Premises sterile product manufacturing

For additional guidance on premises for Sterile Products Manufacture, see section 9). 

Vacuum or wet cleaning methods are to be preferred. Compressed air and brushes should be used with care, and avoided if possible, as they increase the risk of product contamination. (For additional guidance on premises for Sterile Products Manufacture, see Section 9.)... 

Clearly reproducibility, regular monitoring and documentation are required. However, parametric release would imply abandoning the sterility test, an option that many manufacturers have not yet adopted, possibly because of the fear of litigation based on the premise that any sterile product would, if tested, have passed the test for sterility. 

The manufacturing operations shall be performed in suitable areas provided with the necessary equipment. Whenever part of the equipment is used commonly in several operations, suitable measures shall be adopted to rule out the possibility of cross-contamination and mistakes. Simultaneous operations on different drugs in contiguous working areas shall be avoided unless these areas are separated from each other. Operations in an aseptic environment shall be performed in rooms designed and constructed for this purpose as indicated section 4 (Premises). The sterilized products and the products which are to be sterilized shall be clearly identified in order to allow their distinction from each other. 

More than any other medicine, sterile preparations must be produced according to procedures carefully establishes and rigorously applied in order to guarantee product sterility and to prevent particulate, and possible pyrogenic, contamination. Their production requires that special precautions be taken concerning the training of staff, the premises,equipment, raw materials, the environment in the production areas and the manufacturing process. 

The processing of animal tissue materials and of microorganisms (not required for the current manufacturing process), the performance of test procedures involving animals or microorganisms, and any animal houses, must be well separated from premises for manufacturing sterile medicinal products, with completely separate ventilation systems, and separate staff. 

Annex 3 (Manufacture of Radiopharmaceuticals) is the only part of the GMP framework entirely dedicated to radiopharmaceuticals [10]. Preparation of radiopharmaceuticals using authorised generators and kits is excluded from this Annex. The production of radionuclides in reactors and cyclotrons is a physical process and is regarded as a non-GMP activity. Annex 3 describes general GMP principles (quality assurance, personnel, premises and equipment, documentation, production, quality control, reference and retention samples, distribution) in relation to radiopharmaceuticals. As with other medicinal products, other GMP annexes may be applicable, for instance Annex 1 Manufacture of Sterile Medicinal Products [11]. 

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