Sterile pharmaceuticals preparation

Sterile pharmaceutical preparations must be tested for the presence of fungal and bacterial contamination before use (see Chapters 18 and 23). If the preparation contains an antibiotic, it must be removed or inactivated. Membrane filtration is the usual recommended method. However, this technique has certain disadvantages. Accidental contamination is a problem, as is the retention of the antibiotic on the filter and its subsequent liberation into the nutrient medium. 

The most obviously recognized sterile pharmaceutical preparations are injections. These vary from very small volume antigenic products to large volume, total parenteral nutrition products. Other... 

The use of purified water is recommended to keep the initial contamination low and thereby to hold the Ph. Eur. requirements for microbiological quality of non-sterile pharmaceutical preparations. The requirements of the chemical and microbiological purity of purified water are well defined, see Sect. 23.3.1. The concentration of ions in purified water is low, which is an advantage as they may catalyse degradation of active substances and excipients and form complexes with active substances and excipients. 

Raw materials. Raw materials from natural origin may be highly contaminated with micro-organisms especially spore-forming bacteria and moulds and in some cases with more critical Enterobacteriaceae. Soon after a publication on salmonellosis in more than 200 persons caused by the contamination of thyroid tablets with two types of Salmonella originating from the raw material [53], proposals for the examination of non-sterile pharmaceutical preparations and acceptance criteria were published [54]. 

Sections 5.1.4 and 5.1.8 of the European Pharmacopoeia [61, 62] specifies microbiological quality criteria for non-sterile pharmaceutical preparations and raw materials. They are stated as Total Aerobic Microbial Count (TAMC) and Total combined Yeast and Mould Count (TYMC) (see Sect. 19.6.3) and requirements regarding specific micro-... 

The Ph. Eur. summarises the quality requirements for the microbiological purity of non-sterile preparations in monograph 5.1.4 Microbiological quality of non-sterile pharmaceutical preparations and substances for pharmaceutical use . For raw materials quality requirements are described in individual monographs or in the general monograph Substances for Pharmaceutical Use . 

Where small quantities of high-purity steam is required for electronic chip, pharmaceutical, sterilization, food preparation, and similar process applications, a small risk of steam contamination may exist. This may be caused directly by the use of amine treatments or indirectly through process contaminants or the transport of iron oxides. Consequently, alternative arrangements for steam generation are made. 

Distilled water is often used in the formulahon of oral and topical pharmaceutical preparations and a low bacterial count is desirable. It is also used after distillation with a specially designed still, often made of glass, for the manufacture of parenteral preparations and a post-distillation heat sterilization stage is commonly included in the process. Water for such preparahons is often stored at 80°C in order to prevent bacterial growth and the production of pyrogenic substances which accompany such growth. 

Bortezomib was kindly provided by Millennium Pharmaceuticals. Prepare a stock solution of 500 pM in Milli-Q sterile water. Store at -20°C. 

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. 

Aseptic compounding is often a required activity for sterile products that cannot be filter sterilized. The preparation of the sterile solids for use in these formulations is outside the scope of this chapter, but it is often acknowledged as the most difficult of all pharmaceutical processes to properly execute. Handling these materials at the fill site is performed using ISO 5 environments, and the use of closed systems is preferred [34],... 

Food and Drug Administration (FDA) (1991), Use of aseptic processing and terminal sterilization in the preparation of sterile pharmaceuticals, FR 56, 354-358. 

Common to all parenteral pharmaceutical preparations is the necessity for controlled pH and sterility. Packaging materials used for these purposes must be well-validated for their uses, because impurities in these drug preparations can have particularly disastrous effects. 

USE OF IONIZING RADIATION IN THE PREPARATION OF STERILE PHARMACEUTICALS FOR HUMAN USE... 

Sterile water for drug products and pharmaceutical preparations not suitable for use in the manufacture of parenteral products. Diluent for inhalation therapy products. 

Preservatives. These are included in pharmaceutical preparations to prevent microbial spoilage of the product and to minimize the risk of the consumer acquiring an infection when the preparation is administered. Preservatives must be able to limit proliferation of microorganisms that may be introduced unavoidably into non-sterile products such as oral and topical medications during their manufacture and use. In sterile products such as eye-drops and multi-dose injections preservatives should kill any microbial contaminants introduced inadvertently during use. It is essential that a preservative is not toxic in relation to the intended route of administration of the preserved preparation. 

Veterinary pharmaceutical preparations Vitamin preparations Water decontamination or purification tablets Water, sterile for injections Zinc ointment... 

Parenteral Drug Association (PDA) and British Parenteral Society (BPS) Technical reports and guidelines prepared by industry on various parenteral topics, e.g., Sterile Pharmaceutical Packaging, compatibility and stability (PDA) PDA Archive containing research papers, technical reports and conference proceedings available on CD-ROM updated annually... 

Photochemical reactivity of drug formulations is an important aspect to consider during development, production, storage, and use of pharmaceutical preparations. However, photochemical stability of drug substances is rarely as well documented as thermal stability of the compounds. For instance, in order to obtain a high sterility assurance level of the product, a parenteral preparation is sterilized in its final container if possible. Steam sterilization at minimum temperature of 121°C for... 

As with sterile pharmaceuticals, pyrogens are of significant importance to medical devices. Any device intended for administration of a sterile parenteral pharmaceutical must (like the pharmaceutical preparation) be pyrogen free. So must all invasive and implantable devices. 

Maxwell Bryce. D. (1956). Tests for the sterility of pharmaceutical preparations. JtHOTuil of Pharmacy and Pharmacology 8 561—572. 

Preparations containing live microbiological organisms should not be made or containers filled in areas used for the processing of other pharmaceutical products however, vaccines of dead organisms or of bacterial extracts may be dispensed into containers, after validated inactivation and validated cleaning procedures, in the same premises as other sterile pharmaceutical products. 

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