Mapping the Secure Temperature-Controlled Supply Chain Requirements

• Eli Lilly and Company
• Pharmaceutical Cargo Security Coalition
• ASC Associates Limited

Introduction

In recent years, global pharmaceutical supply chains have increased in complexity and scrutinization, due to the involvement of many players with new guidance, regulation and compendial requirements.^1-4 For example, compliance with the European Good Distribution Practice (GDP) of Medicinal Products for Human Use guidelines will ensure control of the distribution chain and consequently maintain the quality and integrity of the medicinal product as it is being handled by many different players.¹ In addition, the newly published United States Pharmacopeia <1079>, Risks and Mitigation for the Storage and Transportation of Finished Drug Products presents arisk-based approach for the development of Quality Management Systems (QMS) that includes product and process knowledge, risk identification, and mitigation strategies with focus on documentation, training, resources, and qualification/validation.² Furthermore, pharma serialization has been developed by governments to combat drug counterfeiting that may directly affect the public health. The main goal of this requirement is to be able to track and trace the medicines during the supply chain process.^3-5

In the current, very unique, time of the COVID-19 pandemic, temperature control of transporting vaccines and medications is becoming even more important and may be unusually challenging, as some shipment sequences would require cryogenic shipment protocols at -80°C, in addition to the refrigeration 2 – 8°C, and/or freezer between -25 and -10°C, conditions. Cell and Gene Therapies may require the cryogenic temperatures at -196°C and -80°C, respectively.

Shipment Mapping

With regards to the complexity of these global, temperature sensitive, supply chains, the “mapping” of the various tasks in the handling, storage, and transportation of the shipped medicinal products is an activity, that in many instances, is not documented in enough detail.

A complete and accurate mapping process should help to identify all entities that would ultimately “touch” the shipped product, in both storage and transit, as well as the lanes the product will travel through (from origin to destination), where and for how long the product might come to rest - recognizing that “cargo at rest is cargo at risk”, as well as all of the flow of information surrounding the shipment. In regard to this process, attention should be paid to the details of the distribution practices, required environmental conditions, the benefit technology might provide, and the overall risk evaluation of the entire process.⁶

In this paper we will present a model for mapping secure, temperature controlled, supply chain lanes - as well as comment on secure shipment practices.

The Mapping Process

In this model we are assuming that the product could be shipped virtually anywhere around the globe, from the site of origin (manufacturer, packager, distribution center, etc.) to its ultimate destination.

Security Check Assessment

Once the shipping origin and destination have been identified, investigative inquiries should be made of industry associations who monitor global counterfeiting and product diversion – for any threats relative to manufacturing, clinical trial processes and ultimate product distribution. One such organization is the Pharmaceutical Security Institute.⁵ It is widely known that counterfeiting groups thrive in countries where the anti-counterfeiting laws are weak; the drug regulatory agencies are underfunded and understaffed; and legal sanctions are ineffective. Those factors will become more important as the planning of the shipping and storage of newly developed vaccines and medications, for the treatment of the Coronavirus, are considered.

Shipping Mode

Shorter distance, less time, and as much direct travel as possible should be of a high priority in determining the shipping modes that will be used to move the product from origin to destination. The central part of Figure 1 shows that the product will move from the site of origin, by ground, to the origin airport; fly to the connecting airport; fly to the destination airport; move by ground transportation to a temporary storage facility; and finally, by ground to its destination.

In air freight supply chains this is commonly known as a “multimodal” transport model. Direct flight from the origin airport to destination airport, and direct ground transportation from origin to destination are shown, in the upper and lower part of the Figure 1, respectively.

It is important to note that irrespective of the mode of transport a risk-based approach should be taken when planning transportation and transportation routes.

The Packaging for Transportation

The proper primary and secondary containers should be determined by the shipper of origin. In addition, the tertiary and/or the shipping packaging for transportation, as well as the labeling, must comply with the good manufacturing practice procedures (GMP). It is recommended that the shipments be placed in cardboard master cartons which would have an identification label, as per the manufacturer GMP procedures, on its outside. It is recommended not to place specific branding on the master cartons. The carton labels would have the manufacturer name of the product, a unique identifier as a part number by the manufacturer, a lot number, an expiration date; as well as any other information included in the manufacturer’s procedure. For air freight shipments, the IATA Time and Temperature Sensitive label is required to be used.

Environmental conditions of the shipped product needs to be managed to prevent any excursion during the transportation. This is accomplished using active or passive thermal packaging, which has been qualified from origin to destination - for the time and temperature of the specific shipping lane. Details of the temperature monitoring should be justified using the proper loggers and/or qualification data. Realtime data loggers should be considered – which could allow for real time corrections over the entire shipment process.

The number of cartons per pallet and the number of pallets per container should be determined in either a technical or service agreement between parties. Carrier dedicated containers are preferred to enhance the opportunities for the shipper’s cargo to be exclusive, within the container itself. Carrier containers need to be sealed and all sealing devices, and their associated serial numbers, documented on all shipment paperwork.

Shipping Logistics Coordination

Mapping of the logistics details should be documented. This would include the ground and air movement of the product by each carrying entity, each storage entity, any subcontractors, to include the details of all shipment “hand offs”.

The freight forwarder, for the shipments leaving origin, should be a recognized (either national and/or international) entity with verifiable protocols for coordinating the handling of urgent and dedicated, secure, temperature-controlled pharmaceutical products. Hence, freight-forwarding entities that have acquired a Good Distribution Practice (GDP) certification, are in possession of a WDA (Wholesale Dealers Authorization), are working to GDP compliant standards, and participate in IATA’s CEIV Pharma Program, should be preferred.⁷

It is advantageous that all delivery conveyances, themselves, be temperature-controlled and that those entrusted with transporting the shipments be well versed/trained on Good Distribution Practices.

As many of the transporting entities as possible, involved in the movement of these temperature sensitive shipments, should be able to be “tracked” by both the shipping and the receiving entities. In certain cases that may involve the use of GPS technology. As an example, all “ground” transportation vehicles, whenever reasonably possible, should be equipped with GPS tracking devices. It is recommended that the shipper, itself, imbed a GPS tracking device(s) into the cargo whenever possible. The use of real-time GPS, combined with an environmental (temperature) monitoring device, is encouraged.

Subscribe to our e-Newsletters
Stay up to date with the latest news, articles, and events. Plus, get special offers
from Pharmaceutical Outsourcing – all delivered right to your inbox! Sign up now!

Whenever possible, dedicated shipment trips, with only the specific product to be shipped on board the ground transporting conveyance, is preferred.

It is recommended that the freight forwarder, as well as any ground transport entity, be Transported Asset Protection Association (TAPA) and/or Authorized Economic Operator (AEO) certified.⁸ To have attained those certifications it would be reasonable to believe that the transport company’s vehicles and trailers would be “hard sided”, appropriately sealed, tracked by GPS technology, and their drivers fully versed in supply chain security and GDP protocols.

Finally, ground transportation between two destinations, whenever possible, should be in a direct non-stop mode. If the distance is long and would require some rest for the driver, proper parking precautions, such as those recommended by TAPA, should followed.

Quality, as well as Technical, Agreements should exist between all stakeholders handling the product from origin to the ultimate destination. These agreements document the what, who and how the handling, storage and transportation will be performed - and should also identify important contacts in the case of emergency, deviation, temperature excursion or a security breach. The agreements should clearly delineate roles, responsibilities and duties of each party.

Example of A Shipment Trip

Time of pickup from the origin should be established and the shipment be readily prepared and sealed with an integrity seal by a proprietary employee of the shipper of origin. Experience has shown that it is helpful if the selected freight forwarder coordinates the acquisition of any shipping conveyances/containers deemed necessary, for what will be the air carrier of record.

The shipment itself is ultimately loaded into a delivery truck. It is preferred that the transportation entity selected utilize proprietary vehicles, as well as proprietary employees (drivers). No subcontractors should be used without the shipper’s knowledge and permission.

Whenever reasonably possible, ground shipments should be “dedicated”, meaning that the products being shipped would be the sole products within the conveying entity.

It is preferred that the freight forwarder have finalized all of the necessary documentation before the goods are delivered to the airline for screening and accepted for the flight. With regards to any potential screening prior to flight, it is helpful if the shipper becomes a "known consigner", within EU transportation protocols, or a participant in the United States TSA “Certified Cargo Screening Program” which would allow for screen-free handling at any airport.

If airport screening is required, that screening should be taking place in temperature-controlled environments and, where available, be under full Closed Circuit Television (CCTV) surveillance coverage - with a designated witness. Similarly, any areas within an airport cargo handling area where shipments might be staged, pre-flight, should be access controlled and also under CCTV surveillance.

If airport screening is required, once the screening activity is concluded the shipping conveyance should be closed and re-sealed, with a new sealing device. The entity who performs that re-sealing procedure should, whenever reasonably possible, be agreed upon in advance, as well as documented. Any re-sealing device(s) needs to be recorded on the shipping airway bill.

It is recommended that any airline choice be an entity which is certified by the International Air Transport Association (IATA) - "Centre of Excellence for Independent Validators" (CEIV) program. This certification was developed for pharmaceutical logistics to help organizations, and the entire air cargo supply chain, achieve pharmaceutical handling excellence. The certification recognizes the carrier's capabilities in handling high-value, time-sensitive, pharmaceutical products. It also addresses the industry's needs for safety, security, compliance, and efficiency in the transportation of pharmaceutical products.7

All times for transportation, staging, screening, customs clearance and storage, should be documented, similar to what is required of the qualification process. In line with the principles of GDP these key processes should be risk assessed.

Items to Consider for a “Mapping Form”

The following is a non-inclusive list of items to be included in any shipment visibility platform:

• Account number
• Origin
• Destination
• Freight brokerage information: availability at destination, office/agent, estimated customs clearance time, customs operating hours.
• Airport at origin, any connecting airport, and airport at destination
• Availability of temperature control facilities at all airports during transit
• For each flight segment specific flight information, to include airline, aircraft type, routing, and service/handling definition
• Estimated time of departure (ETD), estimated time of arrival (ETA)
• Estimated aircraft loading/unloading times
• Air shipment cut off and/or cancellation protocols
• Specific ground transportation information, to include transportation firms, types of vehicles to be used, and service definitions
• Details for pick up times from airline, collection/delivery notes
• Any locations where shipment might be temporarily “stored” enroute to ultimate destination
• Identifying information on entities providing storage services: company name, person of contact, storage attributes – environmental controls, security
• Total planned transit/storage times between origin and destination
• Standard and emergency contact lists for all parties involved (shipper, receiver, freight brokerage, Customs offices, cargo insurer, and all transportation/storage entities, to include: contact name, company, position, office phone number, mobile phone number, email address
• Route design approval: name, company, signature, date
• Comments on route risk level

Recommendation for Mapping the Risk Mitigation of the Secure Temperature-Controlled Supply Chain

• The entire shipment process should be closely examined, with an emphasis on reducing (whenever possible) the number of handling and manipulation points, as well as “rest points”, a shipment is being subjected to. From a risk perspective, it is known that every “handling and manipulation point” (no matter how familiar, experienced, or “certified” the entity that is conducting it) subjects the cargo to potential mishandling. Ground transportation, as opposed to that in the air, also exposes an increased potential of the product being subjected to unnecessary/unwanted physical contact.
• Investigative inquiries should be made of industry associations who monitor global counterfeiting and product diversion – for any threats relative to manufacturing, clinical trial processes and ultimate product distribution.
• Contingency plans for issues such as areas of high cargo theft risk, political unrest, unusual weather, etc. should be developed prior to moving any pharmaceutical shipment.
• Whenever reasonably possible, shipments should be “dedicated”, and be the only goods being transported within the shipping conveyance.
• Direct ground transportation routes, as well as nonstop flights, should be the preferred mode of moving any shipment as they reduce the number of handling and manipulation points and “rests”.
• All entities that are involved in the handling of pharmaceutical products in that delicate supply chain should be trained/certified in GDP programs and procedures
• Quality/Technical Agreements, between all stakeholders of the shipping supply chain, should outline the desired quality and security requirements.
• Each individual shipment should be accompanied by an independent temperature logger and temperature management should be incorporated in all parts of the handling, storage, and transportation of the cargo.
• The shipper should include at least one, proprietary, GPS tracking device in each of these shipments. The shipper should also require tracking technology be provided, through the freight-forwarder, by all transportation vendors. These devices, collectively, would not only monitor the shipment while in transit, but also whenever it was staged or resting in storage between movements.
• The privileges of being designated a “known cosigner”, particularly in Europe, should be investigated to eliminate the need for airport cargo security screening – before a shipment is placed into a transporting aircraft. Similarly, membership in the US TSA’s Certified Cargo Screening Program would be just as beneficial. What you want to avoid, in case of the cosigner, is the opening of any conveyance/container by airport security entities to comply with government security screening requirements.
• Ground delivery vehicles should be as nondescript as possible. Hence expressive “vendor brand” or “pharma” markings should be avoided. Research has shown that a delivery vehicle that is free of such markings draws far less illicit attention than one that has them.
• The cargo compartment of the vehicles, making a pickup at facilities or directly to/from airports should be sealed with a security seal and the truck be alarmed in the event someone tries to illicitly enter the cargo compartment.
• Partners in the secure temperature-controlled supply chain should be certified by TAPA under the Association’s Transported Security Requirements [TSR] and Facility Security Requirements [FSR].⁸
• The mapping process should be verified on a regular basis and should be updated as experience is gained, the regulations have changed, as well as if any specific contacts have changed.
• Best practice involves a physical audit of the secure temperature-controlled supply chain. The use of experienced Supply Chain Security and GDP auditors should be considered.
• Only qualified and approved subcontractors should be used to ensure GDP compliance at all levels of the supply chain.

Disclaimer

The content and the views expressed in this document are the result of a consensus achieved by the authors and are not necessarily views of the organizations they present or represented.

The mention of a product or service provider does not mean it is the sole product or service that is available for use.

Acknowledgement

The authors would like to thank the following colleagues for their review and comments while preparing this article Zvonimir Majic, Ph.D., TEVA Pharmaceutical Industries Ltd., Erik J. van Asselt, Ph. D., Merck, Robert H. Seevers, Ph.D., Pearl Pathways, and Nina Heinz, DHL.

References

1. European Commission: Guidelines on Good Distribution Practice of medicinal products for human use, 2013/C 343/01, November 2013.
2. United States Pharmacopeia, USP, <1079> Risks and mitigating strategies for the storage and transportation of finished drug products.
3. The European Falsified Medicines Directive.
4. ITS (Turkey), website (in English): https://www.its.gov.tr/index.php?run=home.
5. Pharmaceutical Security Institute (PSI), www.psi-inc.org.
6. Van Diest, G-J., and Bishara, R. H., et. al.: Pharmaceutical Supply Chain Security Risk Assessment for Shipping Lanes. Journal of Pharmaceutical Outsourcing, Volume 18, Issue of September/October 2017, pp. 16-25.
7. https://www.iata.org/en/programs/cargo/pharma/ceiv-pharma/ .
8. https://www.tapa-global.org/information/latest-news-views/news-detail-view/fsr-and-tsrsecurity-standards-certifications-continue-to-climb-in-emea.html.

Author Biographies

Dr. Rafik H Bishara has become one of the most respected figures in the pharmaceutical supply chain distribution sector, following a distinguished 35-year career with Eli Lilly and Company as Director, Quality Knowledge Management, and Technical Support. He is the former (1999-2019) Chair of the Pharmaceutical Cold Chain Interest Group, US branch, within the PDA. Rafik is currently on the pharmacy advisory council Utilization Review Accreditation Commission. He was a temporary advisor to WHO 2007-2018 and acted as mentor and training advisor to the WHO-PDA Pharmaceutical Cold Chain Management on Wheels.

Chuck Forsaith has been involved in pharmaceutical supply chain security for more than 20 years, after having served as both a New Hampshire municipal and State Police officer - and formally directing security operations for a United States military intelligence gathering installation. His responsibilities with the Healthcare Distribution Alliance’s “Pharmaceutical Cargo Security Coalition” include offering supply chain security intelligence; access to contacts from industry, government, and vendor trade disciplines; as well as education. The PCSC, which consists of many individuals from a wide variety of disciplines, monitors the security of pharmaceutical goods in both transit and storage - all over the world. Primarily (but not exclusively) focused on the pharma industry, the PCSC provides useful insights for anyone interested in supply chain security.

Henry Moran joined ASC Associates in January 2016 as Director. The role allows him to use his operational and academic experiences to support clients in obtaining their respective GDP accreditation, providing GDP compliance and supply chain security audits, gap analysis on the GDP requirements, combined with facilitating the ASC GDP and RP for Logistics courses. Prior to joining ASC Associates, he worked for Mundipharma where he started in 2006 as the International Supplies Manager. In the role he had responsibility for the global supply and logistics of delivering product to the customer. The role also included the evaluation and mitigation of risks of pharmaceutical products in the Global Supply Chain, compliance with regulatory guidelines and Cool Chain Management. Prior to working at Mundipharma, Henry worked in numerous logistics roles in Hi-tech Electronics, Global Logistics and Freight Forwarding. Henry is a Six Sigma Black Belt and studied in the UK at the University of Plymouth and at University College Dublin and holds a Master’s in business studies specializing in Manufacturing and Logistics.