What is the biggest challenge in your industry right now?
AvS: Trials for cancer and orphan diseases are a very important trend in our industry. Most of the new drugs for these indications are posing challenges for the pharma industry on several fronts. First, the protocols are more complex, requiring more treatment steps. Second, the patient screening criteria is becoming more difficult to satisfy, forcing higher recruitment costs and causing CROs to search in more remote locations. Third, more of these patients are very sick, making recruitment, compliance, and retention more difficult. And finally, the types of drugs that are being developed for these diseases are increasingly sterile in their final dosage form, sometimes derived from biological material. What that means for companies like us is that the drugs are more expensive because they are sensitive to handling and temperature, which is where we specialize. In order to assist and overcome patient compliance and retention issues, Marken has a Direct to Patient solution in place, which allows delivery of clinical trial materials directly to a patient’s home and then retrieval of biological specimens to be sent back to the lab for testing. We offer personalized, compassionate service, and state of the industry packaging and temperature monitoring of the products (when required).
CBJ: How to collect and use data to monitor product performance or condition. There’s been hype about real time visibility for years and availability of converged technology that monitors both temperature and location. But it boils down to—will the customer pay for it? Under increasingly tight budgets, pharmaceutical companies have to differ between ‘nice to have’ and ‘need to have.’ The offers are out there for tracking location visibility by all the major forwarders and also by several large container companies now. But again, will the customer pay for it? And if your product is being tracked by the forwarder or container company, why will pharma invest themselves, especially when the infrastructure and resources are not there.
Rather, we see customers focusing on ‘need to have’ priorities. The most pressing is making go/no go decisions to release product based on its temperature condition at point of receipt/destination. Right now this process is cumbersome and time consuming because they don’t have sufficient information to make these vital decisions. For example what happened in previous shipment ‘legs’ and during different storage points before it reached destination? If there were temperature deviations previously, for how long and what were the limits? This is where managing a stability budget comes in. It’s a lot of work to collect this information and do the calculations manually. But it could certainly be worth it if you could ‘save’ a payload from being rendered bad, not fit for use. Some companies are starting to use software to manage stability data across all legs of the supply chain. In addition, the data may also have to be collected from various legal entities (intercompany, 3rd parties or CROs) on different platforms, and possibly with devices from different manufacturers with non-compatible formats. On top of these technical data handling challenges, does the pharma company have enough knowledgeable staff to perform the post-shipment analysis to realize the biggest benefits of making cost saving improvements? Today the focus is on gathering data, and not enough on what to do with all the data and the staff to perform analysis once it's there. These two things should go in parallel and not one after the other.
VK: Sonoco ThermoSafe recently conducted a forward-looking industry survey entitled, “Assessing the Future of the Cold Chain Industry.” The respondents expressed their desire to improve upon a few key areas, namely environmental responsibility, which includes re-use of temperature-controlled shippers, lowering total cost of ownership comprising the cost of packaging and shipping, and understanding and implementing regulations. Drug manufacturers are facing increased pressures to reduce costs while balancing regulations that mandate drugs must be stored and shipped within their stated temperature range. There can be no compromise on drug quality so therefore, companies are looking to temperature controlled shipper manufacturers for innovative products and creative value added services.
RB: The discussion about cold chain has to migrate to temperature-controlled products to cover frozen, refrigerated, and controlled room temperature products. Mapping of facilities, lane qualification, and dynamic stability (eg, shake, drop, temperature, pressure, and location stability) are needed to prove the quality and integrity of the product during its transportation from the manufacturer to the ultimate end user: the patient.
What is the biggest growth trend in the cold chain industry now?
AvS: There are several trends and areas of focus currently. The safety and security of the global pharmaceutical network, full traceability of clinical trial materials and drug products, geofencing, GDP compliance, and overall de-risking of the supply chain are all critical to growth in the industry right now. As a provider, Marken specializes on providing a secure supply chain network to bring safe and therapeutic products and treatments to the market, to the patient directly, to the various parts of the globe where treatments are needed, even if those areas are hard to reach.
CBJ: Centralized data management and analysis. Using a web-based platform to access your temperature data from anywhere in the world. Because it’s so easy to upload information to a web-based system, pharmaceutical companies are collecting more than ever valuable product and shipment data to help them cut costs. At the same time, SaaS cloud platforms are very secure, and if set up right, can be controlled centrally by QA or Logistics without supply chain partners, CROs, clinical sites, or customers seeing the data, very important for some companies. Having the data centrally accessible and retrievable enables companies to have sufficient evidence in demonstrating to regulators that there has been sufficient temperature control measures in place and that you have put in corrective actions for any ongoing temperature deviations. From a logistics point of view, having all your temperature and shipment data all in one place, means you can search and analyze. Companies are able to cut significant cost out of their cold chains by changing choice of packaging, changing mode of transport, or simply identifying a root cause of a problem. If, for example, the pharmaceutical company identifies systematic excursions taking place in a particular lane with a certain forwarder, they can pull the data from that lane over the past year to determine exactly where and why something is going wrong. The data can be used to discuss performance improvement, SOP changes, or contract modifications with logistics partners. Of course this is all driven by GDP regulations that continue to develop and look similar all over the world in the major regions. Specifically, EU GDPs Chapter 9.3 states “Customer should be provided with temperature control evidence.” Also US standards include USP updates to 1083 on Quality Management “Systemic problem with excursions must be addressed including written deviation, root cause analysis, use of trending to determine corrective/preventative actions and impact to quality.”
VK: Due to the implementation of Good Distribution Practices (GDP) in Europe in 2013, controlled room temperature (CRT) is a new and growing area in the cold chain industry. Previously, it was not mandated that room temperature drugs ship under temperature-controlled conditions. Now, with the advent of these GDP regulations, drugs must ship according to the temperature listed on the label. This is forcing drug companies to re-evaluate a large percentage of their tertiary packaging and replace non-temperature controlled boxes with temperature-controlled systems.
RB: The biggest growth trend in the cold chain industry now is the conversion of the environmental and security monitoring.
What are cold chain product and service providers doing to confront needs for compliant cold chain processes?
AvS: Marken assesses each vendor with ongoing reviews of their quality agreements, continuous oversight and implementation of quality management systems, validating their GDP compliance, qualification of shipping lanes, packaging innovations. We consistently monitor every partner with ongoing evaluations to ensure compliance and supply chain safety.
CBJ: Regulations are driving the need for more transparent temperature handling processes. Auditors want to see evidence of end-to-end handling and those processes documented and in practice. If there are temperature excursions reoccurring they must be corrected. Recently at the ELPRO Boston workshop, the United States Pharmacopeia spoke, who interviewed an FDA auditor who said “I know temperature and how the data is documented and how it is retrievable is something that I could review, but I don’t routinely ask for that data. This is an area that can be a rabbit hole if the data is not available but I have not spent much time looking for it unless there is a problem. Then I’m going down that rabbit hole.” Point is, if there is a reoccurring problem, FDA will investigate further and Pharma needs to have the data to prove process improvement to correct the problem. This translates into solution providers in that forwarders, 3PLs, packagers, and data monitoring company's alike need to be holistic partners for the pharma companies entire cold chain or entire process (whether that’s transport, packaging, or data). The solution provider needs to understand the pharma business and be in it for the ‘long haul.’ There are a lot of new vendors that have a widget or quick fix for a low cost but they soon realize pharma is a complex, multi-layered, highly regulated industry. Yes pharma increasingly needs lower cost solutions, but not at the risk of a less robust and less capable temperature control chain. From a data perspective, we have customers that initially look at price of the data loggers only—their number one priority. That is until we get further into discussions and they realize the enormous benefits of integrating data at the sender level so shipment data and logger data can be combined to allow for meaningful analysis post-shipment. By having full data monitoring system in place that connects the data loggers with a database, huge amounts of time can be saved in making quicker product release decisions at destinations. Huge cost savings can also be realized by being able to pinpoint and detect weaknesses in the cold chain. However—implementing a global data monitoring system is a big project and Pharma needs a reliable partner to help define requirements, update process, and get the project up and running.
VK: There are great concerns over regulations that are currently in place and others that may be implemented in the near future, especially in the US. European companies are already implementing new temperature-controlled packaging solutions, especially for CRT shipments. In the US, many companies are implementing or investigating temperature-controlled packing with the expectation that new regulations will be in place in the near future.
RB: They are providing timely solutions to meet global changing requirements such as those mentioned above. They are getting more involved in developing training materials, webinars, workshops, and presenting in technical conferences to educate their current and potential clients in regard to the new solutions they offer.
What challenges do increased shipments of biologically based products present?
AvS: Increased investment means that safety and supply chain security are even more important. Temperature, shock, vibration, and humidity variations can affect the efficacy of clinical trial materials, and with the increased scrutiny of regulatory bodies and agencies, can mean the loss of trial data or even the trial itself. It’s critical to have a detailed plan in place for temperature-sensitive drugs during shipping, handling, and storage. For that reason, we’ve seen an increased demand for our depots in key geographies like Latin America, Singapore, and China due to the growth of clinical trials in these regions. These high-value, temperature-sensitive products and materials can be safely stored and then distributed to investigator sites where needed. Marken carefully maps out the shipping lanes for these high-value products, building in contingency plans right from the start. It’s important to choose a dedicated logistics provider who already has systems in place to protect your drug products, is focused on enhanced service offerings to optimize clinical trial logistics, provides ongoing training to all of our partners, and most importantly, provides the highest quality service that de-risks the supply chain for our clients.
CBJ: There’s been a lot of attention on CRT products because of the high volumes and need for lower cost solutions. However biologics fill current pipelines and their net worth will drastically exceed the CRT products traveling in the cold chain, especially as biosimilars continue to come off patent. There is a greater need for product development to collaborate with supply chain teams to ensure the right stability studies are done and the long-term quality of the biologics can be maintained in a global supply chain. Biologics can be susceptible to shock or vibration; however temperature is still the most predominating factor affecting quality of biologics. In addition, the R&D of more biologics also means bulk shipments of proteins and bio APIs have to be shipped globally as well—who’s monitoring and regulating this part of the supply chain? The FDA’s Drug Quality and Security Act (DQSA) will help once that is fully implemented (years to come) monitor APIs coming out of some Asian countries, but the rise in biologics production makes it clear there also has to be the temperature control measures in the pre-manufacturing stages.
VK: Most biologics must be stored and shipped under temperature-controlled conditions. Due to the growth of biologics worldwide, more and more drugs are being shipped in temperature-controlled systems. These can be fairly sophisticated and having a cold chain packaging expert within the drug manufacturer can prove quite valuable in the long term. For smaller companies who cannot dedicate a resource, partnering with a reputable and experienced temperature-controlled packaging company will aid in the assessment of needs and ensure the proper solution is implemented in the most cost-effective manner. Due to the global nature of drug distribution, numerous factors must be addressed including duration of shipment, destination, size of shipment (parcel or bulk), and if return/reuse is feasible.
RB: The effects of shaking, vibration, dropping, pressure, and temperature must be studied and documented. Security and guarding against theft, diversion, tampering, and the introduction of counterfeits present additional challenges.
How do you foresee cold chain technologies shifting over the next 5-10 years?
VK: Increased drug temperature stability, increase in 3PL usage, [and] increase in value-added services such as return/reuse and recycling.
RB: There will be a continuous shift from small molecule pharmaceuticals to more specific biologically based and genetically engineered pharmaceuticals and vaccines. The tracking and tracing of the active pharmaceutical and the final products will have to be established as one measure against counterfeiting, tampering, and diversion. The patients will also require more education on how to handle, store, and use these medicinal products.
Any closing thoughts?
AvS: Our decision and focus to be 100% dedicated to the life sciences and pharmaceutical industry is important not only to our clients, but also to the industry because of the increased scrutiny from regulatory bodies all over the world. Marken’s commitment to the industry, the client, and the patient means that Marken will continue to be the supply chain partner of choice for the clinical trials market.
CBJ: Cold Chain seems to be a disappearing science in some organizations. Whether that’s because pharmaceutical manufacturers continue to outsource logistics, or the internal logistics teams think they have ‘cold chain figured out.’ I think some cold chain professionals can find it difficult to convince senior management that cold chain IS a complex, multi-functional science, and if studied carefully, can actually reduce costs and protect those extremely valuable molecules coming though pipelines—instead of being blamed for logistics always adding cost. Back to what I was saying before, instead of looking at each step in the cold chain separately as tasks, such as monitoring temperature from point A to point B—take a step back, look at the whole process and how you can optimize it. Taking a smarter, long-term approach may require up-front investment, but save significant cost and resources in the long run.
VK: To gain more insights into the future of our industry, we encourage the readers to download the detailed report or view the video of the survey “Assessing the Future of the Cold Chain Industry” at www.thermosafe.com/survey.
RB: Mapping the supply chain should be a priority to educate all partners touching such a sensitive product while they are participating in its transportation—from the manufacturer to the patient.