Quality Experts Share Keys to Medical Device Design Controls Success
Full transcript below:
Danielle Kirsh:
Hello, everyone. Welcome to the webinar, “Quality Experts Share Keys to Medical Device Design Control,” brought to you by Medical Design & Outsourcing magazine and Arena. We would like to thank our presenters: Ann McGuire, Manager of Product Marketing at Arena; Christopher Hill, Director of Quality Assurance at Organ Recovery Systems; and Vis Ayer, Senior Director of Quality at Nevro, for being here today. I’m Danielle Kirsch, Associate Editor, filling in for Nancy Crotti, and I’ll be your moderator for today.
Just a couple of housekeeping details before we get started. You will see several boxes on your desktop, all of which can be moved around to suit your preferences. You can enter your questions in the Q&A box and they will be addressed after the presentation. Another box to note is the additional resources box. This box has websites and other information on this subject. And without further ado, I will hand the presentation over.
Ann McGuire:
Thank you, Danielle. Welcome to “Medical Device Design Controls Quality Experts Share Keys to Success.” Here is our plan for the next hour or so: I will start by talking about the importance of design controls, then briefly overview the elements of design controls. Next, Chris and Vis will share lessons learned, best practices, and solutions for addressing design controls challenges. Finally, we’ll answer your questions.
Let’s look at why we are focusing on design controls today. First, design controls encompass good design and engineering practices, practices that yield consistently high-quality products. The second, for medical device companies like most of you, formal design controls are mandated, so it’s about avoiding FDA inspection observations. Looking at the inspection results from 2018, issues with the quality system, everything covered under 21 CFR 820, accounts for almost 90% of the 483s issued. I notice that this percentage has remained consistent over the last few years.
Within those quality system findings, you can see in this pie chart that about 14% are design controls related. On the other side of the pie chart, you can also see that CAPA processes are cited at about the same rate. Maybe that will be another webinar, let us know if you’re interested. To put a finer point on this, think about the impact of these 483s, which is the FDA’s lowest escalation level when they do find an issue. Each 483 is published on the FDA website, so the impact can be wide. Physicians, patients, investors, even employees, could lose confidence in your ability to execute. Competitors may see it as a weakness to exploit. And internally, management needs to reallocate their time away from established priorities and toward resolving the issues identified by the inspectors. Having a solid design control foundation could prevent the expense and unwanted attention of a 483, but also a warning letter or even a device recall.
Let’s overview briefly the elements of design controls. Design controls start at the beginning of the product concept stage through to production and ongoing improvements, the complete product development cycle. Planning is the first element in the design control process. The plan, like all plans, includes the activities, dates, and responsible people. You update the plan document as your plans evolve. Design input comes from users, patients, and physicians, as well as other stakeholders. The design process results in design output, documentation that describes the product. Design reviews are throughout design development to check the design results and to identify issues.
Verification means making sure that the design outputs completely and unambiguously match the design inputs. In verification, you should be able to answer questions like, “Do we have all the documentation we need? Who’s approved it and when? What’s missing?” Design transfer is the process of providing manufacturing with the information they need. Design transfer is worth noting today, even if it’s not as frequently cited in the 483s, because in our experience, we so often meet companies where the transfer of information from engineering to operations is manual, risking delays and errors. The process usually involves fixing a bill of material that’s stored in a spreadsheet, removing columns, maybe reformatting numbers, exporting a CSE, then uploading it into the ERP system.
Next, manufacturing builds the medical device using design output, and that would be the bill of material, drawings, assembly instructions. The next step then is validation. To make sure that the product, as-built, will function to meet the user needs. All these tests and results must be documented. Validation is the most commonly referenced sub-part of the design controls 483s. Design changes are the second most cited issue under design controls. After that first revision, updating ERP and other downstream systems can become tricky. What has changed? What parts were added or removed? Is all the supporting documentation updated? You can run into trouble here. And change processes can have many variables. We’ve seen people stumble over documenting this process and then following it.
Finally, the design history file is the compilation of your design documentation and its changes over time. This is another administration-heavy element that can be cumbersome. The resulting file, too, can be hard to search and use. A QMS system can simplify these processes and others related to compliant quality practices. A product-centric QMS system leverages a single system of record to manage the product and related quality processes. It manages the product bill of material, drawings, specs, the AML, and changes. The quality processes are in the same system. For example, CAPAs can be linked to ECOs when it makes sense, and complaints can link with sub-assemblies that are causing the problem.
Today, our experts will discuss how using a product-centric QMS dramatically improves design transfer and design change processes, as well as quality processes.
Now that we’ve set the table on the importance of design controls, let’s get some insight from our two quality veterans. Chris and Vis, thank you for joining us today. You both have extensive backgrounds in quality and compliance for medical device companies and surely realize the importance of design controls. I was hoping you could share a little bit about a lesson learned from your career where design controls had a major impact on your validation, product launch, or production. Chris, let’s start with you.
Christopher Hill:
Sure. But before we talk about the challenges, I did want to reiterate one point from what Ann described. The FDA design controls are required and it’s something that we all have to comply with, but it’s also good business practice. In planning your projects, identifying data sources, deliverables, responsibilities, and risks, those are all good steps for any product launch whether it’s a regulated device or not. So, we don’t just follow the best practices because we want to avoid the 483s, we follow them because we want our final products to be well-designed, well-controlled, and well-documented.
To answer your question, my biggest challenge when I first joined Organ Recovery Systems was really collecting and organizing all the historic design documentation and putting them into some kind of logical and sustainable format, and that was a several year project and really, is still in process to some extent. Our documentation was spread across paper copies in binders, electronic files on the network, files stored only at our contract manufacturing sites. We’re a pretty small company so we needed an efficient way to centralize everything and then keep it current. To do that, we created the electronic device history file that linked all of the required files, whether it was scanned or native, in an electronic format. Since all the documents are now controlled electronically, our design history file always contains the correct version of every document with minimal upkeep.
Ann McGuire:
Wow. Several years to organize all those binders and electronic files? That is a big challenge and certainly a big expense, especially for a small company. Vis, what lesson would you like to share?
Vis Ayer:
Sure, Ann. When I joined Nevro about eight years ago, I realized that we outsourced all of our design and development activities. So you can imagine that working for a class A compatible company, you have a lot of documents that relate to design and development. So we used to have these documents shared through emails and FTP sites for review and approval. And internally, we used to have a paper-based team-controlled process and we built DHF using binders. When we wanted these binders to be ready for audit purposes or for our internal videos, it was really time-consuming. Now, what we have done is over the last few years we have grown, so we went to the electronic system to manage our change control process and DHF. So working with an outsourced partner, we let them know what our different phases of design control are, and what our requirements are. In the past, when we used the paper-based change control process, when it comes to when and how it needs to happen, the problems are open and more defined.
Ann McGuire:
Yes, we hear over and over that building, maintaining, and making the paper or electronic paper hybrid DHF audit-ready is a huge administrative burden. Adding international markets like I know you have, and more products only expands the workload.
Let’s do a quick audience poll; this will be the only one today. We want to get a feel for who’s in the audience today so we can better focus our discussion. Please complete this quick poll. How do you manage design controls today? Do you have no design control processes yet? Are you using a paper system? Have you put together a combination of spreadsheets, shared drives, and email for a homegrown system? Have you purchased a commercial system like document management, PLM, or QMS? Or, are you not sure?
Select your current situation and submit. You’ll see the results on the next slide in, let’s see, 5, 4, 3, 2, 1. Okay, let’s see. Okay, interesting. It looks like most of you have either a homegrown electronic system or have invested in a commercial electronic system. I see some people have no design control processes yet. Well, I’m guessing that the situations, especially with the homegrown system, that the situations that our experts have talked about so far resonate with you. Well, rest assured there is a better way.
Let’s get back to our experts. Okay, like we talked about in the introduction, accurately performing and documenting design controls is a crucial aspect of meeting 21 CFR part 820.30 compliance for most medical device companies. And design controls covers a lot of territory in terms of teams, data, and processes over the life of the product. The poll results show that a few members don’t have any processes yet. Can you talk about the biggest challenges and how using a product-centric QMS system helps? Let’s hear from Vis first.
Vis Ayer:
Sure. Like I mentioned before, we are a manufacturer of a class III active biomedical device that includes software, hardware, and mechanical components. So, from a design perspective, you want to make sure that you ensure that not just the individual components are working when they integrate, it also works as intended. So, planning is key—at the beginning of the project you want to ensure all requirements, including for the class III, that our essential performance requirements are captured. And if you’re outsourcing, you want to make sure that roles and responsibility between you and the outsourcing partners are clearly laid out. And if the outsourcing partners are really doing all of the design and development activities, you want to make sure they’re qualified and approved.
If there’s a big project, you can imagine working with an outsourced partner—managing the changes, review, and approving documents are huge and are a significant effort. So, here is where the design system is going to make it effortless. So, having a design system makes the change process very seamless. You can track changes related to the document. You can review and approve the document using the built-in change control process. In addition, you can even build your DHF using the electronic system. This way it ensures that the DHF is current and all your project documents are linked appropriately.
Ann McGuire:
Yes, good point Vis. Managing a complex product, which is what we call a product with electronic, mechanical, and software parts, is far easier with a product-centric QMS system. So are planning, and revising the plans, requirements management, vendor management, and product change management. And all are crucial in realizing an implantable class III product, especially using an outsourced manufacturing model. Chris, what do you see as the biggest challenge and how is product-centric QMS helping?
Christopher Hill:
All right. Well, we don’t have an implantable class III product, but we do cover electronic, mechanical, software, and chemical as well, in our products. But the QMS system has definitely been helpful when we cross-reference the source documents. Now, a single document may capture data that satisfies multiple requirements. For instance, a risk analysis is an output of a design control process and it’s linked to the design history file, but it’s also a component of our risk management file, and a component of the usability and human factors engineering file. So, instead of maintaining three separate binders of paper copies, outside of the document control system, we’ve been able to link individual electronic documents to multiple locations, and that way we’re covering the different standards. Plus, as I mentioned before, the electronic documents are linked so they’re always current and having a QMS system makes this far easier to maintain and more effective when I present this at audits.
Ann McGuire:
Well, this echoes with my experience when first meeting with medical device companies. I wondered why there were so many filing cabinets and shelves of binders, even for small, single-product companies. Then I realized that much of it was duplicates, duplicates being stored in different binders and folders that must be kept in sync. I knew it could be simplified.
Now, let’s talk about maintaining design controls with design and manufacturing partners. Many medical device companies outsource their manufacturing, which can add complexity when managing information for compliance. Vis, you mentioned at the beginning of this discussion that the biggest impact of design controls for you was related to working with your supply chain partners. Can you briefly describe your environment and how you are able to maintain proper design controls at your company?
Vis Ayer:
Sure, Ann. So, as I had mentioned before, we outsource everything, from all of our design element activities to all of our manufacturing; we don’t do manufacturing in-house. So for us, planning is the key. At the planning phase, we define who’s doing what. You want to ensure your recurrent deliverables are clearly laid out, and when you do your design info eval meeting, you call out what you’re planning to build and so that when you’re going through your design output process, it’s very clear. So when you get ready for building units with your contract manufacturer for design modification testing, it would ensure that you are both using the correct materials.
This is where the electronic systems, the PLM capabilities, really help to achieve that. One of the challenges we used to have was we managed through Excel 5 and tracking changes were difficult. I can see from the poll that there are quite a few users who are using Excel and Word and I assume they have similar systems as to what I used to have. The changes are noted in columns and we ended up creating duplicate parts. And if you want to know if a part is used across different product lines, you had to open each of the BOM files to find out where the part was used.
Ann McGuire:
If you had an issue with a component you had to open each BOM spreadsheet to find out where the component was used?
Vis Ayer:
Yeah. I mean, so you could imagine how much time it took and you weren’t even sure—did we find everything? There is a position to miss one, too. But now, just to take it further, now we started using the electronic system to build and manage the rough materials, the parts are linked across the product line, there are options, so you can just type the part number and it tells you which product lines use that. If a part has changed you can manage the insertion of the image dissolution pretty easily. We are even taking it one step further now trying to implement something called supplier access. So, when a part is changed, our current process is we notify our suppliers through email and what we want to do is, we want the systems to send an email to our supplier, so our partners can log in to the system and see what part changed and they can even see when the changes become effective, how many old components they had, should they use it, or should they scrap it? All those things, instead of relaying all of this on an email.
Christopher Hill:
Similar to what Vis is describing, we also outsource nearly everything at Organ Recovery Systems. A few years back we had an FDA 483 associated with our device master record and the control of our subcontracted manufacturers. They argued that our device master record must contain the current device history record or the batch record and up until then, our contract manufacturers controlled them. We were involved in any major changes that had the potential to impact compliance, but we didn’t approve every change to documents. We didn’t have copies of the most recent version. So, as our corrective action, we had to revise the quality agreements with the contract manufacturers so that we approved every change to our product-specific manufacturing documents. Then once we were in the approval routing, we were able to keep those current copies of the device history record electronically linked in our device master record. So now, as part of lot release, we can check the contract manufacturer’s device history record revision against what we control in our system to make sure that we’re using the current approved instructions, or that they were using them.
The FDA did come in, they approved of the solution and closed out the observation, so it did have a happy ending.
Ann McGuire:
Well, that’s good news. Based on what you’re both saying it’s apparent that a product-centric QMS system supports the outsource business model by helping with communication and collaboration.
Let’s talk about the challenges with risk management, which ensures that the product works as intended and does no harm. Risk management is a fact of all product development and particularly in the regulated medical device world. How have you seen the way you approach design controls as helping risk management efforts? Chris, let’s start with you this time.
Christopher Hill:
All right. Now with the release of ISO 13485, the 2016 version, risk management is now pretty much part of all processes in a quality system, including design control. So, when changes to a design are proposed, we should be assessing the risk as part of the review process. At Organ Recovery Systems, our change management process requires a review of the risk management file, or the RMF, as part of any changes to the device design, labeling, or manufacturing processes. Now the RMF contains separate risk analysis documents covering the design, the manufacturing process, cybersecurity, user application. You know we have a different FMEA style of document for each one of those.
The documents are all linked in the system, though, to make it easy for the engineer who is proposing the change to open up the applicable risk analysis and then decide if that design change will introduce a new risk or it will mitigate an existing risk. Then, with the risk analysis, the FMEA needs to be updated as a result of the design change, we can update that document and add it to the same change order as the design change order so it all goes through together.
Ann McGuire:
Great. Vis, what has been your experience with risk management?
Vis Ayer:
Sure, Ann. It’s really similar to what Chris was explaining. You can hear from Chris, risk management plays a really important role. It’s a key process in the old design control, plan control process, so, it’s very important that all of your risk is identified early and it’s incorporated while you’re designing your product. So, the key is, when you’re developing your user needs and design input, you understand what the risk is going to be. This will help in achieving a good design output. When you design a product and when you test a product, you know for sure that you are mitigating the risk, and the product is working as intended.
Ann McGuire:
Great. Well, for both of you, using a product-centric QMS system, it sounds like your risk management files are controlled, accessible, and linked into the design process throughout the product development cycle.
Christopher Hill:
Yes, it is.
Vis Ayer:
Yes.
Christopher Hill:
Yeah.
Ann McGuire:
All right. Well, we have heard a lot of good information today. Before we end our discussion, let’s ask our experts for final advice on successful design controls.
Some of our audience members are just beginning their medical device development journey, well, some are struggling with their current processes and systems. Based on your extensive experience in the medical device industry, what advice or tips would you suggest as keys to successful design controls? Chris?
Christopher Hill:
Sure. Our QMS is based around the bill of material, as you described, and all of the other subsystems, including change control, can be linked to the products. Our electronic design history files were created first, and then we added the electronic device master records and risk management files. A few years later, the usability and human factor engineering files. We implemented online workflows for the complaint investigations, nonconformances, CAPA audit observations. If I could do it all over, if I could see the future, I would have mapped out all of those different processes in advance and how they were going to interact. Now, organic growth can sometimes be very good, but I would have loved to have had a documented overall strategy of everything I was going to do with the software before I started. It would have saved me a lot of time going back and forth and tweaking the processes and workflows to get everything connected right.
Ann McGuire:
What advice do you have for our audience, Vis?
Vis Ayer:
Sure. Understand what you’re developing. You want to make sure that the elements are clear, not vague. The requirements are thorough, and that you can read them. Incorporate risk management activities early in the development process. When you are doing the design input, make sure the user needs and requirements are clearly defined. So this way, when the design output reaches the design input stage you can successfully make it. Also, in order to achieve all of this, doing the design review at the end of each phase is very important. If you’re doing a large and complex project, it’s okay to have multiple design reviews. This will enable the project team and the stakeholders enough information and time and also the stakeholders can assess the progress of the development of the project, which would also ensure that the critical risks are identified and addressed.
Understand the difference between design verification and validation. And last, but not least, make sure you have a good change control process, which is key to success with design control.
Ann McGuire:
Well, thank you both for sharing your keys to success with managing design controls. I am going to pass the mic over to Danielle to kick off our Q&A.
Danielle Kirsh:
Thank you, Ann. As Ann said, we are open to questions now. Feel free to send your questions in the Q&A box on your screen. We do have a couple of questions here. The first one is, “Many of our CAPA’s include a PCN. Is there a way to link these two processes for an audit? And how are product changes managed?”
Christopher Hill:
PCN, product change notification, we use the terminology ECO or engineering change order, but I think it’s all the same. Linking them is pretty easy in our system. We can even link document updates, change orders, investigations of any external documents. For CAPA in particular, it’s pretty handy to have the change order linked to the CAPA, so that you can check the status or access content from within the CAPA when you’re conducting the effectiveness verifications. Yeah, it’s all linked in our system, they’re all changes.
Vis Ayer:
Same here, you know, if you use quality models, field assessment quality review models and we have CAPA, with that process we cannot print multiple documents. We can use different phases within the CAPA and we can approve each phase.
Danielle Kirsh:
Another question, “How do you handle complaints or investigations with this system?”
Christopher Hill:
For Organ Recovery Systems, the complaints or the initial customer call is actually received in an external system, and then we document the investigation in our QMS. We have got a custom workflow that we built. We capture the critical data and the workflow, summarize the investigation, and what caused the corrective actions, and then we upload a PDF of the whole investigation report as a reference. So, complaints can be linked directly to the product, just like we do for a CAPA or a nonconformance. That way we can pull a list of all of the complaints or a CAPA or nonconformances from the system for any given product.
Danielle Kirsh:
“Have you experienced an audit? And how do the auditors like your system?”
Vis Ayer:
Sure, I’ll take that. We recently had an audit and we shared our electronic data within the system, and the auditor liked it. They were able to see how we uploaded the link, when it was completed, which phase it was linked to, they liked the whole solution.
Christopher Hill:
We’ve also presented our, in the last two years we’ve had FDA, ISO, and customer audits. We’ve shown them the design history files, the risk management files, the device management records, live on-screen during the audit. They were all very impressed and happy with it.
Ann McGuire:
Chris, this question about audits got me thinking about something that I hear a lot from medical device companies. I’ve heard that preparing for an audit is a lot easier with Arena. Can you compare how you had to prepare for an audit before, and then after using Arena?
Christopher Hill:
Sure. Before we had Arena it was typically paper binders and you would go through and kind of do a pre-audit audit to review the binder to be sure that everything was current, make sure everything was there. There were certainly a couple of hours of preparation depending on if it was a smaller audit, or if it was FDA, a lot more than that. But we don’t have to do that if everything’s in the system and everything is current. It makes it much easier.
Ann McGuire:
Vis?
Vis Ayer:
Sure. I know before, we had a complex system and our binders are really big, and there are times when you’d like justification, rationale, we write a memo on the file and then go to the DHR finder, and when we do the rearview, like eight months after the project or one year into the project, we don’t know where that justification memo or what that memo was written for really. We spend a lot of time thinking about how we correct that. With the modern electronic system, you spend way less time searching for that information and if it is linked it is much more straightforward.
Ann McGuire:
Thank you. Danielle, I’ll hand it back to you.
Danielle Kirsh:
“Switching to an electronic system seems like a big undertaking. How did the conversion go from paper-based to electronic?”
Vis Ayer:
Sure. I can take it. We have between two years, we have moved from paper to the electronic system. Depending upon how complex your paper-based system is, how many records do you have, you usually get it done within 3-6 months or depending upon how quickly you want it done. With my experience of implementing an electronic system and going from paper to an electronic system, the question always comes down to, “Hey, do we build our existing paper-based process into the system or should we just go with what the system has to offer?” And as I implement more systems, I always share my two cents worth. Go with what the system has to offer. The systems have been really good at implementing changes and keeping up with regulation changes. The current Arena system has a built-in process that is compliant with the FDA and other regulations.
Christopher Hill:
Our transition at ORS, Organ Recovery Systems, went very smoothly, probably because the system we had before was very inefficient. We have a lot of remote employees in multiple sites, even though we’re small. Before we had the electronic approvals, we were scanning and faxing documents around trying to get signatures, so when we had the opportunity to do it all electronically, I think everyone was motivated. They all got on board and it went very well.
Danielle Kirsh:
“Could either of you provide some advice on design controls for outsourced prototype development? What’s needed during early development phases?”
Vis Ayer:
Sure. Can I take it first?
Christopher Hill:
Yeah, go ahead.
Vis Ayer:
Sure. This is my experience, how we do some of the ways of doing that. You could come up with an engineering drawing, right? You can have a basic version of what you think you want to build. You can release that, you can build something that changes your plan, which is basically what I’m thinking of building. You can share with your outsource partners and see. Get them all together and say, “Hey, this is what I would like for you guys to build. What would it take? What is the segment of work we applied? How many prototypes do you want? How many test situations do you want to go through and those kinds of things.
Christopher Hill:
For us, the prototyping process, initially it’s going to happen earlier in the process, and in some cases before the official design control kicks in. If we’re doing feasibility, that’s outside of the design control system. If you’re doing prototyping of more advanced models, and once you’ve already gotten into it, we just keep track of each of the drawings in the system and as there is a change to the drawing, it just gets updated pretty easily into the electronic system, so we’ve got a historical record of each of the different designs and what the prototypes represent.
Danielle Kirsh:
“If the method of verification and validation is changed for a particular design, does it have to be included in design change control?”
Christopher Hill:
For us, it definitely would be. I’d have to know the exact context of the question, but yeah, if we made a change as it’s described in our design verification plan, we would simply update the plan and include the rationale for why that was changing. Again, not a real big deal, and then the plan is still, all the different revisions of that plan are part of your design history file, so it’s a fairly easy thing to document.
Vis Ayer:
Yeah, I think Chris’s statement was right. If it will change to your testing strategy, your verification, your test line, you repeat that and you control as to your change control process.
Danielle Kirsh:
“Is there any way that we could have a quick look at what Arena looks like? And also, is Arena only for devices, or can it be adapted for other needs?”
Ann McGuire:
Okay, I’ll take that one. Yes, you can see what Arena looks like. Just contact us at Arenasolutions.com and we would be glad to show it to you. And then, Arena is used for medical devices, but also high tech, less regulated devices. Then more recently, ITAR regulated devices as well. So, when you do meet with a person from Arena for the demonstration, we can talk about what exactly your needs are, and then be able to answer your specific issues.
Danielle Kirsh:
All right. I think that’s all the questions that we have the time for right now. Before we sign off, I just wanted to let you know that there will be a post-webinar survey at the end and we would really appreciate it if you would take the time to give your feedback. This presentation will be emailed to everyone later today. I want to thank Ann, Chris, and Vis for their insights. Thank you everyone for attending this webinar from Medical Design & Outsourcing and Arena.