Sterile medicinal products

The Rules Governing Medicinal Products in the European Union, Vol. 4, Good Manufacturing Practices— Medicinal Products for Human and Vetrinary Use, Annex I Manufacture of Sterile Medicinal Products, Commission Directive 91/356/EEC of 13 June 1991. 

Manufacture of sterile medicinal products Manufacture of biological medicinal products for human use Manufacture of radiopharmaceuticals Manufacture of veterinary medicinal products other than immunologicals... 

EC (2003), Guide to Good Manufacturing Practice Manufacture of Sterile Medicinal Products, Revision to Annex 1, Brussels. Available at http //europa.eu.int/comm/ enterprise/pharmaceuticals/eudralex/vol-4/pdfs-en/revanl vol4 3.pdf (accessed October 2006). 

European Union (EU) (2006), Annex 1—Sterile medicinal products—draft revision. 

European Union Guide to Good Manufacturing Practice Annex 1 on the Manufacture of Sterile Medicinal Products European Commission, 1996.. 

It may be necessary to include intermediate steps within processing to reduce the bioburden and improve the efficiency of lethal sterilization cycles, or to prevent swamping of the preservative in a non-sterile medicine after manufacture. Some of the newer and fragile biotechnology-derived products may include chromatographic and/or ultrafiltration processing stages to ensure adequate reductions of viral contamination levels rather than conventional sterilization cycles. 

European Commission. 1998. EC GMP guide to good manufacturing practice. Revised Annex 1 Manufacture of sterile medicinal products. In The rules governing medicinal products in the EU. Vol. 4 Good Manufacturing Practices. Luxembourg European Commission. 

In the case of Tc pharmaceuticals, chemistry and safety have been compounded into kits, which have overcome the limitations set by radioactive decay and the risk of bacterial contamination. Kits are manufactured in advance in accordance with GMP requirements for the manufacture of sterile medicinal products, have a long shelf life, and facilitate ad hoc labeling whenever there is a demand in nuclear medicine. Kits provide safety and ease of preparation of highly complex molecules by using aseptic techniques for labeling. Consequently, quality control requirements for kit preparations rely merely on testing the radiochemical purity of a " Tc pharmaceutical to demonstrate stability in compliance with the purity requirements stated in the pharmacopeia. 

Numerous other medical products are not required to be sterile. Medicines to be taken by mouth, enemas, inhalations, most topical products, etc., need not be sterile. In some cases there may be a need to ensure that these products are microbiologically clean, or free from specific pathogens or from, microbiological contamination indicators, but there is no obligation to sterility. 

NOTE The different degrees of environmental control are defined in the Supplementary Guidelines for the Manufacture of sterile medicinal products. 

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

Preparations of microbiological origin should not be made or filled in areas used for the processing of other medicinal products however, vaccines of dead organisms or of bacterial extracts may be filled, after inactivation, in the same premises as other sterile medicinal products. 

NOTE The general chapters of the guide to Good Manufacturing Practice apply to products derived from human blood or plasma, unless otherwise stated. Some of the annexes may also apply, e.g., manufacture of sterile medicinal products, use of ionising radiation in the manufacture of medicinal products and the annex on biological medicinal products. 

For the manufacture of sterile medicinal products normally 4 grades can be distinguished. C Preparation of solutions, when unusually at risk. Riling of products. 

Radiation sterilization is used mainly for the sterilization of heat sensitive materials and products. Many medicinal products and some packaging materials are radiation-sensitive, so this method is permissible only when the absence of deleterious effects on the product has been confirmed experimentally. Ultraviolet irradiation is not normally an acceptable method of sterilization. 

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