Packaging

Bayer Warms Up to Cold Chain Supply

Careful validation and quality assurance work, and close collaboration with vendors, was a “win-win” for all who helped develop Bayer Biological Products’ cold chain solutions.

Bayer teamed up with Envirotainer
to achieve its current global shipping
solution. Shipments using the jointly
developed I-box have provided excellent
flatline results in the 2° to 8°C range.



By Jim Bacon, Director of Global Supply Chain
Bayer Healthcare - Biological Products Division


In the comedy Planes, Trains and Automobiles, Steve Martin and John Candy bumbled and cajoled their way across the country. The film’s enough to send shivers down the spine of anyone involved in the pharmaceutical cold chain. Pharmaceutical and biological products also move over land and sea, and through the air, but their journeys are dead serious, and these sensitive, valuable materials must be kept at optimum temperature throughout their travels.

The increased pressure to ensure cold chain integrity has made developing and controlling shipping conditions a top priority for pharmaceutical manufacturers, and many are responding with innovative guidelines and solutions. Working closely with in-house quality assurance and validation teams and vendors, Bayer Biological Products was able to develop an all-season containment design, using a “worst case” scenario to ensure that product integrity would hold up even at extreme temperatures. In this article, we’ll discuss the approach we took and what we found to be “best practices.”

Vendor partnerships critical

When designing a cold-chain solution, it’s important to focus on practicality, which equals ergonomics plus economics.  To put it bluntly, the best design is worthless if your company can’t afford to ship it.

The key to cold-chain success is selecting a vendor that has handled a wide variety of projects for different customers. Companies whose hands are tied by proprietary agreements can only provide limited benefit. Cultivating a good relationship with the vendor is essential, as the company needs to understand your specific needs and the interplay between your product, its packaging and the shipping environment. It’s also important to find a solution that you will be comfortable with, since changing strategies can be extremely costly.

Bayer worked with one design and testing vendor to devise and carry out an effective cold-chain packaging solution. The company helped us create a structured approach to design and execution, and then worked with our Quality Assurance (QA), Validation and Customer Operations staff to complete the process.

The result was the following step-wise approach.
  1. Establish a test profile based upon shipping requirements, current packaging methods and proposed shipping systems.

  2. Conduct baseline tests of current and proposed shipping systems with test profile(s) created in step one.

  3. Analyze and adjust packaging as needed. Create a test protocol for approval.

  4. Approve protocol and qualify shipping systems.

  5. Based on final report and approval, implement the system and generate the standard operation procedures (SOP) and training required.
The first step was to develop testing parameters. When anticipating shipping conditions and ambient temperature profiles in all the global markets we serve, we found it best to apply our product stability knowledge to real-life examples. For example, if we knew that a product could successfully withstand temperatures of 2°C to 25°C for 30 days, we determined what ambient temperature range the shipping container might experience on the trip and used that figure to calculate what would be needed to keep the product within its temperature limits.

Following Parenteral Drug Association (PDA) recommendations, we tested seasonal extremes by assessing summer and winter conditions for each shipping destination. Our challenge was to develop an economical, ergonomic solution that we were confident would protect the product.

Our QA, Validation and Customer Operations staff worked in concert with the vendor’s project team to figure out time, locales, local temperature extremes, distance and other logistical details that would be important in predicting what the shipment would be exposed to throughout its journey.

The vendor designed testing protocols. Once Bayer approved, the company then executed the protocol to test the design, requiring the temperature challenge to be repeated three times for acceptance. Following testing, the shipping vendor drafted an executive summary providing highlights, including the minimum and maximum temperatures achieved during the test.

Each test should have the same outcome; if not, differences should be explainable or resolved. Surprise results needn’t always be cause for concern. For instance, testing may suggest different placement of temperature monitors. Once we approved it, the final report, signed by the vendor, became our official qualification document.

We needed to ensure the solution’s practicality. One key question was what the inner and outer dimensions of the package should be. Among the questions we needed to consider:
  • How well will each solution fit on a standard pallet?

  • Is there enough room for the product to make it worth shipping?

  • How much product will fit inside each desired size option?

  • Is there enough differentiation between size options?
Find a domestic solution

To handle domestic shipments requiring temperatures of 2° to 8°C, we established a partnership with the carrier, Skelton Truck Lines, to design, test and qualify trailers for frozen and refrigerated conditions. Skelton had already introduced some innovations. It was one of the first carriers to link temperature monitors and controls inside the trailer with an in-cab alarm system that notifies drivers of sudden changes in temperature. Temperature data can be downloaded and printed upon request, and the system has a backup unit.

We developed a protocol, which was executed by our Validation department, to qualify their trailers for dedicated < -20°C use. We performed these tests on-site at our facility. Once completed and approved, and prior to using the trailers, Skelton developed additional SOPs that adhered to our existing SOPs for transportation and the handling of plasma products. Finally, we completed a vendor and operational audit of Skelton’s operation.

Both Bayer and Skelton were also interested in qualifying the trailers for 2° to 8°C service, so we shared development resources. Skelton worked with our QA, Validation and Customer Operations staff to set logistics and validation parameters. The company contracted a third-party validation firm to qualify the trailers for 2° to 8°C, and developed a testing protocol with that firm. Our experts provided technical advice and approved the final test protocol. Skelton then approached other customers to share in the development costs. The end result was the qualification of their entire fleet. Skelton retains ownership of the qualification of the trailers to benefit their offered services.

Once qualification was complete, summary reports were provided to us for review and internal approval. We incorporated the reports as supporting documents within SOPs for shipment of product procedures. Skelton provides exclusive-use trailers for transport of our biological products. Now that we have a great deal of shipments and data, we are retrospectively reviewing this temperature data to ensure compliance and continuous improvement.

Find a global shipping solution

For global shipments, we collaborated with Envirotainer (Knistva, Sweden), a specialist in active temperature-controlled air transportation solutions. Working with Bayer’s QA, Validation and customer operations staff, Envirotainer established logistics parameters and assigned staff to help us design a secondary packaging system. The team also developed procedures to ensure product stability throughout the shipping process. We shared development resources and Envirotainer used our discoveries to further develop a specialized business unit: Cold Chain Management Service.

Envirotainer collaborated with us to develop trial runs that would lead to a shipping process for actual product. The shipping trial included evaluating logistics parameters, conducting collaborative meetings with the shipper, forwarder and airline, and pre-conditioning the container to +5°C. The next steps included writing container-loading procedures, determining the best locations to place temperature monitors, creating summary reports, and co-developing preliminary shipping guidelines.

In the early stages of development, we worked with Envirotainer to create engineering tests and trial runs for our targeted primary shipping lanes. We visited the San Francisco, Atlanta, and Philadelphia airports and met with freight forwarders and airlines to map out process and responsibilities. After about four months, Bayer and Envirotainer jointly developed the “I-box” solution for shipping product at 2° to 8°C in ambient conditions outside the standard Envirotainer specifications.

Creating testing protocols

Creating testing protocols means first selecting an ambient profile and the transit time needed for the longest anticipated shipping routes. Your process should mimic actual events. Walk through the entire shipping process – don’t forget to involve your shipping team in this process.

Keep in mind the geography of your shipping regions and their respective seasons. A testing protocol should include, but not be limited to the following:
  • introduction and purpose
  • test duration
  • equipment to be used
  • where and how the test will be administered
  • number of repeat tests
  • procedures to be followed and who will execute each procedure
  • thermocouple placement
  • expected outcome.
To arrive at our current 2° to 8°C solution, we used a number of TempTales, temperature measurement devices developed by Sensitech, Inc., to monitor the inside temperature of the container. In this case, we have incorporated the I-box solution, recommended by Envirotainer, to meet our requirements. The Envirotainer is designed to hold 2° to 8°C during 72 hours when ambient temperature is more than 5°C and less than 25°C higher than the temperature of the shipped product. Our ambient range was wider. Essentially, we have an insulated box inside the Envirotainer that helps to stabilize temperature fluctuations during shipment.

We found that it was extremely important to monitor the outside, or ambient, temperatures during shipment. This exercise helps us determine how well our planning has been executed, and provides additional data for future improvements.

The components of the I-box are first pre-chilled in our +5°C warehouse. The skid is then assembled inside the warehouse, complete with temperature monitors, and loaded into the Envirotainer. Shipments using the I-box solution have provided excellent flatline results in the 2° to 8°C range, even in conditions outside the Envirotainer container specifications. We currently use two sizes of Envirotainers for shipments in the 2° to 25°C range. No additional packaging material is required for these shipments.

As a cold-chain management service, Envirotainer helped us create a shipment summary report. This report allows us to strengthen our relations with service/transportation providers and recommend improvements. It also defines base guidelines for handling cold-chain products and identifying any temperature deviations and pinpoint problem areas.

Creating and implementing shipping guidelines

Once the solution was designed, we needed to create the procedure document that would show how to ship the product. This document should include comprehensive details about:
  • pre-chilling of containers or ambient start (how many, when, who
  • staging
  • temperature monitor placement
  • monitor checklist
  • diagram and container sealing details.
A good procedural document should be concise yet thorough, easy to read and free of jargon. The document should identify actions required throughout the shipping process, and determine who is responsible for each one.

As we implemented the solution, we found that adhering to and qualifying the cold-chain process that had been written was often challenging, since many commercial shipping vendors are not accustomed to the levels of regulation that drug manufacturers must comply with. For international shipments, we worked exclusively with Uti, an international freight forwarder. UTi acted as a broker and logistics facilitator to make sure the shipping was handled efficiently and according to guidelines. Our excellent relationship with UTi has allowed us to ship with piece of mind, due to their attention to our needs and adherence to our process and procedures.

When developing a cold-chain shipping solution, there are many aspects to consider. Close collaboration and good working relationships are critical to any successful solution. Other important elements include the qualification of solutions, creation of testing protocols, and placement of temperature monitors. The final step is to utilize your vendors’ insight, experience and resources as completely as possible to establish and implement shipping.

With patience and resolve, and vendors you can trust, your shipping solution will turn out much better than Mr. Martin’s and Mr. Candy’s ill-fated journey.

About the Author
Jim Bacon is director of global supply chain for Bayer Healthcare — Biological Products Division. He is responsible for the allocation and movement of all the division’s products, from manufacturing sites to Bayer regional and third-party affiliates worldwide.


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