ICH Q9 (R1) Part 2-Risk based decision making

After discussing the topic of formality within the QRM process (Blog post part 1), we continue the blog post series on the revised ICH Q9, this time focusing on risk-based decision-making.

Part 2: Risk-based decision-making

Independently of the QRM activity in question, risk-based decisions are integral aspects of all steps within this process. Although risk-based decision-making was already referenced in the previous version of the guideline and significant research exists in this area from other fields, the council considered it as one of the topics that needs further clarification as it has been poorly understood.

Decisions during the QRM process- When?

As previously discussed, (Blog post part 1), decisions on the level of required formality shall be made after considering at which level of the “spectrum”, the uncertainty, importance and complexity of the topic in question resides. In other words, one needs to consider the risks arising from the given QRM activity and then decide whether to continue with a formal process (e.g. FMEA or HACCP), increased effort (use of cross-functional team, experienced facilitators) and by producing all related stand-alone documentation (reports) or with an informal process where the set up is more simple (Figure 1).

Figure 1: Knowledge-based Decision-making is required throughout the process of QRM

Once these first decisions have been made and the QRM activity begins, additional decision-making is required, at every step of the process (Figure 1). Some of the questions that require decision-making include the following:

↘ Which hazards exist?

↘ Which are the risks which are associated with the identified hazards?

↘ What controls are required to mitigate the risks?

↘ Is the residual risk after control implementation acceptable?

↘ How will the information about the risks and their management be effectively communicated?

↘ What is the strategy for long-term risk monitoring?

Explicit knowledge is the key

One might wonder how the decision-making process works in this case. There are several approaches to reach risk-based decisions but all of them have one common element: knowledge.                                                                                                                                                      As described within ICH Q10 Pharmaceutical Quality System, knowledge management, is a key enabler of many aspects of an effective quality management system (QMS) including the establishment and maintenance and a state of control and facilitation of continual improvement. Decision-making within the QRM scope, relies on leveraging knowledge which is already available but also seeking knowledge from additional sources. When using a multi-disciplinary team for the QRM activity, everyone can contribute at different levels depending on their background, qualifications or area of expertise. Likewise, QRM facilitators can enhance the process with their specific knowledge and experience.

Furthermore, teams involved with the QRM activity can seek additional knowledge by gathering available documentation, information from similar activities, or case studies from the industry.

Just as knowledge, the list of sources is infinite. Independently of whether the knowledge used for the process is explicit or tacit (formally documented knowledge that comes from information from objective data and experience-based respectively, as described within the ISPE Good Practice Guide: Knowledge Management in the Pharmaceutical Industry), decision makers need to use this tool to make informed decisions as risk and knowledge are inversely proportional (Figure 2).

Figure 2: The Risk-Knowledge Infinity Cycle: Decreasing Risk through Increasing Knowledge, as depicted within Lipa et al., 2020

Approach is all about structure

Now that we have clarified the decision-making points within the QRM activities and stressed out the importance of knowledge for making the proper decisions, let’s explore what are the available approaches to risk-based decision-making.

Here again, the level of formality plays a central role. Depending on the degree of formality which has been previously decided for the QRM activity (Blog post Part 1), one can choose the respective appropriate decision-making approach. Approaches vary mostly with regards to their level of structure. Structure is proportional to formality, meaning that the more formal the QRM activity is decided to be, the more structured shall be the approach used for decision-making.

Like in the case of formality, structure shall also be viewed as a spectrum, resulting in a variety of approaches with specific characteristics:

• Highly structured approaches

→ require formal analysis of available options when uncertainty and/or complexity are  high

• Less structured approaches

→ rely on existing knowledge, ideal for low uncertainty and/or complexity

• Standardized approaches

→ decisions do not require additional risk assessment efforts but rather rely on the QMS; policies, SOPs or WI (Work Instructions), where defined rules direct the strategy for decision-making

Standardized approaches can be beneficial for regulated companies as they provide a precise roadmap that one can follow when wondering about decision-making during the QRM process. When standardized approaches are built by experts on QRM that are also aware of the company-specific processes, the combination enhances effectiveness and harmonization.

Do you need help with deciding the best approach for your QRM activity or with establishing a QRM process that fits your needs? GxP-CC can support you with both! Contact us today to get started.