It concluded much more favorably than anyone involved had anticipated. From the organizers to the attendees, everyone I spoke with agreed that the event exceeded their estimates and expectations. Registrants got their money's worth, the PDA gained new members and the PCCDG increased its momentum and credibility among the industry and the world's leading pharmaceutical regulatory agencies. Even the jaded and hard-to-please came away from this week's conference satisfied.

The relevancy and quality of content from the presenters surprised many. Much of that credit has to go to Bob Dana, Vice President Quality and Regulatory Affairs, PDA; and the highly respected PDA-PCCDG chair, Rafik Bishara, who used their significant influence, dash and charm to coerce even the most stubborn leaders within the pharmaceutical cold-chain industry to "volunteer," moderate or present at this inaugural conference. This was most evident by convincing the elusive FDA to attend and present. (See March 27th posting: Regulators Comment on Technical Report No.39, Shipping Outside of Label Claim and Monitoring).

In addition to the recap of events outlined in that posting, the highlights of the two day  event were:

The chairs of the European Cold Chain Committee (C3) and the Pharmaceutical Logistics Forum (PLF) attended and agreed to begin a dialog with the PCCDG on unifying efforts.

The endless stream of presenters referencing TR 39, the need for current good distribution practices (cGDP), quality agreements, procedures, training, and above all, good science.

The importance of including distribution temperature cycling studies as part of the overall product stability study programs.

The importance and advantage of including such studies in PLA filings.

The hope of the PDA was to have 75-80 in attendance. A total of 116 people registered. 10 exhibitors, all directly involved in cold-chain, helped sponsor the event. The PDA staff were extremely well organized and efficient. The hotel, if not a little inconvenient to the area's 3 airports, was elegant, the food a few notches above most and the venue was dramatic and spacious. The IT/AV crew never left the room and not a single technical mishap occurred.

The goal, of course, was to educate, inform, increase awareness of and involvement in, cold-chain. In my opinion, it was a home run!

If any of you who were in attendance have comments to make about the conference, or ideas and suggestions for improving the next meeting, why don't you share them with us? I'm sure the PDA and the organizing committee would appreciate the feed-back too.

* * *

I suspect the next PDA-PCCDG conference will outdistance this one. There is talk of a European meeting and making the Bethesda summit an annual event. My, how far we have all come in cold-chain in a few short years!

The much anticipated PDA Pharmaceutical Cold-Chain Management Conference concluded its first day of activities in Bethesda, Maryland today. Keen interest was paid by the 116 attendees on the FDA's first public acknowledgment of Technical Report No. 39, Cold-chain Guidance for Medicinal Products: Maintaining the  Quality of Temperature-Sensitive Medicinal Products Through the Transportation Environment.

There were three regulating authorities among the presenters:

John Taylor, Quality Systems Manager of the MHRA (UK),

Vincent Tong, Compliance Officer, GMP Inspection Unit, Health Canada and

Nicholas Buhay, Acting Director, Division of Manufacturing and Product Quality, Center of Drug Evaluation and Research, FDA

In addition, there was one compendial affairs presenter, Claudia Okeke, PhD., Associate Director General Policies and Requirements Division, USP.

Each of these regulating authorities reiterated the need for good distribution practices, policies, procedures, training and adherence to their own governmental guidance and requirements documents. They are remarkably similar in content but enforcement varies as the meaning of the word "guidance" differs from country to country.

Mr. Taylor's presentation was, as always, button-down and to the point.

Mr. Tong's soft spoken and calculated presentation revealed no surprises as most are now familiar with HC's stringent regulation enacted last fall.

Ms. Okeke gleaned a pertinent few slides from her usual USP overview to deliver a well focused differentiation on the organization's mandatory requirements vs. guidance documents.  

Mr. Buhay glided through FDA's expectations of compliance with a well prepared and sanitized presentation. However, he was remarkably non-committal and vague during the question and answer session as he carefully negotiated the regulatory waters with nearly incomprehensible double-speak. He did relinquish a glimpse into the mind-set of the agency when he stated that "in the future, the lack of temperature cycling studies will result in deficiencies".

On the bright side, he did state that when it came to the efforts of the PCCDG to promote and implement good distribution practices for the transportation of temperature sensitive products "the agency was quite satisfied with current level of activity" and alluded to areas of greater concern to the agency than what takes place in our little cold-chain corner of the world.

* * *

At the conclusion of their presentations, the regulators were asked to comment on several questions  from a captive and information-starved audience desperate for guidance. Most notable were two questions that PCCDG members have agonized over and discussed adnausium at every conference:

Q: does your agency allow shipping product outside of label claim provided there is sufficient stability data to support it?

Taylor: Yes, it is allowed by the MHRA provided it has been reviewed by the regulatory authority and an application for variance has been submitted.

Tong: Yes, it is allowable with supporting stability data and the consent of the fabricator (manufacturer).

Buhay: Yes, with supporting stability data.

Okeke: Yes, as long as cycling studies have been performed and support it.

Q: Is it necessary to monitor every shipment if validated packaging is used in a qualified distribution process?

Taylor: No. Periodic monitoring is acceptable

Buhay: No, as long as you can show control of your process and the occasion with a program that organizes your rationale.

* * *

Overall, the panel were pleased with our efforts and encouraged us to proceed with developing additional industry guidance. The panel, at the invitation of committee chair Rafik Bishara, agreed to meet in the future with the PCCDG to address concerns they might have regarding future guidance. In all, it was a good day.

Last week I arrived in New York City a day before Interphex began and had the rare opportunity to meet with and spend the day with my daughter, Haley. We took a stroll through Central Park where she captured these photos of the Balto sculpture - meaningless unless you read the March 16th Posting "Cold-Chain Chronicles: A Sled-Dog, A Bacterium And A Pharmaceutical Company."

Click below on attachments to view the photos. It is an inspiring piece in a perfect setting and location. Enjoy.

It was an interesting, diverse and exciting trip to New York City this week. I'd like to thank all of you who took the time to stop by the booth at Interphex and chat about the blog and discuss what you've been working on, issues you're dealing with, or packaging conundrums you're trying to resolve.

One of the more interesting technical questions I was asked came from a bio-tech researcher from Cambridge, MA. Although I could not answer his question directly, I assured him I would post it to the blog and with over 1,700 visits here a month, hopefully he can check back and see if anyone has any information they would be willing to share and post.

Question: What, if any, are the effects of gamma radiation sterilization on temperature data logger performance? How does this affect the componentry, memory chip, battery, etc.?

Apparently, his company packages their temperature sensitive product (complete with data logger) into distribution packaging and zaps it afterward. Currently, they use a TempTale 4 Dual Sensor with a flexible external thermocouple, and place the logger outside the box in a lead pig before sterilization.  I'm sure any information you can share would be appreciated.

A second question was asked by a fellow member the . He broadcast it to the members of the cold-chain discussion group and I thought I'd post it here as well to see if any of you can provide him with the information he is requesting.

Question: "I am currently working on a new project where we are looking at standard 5 and 10 Liter bags that will be filled with various Biological and culture media products.  We will be transporting these between sites, potentially at -70C.  Trying to get a benchmark on what everyone is doing. Specifically, the type of secondary packaging, totes, cages etc., quantities currently shipping, and experiences, if any, with bag materials at these low temperatures".

* * *

Next week I'm off to Bethesda to moderate at the inaugural PDA Cold-Chain Management Conference. There should be plenty of information to share when I return...

If any of you are planning to attend the Pharmaceutical Manufacturing Conference & Exhibition, Interphex, next week at the Jacob Javits Convention Center in New York City, stop by Booth P 2056 on Tuesday the 21st or Wednesday the 22nd and say hello. I'll be passing through on those days and we can chat about the blog and perhaps I can get your thoughts on a research project I've been working on.

This is a cold-chain story of sorts, about a hero dog named Balto, a bacterium named diphtheriae and a pharmaceutical company named Merck - and how these three, completely unrelated entities, converged in a monumental and historic event that inspired one of the most unique and arduous athletic tests of our time.

The year was 1925. An epidemic of deadly Diphtheria had crippled a small town on the edge of the Bering Sea. An antitoxin for the disease, developed by Merck & Company, was on-hand but had expired. The town's only doctor was in desperate need of replacement but it did not arrive in time for winter, and the port would remain closed from ice until the spring thaw in June.

 It was late January, the middle of the frigid arctic night. The nearest serum necessary to save the population of the town of 1,400 lie across 1,000 miles of frozen wilderness.

The only way to deliver the life saving medicine was overland, ferried first by rail until the track ran out 250 miles up the line. From there, 20 volunteer dog-sled drivers relayed the serum non-stop the remaining 674 miles.

Time was of the essence. A few people had already died. Twenty-eight others were currently suffering from the insidious disease and there was only enough life-saving serum on the dog sled for 30 patients. The serum had to arrive before the threat of the highly contagious infection spread to the entire population of the region.

In what was called "The Race For Mercy", the first musher in the relay was handed the 20 pound package of serum at the train station in Nenana, the terminus of the railroad line. The temperatures were at a twenty-year low and hovered at -45C. Through the constant dim of the polar night men and dogs drove blindly against raging blizzards, bitter cold, glare ice, and rugged mountain terrain. They wove their way northward through the forests and "buffalo tunnels" and along the frozen rivers of the trail called "the far distant place" in the native Athabaskan language. Through the spectacular wilderness only the panting of dogs and the swish of the sled runners punctuated the vast stillness. From the interior, the journey crossed the barren and treacherous expanse of Norton Sound where there was no protection from the gales of blowing snow, ice-fog and shifting pack ice.

Conditions only worsened as the brave men and anxious dogs made their way northward. Mushers hands were frozen to their sleds and they had to have hot water poured over them to release them from their handles. Eddies of drifting, swirling snow passing between the dogs legs and under their bellies made them appear as if they were fording a fast-running river. Many dogs were lost to the elements and exhaustion as a result of the harsh conditions. Every few hours the teams had to stop at trail camps and thaw the serum next to fires.

The final leg of the journey, over Topok Mountain, was taken up by Gunnar Kaasen, a dog-sled veteran of 21 years. His lead dog, Balto, well known for his tireless strength and acute sense of danger, safely pulled the team over the shifting ice through visibility so poor that Kaasen could not always see the dogs harnessed closest to the sled. He was 2 miles past the town of Solomon before he even realized it. The winds were so severe that they flipped the sled and the cylinder containing the serum fell off and became buried in the snow. Kaasen acquired frostbite when he had to use his bare hands to forage for the package through the drifting snow.

Kaasen told reporters at the time: "I couldn't see the trail. Many times I couldn't even see my dogs, so blinding was the gale. I gave Balto, my lead dog, his head and trusted to him. He never once faltered. It was Balto who led the way. The credit is his."

Balto led the team into the dire town at 5:30 in the morning on the fifth day of the relay and then collapsed from exhaustion. The serum arrived without a single ampule broken. It was thawed, and by noon administered to those infected. It saved their lives and saved the town. In all, 7 people died before the antitoxin arrived - but the situation could have been much, much worse.

***

Today, a statue of Balto, commemorating his incredible feat stands near the Willowdell Arch on the main path to the Children's Zoo in New York City's Central Park (leading north, of course). In a bold pose with a harness hanging from his back and legs braced, he is perched atop a rock - panting, and surveying the distance. It stands appropriately, in glowing bronze, reflecting the love pats of countless children and appreciative adults who happen by.

Diphtheria has been all but eradicated from most countries of the world thanks to the development of vaccines by Merck, and others, and inoculation programs.

And what began in the Alaskan Territory as an epic 5 day, 674 mile, life-saving race against time, has become one of the most celebrated challenges in modern history. We recognize it as The Iditarod, "The Last Great Race On Earth." Few are familiar with its incredible origin; or that teams of dogs and hearty mushers commemorate the race for mercy by retracing the "serum run", along the 1,049 historic miles of the Iditerod Trail -from Anchorage to the Diphtheria-free town of Nome.

Walter Soroka, author of the packaging bible Fundamentals of Packaging Technology stated:

"You must thoroughly understand the nature and extent of the hazards within the distribution environment through which the product must travel."

Now, there are obvious hazards within the distribution environment that packaging engineers can design for - and then there are perils one could never expect, predict or explain. For a slide show, click on the Photos Tab to the left, then click on Worst-Case Scenarios. If you have any others you would like to share, by all means post them!

The first PDA Cold-Chain Management Conference will be held at the Bethesda North Marriott Hotel & Conference Center on March 27th & 28th, 2006.

By taking an in-depth look at the factors affecting the cold-chain management of pharmaceuticals, the conference will feature 8 plenary sessions providing guidance on how to effectively implement technologies and quality systems within regulatory requirements and public standards to guarantee the safety, efficacy and quality of pharmaceutical products.

You can click here for a pdf. version of the current agenda.

I spoke with Rafik Bishara, PhD., Program Chair of the event this morning. He informed me of a couple of updates. Hugo Wegewijs, Chair of the European C3 will also be presenting a European perspective. Unfortunately, Chris Landauer, Senior Validation Engineer, Amgen, had to withdraw due to a last minute priority and as a result, Rafik will lead the session on Quality Standards.

I have been involved with this event as a planning committee member and will act as moderator at one of the sessions. It will be refreshing to see many new members involved, presenting fresh ideas, topics and procedures in an effort to continuously upgrade cold-chain distribution practices.

PDA Members and non-members can register on-line here.

I look forward to seeing you there!

According to my partners in cold-chain at Sensitech, there has been an overwhelming response to their FREE webinar on The Impact of USP General Chapter <1079> on Cold-Chain Management. Currently, 125 participants are registered. There is a finite number they can accommodate and only a few spaces remain for the March 16th, 2:00 pm (EST) event. 

As mentioned in my February 16th posting, anyone participating in the manufacture, storage, distribution, and shipping of temperature sensitive pharmacopeial products needs to familiarize themselves with this document . This is a perfect opportunity. You can link directly to Sensitech's webinar registration page here.