Packages can experience delays when initially surrendered to the distribution system awaiting pick-up, or at numerous points along the way: at customs, freight forwarders, after-hour deliveries, etc. Well intentioned individuals may see "refrigerate upon arrival" labels on the packages and immediately place them into refrigerated storage. At first blush, this may seem a harmless, even helpful practice. But it can result in disaster for temperature sensitive products where no excursions in temperature are allowed beyond their narrow range.

Unraveling the Myth

Temperature controlled packaging design and performance is characterized by regulating the rate of heat transfer throughout the package. This is acheived by taking advantage of the Latent Heat of Fusion of the gel packs - the energy absorbed in the form of heat that results in a cooling of the surroundings. There is a finite amount of energy the gel packs will abosorb as they melt, or release as they freeze. Thermal packaging attempts to control that energy in a way that maintains the desired temperature of the payload within the package.

You need enough 'gas in your tank' to get you to your destination. The performance and longevity of a hermetically sealed insulated package that contains refrigerant designed to maintain its contents within a specific temperature range, is dependent upon 6 inter-related input factors:

1. The type of insulating material used and its resistance to heat flow (R value)
2. The quantity and the phase change temperature of the refrigerant
3. The temperature to which the refrigerant, product and packaging are pre-conditioned
4. The ratio of refrigerant to product size and mass (and to a lesser extent its geometry)
5. The packing configuration
6. The environment to which the package is exposed (ambient temperature)

Heat moves to cold. Fluctuations in ambient temperature, a normal condition in the transportation environment, will affect the rate of heat transfer. The higher the ambient temperature, the faster the rate of heat transfer, which will decrease the longevity of the package at its specified internal temperature range. Conversely, the lower the ambient temperature, the slower the rate of heat transfer.

Since a certain amount of heat is estimated to enter the package under normal conditions, interfering with or inhibiting that process will cause the package to function improperly.

If excessive temperature (either heat or cold) is applied to a package too quickly, or for extended durations, its ability to maintain the internal contents within a specified temperature range may be exceeded, the extent of which is dependent upon the 6 input factors above.

When a package design includes product and refrigerant all pre-conditioned to 2°-8°C, and it is exposed to a refrigerated environment (2°-8°C) then the package and all of its contents will eventually reach temperature equilibrium.

However, when the package requires frozen gel packs to help maintain its contents at 2°-8°C, exposure to refrigerated temperatures will eventually cause the internal contents to fall below 2°C, to the phase change temperature of the frozen gel packs, typically at or near 0°C. This occurs as the heat transfer from externally applied temperatures slows, and the frozen gel packs, striving to maintain their phase change temperature of 0°C, begin to pull the heat from its surrounding internal contents, including any refrigerated gel packs in the package and, most importantly, the product. 

The PDA-PCCDG working meeting came to a close in San Diego this afternoon but not without turning on the afterburners. Typically, these meetings can get bogged down in debate but committee chairman, Dr. Rafik Bishara, runs a tight ship and kept everyone on task and on time.

Rafik announced that discussions with Hugo Wegewijs, chairman of the European C3 committee have resulted in an agreement between the two organizations to form a mind meld and and will work to unite their efforts and unify their documents - pending approval from the EU board. This is the first step in fulfilling a goal of the PCCDG - to involve other countries and regions of the world to participate in a common goal - good cold-chain distribution practices. Makes sense, as phamaceutical manufacturing and finished goods distribution has become a global process. By the way, the C3 website, for those of you looking for it is: C3info.org not C3 as stated here yesterday.

Excellent case studies were presented again today. As a veteran of many cold-chain conferences as both an attendee and presenter, I can honestly say that the technical reports at this session were far more in-depth, applicable, informative, and practical than any I have seen in recent years. I attribute this to the having a very focused group with no distractions or concurrent presentations, and a real willingness to share sensitive information. The latter results from the the PCCDG's legendary non-threatening, non-competitive environment and willingness to share. This is key to the groups' success and activities. And you can't beat the admission price!

FedEx Custom Critical presented results on their trailer mapping program and outlined their extensive quality systems. Envirotainer detailed the painful process of designing, developing and obtaining airline approval for their now active heating/cooling cargo container. And McKesson desribed their unique challenges in maintaining the cold-chain as stewards of pharmaceutical goods received from the manufacturers through to the pharmacies.

The morning concluded with a spirited discussion on the process for selecting a steering committee for the new organization, yet to adopt a new monikor. Somehow I feel that will be addressed long before an identity crisis sets in. Rafik stepped in and suggested that anyone interested in volunteering for such a position should write their intent on the back of their business card and literally "throw their name in the jar."

The  three breakout sessions that consumed most of the afternoon were: trailer mapping, ambient temperature / profile development, and temperature monitoring devices. Concensus was reached within each group as to what should be addressed, based on priority. Group leaders were identified and deliverables and target dates recorded.

 Rafik indicated that he would consider all those who volunteered for the steering committee and let the group know what his selections will be in a few weeks time.

The intellectually stimulating two days of discussions concluded with a call for a volunteer organization to host the next meeting.

Comments encouraged.

Interesting to see such a diversity of attendees. Most of the usual suspects from Pharma and Biotech are here and participating. The invitation for this particular meeting was extended to partners in cold-chain and they have been actively supporting the cause as well. This is the largest turn-out since the PCCDG was formed some 5 years ago. It feels good to be gaining momentum and receiving recognition for our efforts throughout the industry. It's inevitable then, that these growing pains have forced the group to undertake the process of selecting a "cross-industry"steering committee to oversee the various sub groups that will soon be formed to carry out its vision and mission. The sub groups will have to develop and deliver on proposals to help standardize a laundry list of cold-chain guidance, including testing methodologies, transportation and logistics procedures. As an active member of this organization from the beginning, I have seen a number of eager, well-intentioned volunteers start strong out of the gate only to fade in the homestretchl, due to added workload, added responsibilities and job changes. I hope those who step up realize the time commitment that is required.

The famously fair-haired, and fair-minded director of the PDA-PCCDG, Dr. Rafik Bishara, announced at the top of the meeting of 2 PDA  sponsored events in the coming months. The first is a webinar to be held on February 14th, 2006, "The Role of TR39 In Navigating Today's Cold-Cahin Regulatory Climate". The second is the first PDA Technical Conference on Cold-Chain. That will be held at PDA's offices in Bethesda, MD on March 27-28. Consult the PDA website for more details.

Hugo Weis, (sp?) from the European Cold-Chain Committee C3 is in attendance and has provided valuable input from the European perspective. It appears that the US PCCDG and the EU C3 are, at last, on the verge of a merge - harmonization on their resspective cold-chain guidance documents. More on that tomorrow.

There were a few case study presentations made today, with the one's revolving around trailer mapping and validation garnering lively discussion and debate. Agreement on how to effectively qualify refrigerated trailers remains a contentious issue. This has long alluded the industry and the PCCDG has set its sites on drafting and proposing a standard. Given the data that were presented today, I don't expect agreement will come easily.  This is sorely need - the sooner the better.

Reviewed the draft of the Validation Master Plan guidance document - hammered out in a seesion at Eli Lilly & Company last August. It holds up pretty well - not having looked at it in 5 months. After some minor tweeking, the group hopes to  submit the final draft to the rest of the PCCDG for comment and then it's on to the PDA Science Advisory Board Technical Review Committee for industry comment. If all goes well, publication could be before the end of the year.

I welcome any and all comments on today's events.

And for those of you back east and north who didn't or couldn't make it to San Diego for this event - not to rub it in but... the weather is perfect.  

The Irish Medicines Board (IMB) has drafted a document titled: Guidance Note on Control and Monitoring of Storage and Transportation Temperature Conditions for Medicinal Products. The document can be accessed at the following address: http://www.imb.ie/uploads/publications/8123404_Draft_IMB_Guidance_Temp_monitoring.pdf

The closing date for provision of comments to the IMB is January 27, 2006.

Heavy on recommendations and detail for validation requirements of equipment and processes. Solid documentation and training are also stressed. A bit ambiguous when it comes to storage definitions. My comments are as follows: I would be interested to hear what you think.

The first PDA PCCDG working meeting for 2006 will be hosted by Derrick Gallagher of Amylin at the Manchester Grand Hyatt Hotel in San Diego, CA on January 17-18. The group will continue to iron out the framework for a Validation Master Plan, which promises to be just the follow-up hit the group needs on the heels of their chart-topper TR39, published in September '05.

 Also on the agenda: a proposal for bylaws and charter, a selection of a bylaw committee, updates on the EU C3, a case study on truck mapping and working sessions on temperature profile development and trailer mapping.

I'll keep you posted on the daily activities for your comments.

Coolerheads live for this stuff!