Validation, Qualification and Calibration are ongoing activities covering development, operation, and maintenance.

Validation is a systematic approach to collecting and analysing sufficient data to give reasonable assurance and documented evidence that a process or an analytical method will, when operated within specified parameters, consistently produce results within predetermined specifications. When this approach is related to a machine or equipment, rather than Validation, this is referred to as Qualification. Qualification is part of, but not limited to, a validation process, which in turn can be divided into Installation Qualification (IQ), Operation Qualification (OQ), or Performance Qualification (PQ).

In performing these activities, many documents describing plans and approaches to analysis are generated. These include Validation Master Plan, Qualification Master Plan, GMP Risk Analysis, Validation Protocol, Test Protocol (including specification), Validation Report, and finally a Summary of Deviations/Issues.

Calibration is a necessary component to ensure of the legitimacy of Qualification and Validation, including Computer System Validation.Calibration is a process that demonstrates a particular instrument or device produces results within specified limits, as compared to those produced by a traceable standard over an appropriate range of measurements. Calibration activities must be performed with qualified instruments by an accredited laboratory.

Calibration is of utmost importance in building a solid Quality System Management with experts and well-trained specialists. Additional external support is also requested when refurbishing, upgrading and building departments or plants and when buying new equipment or machines. In this case, service providers can also be contracted to perform and follow, on behalf of pharmaceutical companies, Factory and Site Acceptance Tests (FAT & SAT).

Factory Acceptance Tests (FAT) involves an inspection and includes both static and dynamic testing of systems or major system components to support the qualification of equipment, a machine or a system conducted and documented at the supplier site, before shipping to the plant.

Site Acceptance Tests (SAT) is related to FAT and also entails inspection and dynamic testing of systems or major system components to support the qualification of an equipment, a machine or a system. However, in contrast to FAT, this type of testing is conducted and documented at the manufacturing site.

The Validation Master Plan
The Validation Master Plan is a document that describes how and when the validation program will be executed in a facility. Even though it is not mandatory, it is the document that outlines the principles involved in the qualification of a facility, defines the areas and systems to be validated and provides a written program for achieving and maintaining a qualified facility with validated processes. It is the foundation for the validation program and should include process validation, facility and utility qualification and validation, equipment qualification, cleaning and computer validation. The regulations also set out an expectation that the different parts of the production process are well defined and controlled, such that the results of that production will not substantially change over time.

The Validation Process:
The validation scope, boundaries and responsibilities for each process or groups of similar processes or similar equipment's must be documented and approved in a validation plan. These documents, terms and references for the protocol authors are for use in setting the scope of their protocols. It must be based on a Validation Risk Assessment (VRA) to ensure that the scope of validation being authorised is appropriate for the complexity and importance of the equipment or process under validation. Within the references given in the VP the protocol authors must ensure that all aspects of the process or equipment under qualification; that may affect the efficacy, quality and or records of the product are properly qualified.
Qualification includes the following steps:

Design qualification (DQ) - Demonstrates that the proposed design (or the existing design for an off-the-shelf item) will satisfy all the requirements that are defined and detailed in the User Requirements Specification (URS). Satisfactory execution of the DQ is a mandatory requirement before construction (or procurement) of the new design can be authorised.

Installation qualification (IQ) - Demonstrates that the process or equipment meets all specifications, is installed correctly, and all required components and documentation needed for continued operation are installed and in place.

Operational qualification (OQ) – Demonstrates that all facets of the process or equipment are operating correctly.

Performance qualification (PQ) – Demonstrates that the process or equipment performs as intended in a consistent manner over time

Component qualification (CQ) – is a relatively new term developed in 2005. This term refers to the manufacturing of auxiliary components to ensure that they are manufactured to the correct design criteria. This could include packaging components such as folding cartons, shipping cases, labels or even phase change material. All of these components must have some type of random inspection to ensure that the third party manufacturer's process is consistently producing components that are used in the world of GMP at drug or biologic manufacturer.