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Pharmaceutical Manufacturing and Packing Sourcer

A Tragic Tale?

Dry ice is experiencing a drop in popularity in the pharmaceutical cargo sector for a variety of reasons, so much so that we may be at risk of seeing another species go completely extinct

History is chock full of documented cases of a species that, for one reason or another, has gone the way of the dodo. Even if you aren’t a student of history, you probably recall that the dodo was a flightless bird native to the Indian Ocean island of Mauritius. By the mid to late 17th century, the dodo was toast. While most historical accounts would seem to indicate that the dodo was doomed, its ultimate demise is frequently used as the classic example of an extinct species because its extinction occurred during recorded human history.

There is any number of other species, animate and inanimate, that for one reason or another didn’t make the evolutionary cut. However, those with a vested interest in the cold chain could possibly be witness to one of its long time staples succumbing to a technological, regulatory and environmental executioner.

Dry Ice: The Back Story

Dry ice, the solid form of carbon dioxide, was first observed by French chemist Charles Thilorier. Thilorier is credited with publishing the first account of our frosty friend in 1834. In his experiments, he noted that, when opening the lid of a large cylinder containing liquid carbon dioxide, most of the liquid quickly evaporated. This left only solid dry ice in the container.

Fast forward to 1924 when Thomas B Slate applied for a US patent to sell dry ice commercially. Subsequently, he became the first to recognise the opportunity to create a successful industry out of the Thilorier’s observations. In 1925, this solid form of carbon dioxide was trademarked by the DryIce Corporation of America as ‘Dry Ice’, thus leading to its common name. That same year Slate’s company sold the substance commercially for the first time, marketing it for refrigeration purposes. Thus, the cold chain was born.

Up until recently, dry ice was relied upon as the predominate method used to provide temperature management for everything from healthcare products to frozen fish. In addition to the practical uses for dry ice, I’d be remiss if I didn’t mention its use as a source of amusement for adolescent school children, spooky Halloween displays and grandiose stage effects at rock concerts.

According to Wikipedia, it’s not hard to make dry ice. First, gases with a high concentration of carbon dioxide are produced. Such gases can be a byproduct of another process, such as producing ammonia from nitrogen and natural gas. Second, the carbon dioxiderich gas is pressurised and refrigerated until it liquifies. Next, the pressure is reduced. When this transpires, some liquid carbon dioxide vaporises, causing a rapid lowering of temperature of the remaining liquid. As a result, the extreme cold causes the liquid to solidify into a snow-like consistency. Finally, solid carbon dioxide is compressed into either small pellets or larger blocks of dry ice.

Cold chain knowledge has made significant advances since Slate made our collective world much colder. Today’s healthcare products have forced transportation temperature management processes to undergo massive changes. Product formulations and their ingredients mandate the use of specific temperature ranges that can never be achieved by simply tossing some dry ice in a box and hoping for the best.

If someone would come up with a thermal medicine cabinet, they’d make a fortune. Most temperaturesensitive healthcare products end up in the patient’s medicine cabinet – the hottest, most humid location this side of Miami. Regardless, manufacturers, transportation providers and distributors have a moral, and in most cases, a regulatory responsibility to help insure the product arrives to the end-user intact. Protection of product efficacy demands use of the latest technology available. People’s lives depend on it.

Increased regulatory scrutiny by government entities around the world dictates that greater attention is paid to the temperature conditions during all phases of the supply chain. Highly visible groups such as the World Health Organization and Parenteral Drug Association as well as numerous local, state and national organisations are leading the charge to raise awareness of the implications of poor cold chain management practices. From a pragmatic perspective, one can assume with a great degree of certainty that government involvement in the supply chain will continue to drive many elements related to safe transport of temperature-sensitive products.

Airlines’ Love-Hate Relationship with Dry Ice

One of the problems with dry ice is that it’s classified as dangerous goods (DG) by the airlines. This means additional paperwork, increased handling times, and, of course, increased cost. What’s more, any airline employees or their contract handlers who work with any type of DG must meet considerable training requirements before being authorised to touch any commodity or temperature management materials falling into the DG category. As a result, there are airlines all over the planet who won’t even allow DG onboard because it’s simply too much trouble when measured against the revenue it generates.

To make matters more difficult, airlines can be restricted in the total weight of dry ice allowed on a single aircraft and the maximum weights allowed vary by carrier and aircraft type. Recently, some carriers in the industry have been witness to significant reductions in aircraft dry ice weight limitations due not only to the associated DG problems, but for such seemingly obscure reasoning as concerns over carbon dioxide entering onboard crew rest quarters.

In the grand history of transporting temperature-sensitive commodities by air, dry ice had at one time offered stateof- the-art cooling capabilities when used in conjunction with specialised transport containers or unit load devices (ULDs) (for the uninitiated, ULDs are those big aluminium boxes that you see moving around the airport while you are wishing you were in first class instead of sitting in the back of the aircraft). These specialised ULDs were the first supercharged version of a standard ULD and utilised dry ice, basic insulation, along with replaceable batteries, fans and thermostats to maintain the selected temperature, albeit when transport conditions cooperated.

There are several drawbacks to the use of dry ice-based ULDs. Most importantly, their temperature management capabilities are directly tied to ambient conditions and the ULD set point required of the cargo. Typically, ambient conditions for proper operation of a dry ice-based ULD need to be a minimum of 5°C above the set point. So for a 2° to 8°C shipment with a ULD set point of 5°C, the ambient conditions need to be at a minimum of +10°C for proper operation. In addition, the containers had a maximum operating range of about +30°C above the set point. Obviously, Moscow in the dead of winter or Dubai in the peak of summer offered up real problems. While some airport facilities and carriers have developed specialised handling chambers, the vast majority have not invested in such equipment. The return on investment typically doesn’t warrant the expense.

Ambient conditions and set point temperatures also directly impact the duration of air circulation fan operation and thus, battery life. The circulation fans are what move the cold air into the cargo hold of the ULD. One of the biggest complaints I’ve heard from air cargo operational staff that are charged with monitoring ULDs in transport is that they have to constantly change 16 D-cell batteries on each ULD they monitor due to the power drain of the fans. Since alkaline batteries are mandated for use due to their ability to last longer during high fan use, replacement costs in transit can be quite expensive.

Ambient temperature conditions must be considered not only in the air cargo warehouses, but also on the ramp. Airport ramps are typically the hottest place at the airport and they can run to 7°C or above ambient temperature. Even with expedited transfers of the ULDs from the warehouse to the aircraft, it’s not unusual to have the ULD arrive on the ramp from 45 minutes up to two hours prior to loading. This can be a real problem at this point in the handling process. Depending on the carrier and its capabilities, as well as union and contract handler limitations, the ramp can offer the least amount of shipment visibility.

With the proliferation of biologics and bio-similar products that require reliable transport temperatures between 10° and 25°C under all ambient conditions, dry ice-based ULDs simply are not sufficient. Product lead times for today’s advanced formulations can be many months long, not to mention the extremely high value of the finished products. There isn’t a manufacturer on the planet that is willing to take a chance on using a solution that isn’t going to provide complete assurance of the cargo arriving intact. Having invested too much time and money in the face of regulatory scrutiny, healthcare product manufacturers will not allow antiquated technology to be used during the transport process.

As a further complication, in today’s global air traffic world it’s not uncommon to transport temperature-sensitive commodities across hemispheres. While the current dry ice-based solution offered the opportunity to maintain frozen temperatures and 2 to 8°C temperatures in highly restricted ambient conditions, it certainly was not designed to manage to today’s demanding temperature ranges and transport routings.

‘There’s Gold in Them Thar Hills!’

Transporting temperature-sensitive goods by air has become a science in its own right. Airline cargo product managers and process developers, as well as those involved in creating a new generation of temperature controlled ULDs, have learned what it takes to manage to very specific temperature ranges. Advanced materials, techniques and know-how gained from years of experience are helping to drive airline cold chain advancement. The everpresent quest for higher per-kilo air cargo yields should not be lost in this exercise. Air carriers recognise that the per-kilo yield opportunities inherent in the movement of temperaturesensitive products are far superior to that seen with general cargo. And in today’s air cargo business, yield is king.

A few short years ago there were no more than five airlines in the world with some level of structured cold chain services. Today there are no fewer than 25, with even more airlines working to develop products and services designed to meet the burgeoning demand. Integrators such as DHL, FedEx and UPS have created entire vertical divisions dedicated to the transportation and handling of temperature-sensitive healthcare products.

Freight forwarders and other transport providers are not inclined to miss out on such a grand opportunity, either. Most have seen what’s transpiring in the marketplace and, as such, have created structured products and services designed to assist with the movement of temperature sensitive goods in their respective areas of expertise.

A New Generation of ULDs?

In today’s world of airline temperature management, the gold standard is fast becoming the compressor-based ULD. ULDs of this variant use compressors for cooling and heat strips for heating in order to manage transport temperatures to the product’s specific parameters. These have the ability to operate across a considerably wider ambient temperature range, not to mention the opportunity to avoid some of the pitfalls and challenges inherent in the use of dry ice.

One temperature-controlled ULD manufacturer has created a system that can maintain temperatures at a user selectable set point between +4° to +25°C. This ULD can operate independently in ambient conditions of -20°C to +49°C, within +/- 2°C from the set point for up to 100 hours. This ULD is so well insulated that it can maintain a 4°C internal temperature for eight hours at +43°C ambient without any power whatsoever. Convenience of operation is also a key factor with this ULD. Being able to plug into any voltage globally utilising onboard, rechargeable batteries is a big plus. Eliminating the need for expensive and frequent alkaline battery replacements that we used with dry ice-based ULDs can be a real cost saver.

While the current ULD sizes that are available lend themselves to larger aircraft, there are smaller versions of compressor-based ULDs that are emerging. As this alternative becomes available, routing options on smaller aircraft will increase and shippers of clinical trials materials, vaccines and other smaller volume shipments will reap the benefit offered by compressorbased solutions.

Dry Ice Moves Towards the Gallows

In some countries, dry ice can be difficult to obtain, and when it is available it is usually found in the pelletised form, which evaporates faster due to its greater surface areas when compared to sliced dry ice. Usually, dry ice providers don’t operate on weekends, leaving an airline’s duty manager scrambling to locate an emergency supply. Plus, there are many countries in the world that restrict or forbid access to a ULD while the container is in customs. In these cases, reliable systems are critical to insure product efficacy.

Another recent development in the dry ice debate that could be the most damaging to the technology comes in the form of concerns from some quarters of the scientific, environmental and political communities, who conclude that any additional dispelling of carbon dioxide into the atmosphere is not good for the planet. Whether you subscribe to the same philosophy or not, I think it reasonable to assume that if there is a better technology out there that will accomplish the desired temperature management goals, it’s probably best to let sleeping dodos lie.

Phase change materials used in conjunction with highly advanced insulating materials are increasing in popularity for some shipments, although the true cost of use is rarely calculated. It takes many man hours to assemble the pack-out, not to mention the refrigeration equipment and electricity costs required to condition the phase change materials. When you start adding the costs for packaging storage, repositioning or single-use disposal, this alternative becomes considerably less attractive.

All is Not Lost for Dry Ice…Yet

Even as technological advancements in cold chain transportation solutions have further pushed dry ice to the lower rungs of the sustainability ladder, there may yet be some life left for the inanimate, distant cousin of the dodo. Frozen temperatures are currently the only range not covered by compressor-based ULD solutions. This may offer one saving grace that will temporarily delay the inevitable end of dry ice. Other than a handful of smallvolume speciality solutions, dry ice utilised in old-school ULDs remains the most cost effective way to transport large volumes of frozen product. What’s more, low value, non-healthcare commodities typically do not have the profit margins required to support use of the new generation of temperature management solutions. Temperature management needs in underdeveloped regions of the planet may also serve to prolong the longevity of dry ice, although outside regulatory, taxation and environmental interference will likely become a driving factor that forces change in these areas.

While all is not yet lost for the scientific discovery and marketing efforts of Thilorier and Slate respectively, it’s only a matter of time before history chalks up another man-made extinction. And in this case, it may be appropriate to bid au revoir to an old friend.


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Mark Mohr joined CSafe LLC in July 2011 as Director of Partner Management. Mark has over 30 years of experience in sales, business development, marketing and process management, and extensive experience in the air cargo business. Prior to joining CSafe, he spent fi ve years in a leadership role developing and expanding Continental’s cold chain programme. He was account director for United Airlines Cargo’s general sales agent (GSA) operation in the US, and before that held various sales and operational positions at DHL Worldwide Express. Mark serves on the International Air Transport Association’s Time and Temperature Task Force, charged with enhancing and expanding airline regulations related to proper handling of temperature-controlled healthcare shipments. Email: mmohr@csafellc.com
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