Common Pitfalls in Packaging Validations (and How to Avoid Them)

As regulatory expectations evolve, packaging validations are facing greater scrutiny. Many deficiencies flagged by auditors trace back to recurring pitfalls: inadequate planning, missing acceptance criteria, or weak justification for validation strategies. Other challenges include insufficient sample sizes, overlooking worst-case conditions, and gaps in sterilization timing or aging studies. Even minor design or process changes, if not properly addressed, can undermine compliance. In this Expert Insight, Logan Luke, Expert Technical Consultant at Nelson Labs, shares guidance on avoiding these missteps. He stresses the importance of grounding validation strategies in ISO 11607-1 and -2, as well as ISO 16775, and advises companies to question inherited processes while working with trusted partners. Looking ahead, Logan highlights two emerging pressures: innovative sterile barrier designs that don’t easily “fit the mold” and the industry’s increasing focus on sustainability. Both trends, he notes, will demand innovative approaches to ensure packaging validations remain thorough and effective.

Transcript

00:00:01 Welcome to this expert insight. I'm Sheri Trigg, editor and director of content with medical design briefs. And we're here with Logan Luke, expert technical consultant at Nelson Labs. He will talk to us about common pitfalls when performing a packaging validation. Welcome Logan.
>> Pleasure to be here. Thanks for having me.

00:00:22
>> Logan, today we're discussing common pitfalls. So what do you mean when you say common pitfalls in the context of packaging validations?
>> Yeah. So to me a common pitfall would be something that a regulatory reviewer would identify as a deficiency or a finding within your package validation. I think I'll maybe go a little step further and I'll say if I were to do a

00:00:46 gap analysis on a package validation, it would also be something that I would identify as deficient. So something not meeting the requirements within the package validation standard ISO 11607-1.
>> Okay. So what are some common pitfalls that you've seen?
>> Yeah, I think maybe this might be the one that's on my mind most recently. But what that would be would be just a lack

00:01:15 of a plan or lack of acceptance criteria before you set out to do your package validation. So it's really unfortunate if you were to begin this whole process and maybe for whatever reason you are looking to just find how other folks have done a package validation. So you've done your research, maybe you don't have that expertise necessarily,

00:01:39
>> and so you just kind of choose some tests and you perform them. If you haven't defined what your success criteria is before you set out to do your package validation, then it's impossible to know whether or not your package is actually validated once you've completed all your validation activities.
>> Right? So, um, that would probably be

00:02:04 the first item that I would think of when it comes to a pitfall. Kind of related to that though is also lacking the appropriate justification for your validation strategy. So, once again, this is something that you're doing upfront um before you've even you've even set out to perform anything. ISO 11607 for better or for worse is a standard which leaves uh the door more

00:02:29 or less wide open for what you want to do. It sets the criteria for what you must do and how your packaging must perform. But the way you go about getting there can change and you can justify how you get there. Uh for example, you might have an uncommon sterile barrier system. So, just for context, right, when I say a common sterile barrier system, I'm thinking of

00:02:57 something like a pouch or a tray, right? These are really they're they're the workhorse of the of the packaging industry, right? You put your medical device in there and then you're typically doing some set of standard tests listed within ISO 11607 and proving its its effectiveness as a sterile barrier. However, you might be encountering a new or you might choose

00:03:23 to use a new sterile barrier system which doesn't kind of fit the mold of the old ways of doing things. So if you tried to use the more common strategies that were very much applicable for these uh very common sterile barrier systems but now you have this newer sterile barrier system. I I think this is a pretty drastic comparison and and it highlights my point of saying a pouch is

00:03:48 a sterile barrier system but also something like a syringe can be a sterile barrier system. So if you are trying to apply the testing you do on pouches to syringes, it's not going to go very well. So that's why you have to have justification for why you are doing the things that you're doing before you uh begin on this path of doing your validation.

00:04:16
>> You you talk about uh not addressing the changes properly. Can you expand a little bit on that?
>> Yeah. So ISO 11607 I'm going to say that standard all the time throughout our conversation because that's really the most important place to look when we're talking about this.
>> Um it allows you to like I had mentioned you know choose the appropriate tests

00:04:41 but it also requires you to uh justify that selection. Some of the rationale that I've seen might be as simple as well there's an annex within ISO 11607 which says you can do this test this test this test or this test but I would say that it kind of has to be a little bit more nuanced than that. Uh, I would say your justification is is lacking if if you kind of just say because it's in

00:05:11 the standard, I'm going to do it because those test methods apply to specific kinds of sterile barrier systems. And so you have to you have to understand that why. So if you're if you're changing your your sterile barrier to something that doesn't fit into what you've maybe done previously, now you have to change your thinking and you have to change your justification for why you're

00:05:33 choosing the the tests that you are.
>> So great advice. How would you recommend avoiding these pitfalls? Uh especially if someone doesn't have the expertise.
>> Yeah. So, first and foremost, I would just mention that if you don't have access to ISO 11607-1-2, get access to that. Become very familiar with the content that's within those standards because that's what you'll be

00:06:01 your your validation is judged against. Right?
>> There's also another ISO standard 16775, which is guidance for how to apply those standards. Um, and so it will actually go into greater detail and explain some maybe some some different approaches you might consider.
>> Okay.
>> For example, uh I I actually have some

00:06:25 more pitfalls to uh discuss if if that's all right.
>> Oh yes.
>> Um one of which being sample sizes. So for example, ISO 11607 it states your sample size for the tests that you're that you're using need to be based on statistically valid rationale. Well, now ISO 11607 has included an

00:06:52 entire section, an entire annex that's talk that talks about risk management. And I think that's becoming pretty critical in the industry and it's something that regulatory bodies are asking
>> medical device manufacturers to consider even more so now than they maybe have done in the past
>> and especially within the context of

00:07:14 your sample sizes. So it's pretty common for me to see something like well our our sample size is 29 because that correlates to a 90 95% confidence reliability interval.
>> Oh
>> well how did you arrive at 90 95% as the appropriate confidence reliability interval?
>> Why didn't you do 95 95 or higher or

00:07:38 lower? Um and this this focus on risk maybe will point you in that direction. Right? What's the risk to the patient? What would the risk be if my device were to become compromised? If my packaging were compromised and now my device is no longer sterile, um what what is the result that happens there? Right?
>> Um if I'm if I have a lowrisk device that might just be topical application

00:08:05 or something like that, that's very different than something like an implant which will stay uh inside your body for for a long period of time. So you might consider the difference in risk as a way to justify a difference in sample size.
>> Um does that kind of make sense?
>> Absolutely. Yes. With a avoiding these pitfalls. I know that you've talked about inheriting

00:08:31 validations from previous colleagues. Uh can you expand on that a little bit? Yeah, I think it's pretty common and I I would be shocked if if someone throughout their career in the medical device industry or otherwise doesn't experience, you know, just inheriting work that was performed by someone else. Now, you have to ask yourself, do I know why they did what they did? Can I

00:08:56 continue to do what they did? in in the context of, you know, if you're going to avoid pitfalls, let's make an assumption that maybe a previous colleague did fall into one of these pitfalls, right? Um, you don't want to repeat that.
>> So, I would just invite you to be curious if that's the way that something has always been done. Does it need to stay that way? If you are digging into

00:09:22 ISO 11607 uh yourself or 16775, be curious and ask yourself, is this actually meeting the requirements of these standards? If you've got a new product that you're considering how you're going to perform your sterile barrier validation, your package validation,
>> does your old approach serve you or is

00:09:43 there just a better way of doing it? And even if you're not inheriting a project, right, I would say it's it's just good practice to be thinking that way and to try and be doing things better each and every time you you have to go through these activities.
>> So, what about uh selecting a partner to work with you? How do you go about doing that?

00:10:07
>> You're trying to look for honesty and you're looking for integrity when you're selecting someone to work with, right? So if you're if you aren't performing some of these tests internally and you're looking externally to do them, be open and honest with them with what your needs are, what your product is. I think this kind of conversation is becoming the need to have adjustments to your

00:10:28 validation is facilitating these kinds of conversations even more where you're trying to understand is this is this person the right fit for me? Do they know the standard in and out? Right? Are are what they are recommending sound scientific advice or is it kind of more or less the same of of what you've always done? Right? So I would look for someone and and build a relationship

00:10:54 with them where you know that um whether it's new territory or old territory you know that the two of them uh you together can be united with with integrity and doing the right thing in the right way.
>> Uh so I know that you had uh talked about uh some of the the common pitfalls. What about worst case uh strategies when the sterilization is not

00:11:22 performed or challenges with with timing?
>> Yeah. So I'll start by just reminding what the standard says, right? So you need to perform your package validation on your worstcase packaging uh under worst case conditions. So part of those worst case conditions is worst case serialization. So, as an example, if you utilize EO sterilization, worst case

00:11:49 typically means that you're performing your validated EO cycle twice, a 2x cycle right?
>> If it's something like gamma or radiation sterilization, worst case is not at the validated sterilization dose, but at the maximum dose instead. I would say the common pitfall there right is either the sterilization is not performed at worst case it's just your

00:12:14 validated uh sterilization cycle
>> so that would be the pitfall where you're not compliant with ISO 11607 in that regard and I would say uh you had asked you know about the timing of it all I see more and more commonly people trying to do these validations in parallel sterilization and packaging.
>> The one risk that you know is is

00:12:43 acceptable risk if you deem it so when you do it in parallel as you're performing your sterilization validation if you need to change a parameter dwell time or dosage things like that that has now changed what your worst case sterilization configuration would be. So if you make some assump assumptions of I think that our sterilization validation is going to go down this path

00:13:11 and so you use that worst case for your package validation but oops something changed here now the worst case no longer applies so you have to go back and you have to redo your package validation. So that's that's wasted time that's wasted costs when it could have been prevented if if you did things a little more patiently, but there's there's absolutely reasons and

00:13:38 justification for why you would need to do those in parallel. I I just want to make sure that folks are aware of what the risk might be and and how if if you don't think about that ahead of time, you might accidentally fall into a gap without even realizing it.
>> So, uh how about only performing AA and not RT aging?
>> Yeah. So AA

00:14:05 stands for accelerated aging
>> and RT is real time aging. Uh there seems to just be a trend where folks are only performing accelerated aging. So accelerated aging is where you can you can accelerate the aging process, right? Because it's pretty common for these packages to have shelf lives of one year, two year, three year, five year. And so

00:14:33 when we're talking about real-time aging, we're talking about five actual years of aging. And no one wants to wait 5 years to go to market uh because you may have already been left in the dust at that point. So accelerated aging is an option for you to get accelerated results. But it's it's just becoming more common to only perform accelerated aging. Ah,

00:14:59
>> and I would just caution that the standard is still written that real-time aging is required. So, so don't leave real time aging lost and forgotten as part of your validation. Make sure you include it as part of your plan that you're setting up from the beginning so that you you have all the boxes checked in that regard.
>> Right. Uh so, what are some of the

00:15:22 challenges you foresee for the industry moving forward? Yeah, I mean I've kind of already touched on this a little bit where one of the challenges is that the innovation within the industry is requiring innovation within packaging as well. So, we're starting to get more and more package designs which don't fall into the I don't want to say old, but like

00:15:50 the the more heavily utilized path of validating, right? And so, it requires a lot more critical thinking. It requires uh justifying your approach to meet the requirements of the standard, which it it's potentially different than how it's been done before. So this is something where I would really recommend if you fall into that category and you have to be a bit of a maverick in your

00:16:20 validation approach. Uh wherever possible, take advantage of things like presubmission meetings and align with your regulatory body before you set out to go down this path. Because the worst thing that could happen is for you to say, "We've justified this ourselves. We think it'll work great, not get the buy in from your regulatory body, you charge forward on that path, and then when it

00:16:49 comes time to review, uh there's some disagreement with what should have been done. So, I think those presub meetings are going to be more common and they're definitely uh more valuable in the context of if you're starting to do things a little bit outside of the norm, take advantage of of of the time you can get with your regulatory body to to align in that regard.

00:17:13
>> So, sustainability is kind of a buzzword, but it it has some implications. What do you see for the industry moving forward in terms of sustainability?
>> Yeah, it's a buzzword, but I think it's a needed step towards um how we are stewards of what we have, right? So, the challenge that comes with sustainability with packaging. There are a few ways

00:17:41 that people are thinking about this, right? One way is potentially reusable
>> sterile barrier systems which requires a lot of innovation and like I had just mentioned you know it requires a lot of new thinking and new strategy with how you go about validating that that product
>> right
>> the other way of thinking about

00:18:06 sustainability uh I would mention two more things one potentially using recycled content for your sterile or for your sterile barrier rather than virgin materials. Um, which can be risky because there's not as much data out there as to how the recycled material performs. Um, so that could be challenging in terms of you you might not have access to the mountains of data

00:18:35 that your company might have, right? and and now you need to do more leg work to demonstrate what you're doing is sufficient.
>> And I I would just say that the maybe the final piece of sustainability I would talk about is reduction of materials.
>> So it's it's always if if the purpose of your packaging is to keep your product

00:18:58 sterile until it's used,
>> you can overengineer the heck out of your packaging, right? and make sure that that is going to be so protected. It's got so many layers, nothing is gonna is going to happen to that. But that also means a lot of potentially wasted layers where maybe you don't need two layers, you'd be fine with just one layer. Instead of using a thicker

00:19:26 plastic, now you've got a thinner plastic. So folks are starting to think about what's the risk of removing layers versus the cost of uh including too many layers. So you're always trying to find that balance. And I think as people are are more heavily considering the sustainability piece and reducing waste and they're trying to shed layers, they're trying to reduce material. Um

00:19:54 you're moving into that territory of potentially more risk,
>> right?
>> So I could see that as as being a challenge moving forward as we're trying to collect data about about those kinds of things.
>> Yeah. Wonderful. Logan, thank you for joining me today and especially for sharing your expertise with us.

00:20:14
>> Yeah, absolutely. This was great conversation.
>> I enjoyed being here with you.