Sterile pharmaceutical products

G.J. farquharson. Building and facility design for clean and sterile pharmaceutical product manufacture. In J.H. Vincent, ed. Ventilation SS Proceedings of the Second International Symposium on Ventilation for Contaminant Control, pp. 231-236, Pergamon Pre.ss, Oxford, 1989,... 

Baird R.M. (1985) Microbial contamination of non-sterile pharmaceutical products made in hospitals in the North East Regional Health Authority. J Clin Hasp Pharm, 10, 95-100. 

Principles of the methods employed to sterilize pharmaceutical products are described in Chapter 20. The British Pharmacopoeia (1993) recommends autoclaving and filtration as suitable methods applicable to aqueous liquids, and dry heat for non-aqueous and dry sohd preparatiorrs. The choice is determined largely by the ability of the formulation and container to withstand the physical stresses apphed by moist heat... 

The sole objective of all hygiene and manufacturing controls is to ensure the quality of the pharmaceuhcal product for the safety and protection of the pahent. The manufacture of non-sterile pharmaceutical products requires that certain criteria of cleanliness, personal hygiene, produchon methods and storage must be met. Many such products are for oral and topical use and the question may fairly be posed as to the point of what are now quite stringent conditions. Nevertheless, some carefully controlled hospital studies have indeed shown that both types of medicine may be associated with nosocomial (hospital-acquired) infections and this risk can be minimized by the application of GMP principles. 

Blow-Fill-Seal (BFS) technology was developed in the early 1960s and was initially used for filling many liquid product categories, for example, nonsterile medical devices, foods, and cosmetics. The technology has been developed to an extent that today BFS systems are used to aseptically produce sterile pharmaceutical products such as respiratory solutions, ophthahnics, and wound-care products throughout the world. 

In the case of recombinant proteins intended for use in sterile pharmaceutical products, additional process controls on microbiologic aspects of analysis must be established and validated to ensure aseptic conditions throughout the manufacturing process. 

Anonymous (2002), Annex 6 Good manufacturing practices for sterile pharmaceutical products, in WHO Expert Committee on Specifications for Pharmaceutical Preparations 36th Report, WHO Technical Report Series 902, World Health Organization, Singapore, pp. 76-93, available http //whqhbdoc.who.int/trs/WHO TRS 902.pdf. 

U.S. Pharmacopeia (USP) (2007), Application of water activity determination to non-sterile pharmaceutical products, general chapter <1112>, U.S. Pharmacopeial Convention, Rockville, MD. 

WHO (2002), Good manufacturing practices for sterile pharmaceutical products, Geneva, pp. 76-96 [Technical Report Series, no. 902]. 

Crystallization is the preferred method of forming many final products because very high purification is possible. High purity antibiotic crystals can be produced from colored, rather impure solutions if the filter cake is uniform and amenable to good washing to remove the mother liquor. When a sterile pharmaceutical product is desired, crystals are formed from liquid streams that have been sterilized by filtration. 

Sharp, J. Manufacture of sterile pharmaceutical products using blow-fill-seal technology. The Pharm. J. 1987, 259(106), 22. 

Dry-heat sterilization is generally a less complicated process than steam sterilization it is, however, relatively slow and requires higher temperatures and/or longer exposure times. This is because of the fact that microbial lethality is lower with dry heat than that for steam at the same temperature. There are various temperatures and periods of treatment for dry heat depending on the pharmacopeia. The U.S. Pharmacopeia (USP) states that the dry-heat sterilization process for containers for sterile pharmaceutical products should be at a temperature of 160-170°C for a period of 2-4 hr. The British Pharmacopeia states that items sterilized by dry heat should be kept at a temperature not less than 160°C for at least 1 hr. For the Pharmacopeia Nordica, the recommendation is 30 min at 180°C. Different materials and sterilization equipment used account for the discrepancies between these pharmacopeias, but there is also a lack of sufficient information concerning dry-heat sterilization. ... 

The following guidelines have been completed GMP for Sterile Pharmaceutical Products, Guideline on Pre-Approval Inspection (before granting marketing authorization). Quality System for National GMP Inspectorate, and General Aspects of Packaging Pharmaceuticals. " ... 

Part 3 Compounding and Dispensing. Annex 1 Compounding of Sterile Pharmaceutical Products, 1995... 

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