Validation: Consistently Delivering Quality Products
Validation, on the other hand, focuses on the overall process rather than the equipment. It is the documented act of demonstrating that a procedure, process, or activity consistently produces results that meet predetermined specifications.
Validation is a systematic approach that checks and helps processes to have expected and consistent outcomes. It involves testing and analyzing the process to ensure it meets the required specifications and quality standards.
The validation process in the pharmaceutical industry includes various activities such as process design, process verification, process confirmation, and process qualification. These activities aim to establish objective evidence that a process can consistently deliver a quality product. Validation is directly linked to the process itself, ensuring that it consistently meets regulatory guidelines and industry standards.
1. Process Validation
Process validation serves as the backbone of quality assurance, encompassing various stages of product development, modifications, transfers, and ongoing verification.
As per FDA requirements (Section 820.75 of the Quality System Regulation), process validation involves inspecting the performance of the process to obtain documented assurance that the manufacturing process meets pre-defined acceptance criteria.
Activities related to machines, systems, and equipment are referred to as “qualifications” and include design qualification (DQ), installation qualification (IQ), operational qualification (OQ), and performance qualification.
Read more about process validation in our article.
Validation Approaches
Some of the validation approaches used in the pharmaceutical industry, according to Eudralex Annex 15 – Qualification and Validationinclude:
Concurrent Validation
In exceptional circ*mstances, concurrent validation may be employed, provided it is justified, documented in the Validation Master Plan (VMP), and approved by authorized personnel. Sufficient data supporting batch uniformity and adherence to acceptance criteria should be formally documented.
Traditional Process Validation
The traditional approach involves manufacturing batches under routine conditions to confirm reproducibility. The number of batches and samples taken should align with quality risk management principles, establishing variation trends. Typically, a minimum of three consecutive batches under routine conditions constitutes validation.
Process Validation Protocol
A comprehensive process validation protocol is essential, defining critical process parameters, critical quality attributes, and associated acceptance criteria. The protocol should cover a range of elements, including process description, responsibilities, equipment lists, and analytical methods.
Continuous Process Verification
For products developed using a quality-by-design approach, continuous process verification serves as an alternative to traditional validation. A science-based control strategy for incoming materials, critical quality attributes, and critical process parameters is defined. Regular evaluation of the control strategy, using tools like Process Analytical Technology and multivariate statistical process control, ensures consistent product quality.
Hybrid Approach and Ongoing Process Verification
A hybrid approach, combining elements of traditional and continuous verification, may be adopted based on substantial product and process knowledge. This approach proves useful for validation activities post-changes or during ongoing process verification.
The ongoing process verification, applicable across all validation approaches, involves periodic monitoring, review, and documentation of process trends. Statistical tools support conclusions about process variability and capability, ensuring a state of control.
