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Process validation

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Process Validation is "The collection and evaluation of data, from the process design stage through commercial production which establishes scientific evidence that a process is capable of consistently delivering a quality product."[1] Process validation required to confirm that “Whether your process is enough effective in controlling the quality of your final product”. Once the process validation completes, it shows that your process is consistent enough to produce a quality product batch to batch and unit to unit.[2] Process validation is the analysis of data gathered throughout the design and manufacturing of a product in order to confirm that the process can reliably output products of a determined standard. Regulatory authorities like EMA and FDA have published guidelines relating to process validation.[3] The purpose of process validation is to ensure varied inputs lead to consistent and high quality outputs. Process validation is an ongoing process that must be frequently adapted as manufacturing feedback is gathered. End-to-end validation of production processes is essential in determining product quality because quality cannot always be determined by finished-product inspection. Process validation can be broken down into 3 steps: process design, process qualification, and continued process verification.

As per product life-cycle approach, process validation activities broken down in three stages.

  1. Process Design
  2. Process Qualification
  3. Continuous Process Verification

Process Design (Development and Scale-Up Approach)

In this stage data from the development phase are gathered and analyzed to define the commercial manufacturing process. By understanding the commercial process a framework for quality specifications can be established and used as the foundation of a control strategy. Process design is the first of three stages of process validation. Data from the development phase is gathered and analyzed to understand end-to-end system processes. This data is used to establish benchmarks for quality and production control.

Quality by design (QBD)

Quality by design is an approach to pharmaceutical manufacturing that stresses quality should be built into products rather than tested in products; that product quality should be considered at the earliest possible stage rather than at the end of the manufacturing process. Input variables are isolated in order to identify the root cause of potential quality issues and the manufacturing process is adapted accordingly. Quality by Design comes out as a scientific approach to reduce the process variation and improve productivity. Quality by Design explains an entirely different approach i.e. Building the quality in the product right from the process design stage. Quality by Design helps to find out all the related CTQs and CPPs for the product in scope. Also, it helps to determine the extent of process variation. Tow commonly practiced tools for QbD approach are Design of Experiment and Process Analytical Technology.[4]

"A concept that quality should be built into a product with a thorough understanding of the product and process by which it is developed and manufactured along with a knowledge of the risks involved in the manufacturing of the product and how to best mitigate those risks."[5]

Design of experiment (DOE)

It is an intelligent decision-making tool to identify high-risk factors either affecting a process or a product response targetted to develop and implement design space. The step-by-step process considered right from choosing the objective of performing DOE through various experiments or runs until successful data collection, analysis and conclusion.

Design of experiments is used to discover possible relationships and sources of variation as quickly as possible. A cost benefit analysis should be conducted to determine if such an operation is necessary.[6]

Process Analytical Technology (PAT)

Process analytical technology is used to measure critical process parameters (CPP) and critical quality attributes (CQA). PAT facilitates measurement of quantitative production variables in real time and allows access to relevant manufacturing feedback. PAT can also be used in the design process to generate a process qualification.[7]

Critical Process Parameters (CPP)

Critical process parameters are operating parameters that are considered essential to maintaining product output within specified quality target guidelines.[8]

Critical Quality Attributes (CQA)

Critical Quality Attributes (CQA) are chemical, physical, biological and microbiological attributes that can be defined, measured, and continually monitored to ensure final product outputs remain within acceptable quality limits.[9] CQA are an essential aspect of a manufacturing control strategy and should be identified in stage 1 of process validation: process design. During this stage acceptable limits, baselines, and data collection and measurement protocols should be established. Data from the design process and data collected during production should be kept by the manufacturer and used to evaluated product quality and process control.[10] Historical data can also help manufacturers better understand operational process and input variables as well as better identify true deviations from quality standards compared to false positives. Should a serious product quality issue arise, historical data would be essential in identifying the sources of errors and implementing corrective measures.

Process Qualification

In this stage the process design is assessed to conclude if the process is able to meet determined manufacturing . In this stage all production processes and manufacturing equipment is proofed to confirm quality and output capabilities. Critical quality attributes are evaluated and critical process parameters taken into account to confirm product quality. Once the process qualification stage has been successfully accomplished production can begin. Process qualification is the second phase of process validation....

Continued Process Verification

Continued process verification is the ongoing monitoring of all aspects of the production cycle.[11] It aims to ensure that all levels of production are controlled and regulated. Deviations from prescribed output methods and final product irregularities are flagged by a process analytics database system. The FDA requires production data be recorded (FDA requirements (§ 211.180(e)). Continued process verification is stage 3 of process validation.

The European Medicines Agency defines a similar process known as ongoing process verification. This alternative method of process validation is recommended by the EMA for validating processes on a continuous basis. Continuous process verification analyses critical process parameters and critical quality attributes in real time to confirm production remain within acceptable levels and meet standards set by ICH Q8, Pharmaceutical Quality Systems, and Good manufacturing practice.[12]

See also

References

  1. ^ Guidance for Industry Process Validation: General Principles and Practices. United States: U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER) Center for Veterinary Medicine (CVM). January 2011. {{cite book}}: line feed character in |publisher= at position 45 (help); line feed character in |title= at position 50 (help)CS1 maint: year (link)
  2. ^ "Process Validation - Master Your Concept in 30 mins. » Pharma GxP". Pharma GxP. Retrieved 2021-01-05.
  3. ^ "Guidance for Industry Process Validation: Generally Principles and Practices" (PDF). Food and Drug Administration. Retrieved 16 December 2014.
  4. ^ "Quality by Design and 9 Allied Tools To Thrive Productivity » Pharma GxP". Pharma GxP. Retrieved 2021-01-05.
  5. ^ Research, Center for Drug Evaluation and (2018-11-03). "Pharmaceutical Quality for the 21st Century A Risk-Based Approach Progress Report". FDA.
  6. ^ "A Case for Stage 3 Continued Process Verification". Pharma Manufacturing. Retrieved 22 November 2014.
  7. ^ "PAT - A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance" (PDF). Food and Drug Administration. Retrieved 10 December 2014.
  8. ^ "PROCESS VALIDATION (P2V)". Validation Online. Retrieved 22 November 2014.
  9. ^ "Defining Critical Quality Attributes in the Pharmaceutical Manufacturing Process". GXP-CC. Retrieved 10 November 2014.
  10. ^ "Critical Quality Attributes (CQA)". Atris Information Systems. Retrieved 10 November 2014.
  11. ^ Continued Process Verification
  12. ^ "Continuous Process Verification". Atris Information Systems. Retrieved 17 November 2014.
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