Using the HACCP method in quality risk management in the production of oromucosal gel

Abstract

Introduction. With the adoption in the EU of the regulatory document of the European Medicines Agency (European Medicines Agency) EMA / INS / GMP / 79766/2011 “Quality Risk Management (ICH Q9)”separate guidance was issued in Ukraine in 2011 - Instruction ST-N MOH 42-4.2: 2011 “Medicines. Quality Risk Management (ICH Q9)”. Pharmaceutical industry and regulatory bodies professionals can assess and manage risk using recognized risk management tools and / or internal techniques (e.g., standard working methods).Application of general principles and approaches of the Guideline “Medicines. Quality Risk Management (ICH Q9)”at the stage of pharmaceutical development, using appropriate risk management tools both in general to the manufacture of medicines and to individual processes is an effective measure of quality assurance for the developed medicinal product. The technology of the combined dental gel was developed taking into account its properties as a dispersed system, as well as the properties of the active and auxiliary substances that are part of it. In order to manage quality risks effectively, it is necessary to have data about the sustainability of the process. Critical process parameters that need to be managed or monitored to ensure the required quality of the drug should be identified and specified. Materials and methods of the research. The subject of the study was the technology and technological scheme of the production of a combined gel for the treatment of infectious diseases of the mucous membrane of the mouth and gums. Hazard Analysis and Critical Control Points (HACCP) were used to evaluate and manage risks in the manufacture of the new drug. The HACCP tool, the “Decision tree”, was used to establish critical control points. Results of the research and discussion. An expert group of experts conducted an analysis and evaluation of the danger of individual stages of the technological process and determination of the criticality of the controlled parameters. The group consisted of qualified specialists from the pharmaceutical development department, thefactoryworkshop for the production of soft medicines, the quality control department. Analysis of the technological scheme of production of combined dental, showed that almost all stages of the dental gel manufacturing process are critical and marked in grey. Using the tool “Decision tree”, we identified the critical control points of the technological process of gel production, and set the eligibility criteria. Risk factors were evaluated on the basis of two indicators: the likelihood of a hazard factor and the degree of risk created by that factor. The likelihood of a risk factor was as follows: unlikely, quitelikely, probably, very likely. The degree of risk was assessed on a ten-point scale. During the processing of the gel technology, certain critical control points were monitored with the aim of developing preventive and corrective actions in case of their fall outside the eligibility criteria. in the process of gel production, risk (physical factor) at the stages of metronidazole suspension preparation, preparation of gel base and gel directly is “Quite likely”. “Unlikely” occurrence of a dangerous factor at such stages as the weighing of active and auxiliary substances, the preparation of solutions and during the input control of raw materials. The risk level of each factor, ranging from 2 to 7 points, was determined and corrective and preventive actions were developed for all critical control points to prevent risks to the quality of the medicinal product. Conclusions. Based on the data obtained in the development of dental gel technology and using scientific knowledge and methodology of risk assessment by the method of HACCP, an analysis of technological scheme of its production was carried out. Process risks have been identified, critical control points have been identified and their allowed limits. For each control parameter, the probability of occurrence and the degree of risk were determined, and measures were proposed to prevent or eliminate the effects of the risk.

DOI: 10.5281/zenodo.3885070