The quality of a product is determined through manufacture. Therefore, the production processes occur according to clearly defined and qualified, i.e. validated procedures, which correspond to the principles of good production practises.
Measures for the prevention of cross-contamination and mistakes and the adherence to microbiological requirements are undertaken.
The status of each stored good is made clear so that the same safety is ensured, such as through spatial separation. Source material and new products are held in quarantine until quality inspection has released the batch(es). The ambient conditions in the different storage areas are regularly monitored and corrected if necessary.
Batch technology
Due to the production of different galenic forms there are also divergent batch technologies, which nonetheless, display conformity in their basic requirements.
The objective here is the manufacture of a homogeneous bulk preparation, which will be attained with the help of batch boilers in the liquid area, and with a powder mixer in the solids area respectively.
These standard procedures are described in sufficient detail in the relevant SAA's and VA's respectively, which the procedures themselves qualify, i.e. validate.
Further necessary general conditions for individual galenic forms such as:
• the removal of dust
• class A area for products to be handled aseptically
• agitators or mixers
• cleaning/sterilisation measures for bulk or equipment
• germ reduction - i.e. sterile filtration
are ensured through room technology, unit technology and/or medium supply. The regular checking of these operating parameters is ensured through the existing monitoring regimes, the precautionary maintenance and the calibration of items requiring calibration.
Filling
The filling and sealing of oral/unsterile and sterile products occurs according to the requirements of the respective guidelines. The protection of the product also has the highest priority here.
The necessary general conditions here are also ensured through room technology, unit technology and/or medium supply. The regular checking of these operating parameters is ensured through the existing monitoring regimes, the precautionary maintenance and the calibration of items requiring calibration.
Sterilisation
A number of parenteral products - mainly infusion solutions - are available in a terminal sterilisation in the final repository.
The autoclaves follow the requirements in the relevant chapter of the pharmaceutical books and fulfill the minimum physical requirements. The use of autoclaves is qualified.
The proof of correct final treatment is produced according to batch and is a part of the manufacture documentation.
Packing
All packing procedures are carried out according to authorised product and packing-specific packing prescriptions and documented in the manufacture/packing protocol.
Mid-process inspections
Mid-process inspections serve for the monitoring and control of a continuous process.
Essential parameters such as
• the introduction of exit materials into a batch boiler or mixer,
• the appearance or the pH value of solutions or
• filling volumes in accordance with packaging regulations,
• the completeness and external integrity of bulk
occurs according to batch. They are carried out by production personnel and the results are retained in the manufacture protocol.
Production hygiene
The objective of production hygiene is to avoid the microbiological contamination of products. Therefore, diverse regulations are met.
Germ limits exist for all finished pharmaceuticals. The microbiological condition of raw materials is inspected by quality control according to their origin (chemical, herbal, etc.) and their area of use (fixed dosage form, parenterals, etc.). Biological preparations are put under particular scrutiny. Water purification and water for injection purposes are checked daily.
Production rooms are cleaned and disinfected according to the relevant SAA's procedure. Windows are to be kept closed. In order to achieve a germ-count reduction for the air, a controlled aeration is conducted via filters. The germ-count of the air is inspected and documented regularly.
Personnel are trained with an eye for hygienic behaviour and wear protective clothing.
The equipment is constructed in such as way that simple cleaning is possible. Cleaning takes place according to valid cleaning procedures. No rinse water residuals are to remain. Accordingly, each application area is additionally disinfected or sterilised.
Manufacturing processes preferably, take place in closed systems. Raw materials, by-products and bulk are transported in closed containers.
Measures for the prevention of cross-contamination
When different concoctions are manufactured in one room, appropriate measures must be guaranteed so that the risk of cross-contamination is minimised, e.g. through the use of partitions or through campaign production. Appropriate exhaust systems are used for very dusty processes. The flow of material is efficiently organised. Closed systems and fabrication in one line are desired.
Responsibilities
The production manager is responsible for the deployment of the points concerned here. The detailed demarcation of responsibilities, particularly those of the control manager, is defined in the respective job descriptions. |
