INTRODUCTION

A sound cleaning and sanitization program is needed for controlled environments used in the manufacture of Pharmacopeial articles to prevent the microbial contamination of these articles. Sterile drug products may be contaminated via their pharmaceutical ingredients, process water, packaging components, manufacturing environment, processing equipment, and manufacturing operators. Current Good Manufacturing Practices (cGMPs) emphasize the size, design, construction, and location of buildings and construction materials, and the appropriate material flow to facilitate cleaning, maintenance, and proper operations for the manufacture of drug products. When disinfectants are used in a manufacturing environment, care should be taken to prevent the drug product from becoming contaminated with chemical disinfectants as a result of the inherent toxicity of the disinfectants. The requirements for aseptic processing include readily cleanable floors, walls, and ceilings that have smooth and nonporous surfaces; particulate, temperature, and humidity controls; and cleaning and disinfecting procedures to produce and maintain aseptic conditions. The cleaning and sanitization program should achieve specified cleanliness standards, control microbial contamination of products, and be designed to prevent the chemical contamination of pharmaceutical ingredients, product-contact surfaces and/or equipment, packaging materials, and ultimately the drug products. These principles also apply to nonsterile dosage forms where the microbial contamination is controlled by the selection of appropriate pharmaceutical ingredients, utilities, manufacturing environments, sound equipment cleaning procedures, products especially formulated to control water activity, inclusion of suitable preservatives, and product packaging design.