Sterile Product Manufacturing

5 Aseptic Filling Rooms and Aseptic Processing Area 

Pharmaceutical Manufacturing Handbook Production and Processes, edited by Shayne Cox Gad Copyright 2008 John Wiley Sons, Inc. 

The manufacture of sterile products is universally acknowledged to be the most difficult of all pharmaceutical production activities to execute. When these products are manufactured using aseptic processing, poorly controlled processes can expose the patient to an unacceptable level of contamination. In rare instances contaminated products can lead to microbial infection resulting from products intended to hasten the patient s recovery. The production of sterile products requires fastidious design, operation, and maintenance of facilities and equipment. It also requires attention to detail in process development and validation to ensure success. This chapter will review the salient elements of sterile manufacturing necessary to provide acceptable levels of risk regarding sterility assurance. 

Commensurate with the criticality associated with sterile products, the global regulatory community has established a substantial number of the basic requirements that firms are expected to adhere to in the manufacture of sterile products. The most extensive of these are those defined by the Food and Drug Administration 

The production of sterile products is profoundly impacted both by formulation and the selection of primary packaging components. Design parameters for a facility and selection of appropriate manufacturing technologies for the product require that the formulation process and packaging components be chosen and evaluated in advance. 

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Dedicated air handling system for specific manufacturing departments, for example, dry, liquid, and sterile product manufacture... 

For sterile product manufacturing, five areas that have a direct impact on the quality of the manufacturing are defined as ... 

In sterile product manufacturing, five major steps are involved in approaching the validation of a sterile process. These are outlined below using thermal sterilization as the example process. 

Historically, and even today, emphasis on the validation of sterile products is placed mainly on the sterilization processes. No manufacturing operation can be considered under complete control without qualification of every system that can potentially affect product quality, however. The following discussion will touch upon other systems and processes involved in sterile product manufacturing expected to be validated. Much of this section relies on the following literature sources [Refs. 43,73-80], Also refer to other chapters in this book that discuss certain topics in much greater detail. 

The effort spent in qualification and validation of the utilities, equipment, and processes that make up a sterile product manufacturing operation is wasted unless the manufacturing environment is maintained under control at all times during production. 

Aseptic processing and processes related to sterile products manufacturing should be carried out in the environment of the area under the defined air quality. 

Much of what has been proposed as finite standards for successful sterile product manufacture is little more than documented prior success. Alternative conditions might be equal to or even superior to the prior success in their performance. 

James Agalloco, Agalloco Associates, Belle Mead, New Jersey, Sterile Product Manufacturing... 

During inspections, FDA places a great deal of emphasis on the following systems they feel most directly will impact the safety and efficacy of sterile products manufactured, namely ... 

The principal industry drivers generating the interest in isolators in the last few years have been focused on improvements in process integrity. This includes operator protection from potent and hazardous materials and, in the case of sterile products manufacturing, to reduce the potential of contaminated non-sterile imits from being produced by a specific process. There are some circumstances in which reductions in occupied space and operational cost savings have been essential objectives. 

Determine what the scope and depth of the inspection will be to enable you to prepare for it properly. (For a company producing sterile products, prepare by reviewing the guidelines for sterile product manufacture in addition to the general GMP guidelines.)... 

The term environment in sterile product manufacture means more than air quality and surface cleanliness. Other environmental concerns include water systems, compressed air and gas systems, temperature and humidity control, and the monitoring of personnel. 

These themes of the ISO standards in no way contradict the themes that have been emphasized in the earlier and parallel pharmaceutical and medical devices GMP Regulations and Guides. Indeed many pharmaceutical companies are already putting pressure on their suppliers to gain accreditation with the ISO 9000 series of standards. It is possible that the way forward for GMPs in the sterile products manufacturing industry as a whole may eventually defer to these standards in the way of the Blue Guide. 

A further purpose of this book is to bridge the knowledge gap for students and recently qualified graduates who may be moving or wishing to move into the sterile products manufacturing industries. There are few sources of information... 

For additional guidance on premises for Sterile Products Manufacture, see section 9). 

Vacuum or wet cleaning methods are to be preferred. Compressed air and brushes should be used with care, and avoided if possible, as they increase the risk of product contamination. (For additional guidance on premises for Sterile Products Manufacture, see Section 9.)... 

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