Cold Chain Roundtable

1. How are new software developments contributing to cold chain logistics?

MT: It seems that when American Thermal Instruments introduced our cloud-based temperature management system two years ago, we were the only company that had a flat screen in our tradeshow booth talking about transmitting data and apps. Now, it does not matter what the product line is, every supplier is talking about their cloud and the need to hire software engineers and suppliers to their workforce.

CRG: The accelerated growth of computer capacity and the reduction in the size of the computer chip have moved the cold chain industry into a new era of technology. Moore’s law, which states “that the number of transistors in Intel microprocessors would double every two years”, has produced many results since the mid-1970s that are responsible for the bulk of our present-day capability to handle powerful software. The results of exponential growth of computing have delivered information faster, cheaper per transaction, from smaller devices using less energy. In addition, the ability to store software onboard and compute faster means that recording and storing data for the entire cold chain with internal systems, will modernize cold chain products and services.

The new cold chain products and logistics services will: 

• operate larger software programs on-board
• access more data,
• communicate outward and receive from the container
• transmit transactions
• utilize a device which is smaller size than the original singlefunction temperature monitor

Some of these features are available today at a premium cost. The next phase forward will be standardization of transactions, addition of artificial intelligence (AI) functions and mass production of devices at lower unit costs. Artificial intelligence (AI) will play a major role in:

• mode, route and energy decision-making
• courier and shipping scheduling
• packaging decision-making

The step toward computerization allows the cold chain to be interconnected with the future goal of integration into the supply chain.

KML: Software developments are happening in many areas, including track and trace capabilities for security, as well as for asset management purposes in the case of reusable packaging and reusable temperature monitoring applications. In addition, software for the monitoring and logging of temperature data is becoming quite commonplace for the purpose of tracking trends of excursions to certain lanes, carriers, etc.

MP: There are various fields where software plays a role in making cold chain logistics more safe and efficient - simulation technologies, forecasting and planning tools, but also cold chain databases. Today it is possible to install cold chain monitoring solutions, including cloud-based databases that-

• use the stability data configured in data-loggers with multi-level acceptance criteria to speed up product release at the destination and reduce shipping and packaging costs
• collect all data efficiently without software at origin or destination
• manage the continuous improvement process through cloudbased database solutions without installing any software

HA: There is a lot of hype surrounding the use of “cloud-based,” cold chain related applications coming to market, and this information is causing confusion for some life science entities. Strictly defined, the so-called cloud providers manage the infrastructure and platforms within which the applications operate, while the applications leverage a network of information. This is sometimes referred to as “on-demand software” or “software as a service” (SaaS) and is usually priced on a pay-per-use basis or a subscription fee. The confusion arises because some life science companies are not accepting true cloud-based applications, particularly when it comes to housing data that serves as the “file of record” - as cold chain data does. There are problems with being able to validate software applications when the data is stored on disparate servers in unknown locations – as in a true cloud-based system. This said, the life science industry has become much more open toward utilizing web-based hosted software applications managed through a third-party on a “private c loud.” The primary difference between a private and a public cloud-based application is that in the private cloud example, the solution provider and the customer know exactly where the data resides, as well as the underlying security of that information. Sensitech’s ColdStream^® application is exactly this – a hosted webenabled software application that provides all of the benefits of cloud computing but enables appropriate management and controls so that the system can be validated (a private cloud). Sensitech is a global leader in supply chain visibility solutions targeting the temperature-sensitive markets, including pharmaceutical, food, and industrial chemical. Designed with redundant architecture, Sensitech’s ColdStream solution uses a dedicated hosted-server environment for customers to collect data, monitor shipments and provide notifications and alarms. Network infrastructure and servers are fully redundant to ensure minimal impact to customers in the event of a server or network issue. Customer-specific ColdStream databases are hosted in a hardened data center, located in an offsite, independent facility that provides power sources, redundant points of connectivity to the Internet, and security mechanisms against fire, physical threats and natural disasters. All ColdStream databases are monitored and supported 24/7 with a fully-replicated, mirrored site in a separate geographic region of the United States. Data is synchronized between the two sites, regularly audited, and compliant with Statement on Standards for Attestation Engagements (SSAE) 16. The ColdStream application and data hosting components are built to satisfy the requirements of U.S. Food and Drug Administration (FDA) 21 CFR Part 11 and EudraLex Annex 11, including audit trails and traceability for all electronic records, multi-layered permissioning, and backward compatibility for previously acquired data files. Customer data is backed-up according to information technology best practices. Before the data is stored in an offsite data vault, the back-up process includes encryption and compression; these formats remain the same throughout the length of storage. Backedup data is tested and verified annually to be recoverable. Sensitech’s ColdStream environment and Quality Management System (QMS) have successfully passed all customer audits, now numbering more than 100 over the past decade, to the satisfaction of our cGMP customer base. Sensitech securely hosts cold chain and logistics data for more than 200 companies around the globe. While hosted applications and cloud-based systems offer many benefits and cost savings by leveraging and sharing existing infrastructure, one should not be confused between private-cloud based software services and what is commonly referred to as “cloud computing,” because pure cloud computing does not provide the security, control, and visibility requirements needed for validation in the life science industry.

2. How are regulatory movements affecting cold chain technology in biopharmaceutical R&D?

MT: We are dealing with serious risk. If decisions can be made in real time, then the more regulation and infusion of technology, the better.

CRG: The focus of regulatory agencies has been to make every link of the cold chain visible while insisting that biopharmaceutical companies demonstrate control of the product. The scope of cold chain in the past extended from the manufacturer to the wholesaler. Today the scope has extended from the manufacturer to the end-user. The regulatory agencies are holding manufacturers to the product temperature requirements that the manufacturer submitted to the agencies.

The industry has responded to the regulatory agencies with two distinct approaches.

The first approach generates new stability programs, testing to support both storage and shipping temperature ranges identifying specific excursion temperatures and durations. This approach also generated a practice of using pre-qualified shippers without the use of temperature alarms or monitors.

Historically, the stability and shelf life label had designated the storage temperature conditions, considered both the storage and shipping temperature ranges. This created numerous situations whereby shipping excursions beyond the shelf life label required extensive investigations. In many cases this resulted in destruction of good product.

To correct this loss of safe product, manufacturers have chosen to use the first approach to conduct additional testing within their stability program that will support separate storage and shipping criteria and acceptable exposure levels. As an example, the new specification would be: storage conditions 2ºC to 8ºC ± 2ºC and shipping conditions 2ºC to 15ºC up to 5 days with exposure to 25ºC for a cumulative 72 hours.

The second approach utilizes the existing product label temperature ranges, monitors temperature to aid product conditions and applies new shipping container technologies to enhance the protection of the product throughout the shipment. This approach includes utilizing new insulation materials, phase change materials (PCMs), multi-function temperature monitors and effective routing. The result is that the product is shipped under better controls, while the temperature is recorded and monitored throughout the shipment.

Although there are a few companies that implement both approaches, the majority that recognize this risk area, choose to take only one of these approaches.

KML: We are seeing more and more tightening of ‘controlled room temperature’ requirements driving applications to maintain 15 – 25°C more strictly than in the past. Also, we are seeing the involvement of regulatory controls during ‘last mile’ distribution, including that of product samples from individual pharmaceutical sales representatives to the doctor’s office.

MP: I see three driving elements where regulatory pressure is increasing and having great impacts:

• Requirements to control and monitor all products with a label temperature. 

When the "cold chain subject" came up about 15 years ago, the focus at the time was primarily on vaccines and insulin (and a few biotech products) with a classical 2-8°C-profile. The first challenge at the time was to find containers and develop passive insulated boxes being able to keep those temperatures during transportation. Since then the focus has widened step-by-step and for two years or so, most large pharmaceutical companies declare everything temperature sensitive which carries some sort of temperature label – even if the definitions are very generous, such as "0-40°C" or "room temperature".

• Widening the scope vertically along the supply chain.

While the first guiding documents focused on discussing the "production to depot" section, newer documents have a wider perspective on the entire supply chain: from R&D, API, distribution over local distribution, to the last mile and storage in between the differenttransport steps.

• Requirements to install programs for continuous improvement of the cold chain.

Companies not only need to ship and release correctly, they also need to start collecting information and taking conclusions. This has led to installing global cold chain databases that collect and compute cold chain information from data loggers.

KL: Regulatory groups such the MHRA and FDA have increased their scrutiny of drug products that are required to maintain “Controlled Room Temperature” (CRT) during storage. This increased attention is pushing drug manufactures to apply strategies to maintain the CRT environment by means of insulated packaging or specialty logistics services. In many cases, CRT drug products do not warrant the gross trading margin for the drug manufacturer as large molecule biological drugs do. To make matters worse many of these products are quite often “off patent” or generic which drives down margins even further. Our organization and other service providers see this dynamic as an opportunity to develop new products and services to meet our clients’ demands. Respectively, drug manufactures should consider additional stability studies on current products to prove their efficacy to regulatory groups. Point being many of these drug products now being brought under the umbrella of CRT has been in use for decades without significant negative impacts to patients. It is my opinion that a balance needs to be found between the strict thermal requirements of a high end, large molecule biological vs. older less sensitive “off patent” products that have been successfully used by millions of people for decades.

3. What are cold chain product and service providers doing to confront needs for compliant cold chain processes?

MT: I believe you see more collaboration between the suppliers as everyone is interested in delivering a single-source solution. The products need to be interchangeable, so that they can fit the needs of the client. There is not a standard “anything” anymore. Clients want customized solutions.

CRG: First, the industry continues to experience loss due to counterfeit and theft. The answer to this security threat is new technology that must integrate with the compliance process. Second, providers are using new software systems which deliver data to document the controls and show that initiated changes were successful. Providers can simulate the client’s product, shipping conditions and predict the thermal risks areas.

Second, providers are using new software systems which deliver data to document the controls and show that initiated changes were successful. Providers can simulate the client’s product, shipping conditions and predict the thermal risks areas.

Third, reliable packaging and devices are utilized to assure controls are in place during shipment that protect the product and meet the manufacturer’s specifications.

Fourth, the new scope of activity and process coverage now extends from the manufacturer to the end-user. Providers must focus on cold chain expertise and technology solutions for the last mile. Solutions would address qualified packaging for clinical supplies for the last mile, such as hand-carried containers, etc.

KML: If I change the specifics of the question from “confront needs” to “What are thermal packaging manufacturers and service providers doing to proactively lobby for tighter regulatory compliance for the shipment of temperature sensitive drugs that would influence the FDA/EMEA to accommodate as well as implement and enforce new processes to insure payload protection and patient safety?” - I would say I think there is a balancing act that is driving behavior within the pharma and biotech manufacturing industry. In a business environment of cost containment and/or budget reductions, yet one in which there is still a need for enhanced packaging and service processes. Manufacturers can tend to be reactive in behavior specific to their cold chain distribution needs, as an increase in spending on thermal packaging or logistics services reduces their bottom line. They are forced to make up this profit by either identifying alternative savings or passing along the cost to the consumer. Customers may not realize the price increase at the retail level but rather, in increased, out-of-pocket, insurance costs. Traditional large manufacturers have so much capital invested in tooling, equipment and overhead that it is generally in their best interest to support status quo. Smaller companies that are not invested heavily in specific technology are driving new solutions for enhanced protection and cost containment. If the question was, “How are Cold Chain product and service providers working together to develop innovative solutions that support compliant cold chain practices?”, then, I would say, as we do at MTS, "by working innovatively with third party couriers (3 PL’s) to implement more cost efficient container solutions that are smaller, lighter weight, more cost effective, as well as environmentally friendly than other known traditional technologies."

MP: This is exactly what service providers are here for. Everything they undertake should have the ultimate goal to deliver (or support) compliance in a cost efficient and reproducible way. Compliance is not an "ad-hoc” thing – it can only be obtained with a stable, longterm set-up delivering the same results over month and years. Although compliance is finally the responsibility of the pharmaceutical company, (product owner), ideally, supplies are contractually bound in their scope to deliver and/or support compliance. To do so, pharmaceutical companies must define clear expectations (requirements).

Examples:

• How should a temperature-controlled truck perform in hot and cold conditions?
• How long can containers be kept on the apron of transit-airports?
• What are the archiving rules of a cold chain database?

These examples show that it is very difficult for a pharmaceutical company to come up with the correct requirements, as they require a deep understanding of the technologies and processes involved. It is therefore the responsibility of the supplier to come up with clear specifications of their products and services in order to ease the documentation of requirements and validation on the customer end.

KL: Inmark is assisting its clients within its scope of expertise through training and multiple profile thermal testing. The implementation of a new Temperature Control Package (TCP) is critical. All of Inmark’s TCPs have been tested under a variety of profiles and used by multiple customers with excellent results. When excursions do arise, I welcome the opportunity to work with clients to determine the root of such problems and explore what can be done to prevent future excursions. Root cause analysis should establish a sequence of events ^[1] to understand the relationships between contributory (causal) factors, root cause(s) and the defined problem. The first obvious, fixed variable from the perspective of a cold chain package provider is the system itself. If the TCP has been laboratory-tested, has proven field performance, and the product was manufactured to our standards, the package did not fail. Therefore, the excursion took place due to an inconsistency in the packing process, or it was shipped in an ambient environment more extreme than the thermal profile it was tested to. In short, it is critical that TCP system providers include customer training and/or specific and detailed packaging instructions with their systems. Clients shipping high volume expensive products should build their knowledge on basic thermal dynamics and how it applies to the transport of temperature sensitive products.

Recognizing that regulatory agencies and drug manufactures do not have a global standard for the testing and qualification of a TCP, Inmark offers its systems pre-qualified to multiple thermal profiles. This approach demonstrates repeatability for our clients and also allows them to choose a system that matches up best with their shipping lanes and level of risk. In addition, our team is qualified to work with clients to scientifically characterize their shipping lanes and choose the most efficient package for their requirements.

HA: The global regulatory and standards-based guidance is pushing the industry to move from a cold chain monitoring program, where shipments are monitored on an accept/reject basis, to one where aggregated data is used for trending analysis. Specifically, the industry is calling for a "Quality Management System" (QMS) used to document the distribution process beyond the four walls of the drug manufacturer. U.S. PharmacopeiaGood Storage and Distribution Practices for Drug Products states: “Good storage and distribution practices apply to all organizations and individuals involved in any aspect of the storage and distribution of all drug products.” The use of the words “all, any, and all” offers a clear indication of how the industry is responding to the increased awareness of cold chain issues. The document furthers tates: “ Good storage and distribution practices should facilitate the movement of drug products throughout the supply chain that is controlled, measured, and analyzed for continuous improvements…” ^[2]. U.S. Pharmacopeiais just one example – the pending new European Union Good Distribution Practices (EU GDP) offers similar language. The good news is that a hosted web-enabled application such as Sensitech’s ColdStream solution was designed to allow customers to manage their cold chain as a process and is implemented as a critical component of a Quality Management System (QMS). The primary role of this system is to enable the aggregation of time/ temperature data from many shipments including shipment and logistics data (origin, destination, pack-out, carrier, trade-lane, season, etc.) and facilitate the analysis of this information to document compliance within set quality tolerances. This move, from determining if a particular shipment has maintained appropriate temperatures, to the documentation of a system operating within appropriate quality parameters, and the application of a risk-based approach, exemplify the future of cold chain applications.

4. What challenges do increased shipments of biologically-based products present?

MT: I believe that the supplier network for the cold chain market has prepared itself well in the past five years. Quality and Logistics Managers can find a solution to challenge/need immediately.

CRG: Today, the majority of biologically-based products are cold chain. These product temperature ranges are much tighter and require more controls. Ten years ago biologically–based products amounted for less than 5% of the market. Over the next five years the majority of the biopharmaceutical sales will be comprised of cold chain biologically-based products.

• The cold chain biologically-based products as compared to non-cold chain tend to be labor intensive, require extra handling, packaging and shipping.
• The shipments are usually larger and heavier, incurring greater freight cost.
• The destination must be checked to ensure cold storage is arranged and back-up plans are in-place, in case space is not available.
• Other characteristics besides temperature, such as humidity, photosensitivity, vibration, etc. may require changes to the packaging or shipment.

For shipments outside of developed countries:

• There are constraints on the transportation system especially with longer staging or storage times at ambient temperatures between flights or ground transport.
• Customs and security disregard the necessary procedures required for cold chain control by opening and inspecting in adverse temperature conditions.
• There is a lack of availability of reliable temperature control shippers. Most of the advanced materials are not available in other parts of the world.
• The infrastructure of the country for cold storage may not be reliable, for example frequent power outages that limit cold storage capacity can occur.

For shipments to the clinical sites:

• The size of the shipment is often limited by available refrigerator or freezer space at clinical sites.
• Infrastructure and funding to provide public health cold storage may not exist. Non-electrical solutions must be explored.
• There is a lack of design and availability of last-mile containers. Delivery to the patient of temperature sensitive products by hand carried packaging, small volume carriers with a good temperature range is a critical part of the last mile.
• In the past, the cost of containers has been the major deterrent in developing compliant packaging for the last mile.

KML: Increased shipments do not present an additional challenge. The issue at hand is still payload protection and patient safety. We will see the continued outsourcing of key operational activities in the thermal packaging and logistics arena by pharmaceutical manufacturers and drug wholesalers. Again the challenge is not an increase in shipments, but getting shipments into emerging markets that require more robust packaging (longer durations) and more difficult distribution lanes. For instance, South America, India and Russia have unique customs requirements, challenging ambient temperatures and non-traditional last mile transportation logistics.

MP: I do not see extra challenges from a technical point of view. There are sufficient technologies and services solving all requirements to ship biological (highly sensitive) products. Biologicals are not more sensitive than classical insulin or vaccines, which have been shipped since the beginning of the "cold chain industry," in the late nineties. However, I do see challenges in the collection of patient samples, as there is very little experience and equipment available for shipping products from clinics and hospitals. But even this new niche has already been filled by service providers, offering efficient and safe sample collection services.

MG & JPE: With an increase in biopharmaceuticals, more products are requiring tight temperature controls. To maintain the safety and potency of these drugs, increased scrutiny should be placed on a proper cold chain management program. The industry has been focusing on reducing exposure to temperatures above the required temperature range, such as 8°C. Mitigating high temperature exposure is crucial, yet biologically-based products can be damaged faster (and with fewer degrees of freedom) when exposed to freezing temperatures. Interestingly, products are damaged more in the summer than the winter due to freezing, since additional cold sources are added to packaging systems in an attempt to prolong protection during temperature peaks.

The longest period of time that products are in the hands of the manufacturer, distributor, or retailer is during storage. Utilizing a temperature alarm system, with properly calibrated and strategically- placed temperature monitors is crucial to reducing the chances of damaging the products during storage. The placement of temperature sensitive products inside of the storage unit should be considered in order to protect from hot or cold spots. While an emphasis is currently placed on developing and operating a working cold chain distribution and packaging system, it is worthless if the product is damaged before even leaving the facility.

Once a cold chain storage and distribution system has been established, it is important to maintain records of temperature compliance and temperature excursions with corrected actions. By reviewing corrective actions, the facilities can improve upon past errors in order to optimize their standard operating procedures. Quarterly random testing of the cold chain system from product inception to storage then final destination is ideal to ensure the processes, equipment, and packages are working. There are many variables that can make or break a cold chain system, such as employee mistakes, various weather conditions throughout the network, carriers, suppliers, component changes, etc.

Identifying these various aspects and their impacts on the cold chain system is important for enhancing temperature compliance and can reduce temperature excursions. An ongoing review of the cold chain system throughout the year will detect the influence of the changing variables and allow for corrections, which will create a good cold chain management program.

5. How do you foresee cold chain technologies shifting over the next 5-10 years?

MT: We might be biased, but a person’s ability to use their smartphone to scan a temperature label or data logger and deliver data back to the manufacturer or distributor exists now, and we look forward to seeing the last mile of implementation over the next 5-10 years. We are ready.

CRG: Over the next 5-10 years, I foresee five areas of technology emerging:

• Computerization: there will be devices with more logistical functions and information on-board. For example, a smart box that will read the outside environment, collect data on internal product space and adjust temperature conditions for the product.
• Introduction of artificial intelligence (AI): this will allow the on-board system to have some level of logic to decide actions. AI will also give the container knowledge of the path forward and make real-time decisions to adjust energy, packaging and maneuver the route to improve the shipment and product conditions.
• Communication: this will occur inside the container to outside as well as with outside higher level computer systems. At the same time, artificial intelligence (AI) within the shipping container will talk to other systems to maintain the necessary product conditions.
• High tech insulation materials and combination PCM: this will protect and regulate the temperature of the product versus the outside environment. These materials already exist, but are not cost competitive at this time.
• New technology platform: this will be designed to regulate temperature. As an example, the evaporative cycle is the latest approach on the market. Shared discoveries from other industries will reveal a possible new energy platform.

PCM: this will protect and regulate the temperature of the product versus the outside environment. These materials already exist, but are not cost competitive at this time.

• New technology platform: this will be designed to regulate temperature. As an example, the evaporative cycle is the latest approach on the market. Shared discoveries from other industries will reveal a possible new energy platform.

KML: I foresee:

1. Continued growth in cold chain due to increasing sensitive biologics, continued and increased regulatory compliance, and continued challenges in emerging markets.
2. Continued focus on cost reduction in anticipation of a long list of expiring patents.
3. This cost containment focus will lead to more and more outsourcing to global logistics carriers, who may invest in thermal packaging technologies and manufacturers to create a “branded” total solution.
4. The long list of expiring patents will lead to more acquisitions and mergers, as manufacturers look for ways to rebuild their pipeline.
5. Tracking real-time payload and air temperature will become standard operation, as manufacturers and logistic companies track performance in emerging markets.
6. From our perspective, we see reusable thermal shipping solutions representing 30%-50% of the market – while traditional EPS/PUR water base gels will continue to represent the balance.

MP: In my view, Cold Chain has three elements: Packaging, Transportation and Monitoring. Terms of packaging, I expect that the use of phase-change materials and vacuum-insulated panels will grow further and therefore become more efficient and affordable. At the same time more and better stability data will be available and put requirements in a new perspective. As suggested in PDA Technical Report 53 (Stability Testing to Support Distribution of New Drug Products), the focus might shift from "2-8°C strict" to less demanding limits (e.g. "2-8°C but deviations allowed for 10h from 0-20°C"). This will make cold chain transportation much more affordable. 100% monitoring of all cold chain shipments thereby becomes even more important. On the monitoring devices as such, I foresee two trends happening in parallel:

1. Decrease to smaller entities being monitored (on pallet-, box- , or kit-level). By doing so, the data logger or indicator can follow the pallet/box/kit along various logistics steps. At some point there will also be efficient wireless technologies involved to harvest information more efficiently and/or combine temperature monitoring with positioning data to cover the growing needs of supply chain security. But there is still a long way to go before suitable standards and infrastructure is available.
2. Integrate cold chain information with shipment information in ERP solution (like SAP). By doing so, it will be possible to manage the stability budget of products along the entire supply chain. In a long-term perspective, I'm convinced it will be possible to integrate information from storage with information from transportation and therefore manage the expiry date of products from production to the patient.

MG & JPE: Currently, the most common insulation material is expanded polystyrene foam (EPS), which is difficult to recycle and does not degrade in landfills. Cities across the country are beginning to take a closer look at the impact of EPS in landfills, resulting in bans and removal taxes. With an increase in pharmaceutical mail order cold chain shipments and one-time use pallet shippers, more EPS packages are being introduced to communities as waste. Mail order patients can receive between two to four boxes per month, which become trash since they are meant for one time use. EPS is an effective insulator for a low cost and weight; alternative insulations will need to meet similar specifications in order to satisfy the market. Insulations that are easy to recycle will increase in usage in order to meet customer demands of recyclability. Developing recyclable or biodegradable insulations that provide a high thermal protection will allow for a reduction in cold sources, such as frozen gel packs. The cold sources are usually the highest weight-packaging component. Reducing the package weight will reduce shipping costs as well as carbon emissions.

Most closed-loop cold chain distribution networks reuse their shipping packages, especially the insulation material, which reduces waste and material costs. With an increase in technologies allowing for customers to easily return packages, previously open-loop distribution systems can become closed, allowing for the reuse of shipping packages and materials.

As more biopharmaceuticals are being transported around the world, a more cost-effective and temperature-controlled transportation system will emerge. Currently, most temperature-sensitive pharmaceuticals are being air-shipped, which requires high freight charges, and cannot always guarantee a temperature-controlled environment. Land and sea transportation technologies could be viable solutions, by providing a lower cost alternative if the technology can be advanced to allow for high quality and consistent temperature maintenance.

JC: Patient safety is paramount. Over the past several years, we have seen the landscape of best practices and regulation in cold chain work its way through the supply chain. First, regulators and best practices focused on the manufacturing companies. Next, that focus moved downstream to the wholesalers. Manufacturers recognize that if anything goes wrong, it’s their name on the box, regardless of who has title or who is at fault. Manufacturers themselves are taking a more proactive approach and educating downstream distributors of their products. Regulators are also starting to focus more downstream, and future emphasis will be in the last mile. There is much room for improvement in this arena. Educational programs that highlight the importance of keeping the cold chain intact through all touches will become more prevalent. Profit margins dwindle as you move through the supply chain and correspondingly less investment is made in packaging and monitoring at each step along the way. In the next few years, you will see an emergence of high-performance shipping systems and monitoring technologies that are also cost effective, protecting both patient safety and the bottom line. These solutions will be compact, low weight, and utilize environmentally- friendly materials. Patients will be better educated about the importance of temperature control. The market will reward those companies that can prove to patients that product integrity has been maintained, ease of use has been engineered, and environmental impact has been minimized.

HA: Significant improvements in technology and the continued expansion of the use of temperature-monitoring devices have presented opportunities for leading providers to add more value. While just a few years ago, the prospect of providing real-time temperature data for a shipment in-transit was too costly to seriously consider, recently, things have begun to change. First, potential risks in the pharmaceutical supply chain have expanded to include cargo theft - thus increasing opportunities for expanding the Return on Investment (ROI) for real-time monitoring applications. Second, the regulatory and standards-based trends are pushing for convergence of environmental condition monitoring and cargo security applications. In 2006, I wrote an article titled: “Authentication from a Cold Chain Perspective,” published in the July/August issue of Pharmaceutical Commerce. In this article, I drew a connection between high-value drugs (often those requiring special handling) and counterfeit efforts, as well as the broader definition of adulteration, which includes improper environmental controls. Ultimately, the argument was made that efforts to secure the supply chain from risks, including counterfeit, diversion, and theft should be unified with efforts to ensure proper environmental controls are in place. A product that has been temperature-abused has the potential to be just as dangerous as one that is not genuine; a QMS that does not monitor both elements may allow unknown or undocumented risks to continue. Fast forward six years and now there are many examples of this drive for convergence including the new EU GDPs and the pending combination of U.S. Pharmacopeia,, and. The most significant example of this convergence of environmental condition monitoring and in-transit visibility is the FDA’s “Response to Cargo Thefts,” published i n M arch 2 012. The document states: “ The FDA is very concerned about the increase in cargo and warehouse thefts of FDA regulated products, including prescription and over-the-counter medicines, vaccines, medical devices, and infant formula.” The key issue is an overall concern of threats to public health and “adverse reactions, most likely due to improper storage and handling.” Given that the industry has recognized the need for and value in the convergence of environmental monitoring and supply chain security programs, Sensitech, recently purchased FreightWatch International, a leading provider of cargo security solutions – providing realtime visibility of shipments in-transit. Ultimately, the convergence of these solutions from both an application and device standpoint will drive additional value across the pharmaceutical supply chain including areas of regulatory compliance, vendor management, risk management and overall operational benefits.

6. Any closing thoughts?

MT: It’s been an exciting five years for the cold chain market when it comes to technology. We can’t wait to see what the next five years will bring.

CRG: Within ten years, depending on the urgency placed by regulatory and/or cost issues, an alarm will be placed on/at the delivery device. The alarm will be utilized at the delivery device level (syringe, vial or bottle) to assure product temperature and detect tampering.

The growth of artificial intelligence (AI) into logistics and cold chains coupled with the lower cost and smaller computing devices, will replace many manual activities. This will quickly be implemented for developed transportation routes and high volume hubs.

The business emphasis from biopharmaceutical manufacturers will be to commoditize the cold chain and the shipping process. This initiative could reduce special handling and drastically lower costs. Hopefully, this initiative to lower the cost does not overlook any detrimental effect on product quality.

Based on experience, it is evident that as new biologicallybased products are developed and manufactured, new obstacles and challenges will be encountered. This will continue to demand new packaging solutions, delivery systems and distribution networks.

KML: We all work in one of the most dynamic and exciting growth industries in the world, which will bring about rapid change in the future. A manufacturer or service provider’s ability to react to change or implement change will be the key to success. Not change for the course of change, but innovative change, which results in more effective solutions that increase patient safety and reduce overall cost of delivery.

MP: Cold Chain is a joint responsibility of suppliers and product owners – it is an obligation, and at the same time, a great honor to be part of an undertaking which ultimately only has one target: to deliver patient safety.

MG & JPE: Cold chain packaging, transportation, storage, and handling concepts revolve around the basic principles of heat transfer. An understanding of the three main heat transfer principles, convection, conduction, and radiation could benefit the entire industry. Training organizations on the principles would provide an important tool for detecting and solving cold chain problems before they become too difficult to manage.

References

1. "Sequence of Events." Wikipedia. Wikimedia Foundation, 03 June 2013. Web. 06 Mar. 2013.
2. USP-NF Informational General ChapterGood Storage and Distribution Practices for Drug Products, USP 26, NF 31, 2013.