Article Review

Article Review

Introduction

The article selected for this review is “Role of Media Fill in Process Control.” This article reviews current industry practices and regulatory expectations for the media fills and their impact on process control. It provides comparisons and outlines points of tension between current manufacturing technology and capabilities with regulatory "requirements" for this important activity.

Background

In 1988, the Parenteral Drug Association (PDA) published a position paper on media fills in response to intense interest in media fills in the industry at that time and in partial response

to the publication of the Food and Drug Administration's (FDA's) 1987 guideline on media fills. The intent of this review is similar to that of its 1988 predecessor: to identify and discuss the current capabilities of media fills technology.

The improvements to media fills operations described in the 1988 position paper were characterized in the opening section of that document as "evolutionary:' The improvements in media fills technology that have occurred since 1988 would perhaps be better characterized as "revolutionary:' We believe that the practices described in 1988 are, by and large, as valid now as they were then. We also believe that products manufactured in compliance with the underlying principles outlined in the 1988 document are still inherently safe.

The aseptic manufacture of sterile products is perhaps the most difficult challenge faced within the health care industry. Media fills requires the careful application of microbiological contamination control principles to exclude infectious organisms from sterile products. We reaffirm our belief stated in 1988 that, "the major variable in the control of media fills arises not from the sterilization processes, the cleanroom, or the filtration processes that are so often the subject of technical papers and regulatory guidelines, but rather from the workforce itself" (1). Industry findings since 1988 confirm the earlier statement that humanborne contamination is the most critical risk factor in media fills. Numerous industry surveys and technical articles published since that time are in accordance with this statement. (3-8).

Since the publication of the 1987 guidance, firms have continued to implement new technologies and media fills improvements to better control humanborne contamination. At the same time, the industry has implemented expanded microbial-test regimens and more comprehensive process simulation testing to ensure that media fills systems have adequate process capability and that this capability is consistent and as reproducible as possible within the technical constraints that are inherent in the measurement of aseptic performance.

This article describes the improvements in conventional and new technologies that have occurred since the late 1980s. It also describes the improvements that have been made in aseptic process validation and control. Finally, the paper discusses the technical limitations that still exist in the evaluation of media fills and raises concerns regarding the increasing regulatory tendency to ignore the existence of those limitations.

Discussion

In no other segment of the pharmaceutical industry is the control of manufacturing processes as critical as in the production of aseptically produced products. The recognition of the criticality of these processes has led to the continued ...