Microbiological Skip Test: Fundamentals and Evaluation of Water Activity in Pharmaceutical Ingredients

Research Article

Austin J Anal Pharm Chem. 2023; 10(2): 1158.

Microbiological Skip Test: Fundamentals and Evaluation of Water Activity in Pharmaceutical Ingredients

Natália Silvério de Freitas1; Adriana Nascimento Sousa1; Hussain Ullah2; Wagner da Nova Mussel3; Maria Betânia de Freitas-Marques1,3*

¹Curso de Farmácia, Faculdade de Minas, Belo Horizonte, Minas Gerais, Brazil

²Institute of Chemistry, University of Okara, Pakistan

³Departamento de Química, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

*Corresponding author: Maria Betania de Freitas-Marques Curso de Farmácia, Faculdade de Minas, Belo Horizonte, Minas Gerais, Brazil. Email: betanialf@hotmail.com

Received: September 04, 2023 Accepted: September 21, 2023 Published: September 28, 2023

Abstract

Quality control is essential for Good Manufacturing Practices in the pharmaceutical industry. The time and costs associated with microbiological quality control are well known. It is proposed the reduction of traditional microbiological methods of counting the total number of microorganisms and research of specific pathogens using the water activity (Aw) method, a practice known as the skip test. The raw material selected as a prototype for this study met the criteria for the feasibility of reductions in analyses having synthetic origins, solid physical state, low or high pH in aqueous solution, and Aw results below 0.75 at a temperature of 25°C, and absence of nonconformity records. The risk management process was implemented using risk analysis with the mode, effect, criticality, failure analysis tool, and opening change control with the replacement of microbiological standard by Aw in 20 sequential batches after complete analysis of the first batch received in the year. It was possible to certify the microbiological quality of the selected pharmaceutical ingredients using the AW results, thereby confirming the feasibility of the skip test.

Keywords: Manufacturing; Quality; Control; Pharmaceutical; System

Introduction

Quality is defined by the set of programming, coordination, and execution operations, the purpose of which is to evaluate and ensure that medicines comply with the quality standards required by regulatory agencies. To obtain quality pharmaceutical products using pharmacopeial standards, the entire production chain must be monitored, that is, raw materials, qualified equipment, facilities, and professional staff [1-3].

To reach the objectives, the regulatory agencies in human health advocate norms to be strictly complied with by manufacturers, as in Brazil, the Agência Nacional de Vigilância Sanitária, Resolução de Diretoria Colegiada (RDC) no. 658, March 30, 2022, and the General Guidelines for Good Manufacturing Practices for Medicines in the pharmaceutical industry [4].

Among the quality control analyses, microbiological investigations are mandatory. In non-sterile pharmaceutical products, microbial levels are limited to guarantee harmlessness to human health and inertia of the medicine [5,12,13].

The standard method used in microbiological quality control laboratories for the analysis of raw materials and non-sterile drugs includes counting the total number of mesophilic microorganisms to determine the total number of mesophilic bacteria and fungi. The investigation of pathogenic microorganisms in selective culture media was also carried out according to official analysis compendiums [6-9].

Microbiological analyses of raw materials, specific laboratory conditions, material resources, and specialized labor are necessary to guarantee consistent results with the microbiological quality of the sample. In addition, the time dedicated to the complete series of analyses is highlighted, which is often incompatible with industrial market demand and financial investments. For instance, according to Pharmacopeia Brasileira 6 ed., it is necessary to research the specific pathogens Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus, which means the use of additional selective methodologies and a dedicated time of approximately three days [6].

Given the importance of microbiological research in the context of the pharmaceutical industry and in compliance with laboratory logistics, it was proposed to reduce the methods of microbiological analysis by counting the total number of mesophilic microorganisms and researching pathogens, a practice already known as the skip test. Water activity (Aw) in the raw materials was determined according to the criteria established by the United States Pharmacopeia (USP). In addition to raw materials, products such as tablets obtained by direct compression, capsules, ointments, rectal suppositories, and non-aqueous liquids are suitable for performing the skip test by Aw [7,8,18]

This practice is based on the evidence of microbiological growth at minimum levels of water in the materials; that is, for microbiological growth to occur, limiting levels of water activity are required, as described in Table 1 [7,18].