Q9 (r1) Risk Management Draft

Q9 (r1) starts with all the same sections on scope and purpose. There are slight differences in ordering in scope, mainly because of the new sections below, but there isn’t much substantially different.

4.1 Responsibilities

This is the first major change with added paragraphs on subjectivity, which basically admits that it exists and everyone should be aware of that. This is the first major change that should be addressed in the quality system “All participants involved with quality risk management activities should acknowledge, anticipate, and address the potential for subjectivity.”

Aligned with that requirement is a third bullet for decision-makers: “assure that subjectivity in quality risk management activities is controlled and minimised, to facilitate scientifically robust risk-based decision making.”

Solid additions, if a bit high level. A topic of some interest on this blog, recognizing the impact of subjectivity is critical to truly developing good risk management.

Expect to start getting questions on how you acknowledge, anticipate and address subjectivity. It will take a few years for this to work its way through the various inspectorates after approval, but it will. There are various ways to crack this, but it will require both training and tools to make it happen. It also reinforces the need for well-trained facilitators.

5.1 Formality in Quality Risk Management

“The degree of rigor and formality of quality risk management should reflect available knowledge and be commensurate with the complexity and/ or criticality of the issue to be addressed.”

That statement in Q9 has long been a nugget of long debate, so it is good to see section 5.1 added to give guidance on how to implement it, utilizing 3 axis:

Uncertainty: This draft of Q9 utilizes a fairly simple definition of uncertainty and needs to be better aligned to ISO 31000. This is where I am going to definitely submit comments. Taking a straight knowledge management approach and defining uncertainty solely on lack of knowledge misses the other element of uncertainty that are important.
Importance: This was probably the critical determination folks applied to formality in the past.
Complexity: Not much said on complexity, which is worrisome because this is a tough one to truly analyze. It requires system thinking, and a ot of folks really get complicated and complex confused.

This section is important, the industry needs it as too many companies have primitive risk management approaches because they shoe-horn everything into a one size fits all level of formality and thus either go overboard or do not go far enough. But as written this draft of Q9 is a boon to consultants.

We then go on to get just how much effort should go into higher formality versus lower level of formality which boils down to higher formality is more stand alone and lower formality happens within another aspect of the quality system.

5.2 Risk-based Decision Making

Another new section, definitely designed to align to ISO 9001-2015 thinking. Based on the level of formality we are given three types with the first two covering separate risk management activities and the third being rule-based in procedures.

6. INTEGRATION OF QUALITY RISK MANAGEMENT INTO INDUSTRY AND REGULATORY OPERATIONS

Section 6 gets new subsection “The role of Quality Risk Management in addressing Product Availability Risks,” “Manufacturing Process Variation and State of Control (internal and external),” “Manufacturing Facilities,” “Oversight of Outsourced Activities and Suppliers.” These new subsections expand on what used to be solely a list of bullet points and provide some points to consider in their topic area. They are also good things to make sure risk management is built into if not already there.

Overall Thoughts

The ICH members did exactly what they told us they were going to do, and pretty much nothing else. I do not think they dealt with the issues deeply and definitively enough, and have added a whole lot of ambiguity into the guidance. which is better than being silent on the topic, but I’m hoping for a lot more.

Subjectivity, uncertainty, and formality are critical topics. Hopefully your risk management program is already taking these into account.

I’m hoping we will also see a quick revision of the PIC/S “Assessment of Quality Risk Management Implementation” to align to these concepts.

ICH Q9 Risk Management (r1) in consultation

ICH Q9 (r1) is in step 2, which means it is out for comments.

Section 5, “Risk Management Methodology” is greatly expanded, with a discussion on just what level of formality means in risk management using three criteria of uncertainty, complexity, and importance. Section 5 then goes into risk based decision making to a greater depth than seen previously in guidances.

Section 6 is greatly expanded as well.

I need to read this in more depth before providing a deeper analysis.

Understanding How to Organize Process

Process drives the work we do. We can evaluate processes on two axis – complexity and strategy – that help us decide the best way to manage and improve the processes.

Process complexity and dynamics are what types of tasks are involved in the process. Is it a simple, repetitive procedure with a few rules for handling cases outside of normal operation? Or is it a complex procedure with lots of decision points and special case rules? Think of this like driving somewhere. Driving to your local grocery is a simple procedure, with few possibilities of exceptions. Driving across the country has a ton of variables and dynamism to it.

While complexity can help drive the decision to automate, I strongly recommend that when thinking about it don’t ask if it can be automated, only ask what would be involved if a human were to do the job or how it is done with current technologies. Starting with the answer of automation leads to automation for automation’s sake, and that is a waste.

Dynamics is how much the process changes – some change rarely while others change rapidly to keep pace in response to changes in product or external factors (such as regulations).

Strategic importance asks about the value the process contributes to meeting requirements. Is the process a core competency, or an enabling process that needs to be accomplished to ensure that you can do something else that meets the core requirements? Needless to say, one company’s strategic process is another company’s routine process, which is why more and more we are looking at organizations as ecosystems.

Processes are in a hierarchy, and we use levels to describe the subdivision of processes. We’ve discussed the difference between process, procedure and task. At the process level we usually have the high-level process, the architecture level, which are the big things an organization does (e.g. research, manufacture, distribute), mid-level processes that are more discrete activities (e.g. perform a clinical study) to even more discrete processes (e.g. launch a study) which usually have several levels (e.g. select sites, manage TMF) to finally procedure and task.

Level of Process	Includes	Key Ways to Address
High-Level Process	How key objectives are met, highly cross functional	Organization design. System Design
Mid-level Process	How a specific set of departments do their major work blocks	Process Improvement
Low-level process	How individuals conduct their work in sub-blocks	Knowledge management, task analysis, training

Levels of Process

To truly get to this level of understanding of process, we need to understand just what our process is, which is where tools like the SIPOC or Process Scope diagram can come in handy.

To understand a process we want to understand six major aspects: Output, Input, Enablers, Controls, Process Flow, People.

Complex and Complicated as Tools for Process Understanding

Simple processes usually follow a consistent, well-defined sequence of steps with clearly defined rules. Each step or task can be precisely defined, and the sequence lacks branches or exceptions.

More complicated processes involve branches and exceptions, usually draw on many rules, and tend to be slightly less defined. Complicated processes require more initiative on the part of human performers.

Complex processes are ones that require a high level of initiative and creativity from people. These processes rapidly change and evolve as time passes. Successful performance usually requires a connection to an evolving body of knowledge. They are highly creative and have a large degree of unpredictability. Most complex processes are viewed at the system level.

Sources

Benedict, T. et al. BPM CBOK Version 4.0: Guide to the Business Process Management Common Body of Knowledge. ABMP International, 2019.
Harmon, Paul. Business Process Change. Morgan Kaufmann, 2019.
Nuland, Y. and Duffy, G. Validating a Best Practice. Productivity Press, 2020

The Great Man Fallacy and Pharmaceutical Quality

Primary Investigator, Study Director, Qualified Person, Responsible Person – the pharmaceutical regulations are rife with a series of positions that are charged with achieving compliance and quality results. I tend to think of them as a giant Achilles heel created by the regulations.

The concept of an individual having all the accountability is nowhere near universal, for example, the term Quality Unit is a nice inclusive we – though I do have some quibbles on how it can end up placing the quality unit within the organization.

This is an application of the great man fallacy – the idea that one person by the brunt of education, experience, and stunning good looks can ensure product safety, efficacy and quality, and all the other aspects of patient and data integrity of trials.

That is, frankly, poppycock.

People only perform successfully when they are in a well-built system. Process drives success and leverages the right people at the right time making the right decisions with the right information. No one person can do that, and frankly thinking someone can is setting them up for failure. Which we see, a lot in the regulatory space.

Sure, the requirement exists, we need to meet it failing the agencies waking up and realizing the regulations are setting us up for failure. But we don’t need to buy into it. We build our processes to leverage the team, to democratize decisions, and to drive for reliable results.

Let’s leave the great man theory in the dustbins where it belongs.

Building the Risk Team

Good risk assessments are a team effort. If done right this is a key way to reduce subjectivity and it recognizes that none of us know everything.

An effective risk team:

Has expertise in the subject
Knows how to drive decision making
Includes representatives of all relevant stakeholders
Is cross-functional and multidisciplinary
Allows appropriate and applicable empowerment

One of the core jobs of a process owner in risk assessment is assembling this team and ensuring they have the space to do their job. They are often called the champion or sponsor for good reason.

It is important to keep in mind that membership of this team will change, gaining and losing members and bringing on people for specific subsections, depending on the scale and scope of the risk assessment.

The more complex the scope and the more involved the assessment tool, the more important it is to have a facilitator to drive the process. This allows someone to focus on the process of the risk assessment, and the reduction of subjectivity.