5/6 October 2022
Up-to-date monitoring systems produce vast amounts of data, e.g. pressure, humidity and temperature in clean rooms. In pharmaceutical production practice, there are different approaches to handle this electronic data - alerts especially. Not all options are ideal from a GMP viewpoint:
A: Alams occur, are saved and then… nothing. After a while, the alerts "disappear", because the memory space is full and old data is automatically written over by the system.
B: Alarms occur and are acknowledged by excessive clicking of the "enter" key, followed by the storage of the data in a GMP data archive.
C: Constant review, assessment and aggregation of alarms by criticality; drafting of GMP deviation reports and CAPAs for critical procedures.
D: Each alarm triggers activities of quality assurance, including GMP deviation reports and CAPAs (and soon after, the Head QA will ask the Head HR for more personnel).
Sooner or later, option A and B will lead to deficiency notifications relating to "data integrity" in GMP inspections. Especially large, internationally operating pharmaceutical companies often tend to option D. As a result, there are many QA managers who demand for the technical department to do their groundwork for deviation reports or CAPA measures.
This can be avoided by proper planning of the clean room, equipment and monitoring system. The actual technical challenge is to minimize the number of alarms by implementing a valid system design. The key for this may be delays. The example of the washroom is supposed to show this. Normally, the maximum humidity in a pharmaceutical clean room is supposed to lie below 70% to prevent the formation of moulds. Especially in the case where no double-door autoclaves oder double-door washing machines have been installed this can cause problems.
In the GMP measuring point list, the humidity sensor is usually defined with an alert limit at 60% and an action limit at 70%. In practice, however, steam - such as occurs in kitchens - escapes from the washing machine during the removal of laundry carriers. Depending on the arrangement of the humidity sensor, there is an immediate breach of alert or action limits. The simplest but not appropriate solution would be to relocate the humidity sensor to a corner where the steam cannot reach. To run measurements where relevant variables cannot be measured, however, does not correspond with the concept of GMP. For washing systems a separate exhaust air system which starts when the washing chamber is opened could be a solution but with new risks. The exhaust air has to be handled separately from the clean room and the formation of condensation water has to avoided.
A functional and GMP compliant solution could be delay times, which would definitely be less expensive than rebuilding the washing machine. Effectively, a washing cycle takes 0.5 to 2 hours, which means the excessive humidity values only occur 4-5 times a day for about 5 to 30 minutes. If one delays the alerting by 30-60 minutes, these alerts will no longer occur. In washing rooms with a low air exchange rate, it may in individual cases take 60 minutes for the room humidity value to normalise again (e.g. in class D rooms with 12fold air change). The setting and application of such a delay, however, must be documented in a risk assessment and approved by quality assurance. It is technically valid, because a real risk of formation of moulds only exists if elevated humidity values occur over a longer period of time. The question what a longer period of time means in this instance is justified, of course. Different values for this can be found in literature, like more than three hours a day with a surface humidity of 60-100% (in German language), for example.
According to DIN report 4108-8 (prevention of mould growth in residential buildings), mould formation occurs if the relative humidity of a surface reaches a value of more than 80% for at least twelve hours a day on at least five consecutive days.
The adjusted delay times should be added to the GMP measuring point list and tested within the IQ (of the clean room).
A further possibility lies in designing the HVAC system in such a way that they only raise the air exchange rate when necessary - for washing rooms, this is a little elaborate, but for rooms with humidity-critical products, this solution is ideal from an energy point of view. There, humidity alerts may be triggered due to wet mopping in the course of room cleaning, for example.
It's always critical when programmers define functions without revealing the corresponding rationale.