Validation is the action of proving, in accordance with the principles of Good Manufacturing Practice, that a specific procedure, process, equipment, material, activity, or system actually leads to the expected results (EU GMP guidelines).
It is an overall concept. To gain a complete understanding of this term, it is necessary to define the meaning of the word “validation”.
The word “VALID” was first used in the English language in 1648 and means:
having legal efficacy or force;
well-grounded or justifiable;
In other words, to validate means to make legally valid; corroborate; justify; to give legal force to; legalize.
Validation concepts were initially borrowed from the aerospace industry and used in the pharmaceutical industry in 1960. These concepts were first applied in sterilization processes and the manufacture of solid dosage forms. Shortly after that, almost all processes of manufacturing medicinal products were subject to validation.
In 1987, the FDA issued its guidance on process validation.
At present, validation is an essential part of GMP.
The validation process can be compared to legal practice, in the same manner as a lawyer proves the innocence of his client, so validation engineers using study results demonstrate that the manufacturing process is capable of producing high-quality products.
Validation. Special cases:
Qualification is the action of proving that specific equipment works correctly and actually leads to the expected results (EU GMP guidelines).
Analytical Validation, AV is defined as documented evidence that an approved test procedure is suitable for its use in the manufacture and quality control of medicinal products.
Cleaning Validation, CV is defined as documented evidence that an approved cleaning procedure will provide clean equipment, suitable for the manufacturing of medicinal products.
Process Validation, PV is defined as documented evidence that the process, operated within established parameters, can perform effectively and reproducibly to produce a medicinal product meeting its predetermined specifications and quality attributes.
As we see, qualification has a smaller scope than validation and defines a separate direction related to the testing of the parameters of utilities, manufacturing premises, process and laboratory equipment, and other facilities to ensure their compliance with GMP standards and other regulations governing the safe production of medicinal products of the desired quality.
Design qualification (DQ) is a documented verification that the proposed design of the facilities, systems and equipment (utilities, warehouse, etc.) meets the requirements of the User Requirements Specification (URS) and GMP.
Installation Qualification (IQ) is a documented verification that the facilities, systems, or equipment as installed or modified, comply with the approved design and other technical documentation.
Operational Qualification (OQ) is a documented verification that the facilities, systems, or equipment, as installed or modified, perform as intended throughout the anticipated operating ranges.
Performance Qualification (PQ) is a documented verification that the facilities, systems, or equipment, as connected together, can perform effectively and reproducibly based on the approved process method, master production instructions, and product specifications.
Types of process validation:
Prospective validation is validation carried out before routine production of products intended for sale.
Concurrent validation is validation carried out during routine production of products intended for sale.
Retrospective validation is validation of the routine process for a product, which has been marketed, based upon accumulated manufacturing and control batch data.
Repeated validation (re-validation) is repeated validation of an approved process to ensure that changes in process (equipment) introduced according to the change control procedure do not adversely affect process characteristics and product quality.
Repeated validation (re-validation) is carried out:
- on a scheduled basis within time frames specified by the company in the Validation report.
before production renewal, if any changes in documentation and/or terms of production that may affect the quality of semi-product and finished product have been made. The scope of validation activities is defined by the company based on the introduced changes.
In terms of the abovementioned terminology, it can be seen that the terms “prospective”, “concurrent” and “retrospective” validation refer only to the manufacturing processes of products intended for sale. However, these terms have been used efficiently by validation units for a long time while organizing and planning validation of other processes.
It is a GMP requirement that manufacturers should identify what validation work is needed to prove that critical aspects of their particular operations are appropriately controlled. Significant changes to the facilities, equipment, or processes, which may affect the quality of the product, should be validated. A risk assessment approach should be used to determine the scope and extent of validation required.
All validation activities should be planned. The key elements of the validation program must be clearly defined and documented in the Validation Master Plan (VMP) or corresponding documents (EU GMP guidelines).
The distinguishing feature of validation is that it requires the collaboration of experts from various disciplines: pharmacists, technologists, engineers, metrologists, etc. Generally, validation work is subject to rigorous time schedules. Carrying out validation studies requires a lot of resources to involve highly skilled professionals and purchase special equipment, etc.
All these factors require efficient planning and proper organization for the clear and consistent fulfillment of the validation activities.
The manufacturer's overall policy, intentions, and approach to validation, including the validation of production processes, cleaning procedures, analytical methods, in-process control test procedures, computerized systems, and persons responsible for design, review, approval and documentation of each validation phase, should be documented.
The critical parameters/attributes should normally be identified during the development stage or from historical data, and the ranges necessary for the reproducible operation should be defined. This should include:
Defining the API in terms of its critical product attributes;
Identifying process parameters that could affect the critical quality attributes of the API;
Determining the range for each critical process parameter expected to be used during routine manufacturing and process control.
Validation should extend to those operations determined to be critical to the quality and purity of the API. (EU GMP Guidelines).
Validation is an overall concept aimed at demonstrating the degree of quality assurance of delivered products by testing manufacturing processes, utilities, equipment, manufacturing premises, test methods, etc. This process is logically connected and has something in common with many fundamental sciences (chemistry, physics, mathematics, etc.) that allow studying in detail the properties of medicinal products and raw materials used in their production, stages from processing to receiving the finished product as well as help identify and evaluate the most critical operations, deviations from which will lead to irreparable consequences, thus preventing the release of poor-quality medicinal products in the market.