Sterile preparations quality requirements

The general manufacturing procedures must ensure that the special production conditions inherent in sterile preparations and their required level of quality are met. 

The manufacture of sterile preparations has special requirements in order to minimise risks of microbiological contamination, and of particulate and pyrogen contamination. Much depends on the skill, training and attitudes of the personnel involved. Quality Assurance bears a particularly great importance, and this manufacture must strictly follow carefully established and validated methods of preparation and procedures. 

Method of preparation, release control and quality requirements of sterile vaginal solutions are the same as for irrigation solutions (Preparations for irrigation Ph. Eur., see Sect. 14.7). Preparation method and release controls of non-sterile vaginal solutions are the same as for solutions for cutaneous use (see Sect. 12.6.5). 

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. 

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 . 

Each monograph contains the following information name of the substance or medicinal product, definition, packaging, storage, labeling requirements and specifications (tests, procedures for the tests and acceptance criteria). The USP also contains several general chapters. There are five general chapters about pharmaceutical preparation sterile preparations, non-sterile preparations, pharmaceutical calculations in extemporaneous preparation, quality assurance, and prescription balances and volumetric apparatus. 

Several guidelines are available in the literature for the pharmacist who must extemporaneously prepare an ophthalmic solution. The USP contains a section on ophthalmic solutions, as do other compendia and several standard textbooks. Since the pharmacist does not have the facilities to test the product, he or she should dispense only small quantities, with an expiration date of no more than 30 days. Refrigeration of the product should also be required as a precautionary measure. To reduce the largest potential source of microbial contamination, only sterile purified water should be used in compounding ophthalmic solutions. Sterile water for injection, USP, from unopened IV bottles or vials is the highest-quality water available to the pharmacist. Prepackaged sterile water with bacteriostatic agents should not be used. 

All in-plant lots are being held in quarantine until a final decision is made concerning any potential impact on the quality of products prepared to date. However, a review of historical data collected under current conditions indicates that we have not had a single failure in sterility testing performed on 100% of the 2918 lots manufactured in the past fifteen (15) months [including at least ten (10) lots of the new fill size]. These tests were conducted in full accordance with the requirements of 21 CFR 610.12 and have been validated with respect to sensitivity in identifying minimal levels of contamination. 

For parenteral use, the antibiotic is packed in sterile vials as a freeze-dried power (reconstituted before use) or suspension. For oral use it is prepared in any of the standard presentations, such as film-coated tablets. Searching tests are carried out on a significant number of random samples of the finished product to ensure that it satisfies the stringent quality control requirements for potency, purity, freedom from pyrogens and sterility. 

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. 

It is a requirement that water to be used in preparing parenteral products (including water used for final rinsing of containers, closures and equipment coming into contact with these products), here abbreviated to PFW , is of the quality of Water for Injections BP except that it need not be sterile and that water to be used in preparing parenteral products is produced by distillation. 

The preparation of the materials, the actual production, filling and sterilization are done in separate spaces, and performed in a laminar flow when quality assurance requires such. 

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