Safe trip – standardising insulated shipping containers

Drugs are getting more complex and it's clear that the pharmaceutical industry has shifted its focus towards biologics in recent years. These 'emerging molecules' are no doubt exciting news for drug development, but they can also be highly sensitive, with the briefest of temperature excursions potentially rendering them unusable. In a global market, where drugs often have far to go, the cold chain must not be underestimated.

The International Safe Transit Association (ISTA) had the vision of developing the first international method for standardising performance measurements of insulated shipping containers (ISCs). This emerged as Standard 20 in 2007. With market forecasters at IMARC Group predicting explosive growth for cold chain logistics services, World Pharmaceutical Frontiers went along to quiz ISTA prior to the introduction of ISTA Standard 20 2.0, to find out what it's all about.

World Pharmaceutical Frontiers: How did The International Safe Transit Association (ISTA) come about?

Edward A Church: It started off as a committee as part of the Porcelain Enamel Institute back at the end of the Second World War. In the US, they made appliances out of porcelain and they had an immense amount of damage in shipment, mostly by rail. So they formed a committee to stop the damage. What they came up with was a testing standard. As you're designing a package, before you start shipping it and have high damage levels, you create some testing to validate the packaging design.

That's what they did, and it's been around ever since. And 20 years ago, we really got to a higher technology level by trying to simulate the distribution environment. People were just beginning to understand in much more detail what goes on in delivery, as far as shock, vibration and compression go. So we had a concerted effort to really increase the number and capability of our testing standards. In recent years, the pharmaceutical industry has approached those of us in the realm of the cold chain and convinced us to get involved in the temperature side of things too.

What are the biggest challenges when shipping temperature-sensitive drugs?

Brian Wallin: It's about actually understanding the performance of an insulated shipper. There are so many companies claiming that their shippers can hold a required temperature for all these longer and longer durations. It becomes hard to understand if that claim is true or not. So, what's important is to have a robust and accurate testing approach, and that's what Standard 20 brings. To understand that the ship will actually perform in the field as it will in the lab, you've got to be able to ask yourself the question: 'can you really trust the data that comes out?'. Tested to Standard 20, you can. It tries to level the playing field for everyone.

EC: What initiated Standard 20 was that the users realised these were the problems that were out there. Brian and others were working on processes for developing ISCs. The work of industry experts developed Standard 20 as a process standard. So it was really the industry itself recognizing the need.

Could you talk us through ISTA 7E?

EC: 7E is a profile we developed for two-day parcel shipment. Before that, there was no standard profile to test against. All the different insulated kits, either the users had a profile they were talking about or the suppliers had a profile they developed against, but there was no standard developed by an independent third party and so we wanted at least to understand the two-day parcel delivery environment. And so we did a very extensive study of that environment.

BW: It was a very collaborative effort. The Parenteral Drug Association's cold chain discussion group had a protocol ready. The steering committee for the discussion group all signed off on the protocol. And then, using that protocol, data was gathered all over the US to understand the ambient shipping environment that drugs are exposed to during transit. 7E is the first thermal profile that is backed up by data. Standard 20 is the process of how you test an ISC. 7E is the thermal profile you expose the ISC to during testing.

What obstacles arose when companies starting adopting Standard 20?

BW: I can tell you from experience that we've always had a rule of thumb that no processes or procedures are really any good until you hit revision four or five. So we launched this in 2007 and it was revision 1.0. I knew from day one that we were nowhere close to being done. So here we are, revision 2.0 and if my rule of thumb still applies, there are another two or three revisions to go until this is really dialled in. This is why it's important for people to come and join us, because we're not closed-minded, thinking that we've got it all fixed. There are going to be more revisions in the future. There always will be.

EC: Flexibility with the development process was a concern. We have met some resistance in Europe as far as the 7E profile, in whether or not it's representative of Europe, and that's one of the reasons the next phases we're going into now, with revision 2.0 coming out, is to look at air and other profiles. And we want to do a study within Asia-Pacific and another within Europe to give us an idea of whether it matches or not - and if it doesn't, we'll have to do a bigger study to make a final determination, and we'll look at other profiles. 7E is parcel delivery today. And so there are other channels that can be potentially developed for people. How different is strictly an overnight profile, those kinds of things.

There's some concern about China and the parcel system delivery availability there. And I think the other thing is that some of the supplier elements just wanted to wait and see what impact it had on them. So a lot of people just sat in the shadows waiting to see how much traction Standard 20 was getting. By waiting, I think that did slow us down a bit. However, with version 2.0 we've got more suppliers active in the development of it.

What advantages will Standard 20 2.0 provide for the pharmaceutical industry?

BW: I think it's important when talking about the changes we made, to consider the changes we didn't make. Standard 20 is focused on regulatory compliance for the end user. That was a change we were not willing to make. Standard 20 still incorporates the principles of quality by design. So those foundational principles were not touched at all. The process stayed the same, but depending on whether you're a manufacturer, supplier or end user, we made some of the steps of the process optional.

For instance, the verification shipment at the end of the process doesn't make a lot of sense for suppliers. It makes much more sense for the end user of the ISC to use it, if they're going to expect a Standard-20-tested shipper. So we more clearly defined what were optional steps, what were required steps and who should be doing each step of the process.

Another big change we made was on all the minimum requirements to meet Standard 20, we put references to the guidance documents that are out there. Every single requirement now points to a guidance document, or a reason why it's there, so that the end users have an understanding of what they're doing and why they're doing it. We made a lot of format changes to make the whole standard easier to read, easier to follow, with fewer forms to fill out. We just streamlined the entire process from top to bottom.

I believe 80-90% of the document changes were all end-user requests. So it was the user feedback that triggered a lot of the changes. If you get on the Standard-20 bandwagon and you find something that doesn't work, let us know and, when the revision comes around, we'll incorporate the changes that make sense. I want everybody to come and join in. It's a Standard 20 party here - and everyone's invited.

What's your vision for the future of temperature-sensitive shipping?

EC: I think one of the things that we're still striving for, which was the original purpose of all of this, is to ease the workload of pharmaceutical companies trying to develop and instigate new ISCs, by being able to buy a product that has been developed according the best practice and industry standard process. It relieves them of a lot of the work they would have to do in the development of an ISC. So, up front, they can get to market faster. It also provides them with a data set from the vendor that can meet regulatory requirements.

BW: I would add that we aimed not only to ease the workload of the pharmaceutical manufacturer, but also the workload of the insulated shipper suppliers. Because a lot of the insulated shipper suppliers test and qualify the same shipper five times for five different companies and that just doesn't make a lot of sense. If everyone's working to the same standard, maybe we can reduce the amount of engineering and the amount of qualification that goes into the same shipper over and over. And shipper suppliers can then use the engineering time that gets freed up to develop new and better products.