Temperature Controlled Insights for the Industry by the Industry Part 1

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Contentsv Introduction

v Controlled Room Temperature Market Insights

v The End User Perspective: Graham Martin Supply Chain Excellence Manager at Pfizer

v 8 Steps to Implementing a Robust Room Temperature Strategy

v The Supplier’s Perspective: Ben VanderPlas Global Product Manager at Sonoco ThermoSafe

v Protecting Ambient Products at a Reasonable Price

v From our Partners: Five Tips to Ensuring Product Integrity in Temperature-Sensitive Distribution

v Ambient Profiles - Deciphering the Supply Chain Elements

v Ambient Profiles – The Building Blocks

v Infographic: Beyond 2 - 8°C: The Ambient Explosion

WelcomeNow all ‘ambient’ products need to be stored, monitored and shipped at 15° C to 25º C and inspected by EU regulatory authorities, the industry is looking for new and better ways to protect the integrity of their products throughout the supply chain.

Thermal deviations outside of the CRT envelope can compromise efficacy and patient safety. As a result, international regulators are looking more closely at data results from shipments of temperature-sensitive drug products in the CRT range. For manufacturers collecting data can be a time-consuming and expensive project. There are a number of challenges associated with determining temperature profiles for (15° C to 25º C) and (15° C to 30º C) regimes, distributing to countries with variable climates and redesigning packaging and labels that are mainly for use at chill and frozen temperatures. Plus, there is currently no industry-defined temperature standard for CRT transportation.

However, these challenges also present opportunities for temperature-controlled sup-ply chain service and solution providers looking to expand their offerings and customer base.

This attention has changed the industry discussion from cold chain management to temperature-controlled management for all ranges of product temperature sensitivity. In recognition of this ahead of Cool Chain Logistics & Controlled Room Temperature Logistics Europe 2014, Europe’s largest gathering of the cool chain and temperature controlled Logistics community, Cold Chain IQ has gathered together key insights various stakeholders in CRT logistics to bring you an industry first report: The Hitchhiker’s Guide to Controlled Room Temperature. We hope you find this resource pack of interest and we look forward to meeting you in Luxembourg in January.

Best regards

Andrea Charles EditorCold Chain IQwww.coldchainIQ.com

Staying ConneCted

Keep up to date with the latest Cold Chain News3

CRt Market insights “[The Industry] seems to be more focused now

on the CRT portion of shipments as drugs come

off 2ºC - 8ºC and they try to get a wider range

for shipping and storage, which just makes it

easier for the supply chain itself, from a drug

standpoint, but it seems like there’s a new

focus on control room temp from the shippers,

and a little bit closer look at that even from a

regulatory standpoint.”

Jim Lucie, Senior Manager,

Material Control at AMAG Pharmaceuticals

“I think that’s going to be a huge market. I don’t

think the volume is necessarily increasing, but

the stance that the regulators are taking and

even internal quality people at each individual

pharmaceutical company are really starting to ask

some questions about controlled room temperature

and how do we maintain that temperature and

show those controls in our distribution channels as

well.”

Gary Hutchinson, President, Modality Solutions “The ease of storage by the end user

(patient/hospital/pharmacy) has

driven development of CRT products,

and getting them through the supply chain is

the new challenge as these tight temperature

parameters require sophisticated solutions

protecting against the extremes. Increased

use of phase change materials in passive

solutions and further development of heating/

cooling active solutions creates both challenges

and opportunities for solution providers to

meet these changing needs and controls /

requirements from regulators.

As the industry (manufacturer/ provider/

regulator) matures, the need for temperature

controlled distribution is bright. Manufacturers

will seek out those providers that can create

end to end to solutions ensuring integrity of

product and meeting the changing regulations.

Cold Chain IQ and industry groups create the

collaborative platforms for all participants to

map out guidelines that can or could become

global standards in the future. As well, the

need for real time data not only for temperature,

but also shock, humidity, light, etc and security

concerns is leading to integrated approaches to

measuring and maintaining integrity of shipments.”

Jim Bacon, Senior Director,

Grifols, Inc

“A lot more questions over the control of these products are coming up for transit and there are several attempts to maintain this tight range especially for clinical items. I think manufacturers are better able to demonstrate robustness of these products for ambient shipping and should do that. ”

Michael English, Senior Product Engineer of Packaging Technologies, Merck

In an article for Pharmafile on providing controlled room temperature logistics using specialist packaging

Nathan Barnard , Cool Chain Manager at Biocair said: “At Biocair, we see requirements for Controlled Room Temperature packaging and logistics vary over

the year. Requirements increase during the winter as colder temperatures give more concern over cold temperature risks. Similarly, some hot emerging market

destinations justify a CRT logistics solution in the summer, especially if there are potential delays in an

uncontrolled Customs warehouse. In conclusion, for some products and research samples, specialist logistics solutions for Controlled Room Temperature shipping are available. For some products and research samples, a CRT option must always be selected as a specific temperature band such as +15°C to +25°C is required. With many other

products and samples, the risk of degradation is limited

and an assessment can be made as to what level of logistics solution is required. By using support from their

specialist logistics provider, smart decisions based on a

risk assessment of the route can be used to ensure the

solutions chosen are appropriate and efficient.”

Nathan Barnard, Cool Chain Manager,

Biocair

AstraZeneca’s Christine Foster on CRT Trends & Quality Control

Stability Protocol Strategy for Ambient Temperature Logisitics- An Interview with Gino Vleugels

CLiCK to PLay CLiCK to PLay

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Pfizer on Controlled Room temperature

Graham Martin has 20 years in pharmaceuticals with broad experience in both operational and technical aspects of supply chain logistics and temperature sensitive distribution. He also has a total of 25 years in materials and logistics management specialising in developing and leading strong teams in operational excellence. Graham is a highly developed specialist knowledge in warehousing facility design and operations, third party contract management, global distribution flow modelling, cold chain design and qualification and cost effective solutions.

g Martin: Transportation companies are developing stability data for their DC end markets and sharing what they call position papers, and this has been developed to aid excursion management decision making in the market. If we take 15°C to 25°C or CRT this is the new 2°C to 8°C example. It’s more challenging, to be compliant, but cost effective solutions are sought and generally CRT has high volumes, lower value products as opposed to bio and stability license data is absolutely key to its success. Cold Chain iQ: What is the biggest challenge the company is seeing with regards to controlled room temperature logistics?

g Martin: I think I can share my thoughts and some of others in this, because there are developments to be made yet and we still have to go through these guidelines to see exactly what they mean and what the interpretation of that is. But I can give a personal view that mean kinetic temperature is a useful mechanism for equating the cumulative effect of real time variations in temperature to conditions, and therefore to the product quality.

The calculation of mean kinetic temperature (MKT) for a particular product lot that has been exposed to temperatures outside the labelled storage conditions for a defined period of time can help establish if the cumulative temperature the product is exposed to over its shelf life for the minimum labelled storage conditions and there supports that product will remain within specifications. That’s quite a mouthful, I suppose, but looking at MKT carefully to see how it applies to a product and the variations in the lane.

Cold Chain iQ: Has the increased volume of the product that needs to be handled at CRT impacted Pfizer’s logistics choices, in maybe transport or packaging?

g Martin: Again, we’re still looking at the interpretation of this and setting up a project team to make sure we’re compliant, but the new GDP does not necessarily mean that there is an increased volume of product needing CRT or controlled room temperature monitoring. An assessment of the impact of exposure of a product to temperatures likely to be experienced due to transport for a defined transportation period, considering the shelf life of the product and its stability profile, may be used to determine if the temperature control is required for a particular shipment. For example, insulated containers may be qualified to control the impact of temperature fluctuations during transport rather than the use of temperature controlled vehicles.

It’s more challenging to be compliant, but cost effective

solutions are sought and generally CRT has high

volumes, lower value products as opposed to bio and stability license data is absolutely key

to its success

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8 Steps to implementing a Controlled Room

temperature Strategy

Right now lots of companies are analysing and deciding how to implement a CRT (Controlled Room Temperature) for their products. But many companies are asking; where do I start? Cold Chain IQ asked Peter Lockett, Director of TP3 Global Ltd for his advice:

Know your own products - required storage and distribution temperature guidelines, available stability data etc.

Consider the impact of using either single use or reusable systems. Cost, return logistics, contamination, maintenance, disposal are all aspects that require consideration.

Establish the routes and assess the temperature threat risk of each.

Consider protection equipment availability – global locations, stock, capability etc

One type of protection may not suit all routes and seasons - be prepared to test and adopt a number of protection equipment types to suit different product groups and temperature threats.

Be aware of existing and developing global legislation which could change the criteria required for distribution and storage.

The types of temperature threat (heat/cold/duration) will determine the requirements of the protection equipment required.

Be prepared to lean on the expertise of both 3PL and equipment manufacturer partners. Both can have valuable experience and knowledge to offer.

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the Supplier’s Perspective

Ben VanderPlas is responsible for the global leadership of the Sonoco ThermoSafe product family and service offering. This includes product strategy, product development, and life cycle management.

Cold Chain iQ: What trends are you seeing with regard to controlled room temperature packaging and its strategic importance? How has this evolved over the last decade?

B VanderPlas: Over the last decade, the industry has shifted from very few packages requiring temperature control beyond refrigerated or frozen temperature ranges to an increase in demand for controlled room temperature. I would say that it has really been over the past five years that we have seen a significant increase in requests for controlled room temperature packaging. The pharmaceutical manufacturers are so used to these controlled room temperature products being shipped without proper temperature control that there is really going to bring a big change to the industry as they tighten things up to meet the new regulations that have been issued by many countries.

Cold Chain iQ: How is CRT changing your clients’ processes and needs, and how have Sonoco ThermoSafe responded?

B VanderPlas: It’s certainly changing their distribution practices. They are shifting from a corrugated shipper or unprotected palletised load and moving those products into temperature assurance packaging or active temperature control. It really changes the whole dynamic in which they have to protect these products.

What we’ve done as a company is begun to create extensions from our existing product lines to cover off on these controlled room temperature ranges. One of the difficulties is that controlled room temperature defined by the USP is 20 °C to 25 °C, but what we know now is that it ranges across the board, company to company, product to product. Typically, it’s never any tighter than 20 °C to 25 °C, but you’ll find 15 °C to 25 °C, 15 °C to 30 °C, 2 °C to 25 °C, and a variety of instances in between.

Cold Chain iQ: In your opinion, what is the biggest challenge with regards to CRT packaging?

B VanderPlas: : I think it’s just that - it’s that it’s undefined as to what that range is. There’s such a scattered range of temperature ranges, and it makes it difficult, from our side, to have something that’s ready to go for our customer. But, at the same time, what we’ve done is begun designing on the tighter side, and it’s relatively easy to make modifications to then satisfy those broader temperature ranges. Then, on the customer side, any customer that’s new to shipping controlled room temperature and holding those temperature requirements, the challenge is they don’t understand the difficulties, typically, with holding controlled room temperature. If the temperature range is very tight, it’s a lot harder to hold than refrigerated temperatures in many cases, This is especially true when you’re using water as a refrigerant, because it’s so far away from those temperature ranges you’re looking to hold that you need to use some advanced phase change materials in order to optimise the package size.

Cold Chain iQ: What are some of the regulatory hurdles, and how does the new Certis Silver Universal controlled room temperature series meet the increasing global regulations facing the industry?

B VanderPlas: Certainly holding temperature requirements on a product that you haven’t had to prove temperature control on in the past is the challenge. It’s changing those operations to uphold temperature requirements and have proof for the

The pharmaceutical manufacturers are so used to

these controlled room temperature products being shipped without proper temperature control that

there is really going to bring a big change to the industry as they

tighten things up to meet the new regulations that have been issued

by many different countries.

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regulatory agencies to show that you’re now holding temperature per label claim. Certis Silver Universal for controlled-room-temperature is one of our products, but we’ve also introduced a product specific for the European market by the name of Aeris. Aeris was first launched in September as a 2-8C product but we also have controlled-room-temperature configurations that will launch at the end of this year, again, to satisfy those needs. So, we continue to expand our product line, multiple durations, temperature ranges, and payload sizes in order to satisfy these new and evolving controlled-room-temperature regulations.

Cold Chain iQ: Could you just give us a brief overview of how the Certis Silver Universal’s controlled room-temperature shippers ensure absolute thermal protection, and what’s the duration?

B VanderPlas: We have multiple durations. Today, ready to go, we have three and four day solutions. With slight modifications we can alter those designs to satisfy other needs. The Certis platform is modular. If a shorter duration or larger payload is desired the quantity of phase change material can simply be reduced to allow for such flexibilty. But we’ve tested these boxes against robust ambient test profiles, we’ve bracketed the product loads, in a way that satisfies most users’ product needs, and we’ve monitored temperatures not only in your safe locations within those payload sizes, but also out into the more extreme location. So, when any product is loaded into these payload boxes, we know it’s going to hold the temperatures that it was tested to hold.

Cold Chain iQ: Do you have any end user or success stories that you’d be able to share with us?

B VanderPlas: That’s a good question. What rises to the top of my head right now is there are a number of clinical organisations that have used our products for a good number of years, and now, over the past five years or so, have had to require controlled-room-temperature. They now have the need to ship controlled-room-temperature, refrigerated, and frozen. What we’ve done is take or modular Certis platform and we’ve been able to take the same box and they can then pack it out with slight modifications, changes to the phase change materials, and use that same outer insulated shipper and hold 2°C to 8°C controlled-room-temperature, and frozen. And they’ve really appreciated that flexibility as it’s brought a lot of value to them where they don’t have to stock three different size of shippers. Instead, they just have to change out the inner refrigerants in order to hold those temperature ranges.

Cold Chain iQ: What would be your top tip for finding the right solution provider(s), for meeting your controlled-room-temperature strategy?

B VanderPlas: I’d certainly have to say that when looking around for the right provider of packaging, you have to understand where they’re located. You never want to have to ship the packaging all too far as it becomes cost prohibitive. But you need to make sure you understand the design constraints and the variables that were used as these packages were put together, make sure that the product loads tested are

representative, or, worst case than the products you’re shipping. That the probe locations

used were not just in the centre of the container, or on the top or the bottom, but they also took a look at the corners. And some of the more extreme locations, where it’s common that the temperatures will fluctuate more frequently than some of the safer locations. And, finally, that the ambient profiles that they were tested against are relative to the region in which these packages are going to be used because, if you use something that, for instance, a controlled-room-temperature package that spends a lot of time at controlled-room-temperature, a few dips and spikes out here and there, of course, it’s going to pass, but it might not be representative of what’s actually going to happen in the field.

Cold Chain iQ: What the key considerations for better protecting controlled-room-temperature products in the supply chain?

B VanderPlas: In my mind, one of the key things on controlled room temperature products in the supply chain is it’s in the package itself and it’s when you’re designing water-based refrigerants, you need a lot of mass in order to hold temperatures that are above, certainly above 2º C, but to hold it above 15º C, I’d say, it’s just a lot of mass because you’re not going to get any benefit of that phase change until it was well below the temperature in which you’re trying to hold. Instead, if you use the phase change material that phases within the temperature range you’re looking to hold, you can get away with using a lot less weight, which again reduces the size of the package at the same time, and just provides a lot more security in temperature control than using some standard water-based gel pack.

about Sonoco thermoSafeSonoco ThermoSafe is the leading global provider of temperature assurance packaging for the safe and efficient transport of pharmaceuticals, biologics, vaccines and other temperature sensitive products. Sonoco ThermoSafe shipping solutions mitigate risk for customers and ensure product efficacy throughout the extremes of a supply chain. With operations in North America, Europe, Asia and South America, the Company has a vast product offering featuring industry leading technology that encompasses refrigerated, frozen or controlled-room-temperature applications. In addition, Sonoco ThermoSafe’s ISC Labs® design and testing services deliver individualized and innovative packaging solutions along with qualification and validation services to meet all regulatory requirements. More information on Sonoco ThermoSafe can be found at www.thermosafe.com

You never want to have to ship the packaging all too far as it becomes

cost prohibitive. But you need to make sure you understand the

design constraints and the variables that were used as these packages

were put together, make sure that the product loads tested are

representative, or, worst case than the products you’re shipping.

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Protecting ambient Products at a Reasonable Price

Kevin Kohleriter, director of Marketing for infitrak

Ambient, or in some cases called ‘room temperature’, is a term used within the pharmaceutical, food and drink manufacturing industry related to either product types or storage. Unlike chilled products that require a chilled environment, or like frozen foods that require a frozen environment, ambient products require the surrounding environment to be at “room temperature”.

Ambient products are what form a good portion of a drug store or supermarket and can include (but are not limited to) soft drinks, aspirin, cold remedies, tea and coffee, cereals, canned meat, rice, and pasta. They will often have a very long shelf life and are at low risk or a low purchase price for the consumer.

Because the end-product is typically lower in cost, protecting these products requires a cost effective means to protect them from temperature excursions that may spoil them or shorten their shelf life. This requires a balance of packaging cost and product protection.

What influences ambient temperatures?

Ambient temperature is determined by a number of factors, including:

the weather outside

the quality of insulation in the room or transport vehicle

what or who is inside the room

the use of heating and cooling systems

For example, a data center with a lot of servers will be warm due to the heat generated by the computer systems. Body heat caused by people or even animals will also have an ffect. Ambient temperatures can also be affected by humidity.

Protecting products that are affected by ambient temperatures

Similar to frozen or refrigerated products, when qualifying your protective packaging, you need to first identify and document the requirements, including identifying product stability data, mode of transportation, and temperature sensitivity.

After you have your requirements, package design and testing can begin. Start with an understanding your product’s ambient temperature profile as defined by PDA Technical Report 39. What are the acceptable environmental conditions the product itself can be exposed to and how does it affect the products efficacy.

Three methods for creating an ambient temperature profile (and how to save money doing it)

There are three methods for creating a ambient temperature profile that can be used to design thermal packaging:

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The first is for you to provide it (it may be a company standard or you can use data from a data logger).

The second is by using predetermined profile developed by a trusted 3rd party, who has mapped out 24, 48, and 72 hour profiles based on ISTA standards and tested them for the critical variables.

The third method, and likely the most effective, is to get the profiles from a company, like Infitrak, who has been performing studies long enough to have temperature profiles already available.

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this may include:

c Air pressure cycles and their effect on containers and venting,

c Compromised packaging due to security inspections, tampering, or radiation exposure

c Duration length and variability of shipment or storage time,

c Origins and destinations per geographical regions

c Physical stresses, like vibration effects on material being shipped, crushing / handling / dropping, leakage from/ onto packages, package orientation, package placement,

cSeasonal differences in temperature and humidity (Summer, Spring/Fall and Winter),

c Transportation modes

This last method, getting the profiles from a 3rd party, is the most cost-effective when you either want to confirm your existing profiles or when you need to move quickly.

Once you determine and test the possible scenarios, you can integrate a means of protecting the products. Cost effective options for protecting cold chain products during transportation

There are multiple directions to take in building a complete packaging system for ambient products. With the data you have collected during the profiling process you can now balance the amount of insulation, number and type of gel-packs, the size of payload box needed and develop an SOP on how to pack it.

You may also want to consider adding temperature indicators and data loggers to not only confirm your packaging is effective, but also to provide a bit of accountability. Knowing when or where an indicator activated or an excursion occurs allows you to assign accountability to the carrier, a location or an individual. Spending a couple dollars on each box to place an indicator and a bit more for a data logger on each shipment can provide evidence of temperature compliance. The number and cost of these measurement tools can be based on either the cost of the product, or the likelihood of exposure (crossing climate zones, length of transport, or breaking down shipments).

The lowest cost temperature indicator, a ShockWatch Temperature Indicator for example, may be as low as $1 and will take a snapshot of a temperature excursion and show the length of that exposure. Passive temperature data loggers, like the Logtag TREXI8 Temperature Data Logger can cost as little as $50 and store up to 8,000 readings.

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From our Partners: Five tips to ensuring Product integrity in

temperature-Sensitive distribution

UPS points to risk management planning, limiting supply chain handoffs, and quality agreements among five vital tips for temperature-sensitive product packaging and distribution.

By 2016, eight of the top 10 and 27 of the top 50 best-selling global pharmaceutical products will be biotechnology-derived temperature-sensitive products (according to Cold Chain Biopharma Logistics Sourcebook 2012) which means many factors need to be addressed to ensure product integrity.

It’s essential for manufacturers to take steps early to prevent temperature excursions during the supply chain journey. From monitoring temperature stability throughout the different transportation lanes to choosing the right type of external packaging to ensure protection, new technologies and innovations enable more proactivity in protecting temperature-sensitive products. Here are five tips to consider when planning for temperature-sensitive product packaging and distribution:

1. think outside the package to understand the transportation environment. Packaging is the first line of defense in protecting temperature-sensitive products, but the key to success is in understanding that packaging decisions go beyond the package itself. Manufacturers need to know exactly how their packaged temperature-sensitive products will perform in a specific transportation environment. Some carriers can provide a detailed temperature profile map of their network, which will help in selecting the best packaging solution by lane. Consider either engaging a third-party logistics provider with extensive background in these areas or hiring an in-house packaging specialist. Also, ensure that you have access to regulatory expertise to stay ahead of complex global and regional compliance requirements.

2. develop a risk management plan for temperature-sensitive products.By far the most important aspect of developing a supply chain plan for temperature-sensitive products is ensuring contingency plans are in place. While protective packaging and visibility data are important, manufacturers could lose hundreds to millions of dollars from spoiled products if they are unable to intervene when products deviate from their temperature range. A good risk management plan, created with a third-party expert logistics partner, will leverage historical product-specific temperature data to help map out potential scenarios and step-by-step solutions that can save entire shipments.

3. Limit supply chain handoffs.In an increasingly geographically diverse marketplace, limiting supply chain handoffs—or the number of times your products change hands from one party to another in the supply chain—can be difficult. It’s also more important than ever. The more handoffs that occur, the higher the likelihood of compromising a temperature-sensitive product. In conjunction with having a holistic view of the supply chain, manufacturers should have a partner who can help them map their products’ entire journey and limit hand-offs.

4. ensure visibility solutions provide actionable data.Visibility is especially important with potentially life-saving temperature-sensitive healthcare products. Not only is it vital to have advanced tracking technologies that allow you to monitor a shipment’s location in real time and at any time, but healthcare manufacturers also need to know their products’ temperature conditions at any point during the journey from distribution facility to end customer. This way, if a shipment goes outside of its temperature range and is in danger of spoilage, manufacturers can take action before it’s too late. Specific actions may include re-icing a shipment during transit, redirecting a shipment or alerting customers of potential delays.

5. Create a transportation-specific quality agreement.Quality agreements are an essential part of distribution planning for temperature-sensitive products. While most manufacturers include inventory storage providers in their quality agreements, it’s important to also develop a transportation-specific quality agreement with your carrier. This agreement should include specifics that impact safety, potency, and purity of the product. Best practices include ensuring the agreement avoids generic language and clearly delineates the responsibilities of each party to ensure accountability. It should also include factors that could impact the compliance status of either party. To ensure everyone is on the same page, it’s vital for the manufacturer to document the specific supply chain requirements for its unique lanes and products including time-in-transit, temperature control method and quantity shipped, as well as ambient temperature requirements, origin, destination, and transshipment point needs.

As the market has grown, so has the breadth and sophistication of solutions for protecting temperature-sensitive products in the supply chain. If you have not recently analyzed your supply chain’s ability to support these products, the time is now.

First Published on

www.healthcarepackaging.com11

Article by Justin Bates, director of healthcare strategy for temperature-sensitive products at UPS. Click here for more information on UPS’s broad healthcare logistics capabilities.

Carlos Castro, Clinical Supply Chain, gilead Sciences: ambient Profiles:

deciphering the Supply Chain elements

Selecting or building ambient profiles for the shipping container qualification is a difficult and intense task because an ambient profile requires a deep understanding of the distribution process and the logistics involved. .

Ambient profiles are as intricate as Greek mythology

Carlos Castro has more than 15 years of combined experience in supply chain, temperature-controlled logistics, transportation and packaging. His work experience includes supply chain, logistics and packaging projects for medical devices, pharmaceutical, biologics and combination products

Mr. Castro holds a Masters in Supply Chain and Logistics from Massachusetts Institute of Technology and another Masters in Packaging from Michigan State University. His experience and education in supply chain and engineering has focused his work on providing robust supply chain solutions.

Mr. Castro’s current focus is temperature controlled supply chain in emerging markets, sustainability and last-mile distribution ambient profiles - deciphering the supply chain elements.

Weather has fascinated humans for thousands of years because it has a positive or negative affect in daily life (e.g. food supply in gathering, hunting, fishing, agriculture, traveling, etc.). Throughout history men have created explanations for these climatic events that were not only poorly forecasted but also misunderstood. The ancient Greeks for example, attributed these climatic changes to specific gods and their temperamental natures to explain everyday weather and gave meaning to the world around them. Greek mythology includes many fascinating and colourful stories of more than 40 gods, goddesses, nymphs, monsters and heroes related to weather and climate. For example, Aeolus was the god and ruler of the winds. All occurrences of favourable or unfavourable weather were interpreted as a sign of divine intervention.

Cold Chain Supply also demands understanding and managing the ambient temperature that a shipping container is exposed to during its transport (i.e. ambient profile) because these ambient temperatures greatly affect the cold chain supply performance.

Ambient profiles can be not only as fascinating but also as intricate as Greek Mythology. Fortunately, Cold Chain Supply professionals do not need the Greek weather deities and their divine interventions to manage the ambient profiles but a set of tools and practices to manage the temperature and other logistics factors during transportation. Keep in mind (and this is an important concept) that the ambient temperature may or may not be the same as the actual weather temperature because a container can be stored inside a warehouse with a temperature different from the actual outdoor temperature . So let’s start with two frequently asked questions many cold chain supply professionals deal with, “What is an ambient profile?” and “Why are ambient profiles important?”

An ambient profile refers to the ambient temperature that a shipping container is exposed to during its transportation. It is common to find three elements in an ambient profile; the temperature, the transit date and time and the logistical step associated to this temperature/date-time point. Note that placing an external temperature logger to collect temperature data will provide the temperature the loggers were exposed to but may not guarantee that the shipping container is always exposed to the same temperatures. Temperature variations in storage areas (refrigerated or non-refrigerated warehouses), carrier fleets (aircraft, trucks, etc.) and logistics handling procedures could lead to differences in ambient temperatures. The geographical location and season in which the transport is performed may impact the temperature variations as well. A well-managed supply chain will be less influenced by weather variations due to location and seasons because the shipping container is moving through controlled and semi-controlled conditions of storage, carrier fleet and logistics handling instructions.

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It supports the optimal packaging design of the shipping containers. An incorrect profile drives over or under designed shipping containers. For example, a profile with unrealistic extreme cold temperatures will require more insulation and less frozen gel packs to reduce the risk of product loss due to freezing. On the other hand, a profile with unrealistic mild cold temperatures will demand less insulation and more refrigerated gel packs but will introduce a higher risk for product freezing.

It helps the selection of the right distribution and logistics partner. Long transit times as well as extreme temperatures in the profiles may be an indication not only of limited supply chain integration but also poor collaboration among the distribution and logistics partners. This lack of integration and collaboration may increase risks such as product loss or delays.

defining ambient profiles is critical to the performance of the supply chain for many reasons:

Increases compliance by ensuring the container is qualified for the worst case scenario so the Quality team has less temperature deviations to process and the Regulatory team has a modular qualification document that can speed up the submission to new markets.

It reduces material (i.e. shipping container) and freight costs by removing inefficiencies in a container design (under or over design). The unrealistic profiles usually drive over-design that translate in bigger and heavier containers because more insulating material and gel packs are added.

It reduces the safety stock and pipeline inventory by reducing transit time and temperature variability. Transit time and temperature variability increase risk so lowering the risk provides less inventory overall

It increases customer satisfaction by minimising product loss or temperature deviations that require product quarantine and investigation. A product loss event may require reverse logistics to bring the product back to the manufacturing location, to send the product to a laboratory for further testing or to ship it to a controlled site for incineration (i.e. destruction). An investigation will delay the product release upon arrival and may cause a stock out situation.

It ensures patient safety by maintaining the product temperature within the manufacturer’s recommended allowable temperature ranges for storage and distribution.

It helps to maintain the identity, strength, quality, and purity of the product from beginning to end. Unrealistic profiles create over and under designed containers that expose the product to hot and cold temperatures. Creating a profile requires not only understanding of the storage and transportation steps but also proper management of the distribution and logistics partners to provide realistic expected temperatures for the shipping container design that are aligned to the distribution and logistics handling procedures to protect the product.

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It calibrates and validates the dynamic environment found in the logistics by ensuring regular confirmation that the distribution and logistics handling instructions are being followed by the logistics partners. Selecting or building ambient profiles for the shipping container qualification is a difficult and intense task because an ambient profile requires a deep understanding of the distribution process and the logistics involved. In my next posts I will describe how to build or select ambient profiles.9

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Carlos Castro, Clinical Supply Chain, gilead Sciences: ambient Profiles – the Building Blocks

On the previous pages I mentioned that ambient profiles must be a true representation of the temperature a shipping container experiences during transit from origin to destination sites. Failure to capture realistic temperature conditions in the supply chain will create inefficiencies and increase the risk. In this second article I will describe how ambient profiles should be built and what practices should be avoided.

Ambient profiles are defined by 3 elements: temperature, time and logistics steps. These elements (i.e. building blocks) are usually recorded in two groups (temperature and time and logistics steps and time). The first group, temperature and time, is recorded by an external temperature monitor while the second group, logistics steps and their start and end times (date and time), are usually compiled by the freight forwarder with the help of all the carriers and handling agents.

Today there are many suppliers of temperature monitors and adding temperature monitors to each shipping container is not only a common but also a recommended practice. Shipping containers may include one or multiple internal and external monitors depending on the objectives defined in the temperature monitoring strategy. The external monitor provides the first data group (temperature and time). The internal temperature monitor also records the temperature data using a predefined interval time and does not provide details about the logistics events (limited data) but it confirms the product stayed within the established temperature range. Figure 1 shows an example of the temperature-time plot recorded by an external temperature monitor attached to the shipping container.

Figure 1- external temperature over time

Note that the following assumption is made: the temperature that the monitors and the shipping container were exposed to is the same and to verify this assumption more than one shipping container and multiple monitor locations must be tested. Variations in temperature in different areas of the cooler or carrier’s vessel and variations in handling agents could lead to differences between temperatures of the external monitors. Also note that the ambient temperature recorded by the external monitor is not the reported weather data.

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The logistics steps are usually defined in the routing or shipping route. The routing is the series of storage and distribution activities taking place during the transportation from origin to destination and which maintain a specific temperature range. Each logistics step has a start and end time as well as a maximum and minimum temperature associated to it. The second data group compiles the logistics step and the time but will not provide the temperature associated to each step. Figure 2 shows an example of a routing.

Figure 2- example of a routing (i.e. logistics steps during distribution)

When the results of the temperatures/time and logistics steps/time information is combined, a new graph is rendered as shown in Figure 3. The new graph shows the logistics steps and the temperature and time associated to each step. Temperature spikes (high or low temperature) are now linked to each step and can be managed to reduce the spikes. Figure 3 shows the temperature spikes are happening during the aircraft loading (i.e. tarmac time).

Figure 3- ambient profile for the specific routing

Understanding each routing is critical to building a profile because each logistics step has a potential impact on the temperature found during distribution. For example, if a shipper has cargo to be moved from San Francisco to Milan (Italy) and tenders its cargo, the Freight Forwarder may present multiple routings for the same origin –destination lane. Four routings for this origin-destination lane are: San Francisco to Milan via Amsterdam (SFO-AMS-MXP), San Francisco to Milan via Los Angeles (SFO-LAX-MXP), San Francisco to Milan via New York (SFO-JFK-MIL) and San Francisco to Milan via Dubai (SFO-DXB-MXP). Each routing may have different logistics steps, duration, and external temperature based on the carrier’s cold chain program (facilities, operating procedures, etc). There is also a variation of weather temperature and depending on the time of the year the shipment is made, the routing will show different spikes. The better managed routing will show an ambient temperature less dependent on the weather temperature.

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in my experience, i have found some the following practices to be useful:

Avoid the pre-conceived thought that summer and winter temperatures are the worst times for shipping. This statement had its origin in the assumption that the ambient temperature is the same as the weather temperature. Before making this assumption, one may test multiple shipments and carriers. The better control the carrier has, the less dependency between ambient and weather temperatures is found.

Long haul destinations are not necessarily the worst-case temperature scenarios. The worst case is defined by those lanes with less controlled logistics steps. Carriers have an opportunity to provide a service that will add value to the supply chain and can become a differentiator from their competition.

A common practice is to extend the profile time till failure and collect data beyond the regular transit time. In my opinion, this practice adds very little value because it creates an over-designed container and will not only cost more but increase the risk of temperature excursions. If there is a delay in the routing, and a delay of more than 6 hours is expected, then the product should be placed in the controlled temperature warehouse.

Collecting ambient data does NOT need to be a time-consuming or an expensive project as it is often assumed. An over-designed container created without the correct data will be more costly in the long run or can induce temperature excursions due to the excessive amount of frozen gel packs.

Rather than use the industry profile (e.g. ISTA) or a profile provided by a shipping container supplier one should take the time to collect his/her own data and create his/her own profile. A profile with a small sample is better than a third party profile.

If the Freight Forwarder decides to base the routing on cost or transit time alone then routings will most likely change from shipment to shipment. These multiple routings with varying amounts of control might show inconsistencies with the data. One must manage the cold chain routes before deciding to build a profile and this requires a higher collaboration with the freight forwarder and carriers.

The profile should be based on the routes that are used most of the time (regular destinations). One time events may be uncontrolled and create a profile with extreme spikes which could lead to an over-designed package.

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The profile must be as accurate as possible and the first step is to build an accurate profile is to understand the logistics steps (routings). The logistics manager must collaborate with the freight forwarder, carriers and consignees to put together a comprehensive routing. The next step is to measure and manage the ambient temperature to ensure the high risks areas are controlled. Finally, the shipping container design with the realistic ambient profiles can be executed. Creating ambient profiles is not a one-time event and they must be reviewed on a periodic basis as carriers and other logistics partners are making changes that will affect the ambient profile.

We have covered what an ambient profile is and why is important in a cold chain supply, how ambient profiles are build and what best practices are needed to collect the data. What we have not covered is how the data is analyzed. I’d love to hear from you, the reader, how you have analyzed or would analyze the temperature data to create the ambient profiles that will be used in the shipping container qualification.

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Cold Chain IQ Goes Beyond 2 - 8°C The Ambient Explosion

Right now many companies are analysing and deciding how to implement a CRT (Controlled Room Temperature) or ambient strategy for their products.

Does this reflect what you are doing in your company?

Question 1: The Heat is On

Question 2: Regulatory Overview

Question 3: Challenges

Question 4: Do you outsource your ambient logistics?

Question 5: Is your company currently investing in solutions for controlled room temperature products?

Participant profile: What percentage of your products need to be stored between 15°C and 25 °C?

Less than10%

Between10–29% 30-49%0%

Understanding regulatory

requirementsPackaging

designFinding cost-

effective solutions

Defining stability profile

and shipping requirements

50-69% 70-99% 100%

Regulators around the globe are paying closer attention to temperature controls and results from shipments of CRT and ambient pr oducts. This attention has changed the industry discussion from cold chain management to temperature control management for all ranges of product temperature sensitivity.

What is the greatest challenge in the distribution and storage of controlled room temperature and ambient products?

Temperature Control is a critical part of product integrity improper handling especially of temperature-sensitive pharmaceuticals, can compromise the efficacy and safety of drugs and pose just as serious of implications to patients’ safety.

81%think regulators around the globe are paying closer attention to temperature controls and results from shipments of CRT and ambient products

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Yes we do!

No thanks

YesNo

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Not sure

The information in this infographic is intended for research and subject to change. IQPC herein take no responsibility for information that may be inaccurate. Statistics from Pharma IQ’s Storage and Distribution of CRT and Ambient Products Survey conducted Dec 2011 – February 2012.

Due to increased regulatory scrutiny, the

number of life science products that need to be

temperature controlled has dramatically

increased, leaving companies to define

15-25 °C regimes

63% Yes

Cold Chain

17

The first-ever online Cold Chain event - connecting the international cold chain pharmaceutical communityPut the dates

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