Qualification / Validation / Commissioning

Validation and Qualification

The term validation originates from the Latin root validus (healthy; strong). In modern European languages, adjectives derived from this root—where they exist—are usually translated as suitable, fit, or acceptable (e.g., English valid, French valide, Italian valido, etc.). Its derivative verb validate is used in the sense of to provide, determine, or confirm suitability, which accurately reflects its use in pharmaceutical manufacturing. The corresponding process is called validation.

The term qualification comes from the Latin root qualis (what kind of). In most European languages, this root gave rise to the word quality. The corresponding derivative verb qualify means to determine or confirm quality. The respective process is referred to as qualification, which, in this context, must be distinguished from the term qualification when referring to a person's professional skills. In the context of pharmaceutical manufacturing validation activities, qualification refers to a process, and therefore expressions like to conduct qualification are correct.

The terms validation and qualification may seem very similar: in both cases, they involve determining or confirming the suitability of something against certain acceptance criteria. However, these terms are not interchangeable, and their usage is clearly distinguished.

The term Qualification is traditionally used in relation to objects that may include:

Process Equipment
Clean Process Utilities Generation, Storage, and Distribution Systems
Cleanrooms
Heating, Ventilation, and Air-Conditioning (HVAC) Systems
Laboratory Equipment, etc.

The EU GMP Guidelines provide the following definition of Qualification: "Action of proving that any equipment works correctly and actually leads to the expected results..."

In contrast to Qualification, the term Validation is traditionally used in relation to processes, which may include:

[Manufacturing] Process
Cleaning Process
Analytical Methods

The EU GMP Guidelines define Validation as: "Action of proving, in accordance with the principles of Good Manufacturing Practice, that any procedure, process, equipment, material, activity or system actually leads to the expected results..."

The word validation is sometimes broadened to incorporate the concept of qualification.

Requirements for qualification and validation are outlined in Annex 15 of the EU GMP Guidelines:

“A quality risk management approach should be applied throughout the lifecycle of a medicinal product. As part of a quality risk management system, decisions on the scope and extent of qualification and validation should be based on a justified and documented risk assessment of the facilities, equipment, utilities and processes. Retrospective validation is no longer considered an acceptable approach. Data supporting qualification and/or validation studies which were obtained from sources outside of the manufacturers own programmes may be used provided that this approach has been justified and that there is adequate assurance that controls were in place throughout the acquisition of such data.”

“1.1. All qualification and validation activities should be planned and take the life cycle of facilities, equipment, utilities, process and product into consideration.
1.2. Qualification and validation activities should only be performed by suitably trained personnel who follow approved procedures.
1.3. Qualification/validation personnel should report as defined in the pharmaceutical quality system although this may not necessarily be to a quality management or a quality assurance function. However, there should be appropriate quality oversight over the whole validation life cycle.
1.4. The key elements of the site qualification and validation programme should be clearly defined and documented in a validation master plan (VMP) or equivalent document.”

“3.1. Qualification activities should consider all stages from initial development of the user requirements specification through to the end of use of the equipment, facility, utility or system…”

“4.1. Equipment, facilities, utilities and systems should be evaluated at an appropriate frequency to confirm that they remain in a state of control.
4.2. Where re-qualification is necessary and performed at a specific time period, the period should be justified and the criteria for evaluation defined. Furthermore, the possibility of small changes over time should be assessed.”

Detailed recommendations on conducting Acceptance Tests and Qualification are provided in ISPE Baseline Guide Vol. 5: Commissioning & Qualification, 2nd Edition, 2019. Unlike GMP guidelines, ISPE guidelines do not hold the status of regulatory requirements.

There are several different types and stages of qualification and validation, each related to different aspects and life-cycle stages of pharmaceutical manufacturing, including:

It is also possible to identify a number of specific qualification activities based on the system being qualified, such as:

Acceptance Tests (FAT/SAT)

Acceptance Tests, unlike Validation and Qualification, are not considered validation activities in the context of GMP/GxP. Acceptance is conducted as a commercial activity, aiming to confirm that the scope of supply and functional/design specifications of equipment comply with the respective contract specifications, and that the supplier has fulfilled its obligations under the contract.

For particularly complex, large, and expensive equipment—such as pharmaceutical equipment—it is often justified to conduct initial acceptance tests at the equipment manufacturer's facility before the equipment is shipped to the client. This type of acceptance testing is traditionally called a Factory Acceptance Test (FAT). Usually initiated by the client, FAT has a purely commercial nature and is not a regulatory requirement. The primary goal of FAT is to identify potential equipment issues before it leaves the manufacturing facility, allowing for quick fixes without incurring additional transport costs. It is also typical that a payment installment is tied to the successful completion of the FAT.

The next acceptance testing activity, conducted at the client’s site after equipment installation and start-up, is the Site Acceptance Test (SAT). Like FAT, SAT is also commercial in nature and not a regulatory requirement. Final payment installments are often contingent upon the successful completion of SAT. It is considered good practice to include a check in the SAT protocol to confirm whether Installation Qualification (IQ) and Operational Qualification (OQ) have been successfully completed.

Sometimes, the process is reversed: filled SAT protocols (reports), provided that the SAT tests have been successfully completed and the results recorded in a GMP-compliant manner, can be incorporated into the validation documentation package. In such cases, the SAT becomes an integral part of qualification tests, such as IQ and OQ.

The specialists at Tarqvara Pharma Technologies have years of experience in conducting qualification, validation, and acceptance tests within the pharmaceutical industry, in full compliance with international, European, and national GMP/GxP regulations and standards.