Ask the Expert: Proactive Measures to Address Drug Recalls

Ask the Expert Video Series

Welcome to the Ask the Expert video series. This series is an extension of the PharmTech Group’s long-running print column in which industry experts answer common quality and regulatory questions from the industry. Have a question you would like answered? Send it to PTProjects@mmhgroup.com, and it may appear in a future episode or print column.

In this episode of Ask the Expert, Susan J. Schniepp, distinguished fellow at Regulatory Compliance Associates, a Nelson Labs Company, and Siegfried Schmitt, PhD, vice president, Technical at Parexel, discussed the recurring problem of product recalls and the proactive measures companies can take to prevent them. Schniepp and Schmitt identify microbial contamination, mislabeling, and physical contaminants like glass particulates as primary drivers of high-level recalls. Despite established quality systems, failures still occur due to systemic vulnerabilities such as reliance on subcontractors, production time constraints, and human error.

Discovery of these issues often occurs "in the field" when patients or doctors report adverse effects to the Adverse Drug Reporting Center. While the FDA usually does not mandate a recall, a company should respond to a high volume of complaints by initiating a voluntary recall to prevent patient harm. Microbial contamination is highlighted as a particularly challenging area because sterility assurance is a matter of probability rather than absolute testing. To combat this, companies should implement a comprehensive contamination control strategy that synthesizes data from environmental monitoring, gown swabs, and water systems.

Schniepp and Schmitt also address the serious risk of product mislabeling, which can lead to patients receiving the wrong dosage or drug. Such errors frequently occur before labeling even begins, such as vials are transported on carts with handwritten, temporary labels that are prone to human error. Because these vials look identical before labeling, a simple human mistake in marking a cart can lead to the wrong product being labeled correctly. To mitigate these risks, the quality unit should not remain isolated but should instead walk the shop floor to identify vulnerabilities that operations teams might overlook due to routine.

Prevention requires more than just possessing standard operating procedures. Companies must regularly test their recall procedures to ensure they can track and retrieve products across complex, global supply chains. Ultimately, the best defense against a recall is a "finely balanced" and well-understood quality system that incorporates International Council for Harmonisation Q10 risk management principles and maintains integrated controls across all manufacturing stages to provide total oversight.

About the experts

Susan J. Schniepp is distinguished fellow at Regulatory Compliance Associates and a member of PharmTech’s Editorial Advisory Board.

Siegfried Schmitt, PhD, is vice president, Technical at Parexel and a member of PharmTech’s Editorial Advisory Board.

Transcript

Editor's note: This transcript is a lightly edited rendering of the original audio/video content. It may contain errors, informal language, or omissions as spoken in the original recording.

Welcome to the Ask the Expert video series. This series is an extension of the PharmTech Group's long-running print column in which industry experts answer common quality and regulatory questions from the industry.

This new video series will expand on topic areas to include development and manufacturing concerns to help those working in the industry better understand biopharmaceutical requirements.

We hope you enjoy the discussion.

Well, hello, everyone.

It's, the next episode of Ask the Expert.

I'm Sue Schniepp, and I'm with Nelson Labs', Regulatory Compliance Associates. And I'm joined by my colleague, Siegfried Schmitt, as always, with Parexel.

And Siegfried, you have a question from an audience member or a follower of ours. So, let's go to it.

Thank you, Sue.

Yes.

Hello, everyone.

And indeed, the question that came in here is, "I see on the FDA website that a variety of recalls occur, and these occur quite often. What can we, in our company, do to prevent having a product recall?"

Sue, do you want to start it off?

Well, you know, that's interesting. It depends on, you know, what the product's being recalled for, and there's levels of recall, right? There's high, you know, level one, level two, level three.

So, let's talk about the serious ones. And a lot of those, from what I see, are, some microbial contamination, mislabeling, and, you know, how there were some glass particulates, in a couple of the products that I looked at. So that is the role of the company then is to find out what's causing those.

How you prevent them, that's another story.

It's, you know, how did they get there drives how you prevent recalls? What are the reasons for these recalls?

What we don't see from there is, of course, what the root causes, for these issues are.

Now, we see, as you said, Sue, there are some that are particulates in there, sterility, and mislabeling.

Now, all these activities are, of course, covered by the quality system.

There are activities, actions, controls in place, be it through testing, be it through, second

person reviews, et cetera, et cetera.

And so still, despite all these activities, we find we have recalls necessary because something's mislabeled.

And we then therefore have to ask ourselves, how can these issues happen despite all these safeguards?

And of course, from our experience in industry, we can say there are many, opportunities that things can go wrong, not least when you do not do things in-house, when you have a lot of subcontractors helping you because you rely on something that is not under your complete control.

Or if you do things in-house, it could be also time constraints. You go rushed through the production, through the release, whatever.

But perhaps we should also look at who actually identifies these issues, who recognize these issues.

So perhaps, Sue, you could say a few words about that.

Who are the ones who make the discovery? Well, that's interesting.

Oftentimes it comes from the field, and you'll get, reports from adverse effects, of patients who have been given the medication, or, in the case of like eye drops, somebody, using eye drops, there were a few, listings of microbial contamination in eye drops.

They'll go to their doctor and complain about their vision and not getting better because the eye drop is contaminated.

So that goes through the Adverse Drug Reporting Center, and usually there's a a tipping point.

You get so many complaints, and those are given to the company who's manufactured the product.

Then they get so many complaints. It, it's interesting in the US, the FDA cannot tell you to recall something. It's voluntary, but they can strongly recommend it.

But when you get so many complaints, then you're obligated to recall because obviously there's something wrong with your product.

Now if we focus a little bit on the microbial because that's the one that is the hardest to pinpoint, right?

And there could be a number of reasons, why, why you're going to get microbial contamination.

And it spans, you know, from medicated hair shampoo, to eye drops, to nasal sprays to injectables.

You can get that microbial contamination.

Is it your cleaning validation?

You know, right, Siegfried?

There's a lot of avenues to go down, and each are important.

So, let's kind of pick apart that yes, you're right. And we have to, of course, also see that sterility assurance is a probability.

You cannot test a hundred percent. You have a probability that things are sterile, And, therefore, there is a higher risk there that you may have contaminated product somewhere. It may not be how you sterilize. It may also, as you say, how you clean, how you sample.

Is your sample even representative of what you're doing in the plant?

So, there are various, root causes that we can think of, and it may take some time to find these root causes.

And something you already mentioned is there are different, seriousness, levels about these, product issues.

Of course, if it's the wrong product label, we don't even know what the product is because it's the wrong label. If it's non-sterile, we may not be able to see it, but we may, suddenly have side effects from it, and so on.

So, it's not always obvious to the patient or to the medical practitioner what exactly is happening here or not. So, sometimes it may be sufficient to provide extra information if it's not a very serious issue.

So, you simply tell the patients who are using your product, maybe they need to avoid using it with a particular liquid, such as milk or so, or maybe they just need to be clear, it is not for, let's say, pregnant women or something like that.

But if it is more serious, then yes, the recall itself means you have to bring it back from the market, and you have to bring it back from the market whether you know the root cause or not, because it causes harm to patients.

That, that means, you will have to try and find each and every piece of product that is out there that has to come back.

And that is something that is not trivial because as we know, supply chains these days are often global.

So, how you recall a product that is on a lorry somewhere in Tajikistan or whoever knows where else, is not trivial.

So, that means you need to be prepared for these things. So, it's not just suddenly being in the situation, oh, we need to do a recall.

Oh, yes, we have an SOP. But have you tested it?

So I think so. You can say things to are you being prepared or not?

It's kind of like car insurance. You have it, but you don't really want to use

It. So yeah, but you do have to test, not your car insurance, you do have to test your recall procedure to make sure that you can account for all the vials out there.

You struck a chord with me when you said the mislabeling because that too is a very serious, recall, and the potential there is for the patient to get the wrong dosage or the wrong drug completely.

And that's, another one, it's hard, you know.

How did that happen?

There's a lot of electronic systems, and I think people are starting to employ AI in their label reading, capabilities, right?

It's no longer the human eye.

Not that the, the human would make mistakes, but how do we prevent that from happening?

I was actually surprised that there were labeling, issue recalls, and it was for dosage strengths.

Well, I have to say I'm not so surprised about this because it is not, in my experience, the activity of fixing the label. It is before that.

What you have is you have the naked vials, the naked ampoules, whatever it is, and they come to the area where all the labeling and packaging occurs.

And you can't distinguish one vial from another.

They all look the same, and they are on carts, and the carts should be properly labeled.

And what happens is these carts aren't labeled permanently because they're reused for

different products, and someone writes in handwriting on there what it is on this cart.

You make an error as a human being, and there you go.

You got the right label but the wrong product.

And because at this point you have already taken your samples and tested and whatever, and you no longer repeat these tests.

So, there is a possibility that it slips through, and suddenly you got the wrong label on the correct vial or the other way around.

Failure of your quality system to catch these kinds of errors. Somewhere you have a vulnerability, kind of like with, you know, data integrity. You look for those areas where you can drive that behavior of poor data, governance.

So, is it the same on the manufacturing line?

Seems to me you have to look for those areas where, at least in the case of the labeling,

where you can have the potential for that kind of crossover mislabeling to happen, and then kind of take the efforts to prevent it. You put some controls in there that prevent that from happening.

I don't know.

You know, it's kind of like that workflow diagram you have to do and say, "Here's my vulnerability." Is that kind of where we're headed with that?

Well, I take exactly what you said now, as one of the things to. Because the question was, how can we prevent these recalls?

Prevention is, you know your processes, so you do have process flows. Not only that, your quality team should be on the shop floor, walk these processes, see where the vulnerabilities are, because the operations team often becomes blind to their environment.

So, really, there is the role of the quality unit to understand, are there any risks somewhere that need strengthened controls or additional controls?

And that typically is the best way to prevent having to recall anything anytime.

Would you agree, Sue?

I agree.

I wanna double back to, the microbial contamination, 'cause to me, that one's also a huge area where you can have gaps that you don't even know.

And it also boils back to your ICH Q10 principles and the risk management, right, type. because, it, we had that, Annex 1 came out, right? Contamination Control Strategy.

And to me, when you have a microbial recall, it's because you don't have that contamination control strategy in place, right? That's the one that makes the environmental monitoring talk to, you know, the, gown swabs, talk to the water system, results.

Would you agree?

Absolutely.

It's not one element.

It's the various elements that come together that assure compliance that provide the control in the totality.

And if this isn't a finely balanced and well-understood system, then there can be these gaps that cause these issues, these risks to the patients.

Anything else you wanna say on recalls?

I don't think so. No. Just, hope it's not you who has to recall something. And the best way is to have a very good quality system in place that is well understood.

Agreed.

Thanks, Siegfried. Good to see you.

Thank you, Sue. Bye.

Bye.

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