Hello and welcome to ValSource Viewpoints. I'm Jim Vesper, director of Learning Solutions at ValSource. At ValSource, we serve the pharma and biopharma industry as commissioning, qualification, validation and consulting experts. On Monday, January 23rd, 2023, the International Conference on Harmonization, Arise Ch, released the long-awaited revision to Q9, their quality risk management guideline. In fact, it was published 2 months. Earlier than they had predicted. What happens next is that health authorities like US FDA will update their own guidelines and requirements. That will happen later this year. The guideline went from 23 pages to 29 pages. Here at ValSource, we have a number of consultants who specialize in risk management. Today, some of them are with us. We have Patrick Maines, Beth Fulton and Amanda McFarland. Welcome. Hi, Jim. Hey, Jim, thank you for this. Hi. Well, this is something that we've been waiting for, for quite a while. It's been talked a lot about at meetings and conversations that we've had with regulators. Amanda, what are some of the significant changes that you see now in the R1 version of Q9? Yeah. Thanks, Jim. You know, I think we have been waiting quite some time for this document to be revised, but not quite as long as they waited for Annex 1 to go through all their revisions. So here we are. We have a number of changes. The first one to think about is just that subjectivity is addressed in QRM. Another change that we saw was a new and renewed focus on product availability risks. We see some more. Information about how formality is treated within the scope of risk assessments. There was a mention of risk based decision making, not just the the decision making element and a big change when we look at hazard identification. So those were some of those key changes that are in scope of this new revision. Great. Well, let's talk about some of those in more detail. Patrick, what did you find interesting? So what? One of the things that I found interesting was about this new and. Well, not new, but there's the concept of informed decision, basically kind of removing or. Uh, you know. Complementing the concept of of this passive decision making that we've seen in the in the past where you really do taking all of that information that we have throughout the entire process, the scientific data that's underpinning the materials that you're building your risk assessment upon. And then drafting up those reports being part of the communication process and then escalating that through the various pathways to the management team and the key decision makers and stakeholders of the organization. And now getting them to um. Officially, uh, sign off that they have accepted these new uh risks if they have to accept them. Now, obviously there's always the desire to reduce or lower the risk level for anything, but as we know you do, will occasionally have to accept those decisions. And now having a much more formal pathway to escalating and documenting those acceptance decisions, I think that's one of the things that I found most. Interesting about this new revision. Yeah, you know, I mean that's really one of the main purposes of, you know, risk based thinking is to to make some better decisions, you know, based on the science, based on the the knowledge that you have and the understanding that you have of your process. So it's nice that they're really emphasizing that in this version. Beth, what about you? What got your attention? Well, there was a note added in Section 3 to include availability risks as quality risk where there's a potential for patient harm and that really kind of dovetails into regulatory agencies increasing concern about drug supply shortages. For example, there was a new guidance document in May 2022, FDA's draft guidance risk management plans to mitigate potential drug shortage guidance for industry and that kind of speaks in a more. Granular right of the content of this section, I think that's shortages hit us really hard starting in 2020 and we're going to be thinking about availability as a quality risk more often. Also risk identification is now hazard identification in sections 4, that's figure one, that's your big, you know, quintessential figure one that's going to be in all your quality documentation. So make sure you revise your quality documents. And that's throughout the document, sections 4.37. So risk identification is now hazard identification. And I'm really excited about this. This change in terminology is a huge win for QRM professionals because using correct terminology, in this case hazard instead of risk, which you could also say failure, that would have been acceptable and interchangeable term to hazard. It means that the facilitator, the team, the decision makers, we can all be on the same page. About where we are in this process of assessing risk. Yeah. You know, I remember when the Q9 first came out and I was talking to one of the people that was on the expert working group and I that was the comment that I made. You know at the beginning you don't know the risks. What you're trying to do is you're trying to identify those sources of harm. So it's, it's a win. That's terrific. Uh-huh. You know, one of the other things that's talked about in this revision, Beth, is formality. You know, talk to us a little bit about formality if you would. This discussion of formality has been going on since the dawn of risk time, and it it does define this a little bit better in section 5.1, stating we should consider factors like uncertainty, importance, and complexity when determining how much formality we apply to a QRM activity, importance and complexity. Those are somewhat straightforward and kind of play into severity. Uh, in many ways. But I'm very concerned about uncertainty and I think it's an important thing to talk about because. Teams and facilitators should understand, because they're talking about the risk activity, the QRM activity, that this is more, I think, speaking to the robustness of risk control measures, the mitigations that are applied, not just the formality of the tool that's being selected for the risk assessment process. Amanda, any any thoughts that you have on on formality and and tools? Yeah, I you know what I think about what Beth mentioned that this is something that is one of those more common questions. How do I know how formal my risk activity is? And I think that what they've added is clarity that the formality is a spectrum. It it can be a less formal application, it can be a formal application. And my level of uncertainty comes from is that formality of the risk question, is it formality of the tool that you're using and I'm not certain that we have a real clear. Understanding of where Icsh wants us to apply this terminology. So if it's formality and quality risk management, that could be in the problem that you're trying to solve. It could be the robustness of your risk mitigation program, or it could be strictly based on the tools. So how we go about navigating this I think would be really interesting. I do know that there are training materials that ICH will publish they had solicited. Professionals from the industry to add their own case studies to that training material. And I'm really hopeful that we see one of these case studies played out so that we get a better understanding of of what the measurements of those 3 components are and and how they'll be operationalized for folks. Yeah, I think, you know, those training materials are something to look forward to because in talking to some people involved in the revision process, they were given by the IC H just very strict limits about what could be changed and what could be looked at. You know, formality, subjectivity bias was another one that was really important and how do you reduce bias as much as possible. So they had some real constraints on what they were looking at. And I know some of the comments that groups like. DEA and other organizations. Supplied. Said you know add this to your trading material, don't think about this, add another definition of this or that. So I think those will be a very useful and very welcome by by by those of us in the industry. You know what, one thing to add to that is in the past it we only had that one tenant that said the formality, documentation and effort that you put into a risk assessment is commensurate with the level of risk. But now it's real explicit, it says you don't always have to use a highly formal risk management method and a tool. And so finally we're we have that concrete language, I think we've we've interpreted that tenant of risk management as a means to use. Less formal tools, but it's very clear now and and that is something to be applauded. Hmm. And I I want to add something to that. I think that we've seen a lot of because of the way it was historically written, I think there's a lot of firms and organizations that have gone very formal and I think this, this new revision, the way it's now worded will give clearance for organizations to to explore the less formal methodologies and feel more comfortable with that decision. Well, this is a question which sort of thought about it just just now and anybody can answer this. But what do you think the impact will be of revision one on the industry, you know how the companies that have been doing risk assessments for many years and you know doing a pretty good job, how do you think this is going to affect an impact what they are doing going to be doing in the future? That's for anybody. Yeah. No, I'll, I'll take a stab. I mean, one of the things that I see as as a positive outcome is, is this new and this new focus on subjectivity and risk assessments. And there's a number of ways to to minimize that subjectivity. But one of them is really with a focus on trained facilitators. And I hope that this is a a pathway. For organizations that haven't identified and entrained up qualified individuals to lead unbiased risk assessments or do their best attempt to to minimize subjectivity that that those organizations develop individuals with the skills, knowledge, and ability to lead these assessments in a way that drives important outcomes. Good. Yeah. The the importance of that facilitator of taking people through the tools of of getting to that right level of detail so you don't, you know, go down to rabbit holes and spend a lot of time that really is a wasted effort. Patrick Beth, anything of that you would add to this? Ohh, go ahead, Patrick. No, I wasn't gonna say anything. I was like you had already had your hand up. Yes, so. I think that this is a wake up call. To Amanda's point, this is a wake up call for industry to say I don't have a, I don't have a facilitator qualification module in my training curriculum. I need to do this because when, you know, inspectors and auditors come in and they pull my training records, they're going to want to know, you know, what qualifications do my facilitators have. Hmm. Good, Patrick. Yeah, I and you know I agree I I think that one of the things I'd like to see is in the industry is individuals with those facilitator responsibilities coming out of the the pool of people that are actually working on the floor and having that those individuals have the knowledge of what's going on tactically and operationally in the manufacturing space, but also have the knowledge of the tools and. Being able to recognize that and using the vocabulary effectively across the organization. And I'd love to see if people could cross talk on that as well, where you might be an upstream operator or upstream SME and maybe support downstream with facilitation because you do have that new set of eyes. And I think that's going to be a critical component of getting outside of bias and really working within the system. To get the best possible risk identification, hazard identification and therefore the best possible outcomes for the patient. Good. Good. Anything else that anybody would like to add as we're wrapping up our time together? Yeah, I I mean just along the lines of of the decision maker responsibilities and roles and responsibilities for management there there is an additional responsibility listed about monitoring and ensuring that subjectivity is identified and minimized within the context of risk assessment. So where we would in in normal risk assessments it would be anecdotal you know you need to take. These measures have well founded risk ranking criteria in order to minimize the amount of subjectivity. But now to have an individual line item that that that must be evaluated by decision makers and it is their responsibility to ensure that that subjectivity is controlled and minimized to inform scientific decisions. I think is is really fascinating and shows just how much. And these, these individuals that contributed to the document have seen that as driving perhaps inappropriate decision making. So that this is a really big win for for the industry, especially as as the other panelists noted, for patient safety. Hmm. And Amanda, interesting question. Go ahead, pat. I was just going to say, Amanda, I think that all ties back to that previous discussion we had about uncertainty as well, where it really is driving you to gather the knowledge you need to make those decisions correctly and appropriately. Absolutely. Well, what I was thinking as you were talking to Amanda, is wouldn't that be an interesting question for an inspector or investigator to ask a member of management? You know, how do you reduce subjectivity? How do you reduce bias in the risk assessments that your teams do? Right. And you know I mean what is that really asking, do you read the risk assessments that are coming out of your quality system, you know how much, how informed are you around the details of those and the attributes that are contributing to those to that knowledge management portion of things. So I I think it's a really big step and and it will be really interesting to see the way that the industry interprets and puts that into action. Yeah. Yep. Just to let people know, in March, pharmaceutical technology is putting out a special edition of their journal talking about. Q9R1 Paul Pluta is the special editor for that. Some of us here at ValSource are contributing articles so that will be available online. Well, at ValSource we have a number of experts who are focused on quality risk management and how risk management can be applied in practical value adding ways. They may be some valuable resources for your organization. So if you're wanting more information about how we can provide help with QRM in general or training for your people. Developing facilitators, let us know. Also we have other podcasts available on cell and gene therapy products and the new Annex one that's available on wherever you get your podcasts and also on the ValSource website. So if you have any comments, any questions, please visit our website or send an e-mail to info@valsource.com. So thank you, Patrick. Amanda, Beth, thanks for being part of this and. Thank you for listening. Bye. Thanks everyone. Bye. Thank you. Thanks.