fda微生物化驗(yàn)室的檢查指南英文稿(已修改)
2025-04-16 23:02 本頁面
【正文】 GUIDE TO INSPECTIONS OF MICROBIOLOGICAL PHARMACEUTICAL QUALITY CONTROL LABORATORIES Note: This document is reference material for investigators and other FDA personnel. The document does not bind FDA, and does not confer any rights, privileges, benefits, or immunities for or on any person(s). I. INTRODUCTION The Guide to the Inspection of Pharmaceutical Quality Control Laboratories provided very limited guidance on the matter of inspection of microbiological laboratories. While that guide addresses many of the issues associated with the chemical aspect of laboratory analysis of pharmaceuticals, this document will serve as a guide to the inspection of the microbiology analytical process. As with any laboratory inspection, it is remended that an analyst (microbiologist) who is familiar with the tests being inspected participate in these inspections.II. MICROBIOLOGICAL TESTING OF NONSTERILE PRODUCTSFor a variety of reasons, we have seen a number of problems associated with the microbiological contamination of topical drug products, nasal solutions and inhalation products. The USP Microbiological Attributes Chapter 1111 provides little specific guidance other than The significance of microorganisms in nonsterile pharmaceutical products should be evaluated in terms of the use of the product, the nature of the product, and the potential hazard to the user. The USP remends that certain categories be routinely tested for total counts and specified indicator microbial contaminants. For example natural plant, animal and some mineral products for Salmonella, oral liquids for E. Coli, topicals for P. aeruginosa and S. Aureus, and articles intended for rectal, urethral, or vaginal administration for yeasts and molds. A number of specific monographs also include definitive microbial limits.As a general guide for acceptable levels and types of microbiological contamination in products, Dr. Dunnigan of the Bureau of Medicine of the FDA mented on the health hazard. In 1970, he said that topical preparations contaminated with gram negative organisms are a probable moderate to serious health hazard. Through the literature and through our investigations, it has been shown that a variety of infections have been traced to the gram negative contamination of topical products. The classical example being the Pseudomonas cepacia contamination of Povidone Iodine products reported by a hospital in Massachusetts several years ago. Therefore, each pany is expected to develop microbial specifications for their nonsterile products. Likewise, the USP Microbial Limits Chapter 61 provides methodology for selected indicator organisms, but not all objectionable organisms. For example, it is widely recognized that Pseudomonas cepacia is objectionable if found in a topical product or nasal solution in high numbers。 yet, there are no test methods provided in the USP that will enable the identification of the presence of this microorganism.A relevant example of this problem is the recall of Metaproterenol Sulfate Inhalation Solution. The USP XXII monograph requires no microbial testing for this product. The agency classified this as a Class I recall because the product was contaminated with Pseudomonas gladioli/cepacia. The health hazard evaluation mented that the risk of pulmonary infection is especially serious and potentially lifethreatening to patients with chronic obstructive airway disease, cystic fibrosis, and immunopromised patients. Additionally, these organisms would not have been identified by testing procedures delineated in the general Microbial Limits section of the Compendia.The USP currently provides for retests in the Microbial Limits section 61 however there is a current proposal
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