Qualification / Validation / Commissioning

Validation and Qualification

Term Validation originates from Latin root validus (healthy; strong). In modern European languages adjectives derived from this root – where they exist – usually are translated as suitable, fit, acceptable (e.g. Engl. valid, Fr. valide, It. valido etc.). Its derivative verb validate is used in the meaning to provide / determine / confirm suitability, which reasonably well reflects respective activities in relation to pharmaceutical manufacturing. The respective process is then called validation.

Term Qualification originates from Latin root qualis (what kind of). In most European languages from this root was derived the word quality. Corresponding derivative verb qualify means determine / confirm quality. Respective process is then called qualification, which needs here to be distinguished from term qualification in the meaning of a person having professional skills. In the context of validation activities related to pharmaceutical manufacturing qualification refers to a process, and therefore expressions like to conduct qualification are correct.

Terms Validation and Qualification may seem very similar: in both cases, it is a process of determining / confirming suitability of something to certain acceptance criteria. Nevertheless, these terms are not interchangeable, and their use is clearly distinguished.

Term Qualification is traditionally used in respect of 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.

EU GMP Guidelines provide following definition of Qualification:

“Action of proving that any equipment works correctly and actually leads to the expected results…”

As opposed to Qualification, term Validation is traditionally used in respect of processes that may include:

  • [Manufacturing] Process
  • Cleaning Process
  • Analytical Methods

EU GMP Guidelines provide following definition of Validation:

“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 widened to incorporate the concept of qualification.

Requirements to qualification and validation are stipulated in Annex 15 to 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 conduction of Acceptance Tests and Qualification are provided in ISPE Baseline Guide Vol 5: Commissioning & Qualification, 2nd Edition 2019. ISPE Guidelines, unlike GMP Guidelines, do not have status of regulatory requirements.

There are a number of different kinds and stages of qualification and validation in relation to different aspects and life-cycle stages of pharmaceutical manufacturing, in particular:

  1. Basic Risk Analysis – BRA
  2. Validation Master-Plan – VMP
  3. Risk Analyses – RA
  4. Design Qualification – DQ
  5. Installation Qualification – IQ
  6. Operational Qualification – OQ
  7. Performance Qualification – PQ
  8. Process, Cleaning and Analytical Methods Validation (PV/CLV/AMV)
  9. Computerized Systems Validation (CSV)

It is also possible to name a number of specific qualification activities based on the system subject to qualification:

  1. HVAC / Cleanrooms Qualification
  2. Clean Utilities Qualification
  3. Pharmaceutical Warehouse Qualification / Thermal Mapping

Acceptance Tests (FAT/SAT)

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

For particularly complex, large-size and expensive equipment, which pharmaceutical equipment usually is, it is justified to conduct initial acceptance tests at equipment manufacturers facility before the equipment is shipped to the Client. This kind of acceptance testing is traditionally called Factory Acceptance Test (FAT). Usually, this acceptance is initiated by Client, and it has only commercial nature, i.e. is not a regulatory requirement. The main goal of FAT is to identify potential problems in equipment before it leaves the facility, where it was manufactured, so that their fixing would be quick, and would not cause extra transport costs. It is also typical that a payment installment is connected to the successful accomplishment of FAT.

The next acceptance testing activity, which is conducted already at the Clients site upon completion of equipment installation and start-up work, is Site Acceptance Test (SAT). This acceptance activity has also only commercial nature, i.e. it is not a regulatory requirement. It is also typical that final payment installments are connected to the successful accomplishment of SAT. It is a good practice to include in SAT protocol checking, if Installation Qualification (IQ), and Operational Qualification (OQ) have been successfully completed. Sometimes though it is done the other way round: filled SAT protocols (reports), provided that SAT tests have been completed successfully, and results have been recorded in a GMP-compliant manner, can be incorporated into validation documentation package, and therefore become in integer part of qualification tests, e.g. Installation Qualification (IQ) and Operational Qualification (OQ).

Specialists of Tarqvara Pharma Technologies have years of experience in conduction of qualification, validation and acceptance tests in pharmaceutical industry, in compliance with respective international, European, and national GMP/GxP regulations and standards.

See also:
Computerized Systems Validation (CSV)
Acceptance Tests (FAT/SAT)
Risk-Oriented Approach