- GIC A3P Validation of Cleaning prepares a practical guide for 2017 Autumn on 10 Chapter of 15 Annex of European GMPs: Presentation & Discussion.
- Cluster consolidation strategies for solid oral forms in multi-product establishments
- The biocidal regulation applied to disinfectants used in the Pharmaceutical Industry: what you need to know ...
- Practice Book - How to Ensure the Success of a Self-Inspection of the Sterility Assurance Process & Related Procedures
- Cryogenics is the study and production of low temperatures
- Cleaning Control Strategy for the Manufacture of Principles Pharmaceutical Assets under Development for Clinical Use
- Indirect visual control modernizes cleaning validation
- The determination of the recovery rate is a preliminary step, necessary during a cleaning validation exercise
- Cleaning Validation for biotechnological substances: What acceptance criteria?
- Vaccines / Biotech "Health-based approach" implementation for setting limits
Visual inspection remains a vital operation in a cleaning validation strategy, which is the prerequisite for starting this cleaning validation step. This is still too often neglected, the conformity of this visual check gives us a first indication of the efficiency of our cleaning step during a process.
It is a pharmaceutical operation in the same way as all operations performed during a manufacturing or packaging.
Historically, with the implementation of cleaning validation studies, the visually clean method was the only method available. It is still used today, but it is integrated into cleanup validation programs and is not sufficient, as GMPs indicate in their 15 Appendix: "§ 10.2. A visual inspection of cleanliness is an important part of the acceptance criteria set out for cleaning validation. Use of this criterion alone is generally not acceptable. (...) ".
For its part the FDA in the “Guide to inspection of validation of cleaning processes” considers that the acceptance criterion based on visual inspection may be acceptable only in the case of inter-batch cleaning for the same product.
These different regulatory sources confirm that visual testing is an important part of the validation of a cleaning process.
Technological progress and the miniaturization of cameras make this test more reliable and still more effective in relation to the places to be reached.
Visual testing must be conducted on a clean, dry surface, (with no trace whatsoever of humidity), as traces appear most often on drying. The execution of a visual test requires that no part/surface of the equipment concerned is forgotten. It therefore involves adopting a methodological sequence in order to make sure that no part of our equipment has been overlooked. This can appear in a visual test performance instruction drafted on site.
As long as “visually clean” status is not achieved, samples for cleaning validation are not taken.
Two types of visual tests may be distinguished: direct/indirect.
Direct visual tests are to be favored but depending on the observation conditions and the geometry of the equipment involved this operation will be combined with indirect visual tests.
Direct visual tests
Visual tests are direct if the optical path between the surface inspected and the tester’s eye is not interrupted. This category includes tests with the naked eye and those using: mirrors, magnifying glasses, etc.
The eye and its limits:
The special characteristics of visual testing give rise to the observation that all individuals in a population do not have the same visual acuity.
• The angle of the visual field normal human is 50 to 55 °. The important thing is to focus the visual control on the possibility of having all the same characterization of the trace that one observes on the surface (trace of product, trace of detergent, trace of rust, trace of limestone ...). The objective is to be able to vary as much as possible the angle of view on the observed surface (optimal angle of 45 °), it allows to see asperities passed unnoticed with an angle of 90 ° for example.
• The lighting of the item where the inspection takes place, the shadows caused by the configuration of the equipment, as well as the operator’s gaze distance relative to the equipment have their importance. This entails training in visual testing for each person who carries out this operation.
Fourman and Mullen determined that most substances would be visible at a rate of around
100μg/ 25cm2 of cleaned surface area that is 4 μg/cm2, taking account of the observation conditions.
Jenkis and Al reportedly observed that with a good light source, the detection limit was 1μg / cm2.
It is estimated on a surface that 10 cm from it, the threshold of visibility to the naked eye of the particles is: 50μm under ambient light and 30μm under intense light (additional, such flashlight ...).
The other limit on direct visual testing, is that the operator conducting the test certifies the test as compliant or non-compliant on their honor.
Indirect visual testing (IVT)
Visual testing is indirect if the optical path between the surface inspected and the tester’s eye is interrupted. This category includes tests using photography, cameras, videoscopes, etc. It allows greater sensitivity than that of the naked human eye to be obtained and permits access to complex or restricted geometrical areas.
In fact it is possible to choose the angle of view of the objective depending on need. An objective with an angle of view:
• >50°, will approach panoramic vision
• <50°, will allow macroscopic vision, therefore magnification and better detection than by eye.
3 other technical criteria must be defined:
• The working distance: : it is the minimum distance between the object to be observed and the objective
• The depth of field of the objective: : this the area where the image is still sharp (distance between the first and last planes in which the image of an object located a certain distance from the objective is in focus)
• The type of viewfinder: axial or radial
IVT produces an image of the item and the indications that are potentially detected. In most cases, this image can be recorded to provide test traceability. In the context of a manual test using optical instruments, the precise determination of the location and dimensions of the indications can be complex; in the context of a mechanized test, this characterization is simple to perform and can be very precise.
The primary goal of using all these new tools is to be able to inspect equipment in all its dimensions. We can safely go see in a tank and no longer have to go down to inspect it. Tense and tedious operations of confined space interventions are more rare. The fast and secure implementation of the VTI hardware increases the frequency of checks.
The improved detectability of residues and the increased frequency of indirect visual tests brings better control of equipment and washing processes. Therefore it should be expected that anomalies not previously seen will be detected and appropriate corrective action plans should be provided for.
In conclusion, indirect visual testing brings significant benefits compared to direct visual testing provided that the choice of equipment is adapted to need. It allows larger difficult-to-access areas to be covered, with improved illumination. Now nothing can escape us.
Currently, indirect visual testing has not yet become a routine standard practice, but this should be encouraged.
Is it possible to envisage a future in which: the performance and reproducibility of indirect visual testing methods will be qualified for pharmaceutical and cosmetic industry applications ; the operator carrying out this type of test will have been certified by an independent approved body
This allows the indirect visual control to substitute serenely for surface sampling ... when the visual detectability of the product to search allows.
Training of operators in the use of the endoscope will be as a minimum provided by the distributor of the test equipment. It is also possible to use the guide “OPÉRATEURS EN ENDOSCOPIE: BONNES PRATIQUES (ENDOSCOPE OPERATORS: BEST PRACTICE)” Editions LEXITIS, developed by a COFREND working group.
This document is intended for all areas of the industry. It aims to describe the "good practices" of the job of operator in industrial endoscopy: its role, the context in which it operates, a lexicon and a number of points that should be considered during its adoption process endoscopy as a means of control, for example elements on the compromises to be adopted.
Guillaume GARREAU - GALDERMA Laboratories
François BLACHERE - COPHACLEAN
Endoscopy: method of medical or industrial visual exploration of the interior (endon in Greek) of a cavity inaccessible to the eye. The instrument used, called endoscope is composed of an optical tube equipped with a lighting system
Inspection camera: it is an endoscope whose probe diameter is greater than 20mm
Goal : Optical component intended to be turned towards the object to be observed
VT: direct visual control (Visual Testing)
VTI: indirect visual control (Indirect Visual Testing)
Fourman and Mullen
Jenkis and Al
COFREND Editions LEXITIS, via this link: http://www.lexitiseditions.fr
GMP in force
FDA - GUIDE TO INSPECTIONS VALIDATION OF CLEANING PROCESSES