Process Validation PDF

PROCESS VALIDATION ❑ Introduction to process validation ❑ Process Design ❑ Process Qualification ❑ Continues Process Verification ❑ Quality by design (QbD)  Process validation is a step-by-step procedure designed to...

PROCESS VALIDATION ❑ Introduction to process validation ❑ Process Design ❑ Process Qualification ❑ Continues Process Verification ❑ Quality by design (QbD)  Process validation is a step-by-step procedure designed to ensure that a manufacturing process can consistently produce quality products. It is performed by a validation team led by the quality What is Process assurance head of manufacturers in the pharmaceutical industry. Validation? Generally, process validation is done before releasing a new product, when applying any change on an existing product, and for periodically verifying the process. Established at the onset, a protocol should specify how the validation process will be carried out, including the parameters to be monitored, the samples to be taken, and the results to be accepted.  Process Validation Guidance: FDA vs GHTF The United States Food and Drug Administration (USFDA) guidance discusses general principles and practices that manufacturers can use to validate manufacturing processes. It covers different categories of drugs such as human, veterinary, and biological or biotechnology products. A voluntary organization of regulatory agency officials called the Global Harmonization Task Force (GHTF) provided process validation guidelines for medical devices. It aimed to support manufacturers in understanding requirements concerning manufacturing, servicing, and installation processes for medical devices.  3 STAGES OF PROCESS VALIDATION STAGE 1: PROCESS DESIGN STAGE 2: PROCESS STAGE 3: CONTINUES QUALIFICATION PROCESS VERIFICATION  STAGE I: PROCESS DESIGN During this stage, the manufacturing process is defined in a way that it can reproduce the delivery of a medicinal product that meets pre-determined specifications and quality attributes. To achieve this, the validation team should have a clear grasp of how the process actually works. Product development activities Functionality and limitations of production equipment Risk analysis tools  STAGE II: PROCESS QUALIFICATION The process qualification stage of process validation entails process design evaluation to determine if it is effective for quality production. First, the manufacturing facility should be designed according to the requirements of current good manufacturing practice (CGMP). Next, qualification of utilities and equipment should be conducted such as making sure that they are built and installed in compliance with design specifications. Finally, process performance qualification should be executed through a protocol and documented in a report.  STAGE III: CONTINUED PROCESS VERIFICATION After process design and process qualification, the third stage of process validation deals with setting systems to continually ensure that the validated process remains in such a state during routine production. Continued process verification often incorporates the use of statistical process control (SPC), the continuous monitoring and sampling of process parameters and quality attributes, and the scheduled maintenance of the facility, utilities, equipment, and related assets. It is essential for good documentation practices to be employed throughout the validation process.  4 TYPES OF PROCESS VALIDATION 4 Types of Process Validation Type 1: Prospective Validation It is implemented when any product will be manufactured with a new formula or within a new facility. Also known as premarket validation. Type 2: Retrospective Validation It is conducted only when the manufacturing process has not formally undergone a documented validation. Type 3: Concurrent Validation It is done during regular pharmaceutical production to demonstrate that the process performs at the level that it should in the course of its actual execution. Type 4: Revalidation Revalidation is more widely used for medical devices than drug products.  STAGE I: PROCESS DESIGN The commercial manufacturing process is defined during this stage based on knowledge gained thorough development and scale studies. 1. Critical Parameters: Identifying and controlling critical process parameters is crucial for maintaining consistent product quality in pharmaceutical manufacturing. Critical parameters are those that significantly affect the critical quality attributes (CQAs) of the product. 2. Equipment Selection: Choosing the right equipment is vital for achieving consistent product quality in pharmaceutical manufacturing. 3. Material Selection: Selecting appropriate raw materials and components is critical to ensure the desired quality standards in pharmaceutical manufacturing.  3 Things To Consider In Stage 1 1. Critical Parameters: Identifying and controlling critical process parameters is crucial for maintaining consistent product quality in pharmaceutical manufacturing. Critical parameters are those that significantly affect the critical quality attributes (CQAs) of the product. 2. Equipment Selection: Choosing the right equipment is vital for achieving consistent product quality in pharmaceutical manufacturing. Factors to consider when selecting equipment include functionality, compatibility, scalability, cleaning and maintenance, and regulatory compliance. 3. Material Selection: Selecting appropriate raw materials and components is critical to ensure the desired quality standards in pharmaceutical manufacturing. Consider the following for material selection like Quality Standards, Compatibility, Stability, and Regulatory Requirement.  STAGE II: PROCESS EVALUTION This is the process design is evaluated to determine if the process is capable of reproducible commercial manufacturing. During process qualification, various activities are conducted to validate and verify the manufacturing process. This includes: 1. Process Design: Defining and developing a manufacturing process that meets the desired product specifications. This involves identifying critical process parameters, equipment requirements, and establishing process controls. 2. Process Validation: Conducting a comprehensive evaluation and testing of the manufacturing process to ensure that it consistently produces products meeting predefined standards. This typically involves performing validation protocols, statistical analysis, and documentation of results. 3. Risk Assessment: Identifying and assessing potential risks and hazards associated with the manufacturing process. Risk assessment helps develop mitigation strategies and controls to minimize or eliminate risks that could impact product quality or safety. 4. Process Performance Qualification: Executing the process under normal operating conditions to verify its performance and assess its capability to consistently produce conforming products. This phase often involves conducting multiple runs of the process and collecting data for analysis. 5. Continued Process Verification: Ongoing monitoring and evaluation of the manufacturing process to ensure its continued performance and compliance. This may include periodic sampling, data analysis, and review of process control data.  STAGE II: PROCESS EVALUTION confirmation at commercial-scale of process design information qualification of equipment, utilities, facilities identify and understand sources of variations identify critical process parameters  STAGE III: CONTINUED PROCESS VERFIFCATION This stage evaluates/qualifies the process designed earlier to ensure it can reproduce consistent and reliable levels of quality. It involves collecting and evaluating data on all aspects and stages of the manufacturing process. This includes: a) The building and facilities, i.e. ensuring they adhere to local regulations as well as pharmaceutical manufacturing regulations b) The transportation of raw materials c) Storage of raw materials d) The knowledge, training, and working practices of production line employees e) Every step of the process to turn raw materials into the finished product. This includes having pre-defined sampling points at various stages of the process. f) Finished product packaging, storage, and distribution  STAGE III: CONTINUED PROCESS VERFIFCATION Ongoing assurance is gained during routine production that the process remains in a state of control Timely monitoring of critical operating and performance parameters Monitor product characteristics, materials, facilities, equipment and SOP changes Activities to assure process remains in validated state  Quality By design The Quality by Design approach is being put to use to make sure the products of pharmaceutical companies are safe and effective and that their supply is of high quality for the consumer’s use. QbD also ends up improving the performance and quality of manufacturing significantly.  The Development Process of the Quality by Design Approach Create a Target Product Profile This profile will include a thorough description of how the product will be put to use, the safety measures included, and the overall efficacy of the final product. Define the Target Product Profile All information about the drug substance, process operations as well as potential excipients are collected Design the Critical Attributes and Process Parameters All critical process parameters need to be identified as well so that a proper manufacturing process can be established. Create a Control Strategy Monitor and Update the Process on a Regular Basis - Design of experiments (DOE) - Risk assessment - Process analytical technology (PAT)  Elements of Quality by Design There are many elements involved in the overall QbD process, which are: Quality Target Product Profile (QTPP): QTPP helps identify various CQAs of the product Product design: This creates understanding and the identification of CMAs Process design: This includes the understanding and identification of process parameters CPPs and different principles involving scaling, which link the CMAs and CPPs to CQAs Control strategy: this includes details of the following – Drug substances – Excipients – Drug product – Controls for all the steps involved in manufacturing Process capability Continual improvement  Advantages of Using a QbD Approach Continuous Improvement in Manufacturing and Quality Support for Change Prevention of Failure THANK YOU FOR LISTENING!