Abordagem microbiológica e estatística aplicada ao monitoramento ambiental em áreas produtivas farmacêuticas / Microbiological and statistical approach applied to environmental monitoring of pharmaceutical manufacturing areas

O controle microbiológico durante a produção de preparações farmacêuticas é de grande importância para garantir a qualidade do produto final, quanto às propriedades terapêuticas e de segurança ao paciente. O monitoramento ambiental é uma valiosa ferramenta como forma de mensurar a efetividade das medidas que integram a estratégia de controle de contaminação microbiana. Neste contexto, pouco destaque tem sido dado à manufatura de produtos farmacêuticos não-estéreis, por representarem as classes cujos riscos de contaminação microbiana são menores, quando comparados aos produtos parenterais. Dessa maneira, este estudo teve como objetivo caracterizar os isolados microbianos de amostras de ar ativo e passivo e de superfícies de áreas produtivas não-estéreis. Ainda, visou-se avaliar estatisticamente os dados de monitoramento ambiental, como base para o desenvolvimento de uma abordagem para determinação de limites de alerta e ação. Os resultados obtidos revelaram que a maioria dos microrganismos encontrados são de origem humana, seguidos por bactérias e fungos provenientes do solo. As diferenças sazonais foram observadas, principalmente, para a ocorrência de fungos, mais prevalentes no período seco. Foi desenvolvida uma abordagem estatística baseada em (1) determinação de subgrupos racionais, (2) avaliação da distribuição estatística e (3) determinação de limites, utilizando, como critério, o índice de capacidade do processo (Cpk). Um melhor entendimento do perfil microbiano das áreas produtivas e a determinação de limites de acordo com a distribuição real dos dados levará à destinação dos recursos necessários a ações que visem a qualidade do produto e a segurança do paciente

The microbiological control during the production of pharmaceutical preparations is of great importance for quality assurance of the final product regarding to therapeutic properties and patient safety. Environmental monitoring is a valuable tool to measure the effectiveness of the actions that integrate the microbial contamination control strategy. In this context, little attention has been given to the manufacture of non-sterile pharmaceutical products, because they represent classes whose microbial contamination risks are lower when compared to parenteral products. Considering this scenario, this study aimed to characterize microbial isolates from surfaces, active and passive air sampling of non-sterile manufacturing areas. Furthermore, it was expected to statistically evaluate the environmental monitoring data, as a basis for the development of an approach for determining alert and action limits. The results showed that most of the microorganisms found are from human source, followed by bacteria and fungi typically found in the soil. The seasonal differences were mainly observed for fungi recovery, which were more prevalent in the dry period. A statistical approach was developed based on (1) the determination of rational subgroups, (2) evaluation of the statistical distribution and (3) limit determination, using the process capacity index (Cpk) as criteria. A better understanding of the typical manufacturing areas microbial profile and the determination of limits according to the actual data distribution will lead to the allocation of the necessary resources to actions focusing on product quality and patient safety

High Pressure Processing of Chicken Meat: Change in Total Aerobic Counts after Pressure Treatment and During Chilled Storage.

Aims: To investigate the effect of pressure, pressurization time, pressurization temperature and their interaction on inactivation and recovery of Listeria innocua inoculated in minced chicken meat. Study Design: Effect of the parameters of high pressure processing (HPP) on the inactivation of L. innocua were studied by response surface methodology using Box- Behnken design. Place and Duration of Study: Study conducted during an 11 months postdoctoral study at Agriculture, Agronomy and Food Sciences Department at LUNAM Université, Oniris, Nantes, France. Methodology: Minced chicken meat inoculated with Listeria innocua strain ATCC 33090 to give a total aerobic count (TAC) of 108 cfu/g and samples were subjected to high pressures of 200, 300, 400 MPa, temperatures of 0ºC, 20ºC, 40ºC and holding times of 5, 10 and 15 minutes. Survival of L. innocua was determined by TAC immediately after pressure treatment and during 35 days of storage at 3ºC. Results: Survival of L. innocua decreased with increasing pressure and pressurization time. Effect of pressurization temperature on survival of bacteria was not linear, giving higher reduction at 0ºC and 40ºC compared to treatments at 20ºC. Analysis of variance (ANOVA) showed that pressure (P<.001), time (P<.001), temperature (P=.05) and interaction of pressure and temperature (P=.05) were significant parameters. After a 10 min treatment at 400 MPa and 0ºC, no survival of microorganisms was detected immediately after pressure treatment. However, TAC increased during storage and reached to about the initial level of microbial load (108cfu/g) in all samples after 35 days of storage at 3ºC. Conclusion: Undetected survival of microorganisms in a nutrient rich food immediately after a pressure treatment does not necessarily mean total inactivation of the microorganisms. Injured microbial cells could recover during the refrigerated storage and compromise the safety of pressure treated foods. Therefore, care must be taken to ensure the safety of high pressure processed foods.