Unit 5 Process Validation PDF

11/2/24 Unit 5: Process Validation Pharmaceutical Manufacturing (with QA and cGMP) 1 Objectives Explain the need for process validation Enumerate the different types of validation Enumerate the different stages of validation 2...

11/2/24 Unit 5: Process Validation Pharmaceutical Manufacturing (with QA and cGMP) 1 Objectives Explain the need for process validation Enumerate the different types of validation Enumerate the different stages of validation 2 1  11/2/24 Unit 5: Process Validation Pharmaceutical Manufacturing (with QA and cGMP) 1 Objectives Explain the need for process validation Enumerate the different types of validation Enumerate the different stages of validation 2 1  11/2/24 Process Validation A documented process that provides a high degree of assurance that a facility, laboratory, computer, process or system will consistently produce product, meeting the predetermined specifications & quality attributes. - US FDA Guidance for Industry (May 1987) It is performed by a validation team, led by the quality assurance head. Process validation is done before releasing a new product, when applying any change to an existing product and for periodically verifying the process. 3 Process Validation Documentation associated with validation: Standard operating procedures (SOPs) Specifications Validation Master Plan (VMP): a document pertaining to the whole facility that describes which equipment, systems, methods and processes will be validated and when they will be validated. Qualification and validation protocols Qualification and validation reports 4 2  11/2/24 Types of Validation Process Prospective Validation It is implemented when any product will be manufactured with a new formula and their manufacturing process or within a new facility. AKA Pre-market validation considered the foundational type of validation 5 Types of Validation Process Concurrent Validation This type of validation involves monitoring and validating a process It gives of the present batch being studied and offers limited assurance regarding consistency of quality from batch to batch. The product is manufactured in the production area using the production facility and equipment. It can provide documented evidence to show that the manufacturing process is in a state of control. 6 3  11/2/24 Types of Validation Process Retrospective Validation It is a documented evidence that products manufactured in the pharmaceutical industry using validated procedure maintain its quality and purity in the market during the period of its shelf life. It is chosen for established products whose manufacturing processes are considered stable The equipment, facilities and subsystem used in connection with the manufacturing process must be qualified in conformance with cGMP requirements 7 Types of Validation Process Revalidation Required when there is a change in: any of the critical process parameters: formulation, raw material, primary packaging components, major equipment or premises. Transfer of a product from one plant to another Changes to the manufacturing process or cleaning process The necessity of periodic checking of the validation results Increase or decrease in batch size or sequential batch that fail to meet product specifications 8 4  11/2/24 Stages of Process Validation 9 Quality by Design (QbD) - is a systematic approach to development that begins with predefined objectives and emphasizes product and process understanding and control based on sound science and quality risk management. ELEMENTS OF PHARMACEUTICAL QUALITY BY DESIGN Quality Target Product Profile (QTPPs) - The Quality Target Product Profile (QTPP) provides an understanding of what will ensure the quality, safety, and efficacy of a specific product for the patient. - Things that are considered when creating a QTPP include the dosage strength, delivery system, dosage form, container system, and more. It should also include considerations such as purity, stability, and sterility. 10 5  11/2/24 Quality Target Product Profile (QTPP) 11 Quality by Design (QbD) ELEMENTS OF PHARMACEUTICAL QUALITY BY DESIGN Product design and understanding - Identification of critical material attributes (CMAs) and critical process parameters (CPPs) o CMA is a physical, chemical, biological, or microbiological property or characteristic of an input material that should be within an appropriate limit, range, or distribution to ensure the desired quality of that drug substance, excipient, or in-process material. - Determines whether the product can meet patients’ needs - Determines whether the product can maintain its performance through its shelf life - The key objective of product design and understanding is to develop a robust product that can deliver the desired QTPP over the product shelf life. 12 6  11/2/24 Quality by Design (QbD) ELEMENTS OF PHARMACEUTICAL QUALITY BY DESIGN Control Strategy - is a planned set of controls, derived from current product and process understanding that ensures process performance and product quality. Design Space - Defines as the multidimensional combination and interaction of input variables (material attributes) and process parameters that have been demonstrated to provide assurance of quality. 13 Quality by Design (QbD) DESIGN TOOLS Risk Assessment - identify potentially high-risk formulation and process variables that could impact the quality of the drug product. - helps to prioritize which studies need to be conducted and is often driven by knowledge gaps or uncertainty. Design of Experiments (DoE) - excellent tool that allows R&D to systematically manipulate factors according to a prespecified design. 14 7  11/2/24 Quality by Design (QbD) DESIGN TOOLS Process Analytical Technology (PAT) - ICH Q8 identifies the use of PAT to ensure that the process remains within an established design space - can provide continuous monitoring of CPPs, CMAs, or CQAs - In-process testing, CMAs, or CQAs can also be measured online or in line with PAT. Both of these applications of PAT are more effective at detecting failures than end-product testing alone. 15 Stage 1: Process Design Elements of Pharmaceutical Process Design and Development Critical Quality Attributes (CQAs) - It is a physical, chemical, biological, or microbiological property or characteristic that should be within an appropriate limit, range, or distribution to ensure the desired product quality. Critical Process Parameter (CPP) - A process parameter whose variability has an impact on a critical quality attribute and therefore should be monitored or controlled to ensure the process produces the desired quality. 16 8  11/2/24 Stage 1: Process Design Elements of Pharmaceutical Process Design and Development Process Limits Edge of Failure (EOF) - where 50% of the time the product meets all process and release criteria Control Limits (CL) - these are maximum boundaries in which the product meets all specifications. Proven Acceptable Range (PAR) - this range is established during the validation process. Normal Operating Range (NOR) - these are the conditions that the production is run at under normal conditions - all criteria are met. Target (T) - this is the middle of the normal operation range. 17 Stage 1: Process Design Elements of Pharmaceutical Process Design and Development Control Strategy - Includes monitoring and testing CPP and the use of quality control tests to verify that the drug product meets the defined specifications. 18 9  11/2/24 Stage 2: Process Qualification During this stage, the process design is evaluated to determine if the process is capable of reproducible commercial manufacturing. Elements of Validation: Installation Qualification (IQ) - During this stage, the manufacturing equipment is installed and tested to ensure it meets the defined specifications. Operational Qualification (OQ) - confirms that equipment operates as intended under normal and worst-case conditions. Performance Qualification (PQ) - demonstrates that the entire manufacturing process consistently produces product that meets predefined specifications and quality attributes. 19 Stage 3 – Continued Process Verification Change Control - Changes should be controlled in accordance with a SOP as changes may have an impact on a qualified utility, system or piece of equipment, and a validated process and/or procedure. Process Metrics - This metric review will give the company an oversight of how well and how efficiently the process is working. Trend Analysis - Trend analysis makes use of the control charts. Annual Product Review - GMPs require that the quality of each product be reviewed at least once per year to assure that the process remains in control. 20 10  11/2/24 Stage 3 – Continued Process Verification Regular monitoring of process parameters, product quality attributes, and process performance data is conducted to ensure ongoing compliance with specifications and requirements. If any issues are detected, Corrective actions are taken, to bring the process back into control and the process is revalidated as needed. This stage is critical in ensuring that the manufacturing process remains consistent and reliable over time. It also helps to ensure that the drug product remains safe and effective even as production volume increases or new batches are produced 21 PROCESS VALIDATION TEMPLATE AS PER INTERNATIONAL SOCIETY OF PHARMACEUTICAL ENGINEERING (ISPE) 22 11  11/2/24 23 24 12  11/2/24 25 Importance of Process Validation Process parameters and controls are determined Helps to determine the worst case and risks Helps to investigate deviation caused during the process Deep study and understanding of the process and equipment The risk of regulatory compliance is minimized A validated process required less process control and product testing Batch to batch variation is minimized Increases production of the manufacturing facilities Decreases the chances of the failure of batches Required by regulatory bodies 26 13  11/2/24 Thanks! Do you have any questions? CREDITS: This presentation template was created by Slidesgo, and includes icons by Flaticon, and infographics & images by Freepik 27 14