The pharmaceutical quality management system, as described in Eudralex Vol.4 Chapter 1, covers all aspects that can influence the quality of a product. In addition to risk management, the quality management system also includes handling of changes, deviations, handling of complaints, selection of suppliers and self-inspections.
The topic of risk management flows into all GMP areas and is widely applied. Risk management is a systematic process for assessing and controlling the risk related to the quality of a product. The process starts with the identification of risks, followed by risk analysis and risk evaluation. Once the risks are known and evaluated, it is decided whether the risks are either a) acceptable, or b) unacceptable. If the risks are not acceptable, measures must be taken to minimize the risks. If the risks are acceptable, no further activities are necessary for the time being. However, the risk assessment must be reviewed regularly to determine whether the classification of the risks is still current and/or whether additional risks have been added.
Guideline ICH Q9 is specifically dedicated to Quality Risk Management and contains detailed instructions on the risk quality management process.
Continuous improvement of systems and processes is essential to achieve consistently high product quality. However, a planned improvement of a process is always also a change to an existing process and must therefore be planned, checked and documented in detail.
After changes have been implemented, it is evaluated whether the change is actually an improvement, whether the quality objectives have been achieved and, most importantly, that there have been no unintended negative effects on product quality.
Investigation of Nonconformances
In everyday GMP, routine processes are defined in advance and recorded in standard operating procedures (SOP) documents. Any unplanned deviation from this standard procedure must be investigated and assessed for (potential) quality impact. In a sound quality management system, the reason for the deviation from the standard procedure is also investigated and appropriate measures are defined to avoid the same errors in the future (Eudralex Vol. 4, Chapter 1).
The procedure for observing a nonconformance from the standard procedure should be well defined. In particular, the responsibilities for opening and conducting the investigation must be clear. An investigation of a nonconformance always starts with a description of the situation and how the issue occurred. What was observed? Who was involved?
Root Cause Investigation
Various methods can be used to determine the root cause. The cause-effect diagram according to Ishikawa, also called fishbone diagram, is frequently used in practice. Here, the issue found is formulated and graphically represented, and then possible influencing factors are listed. For a better overview, the influencing factors are divided into groups (e.g. man, technology, method, environment, etc.). For each of the influencing factors, it is then assessed whether or not an influence can be excluded, e.g. through existing controls.
If the root cause cannot be determined exactly, the most probable root cause can also be defined according to the exclusion principle.
Corrective and Preventive Actions (CAPA)
The deviation from the standard procedure should be corrected as best as possible. This is defined as a measure and referred to as a corrective action (CA). Preventive action (PA) refers to measures that are intended to prevent the deviation in the future. Not only the affected process should be considered, but also similar processes where the same deviation could potentially occur.
Support in setting up the process for deviation handling or execution of the investigations together with your team.
Selection of Suppliers
Raw materials or consumables are usually not produced in-house, but purchased from other companies. Individual manufacturing steps or quality control analyses can also be outsourced. To ensure and guarantee consistent quality, it is essential to evaluate and assess the quality systems of these companies.
Selection of Suppliers
The evaluation and assessment requires very good knowledge of the common quality standards (e.g. ISO 9001, GMP, etc.).
As a trained and experienced lead auditor, I can gladly take on this time-intensive task.
In a comprehensive quality system, especially in accordance with the applicable GMP guidelines, the point of self-inspections must not be missing.
A self-inspection always offers a good opportunity to scrutinize your own processes and systems and to identify possible weaknesses before they are criticized by external parties (e.g. authorities or customers). As an independent consultant I can check your systems for compliance with the guidelines and show you possible GAPs from a new perspective during an audit.