Hi Quark and 91479184,
Thanks for your helpful posts.I found out this particular space has an air change rate of 15.Fine filters are provided in a filter plenum after the AHU and there are no terminal HEPA filters.The space is used for manufacturing plastic syringes.When I referred to GMP guidelines it seems to recommend minimum air change rate of 20 for Grade D areas(class 100000)and terminal HEPA filters in the air distribution system.Any thoughts?
Please find attached below relevant extract from GMP guidelines(
Table 1. Air classification system for manufacture of sterile products
Grade Maximum number of particles permitted per m3 Maximum number of viable microorganisms permitted per m3
0.5–5 mm >5 mm
A
(Laminar-airflow
workstation) 3 500
none less than 1
B 3 500 none 5
C 350 000 2 000 100
D 3 500 000 20 000 500
17.2 The various operations of component preparation (such as containers and closures), product preparation, filling, and sterilization should be carried out in separate areas within the clean area.
17.3 Clean areas for the production of sterile products are classified according to the required characteristics of the air, in grades A, B, C, and D (see Table 1).
To obtain air of the required characteristics, methods specified by the national authorities should be used. It should be noted that:
• Laminar-airflow systems should provide a homogeneous air speed of about 0.30 m/s for vertical flow and about 0.45 m/s for horizontal flow but precise air speeds will depend on the type of equipment.
• In order to reach the B, C, and D air grades, the number of air changes should generally be higher than 20 per hour in a room with a good airflow pattern and appropriate HEPA (high-efficiency particulate air) filters.
• Low values for contaminants are reliable only when a large number of air samples are taken.
• The guidance given for the maximum permitted number of particles corresponds approximately to the United States Federal Standard 209E (1992) as follows: Class 100 (grades A and B), Class 10 000 (grade C), and Class 100 000 (grade D).
It may not always be possible to demonstrate conformity with particular air standards at the point of fill when filling is in progress, owing to the generation of particles or droplets from the product itself.
17.4 Each manufacturing operation requires an appropriate air cleanliness level in order to minimize the risks of particulate or microbial contamination of the product or materials being handled. Section 17.5 gives the minimum air grades required for different manufacturing operations. The particulate and microbiological conditions given in Table 1 should be maintained in the zone immediately surrounding the product whenever the product is exposed to the environment. These conditions should also be achieved throughout the background environment if no personnel are present in the processing area, and if the standards fall for any reason it should be possible to recover the conditions after a short "clean-up" period. The utilization of absolute-barrier technology and automated systems to minimize human interventions in processing areas can produce significant advantages in ensuring the sterility of manufactured products. When such techniques are used, the recommendations in these supplementary guidelines, particularly those relating to air quality and monitoring, still apply, with appropriate interpretations of the terms "workstation" and "environment".
Manufacture of sterile preparations
17.5 Manufacturing operations are here divided into three categories: first, those in which the preparation is sealed in its final container and terminally sterilized; second, those in which the preparation is sterilized by filtration; and third, those in which the preparation can be sterilized neither by filtration nor terminally and consequently must be produced from sterile starting materials in an aseptic way. Area grades as specified in sections 17.5.1–17.5.3, must be selected by the manufacturer on the basis of validation runs (e.g., sterile media fills).
Terminally sterilized products
