE VALIDATION. (d) PROCESS RE-VALIDATION.
- 10. A- Prospective validation: ▫️ is carried out during the development stage by means of a risk analysis of the production process, which is broken down into individual steps: these are then evaluated on the basis of past experience to determine whether they might lead to critical situations. ▫️ Expected that process validation be completed prior to the release of the finished product for sale.
- 11. ►It includes:- • Initial stages of formulation development and process development • Setting of process sampling plans. • Designing of batch records. • Defining raw material specifications. • Transfer of technology from scale up to commercial size batches. • Environmental controls. ► It is generally considered acceptable that three consecutive batches within the finally accepted parameters, that assure product of the desired quality would constitute a proper validation of the process.
- 12. B- Concurrent validation: is used on the batches currently being produced for establishing documented evidence that a facility and process do what they claim to do. ► Examples of these may be when:- A previous validated process is being transferred to a third party contract manufacturer or to another site. The number of batches produced are limited. Process with low production volume per batch and market demand. The product is a different strength of a previously validated product with the same ratio of active or inactive ingredients.
- 13. C- Retrospective validation: > involves the examination of past experience of production on the assumption that composition, procedures, and equipment remain unchanged; such experience and the results of in-process and final control tests are then evaluated. Recorded difficulties and failures in production are analyzed to determine the limits of process parameters. Retrospective validation is obviously not a quality assurance measure in itself, and should never be applied to new processes or products.
- 14. D-PROCESS RE-VALIDATION: > means repeating the original validation effort or any part of it. > Process re-validation is required when there is a change in any of the critical process parameters formulation, primary packaging components, major equipment or premises. For examples when:- Changes in raw materials: (physical properties such as density, viscosity, particle size distribution or changes in source of active raw material manufacturer)
- 15. ► Changes in packaging material (primary container/ closure system) ► Changes in the process (Mixing time, drying temperatures & batch size). ► Changes in the equipment. ► Changes in the plant/facility.
- 16. Cleaning validation: ► Cleaning validation ensures that there is no cross contamination in a multi-product manufacturing plant and also prevents microbial contamination. > Objective.. ► 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.
- 17. > Source of contamination: Cross Contamination product of one product into another. Product contamination by a foreign material. Microbial contamination. ➤ Factors Influencing Cleaning validation: Product, Equipment, Facilities, Cleaning methods, Cleaning agents, Sampling, Testing, Limits, and acceptance criteria.
- 18. Equipment Validation : > Equipment validation is to provide a high level of documented evidence that the equipment and the process confirm to a standard. ♦️ TYPES: 1) DESIGN QUALIFICATION. 2) INSTALLATION QUALIFICATION. 3) OPERATIONAL QUALIFICATION. 4) PERFORMANCE QUALIFICATION.
- 19. Process flow chart: Design Qualification Before purchasing new instrument Installation Qualification At documented installation of new or existing instrument Operational Qualification After installation After major changes e.g., repair, updates. At regulars enterval (risk based) Performance Qualification Whenever the instrument issued, e.g.,daily
- 20. ◽Validation of analytical methods: ► Method validation must prove that the analytical method used for a specific test is suitable for which it is to be carried out. ►Methods should be validated:- When they are to be established for routine use. When the method is to be changed due to change in conditions. Whenever the equivalence between new method and the standard are demonstrated
- 21. ♦️ TYPES OF PROCEDURES TO BE VALIDATED: 1) ACCURACY:- The accuracy of an analytical method refers to the closeness of agreement between the observed value and the value which is either conventially a true one or reference one. 2) PRECISION:- The precision of an analytical method refers to the closeness of values obtained from a series of tests. 3) REPEATABILITY:- Repeatability is established when the same sample is estimated repeatedly by the same analyst using same analytical method within the same laboratory using same instrument and performed within a short period of time.
- 22. 4) INTERMEDIATE PRECISION: When the test is repeated on different days by different persons or using different instruments within the same laboratory, the variation is expressed in terms of intermediate precision. 5) REPRODUCIBILITY: When a method is standardized, the test is carried out in different laboratories using the same method, the precision between the laboratories is referred to as reproducibility. 6) SPECIFICITY:- Specificity is the ability of a test method to measure the analyte explicity in the presence of other components.
- 23. 7) LINEARITY:- refers to it’s ability to measure a specific component within a range. 8) DETECTION LIMIT: the lowest detectable concentration of an analyte in a sample. 9) QUANTITATION LIMIT: the lowest measureable concentration of an analyte in a sample. 10) ROBUSTNESS: ability of a test method to resist the variation in method parameters (small variation). 11) RANGE: interval between upper and lower concen. Of analyte.
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