Only qualified personnel should have access to the aseptic processing area. The personnel is a main source of contamination with microorganisms which are present in the working environment. Organisms may be transferred directly or indirectly. In the case of direct transfer, contamination takes place by mechanical release (e.g. by touching the medicinal product with a hand or sleeve contact). In the case of indirect transfer, the organisms are distributed in the air and can then settle on the medicinal product. This can occur, for instance, as a result of a rapid movement of the personnel in the clean room (removal of organisms from the protective clothing and release into the air).
With the personnel, the germ reduction is naturally limited to disinfecting their hands. In addition to hand disinfection, the clean room clothing / protective clothing has a significant influence on the organisms released by the personnel. The EU GMP Guide provides very detailed and helpful information on this subject in Annex 1. It is always important that this protective cloth-ing be put on and worn correctly in accordance with the requirements for room classes A to D. The protective clothing should be changed after each working period in areas A/B, because the organisms can permeate the material after clothes have been worn for a certain time. A certain degree of additional security is provided by wearing under garments. At the same time if feels more comfortable to wear such under garments rather than just clean room clothing.
Because of the personnel's key position in the context of aseptic processing, a written training programme for qualifying the personnel in accordance with the applicable company-specific instructions is important and indispensable. An aseptic gowning qualification program should assess the ability of a clean room operator to maintain the quality of the gown after performance of the gowning procedure. Before the gowning procedure is actually qualified, the personnel must be trained as part of the qualification programme (see also GMP MANUAL chapter 2.C).
The personnel training should, in accordance with Annex 1 of the EU GMP Guide, include the following points:
Only after the personnel has successfully completed the training the correct gowning procedure will be checked by means of visual monitoring (watching by a control person) and by means of contact plate samples. In order to standardise the visual monitoring, it is helpful to draw up a rating checklist in advance which also defines requirements. The various items in the checklist can then, for example, be assigned numbers of points, thus permitting the rating to yield a final score. The requirement could, for instance, be that the employee must obtain a minimum score in the air lock procedure. However, this minimum score should be high enough to ensure that the passage through the air lock no longer entails a risk of contamination. Reaching this score is the prerequisite for successful completion of the training for any employee.
For the purpose of initial qualification, three successive air lock procedures to enter the clean room should be completed successfully. These air lock procedures should be evaluated by means of taking a microbiological sample from the clean room clothing.
Monitoring the personnel should include the following sampling locations:
These or other possible sampling locations should always be justified.
Because of legal considerations (invasion of personal privacy), examinations of the personnel are only allowed where they cannot be avoided. This is the case in the aseptic working area. However, it is recommendable to conclude a company agreement with the works council in order to guarantee that personal privacy is protected. Nevertheless there must be a way of relating nonconforming results directly to a person (e.g. by a personal number key). The EU GMP Guide provides assistance in Annex 1 by the requirement for a contact person who focuses on follow-up measures from personal hygiene monitoring and supports the personnel in this context. This person of trust could report the results of personnel monitoring to a small, selected group of people and agree with this group on any measures that need to be taken.
The initial gowning qualification of personnel only authorises them to enter areas in cleanliness grade B, in other words no media fill is necessary for qualification purposes in this case. When it is necessary for an employee to intervene in cleanliness grade A, this employee must also be qualified for this area. This is achieved by the employee performing the specified activities which are to be simulated in the context of the media fill. Employees are only qualified to enter clean rooms and to participate in aseptic filling operations after successful completion of the gowning qualification for entering cleanliness grade B areas and successful performance of a media fill.
Successful performance of a media fill means:
The FDA requires requalification to be performed after 12 months. After this time, another successful air lock procedure must be completed. Only then the employee is qualified for another 12 months.
Persons who need to enter clean rooms of grade A/B for purposes other than production processes (maintenance staff, validation personnel, etc.) can be permitted to do so by exempting them from qualification. This should, however, be specified in written instructions. Such exemptions can, for instance, define that an accompanying qualified person should supervise the unqualified personnel.
In addition to the details regarding personnel qualification, the FDA also states what measures should be initiated when defined limit values for the personnel are exceeded. Requalification should thus be carried out if:
This requalification includes the person completing the training again and repeating the air lock procedure which is checked by microbiological monitoring. If a person fails to complete the qualification or requalification process successfully several times in succession, this person should be excluded from the qualification process and further measures may be required.
WDT eG, Germany