微生物污染可能会导致微生物增殖,从而导致制药公司因停产而出现额外问题,产品污染,过程偏差的调查,超出规范的结果和产品处置。这是监管卫生机构的主要关切之一。如果灭菌过程无效和/或由于毒素的产生,微生物负荷(生物负荷)可能代表患者的潜在风险。虽然生物负载可以通过最终灭菌或过滤过程消除,重要的是在最终处理之前监测存在的微生物的量并确定其特性和特征。微生物识别系统的应用对于识别污染类型至关重要,这对调查非常有用。这项研究的目的是评估从溶液中生物负载测定中鉴定的微生物的概况,文化媒体,和来自制药工业设施的产品(SCP)。从2018年到2020年,共分析了来自857个不同批次的SCP的1,078个样本,并鉴定了分离的微生物。在2020年3月之后包括预过滤步骤,以便在灭菌过滤之前降低生物负载。经过综合书目审查后,对所鉴定微生物的定义和管理标准进行了评估,并提出了三个小组(关键,令人反感的,和无异议的微生物)。对于不包括预滤波的样本(n=636),227(35.7%)呈现微生物生长。对于那些包括预过滤的人,在预滤波之前(n=221),60.6%呈现微生物生长,预过滤后,该值降至4.1%,这可归因于采样过程中的污染或错误的过滤。从呈现微生物生长的样本中,678种微生物被鉴定为细菌,59种被鉴定为霉菌和酵母。共120种微生物(革兰氏阳性和阴性细菌56种和27种,分别,31酵母,和六个丝状模具)无法识别,剩余的微生物被归类为令人反感的(n=507;82.2%),无异议(n=103;16.7%)和关键(n=7;1.1%)。大多数生物负载物种(>80.0%)被认为是令人反感的微生物。在对微生物的病原和生理特性进行文献综述的基础上,提出了一种对生物负载分析结果进行分类和管理的过程。
Microbiological contamination may cause microbial proliferation and consequently additional problems for pharmaceutical companies through production stoppage, product contamination, investigations of process deviations, out-of-specification results and product disposal. This is one of the major concerns of the regulatory health agencies. Microbiological load (bioburden) may represent a potential risk for patients if the sterilization process is not effective and/or due to the production of toxins. Although bioburden can be eliminated by terminal sterilization or filtration processes, it is important to monitor the amount and determine the identity and characteristics of the microorganisms present prior to final processing. The application of microorganism identification systems is crucial for identifying the type of contamination, which can be extremely useful for investigating. The aim of this study was to evaluate the profiles of microorganisms identified in bioburden assays from solutions, culture medias, and products (SCP) from a pharmaceutical industry facility. From 2018-2020, a total of 1,078 samples from 857 different lots of SCP were analyzed and isolated microorganisms were identified. A prefiltering step was included after March 2020, in order to reduce the bioburden before sterilizing filtration. Criteria for the definition and management of microorganisms identified were evaluated after an integrative bibliographic review, and three groups were proposed (critical, objectionable, and nonobjectionable microorganisms). For the samples that did not include prefiltering (n=636), 227 (35.7%) presented microbial growth. For those that included prefiltering, before prefiltering (n=221), 60.6% presented microbial growth, and after prefiltering, this value was reduced to 4.1%, which can be attributed to a contamination during the sampling or a wrong filtering. From the samples that presented microbial growth, 678 microorganisms were identified as bacteria and 59 as molds and yeasts. A total of 120 microorganisms (56 and 27 Gram-positive and negative bacteria, respectively, 31 yeasts, and six filamentous molds) could not be identified, and the remaining microorganisms were classified as objectionable (n=507; 82.2%), nonobjectionable (n=103; 16.7%) and critical (n=7; 1.1%). Most of the bioburden species (>80.0%) were considered objectionable microorganisms. A process for classification and management of bioburden analysis results based on a literature review of pathogenic and physiological characteristics of the microorganisms was proposed.