Transport validation to different climate zones

[Wolf.K]

Hello!

I am not sure, that this is the right forum (13485...), but maybe you can give me some directions. I wonder what test protocol I should use to validate our medical devices for shipping to all countries around the world.

I found the information, that ICH has classified four (five) stability zones (I, II, III, IV, IVb=ASEAN). I also know how to test devices according to ISO 11607, ASTM 1980 F, ISO 483) but I still wonder what kind of tests I should perform.

E.g. ICH Q1R2A states "Accelerated ambient: 40°C ± 2°C/75% RH ± 5% RH for 6 months", but that is for medicines /APIs during registration applications.

Now I wonder, what to do with our medical devices. E.g. one product has following storage conditions: Room Temperature (5-25°C), relative humidity less than 60%.

What I want to test:
1. temperature excursions for 24 hours to 40°C.
2. temperature excurions for 24 hours to -20°C
3. 1 month at 40°C and 75% rH.

Do you think this is enough to be confident that the products can be shipped to any place on earth? How do you test your products? Are there standards I have overlooked?

Truly yours,
Wolf

 

[Mark Meer]

...Do you think this is enough to be confident that the products can be shipped to any place on earth? How do you test your products? Are there standards I have overlooked?...

As with many medical device-related questions, the answer always boils down to risk.

Have you assessed that there is some risk of product deterioration in shipping/storage? Any verification activities should be commensurate with risk.

So, if you've identified a particular hazardous situation that may arise from damage due to transport/storage, and think it could lead to serious harm, then perhaps following a standard is appropriate (albeit likely complicated and resource intensive). In most cases, however, where the risk is generally low, it's probably sufficient just to test the boundary conditions of whatever you've specced.

If you have access to an environment chamber, then great! Otherwise, if you have a calibrated measuring device handy, you can simulate these in freezers or ovens (you'd have to develop your own protocols). The third option is to contract a test-lab with necessary expertise & equipment to carry out the test for you.

Hope this helps somewhat...
MM

 

[Wolf.K]

Hi,


Yes, it helps. We will try to put up an environment chamber (I think we have everything we need for that, according to ISO 60068-3-5; this standard is not for medical devices but it was the only one I found defining environmental chambers). The problem I see is: what parameters should we test? E.g. one product is sterilized with EO in a Tyvek pouch. DuPont says, that these pouches are fine until a relative humidity of 60%. 60% is easily reached, even in my office we have often values higher than that. So, somewhere in South Asia it might be quite common. Therefore, the ICH climate zone requirements for APIs: 40°C and 75% rH. So probably I will start with 40°C and 75% rH in the self-built environmental chamber and will check for (1) sterility barrier properties after x weeks, and (2) send some items to our contract manufacturer to perform their final in process tests.



W.

 

[planB]

Wolf,

in lieu of specific procedures provided by other standards, ISTA procedures are typically used by medical-device manufacturers and are accepted worldwide by regulators to be a valid approach to simulate and demonstrate safe product distribution.

ISTA 2A is a typical and commonly used procedure.

HTH,

Gerhard

 

[Wolf.K]

Thanks for the hint!

ISTA 2A is for the packaging. For the transport validation, I wonder how often we have to ship samples to our destinations. The only reference I have found so far is for medicinal products:

<citation>
From QAS/14.598 Supplement 14

Transport route profiling qualification

Technical supplement to WHO Technical Report Series, No. 961, 2011

Annex 9: Model guidance for the storage and transport of time and temperature-sensitive pharmaceutical products

August 2014

The chosen sampling size should reflect the actual application and the practicality of collecting the data. In general, the more data that can be collected, the better, because this will give a more accurate picture of temperature hazards encountered in any given lane. A sample size of 30 trips on a given route over the course of a year is considered to be statistically valid. However such a large sample is not always practical and the decision to choose a smaller sample size for a specific lane is a matter of judgement(12).

(12)There are currently no recognized tools or references to help with this.
</citation>

We will ship our medical devices maybe four times a year to our distributors in Mexico, Brazil, Taiwan, China, Philippines, India, South Korea, Saudi Arabia, and so on. Altogether we have distributors in about 20 countries outside the European Union. 30x20=600 trips is quite expensive. ISTA 2A requires only one sample, but recommends at least 5 samples. But that is for stationary packaging testing, not for transportation validation.

I would like to do not ship hundreds of test samples around the world (field shipments, live shipments). I prefer to use a climate chamber and test our products for excursions to temperature and humidity in the range I expect during shipment to the different countries.

Anyone with experience with transport validations around here?

 

[Ronen E]

There are two parts to it:
1. Establishing the worst case scenario environmental profile(s), and
2. Simulating that profile to prove that the devices can survive it.
You might be able to do item 1 through a written analysis. I always try that first.
You should also consider that transport stresses encompass more than just temperature and humidity extremes.
Wetting, pressurisation and de-, radiation/light, vibration, shock, thermally-induced fatigue (thermal cycling) etc etc.
Send me a PM if you need further help.

 

[Wolf.K]

Our packaging was tested during design and development, so I think it will survive normal shipping stress. Our customers are instructed to not use product if the packaging was damaged/corrupted. Therefore I think simulating high temperature and high humidity might do the trick? Otherwise, a test according to ISTA 2A might be mandatory. For temperature and humidity: some thermal cycling (-20°C 2days/40°C 2 days), and some long term stress testing (e.g. 40°C/75% RH for ? weeks) might be ok. for the 40°C/75%RH scenario I wonder how long the testing period should be. For APIs it is 6/12 month (during accelerated aging studies), but that is not applicable. I have not found any reference yet giving directions for medical devices (normal room temperature).

 

[Ronen E]

Our customers are instructed to not use product if the packaging was damaged/corrupted. Therefore I think simulating high temperature and high humidity might do the trick?

A product can get damaged inside a packaging that looks intact.
Besides, failure modes during shipping and storage are not generic. Who said that it is high temperature or high humidity that are the highest risk factors? It's all about a careful engineering analysis.

Otherwise, a test according to ISTA 2A might be mandatory.

Why? What's the rationale?

some thermal cycling (-20°C 2days/40°C 2 days)

Is this representative of real-world worst-case? How? Thermal cycling is more about day/night cycles / season cycles / high-altitude cruising vs. ground level - it all depends on the actual profiles.

I have not found any reference yet giving directions for medical devices (normal room temperature).

There are none that you can trust, that I'm aware of. Canned methods will lead you to canned conclusions with questionable science-based validity. Nevertheless they might make your regulators happy.

 

[Wolf.K]

Nevertheless they might make your regulators happy.

That's the important part, I guess... One of our products is wrapped in a WIPAK Steriking bag and is sterilized using EtO. So we fear, that high temperature and high humidity might cause a breach in the sterilization barrier. So we want to test that in an environmental chamber. Currently I try to find out what protocol we should use, but I can only find recommendations for APIs and "developing temperature profiles for medicinal products in distribution" and else. As I already stated, I assume that the packaging was designed appropriate for "normal conditions" in Western Europe. ICH Q1x gives some advice for drug substance storage and distribution. There I got e.g. "Stability testing: accelerated @ 40°C/75% RH" for "recommended labeling statement: "Do not store above 25°C". We have shipped to Zone I and II (Moderate/Mediterranean) and encountered not problems. As we want to ship now to Zone III (hot/dry) and Zone IV (very hot/moist). WHO 2005 storage conditions: "30°C/65 or 75% RH". For plastic, there is e.g. SO 291:2008 for testing. US pharmacopeia 659 states "proveded the mean kinetic temperature does not exceed 25°C, transient spikes up to 40°C are permitted as long as they do not exceed 24 h."
So, if I take environmental data from the destinations of the products, and average conditions during transportation (by air) plus the average time it takes until our products reach our customers, I can calculate that our products will not be exposed to environmental conditions above 25°C and 60% RH for longer then x hours. If I test our products in a climate chamber for at least that period of time, and they still comply to the product specifications, that should work, right?

 

[planB]

Wolf,

pointing again to ISTA 2A, which is a recognised guidance document for medical devices and the environmental conditions given there:



I would recommend to use temperature and humidity ranges given there that are applicable to your distribution zones. Alternatively, you could also consult IEC 60721-2-1, and related parts for guidance on standardised environmental conditions.

Comment on sterilisation:
If you suspect a breached sterile barrier due to your sterilisation process, verify this first, prior to any transport simulation.

So, if I take environmental data from the destinations of the products, and average conditions during transportation (by air) plus the average time it takes until our products reach our customers, I can calculate that our products will not be exposed to environmental conditions above 25°C and 60% RH for longer then x hours. If I test our products in a climate chamber for at least that period of time, and they still comply to the product specifications, that should work, right?

Transport simulation should challenge your product in exposure to both environmental conditions and mechanical impact. So no, a test of products in a climatic chamber at static average temperature and humidity does not represent a valid approach for simulating distribution around the globe.

HTH,

Gerhard