During the course of 2004 the Danish Medicines Agency has performed a number of inspections of manufacturers of sterile medicinal products, including terminally sterilised and aseptically produced medicinal products. The inspections included production of marketed medicinal products, medicinal products for use in clinical trials and active pharmaceutical ingredients.

Several deviations from the GMP regulations were demonstrated during the inspections. The companies undertake to adjust this before their company authorisations can be issued/renewed or before authorisation can be given to perform clinical trials. None of the inspections led to withdrawals of products or the like. The main deviations can be found in the following.

Far the greatest share of deviations covered premises and equipment:

• Several companies were not able to document that their ventilation systems work efficiently so that the requirements for clean rooms and pressure difference compared to the surroundings are continuously fulfilled.
• Disinfectants for cleaning rooms with the highest degree of cleanness were not always sterilised and lacked indication of expiry date.
• Many deviations included equipment for which the necessary qualification had not been made before it was first used or for which there were not laid down any procedures for requalification of the equipment.
• In some cases there were insufficient cleaning procedures or procedures which were not followed in practice. Time limits for use of cleaned or sterilised equipment were not always laid down.
• In some cases there were no written procedures for the company’s action in connection with exceeding temperatures or alarming limits regarding stock holding of medicinal products.

The second-largest part of the deviations regarded quality management and quality control followed by deviations regarding organisation and personnel and finally production of medicinal products.