EudraLex: EU Guidelines to Good Manufacturing Practice Medicinal Products for Human and Veterinary Use - Annex 1

TRADELABOR has more than 20 years of experience in the control and treatment of air, working with an experienced and qualified technical staff and with the most advanced technology in this area, which together guarantee the quality of the services provided.

MANUFACTURE OF STERILE MEDICINAL PRODUCTS

Principle

The manufacture of sterile products is subject to special requirements in order to minimize
risks of microbiological contamination, and of particulate and pyrogen contamination. Much
depends on the skill, training and attitudes of the personnel involved. Quality Assurance is
particularly important, and this type of manufacture must strictly follow carefully established
and validated methods of preparation and procedure. Sole reliance for sterility or other quality
aspects must not be placed on any terminal process or finished product test.

Note:
This guidance does not lay down detailed methods for determining the microbiological and
particulate cleanliness of air, surfaces etc. Reference should be made to other documents such
as the EN/ISO Standards.

For the manufacture of sterile medicinal products 4 grades can be distinguished.

Grade A: The local zone for high risk operations, e.g. filling zone, stopper bowls, open
ampoules and vials, making aseptic connections. Normally such conditions are provided by a
laminar air flow work station. Laminar air flow systems should provide a homogeneous air
speed in a range of 0.36 – 0.54 m/s (guidance value) at the working position in open clean
room applications. The maintenance of laminarity should be demonstrated and validated.
A uni-directional air flow and lower velocities may be used in closed isolators and glove
boxes.

Grade B: For aseptic preparation and filling, this is the background environment for the grade
A zone.

Grade C and D: Clean areas for carrying out less critical stages in the manufacture of sterile
products.