The validation process has sad origins: thousands of deaths caused by bad drugs production. To avoid these tragedies the regulatory authorities, require that the drugs are produced, stored and handled in a validated system.
What does “validated system” mean?
The “Validation” of a system means that evidence and guarantees have been provided, given the state of the art in the manufacture of drugs, that the production process under examination operates and continues reasonably to operate according to the criteria provided.
EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use – Annex 15: Qualification and Validation
The main stages of the qualification process are:
I. User Requirements Specifications (URS):
Pre-design activities which define the performance required for equipment, production departments, utilities and plants. The figures involved in this phase are the client and the consultants.
II. Design Qualification (DQ):
Design phase activity in which the solutions adopted in the project are verified in relation to the URS. Any modification to the project, during any stage of the implementation process, must be subject to formal DQ. The figures involved in this phase are the client, the consultants, the designers, the suppliers (when choosing equipment), contractors (in case of changes during the construction process).
III. Factory Acceptance Testing (FAT)/Site Acceptance Testing (SAT):
Construction activities in which equipment and works are assessed to check compliance with the URS. The tests can be carried out in the workshop (FAT), on site (SAT) or in both conditions. FAT/SAT operations must be planned and reported as indicated in the Project Specification. The figures involved in this phase are the client, the consultants, the planners, the work Management, the Commissioning Authority Builders, the suppliers and the contractors.
IV. Installation Qualification (IQ):
Activities carried out in deliver phase aiming to identify whether all the indications envisaged by the project have been applied, such as:
a. Checking the correct installation as reported in the drawings and in the design specifications.
b. Verification of correct installation as reported in previous criteria.
c. Collection and reordering of manufacturers’ operating instructions and maintenance requirements.
d. Instrumentation calibration.
e. Verification of construction materials.
The figures involved in this phase are the client, the consultants, the planners, the work managers, the builders, the suppliers, the contractors, and the Commissioning Authority.
V. Operational Qualification (OQ):
This phase is finalized to test and verify that the systems installed work exactly as expected in the project plan. The “OQ” normally follows the “IQ”, but it is not excluded that they can be combined in case of particularly complex systems. During the “OQ” phase are going to be performed at least the following activities:
a. Tests to verify the operation according to the design forecasts.
b. Tests to verify the coverage of operating limits (min/max).
c. Tests to verify the operation in the most critical conditions.
For utilities, the “OQ” phase must also cover any seasonal effects.
Passing the phase “OQ”, allows to start with Cleaning phases, Operativity in standard conditions tests, operators and maintainers training. The figures involved in this phase are the client, the consultants, the planners, the work manager, the builders, the suppliers, the contractors and the Commissioning Authority.
VI. Performance Qualification (PQ):
The “PQ” phase tests and verifies that the installed systems function exactly as expected in the plan, in operating conditions simulating the production. The “PQ” normally follows the “IQ” and the “OQ”, but it is not excluded that the “PQ” can be combined with the “OQ“ and also with the following validation phase for particularly complex systems. In the “PQ” phase are performed at least the following activities:
a. Tests with the use of production materials (or suitable substitutes) to verify the functionality according to the project’s forecasts under real conditions of use.
b. The tests shall cover the entire range of use of the system.
Once this last phase is successfully overcome, the Validation phase can begin.
The “As-Built” documents related to the systems covered by IQ-OQ-PQ, that the contractor must produce, are:
The author is one of the founding partners of the engineering company Planex s.r.l. since 2002 and for over 30 years, has been involved in the engineering processes of pharmaceutical plants and buildings. His career starts in 1989 with the design and construction activities for a new department of freeze-dried injectable products of the Lepetit company, which at the time belonged to the DOW Chemical group, and continues nowadays with the design and construction management of the new production site M. Polo of the Zambon Group, the site Masterplan of an ITALFARMACO S.p.A plant, the creation of a new production department of Fresenjus Kabi S.p.A., various interventions within the EVOTEC Aptuit research center in Verona.
During his career he has also worked on other type of extremely complex buildings; he has taken care of the realization of the new productive site for Pastificio Rana S.p.A. in San Giovanni Lupatoto – Verona, the new Cetacean pavilion for the Aquarium of Genoa, the testing of Isozaki Allianz tower systems in Milan and many more.