Risk-Oriented Approach

A risk-oriented or risk-based approach is an important tool for pharmaceutical quality management, and, in particular, for validation activities. It is implemented in the form of risk analyzes (risk assessments) carried out at the early stages of qualification / validation, whereby risk analyzes lay the foundation for all further validation activities.

Good Manufacturing practice (GMP) rules, from the very moment of their emergence, are a set of general regulations, i.e. prescriptions in terms of policy and approaches to pharmaceutical production. At the same time, the focus of these regulations has always been on the patients and their safety. Thus, the foundations of a risk-based approach were already laid in GMP from the very beginning.

For the most part, GMP guidelines lack specific requirements in terms of the design of systems and equipment, as well as the parameters of manufacturing processes and quality control of medicinal products. In other words, only general requirements are mainly declared, but there is no description of specific implementation of these requirements. Thus, GMP sets some general framework within which a regulated company must on its own make decisions regarding specific ways to implement GMP requirements. Clearly, such decisions are critical to patient safety, product quality, and the integrity of regulated records and data. Such decisions are sometimes also referred to as regulated decisions, or GxP decisions (x in GxP stands for the type of Good Practices in order to include, along with Manufacturing, other good practices closely related to Pharmaceutical Industry, such as GDP, GLP, GCP, GAMP etc.) When making such decisions, the regulated company should base its considerations on a risk assessment, i.e. apply a risk-based approach.

If we consider the evolution of GMP regulatory documentation, we can see that in new versions of documents, even those few, relatively specific requirements present are gradually being replaced by the requirement to make a decision based on risk assessment. In the course of international GMP requirements harmonization, the risk-based approach plays an increasingly important role, which is particularly illustrated by the adoption by the European Medicines Agency of the ICH Q9 Guideline on Quality Risk Management as a regulatory document.

ICH Q9 defines two primary principles of quality risk management:

  • The evaluation of the risk to quality should be based on scientific knowledge and ultimately link to the protection of the patient; and
  • The level of effort, formality and documentation of the quality risk management process should be commensurate with the level of risk.

In other words, the risk assessment should be based on full knowledge of the system / understanding of the process, and should be balanced so that the resources of the regulated company are spent optimally, and more resources should be spent, where the level of risk is higher. Unnecessarily high use of resources in areas, where it is not justified by the level of risk, can deprive other areas of resources, where they are critical to assurance of patient safety, product quality and data integrity.

Another critical aspect of a risk-based approach is its integrity. The integrity of the risk-based approach suggests that risk mitigation / elimination measures should be applied:

  • firstly, to all elements of the system or process where these risks may occur, and,
  • secondly, to all stages of the life cycle of respective systems or processes.

The practice of conducting risk assessments and the history of incidents in the pharmaceutical industry show that risks can occur in all elements of a system or process that are in any way in contact with the product, or even indirectly related to it, as well as at all lifecycle stages of such systems and processes. Therefore, a risk-based approach should cover all elements and lifecycle stages of such systems and processes, which, in relation to a pharmaceutical manufacturing facility, also includes the stages of its design, construction, as well as installation and commissioning of equipment.

In addition, a holistic risk-based approach should provide full traceability, from regulatory requirements and product quality parameters, to manufacturing process requirements, manufacturing environment parameters and related design solutions.

A very picturesque example of a not integer, unbalanced risk-based approach would be the situation if Nif-Nif pig from the well-known fairytale Three litte pigs, who built himself a straw house, decided to install an iron door to protect himself from the wolf.


Specialists of Tarqvara Pharma Technologies have years of experience in conduction of qualification, validation and acceptance tests in pharmaceutical industry, in compliance with respective international, European, and national GMP/GxP regulations and standards.

See also:
Qualification / Validation / Commissioning
Computerized Systems Validation (CSV)
Commissioning (FAT/SAT)