Active Versus Passive Shipping Solutions For Clinical Shipments

By Kevin Hickman

Many clinical trial materials, through to commercial finished goods, are sensitive to even minor temperature deviations. The integrity, efficacy, and safety of these products and materials depends on selecting the right shipping system. There are two common approaches to temperature control in the pharmaceutical and biopharmaceutical logistics space: active and passive temperature-control solutions. Both solutions are designed to maintain a predefined temperature range throughout transport, but their operational models, performance profiles, costs, risk considerations, and management differ.

This article strives to provide a clear comparison of both systems, their advantages and drawbacks, and the operational considerations supply chain leaders must weigh when designing regional and global cold-chain strategies.

Active Temperature-Controlled Solutions

Active temperature-controlled solutions use powered refrigeration, heating, and advanced control technologies to maintain temperature, similar to your HVAC system in your home. These are typically electric or battery-driven containers, often loaded as ULDs (unit load devices/cargo containers) on aircraft or used in ground transport such as vans, trucks, and tractor-trailers.

Some key characteristics of active temperature-control solutions include:

• Real-time temperature control using compressors, heaters, or similar.
• Active monitoring, with many solutions integrating telemetry/real-time monitoring or control towers/dashboards.
• Wider operating ranges, commonly from deep-frozen to controlled room temperature (CRT). In addition, some solutions can support temperature ranges that are warmer than CRT (i.e., lab study material at human body temperatures).
• Active solutions require continuous power dependency, requiring batteries to be recharged during staging or the unit to be plugged into a power supply for preconditioning and/or during transport.
• Active solutions have high payload capacity and are suitable for bulk shipments.

Strengths of active solutions:

• They provide better temperature stability for extreme external factors. Active solutions can recover from temperature fluctuations and excursions caused by environmental factors such as hot tarmac exposure, extreme cold/polar vortexes, etc.
• They are ideal for long routes or complex lanes and are particularly useful for global shipments involving multiple handoffs/transfers or prolonged dwell times (i.e., customs and regulatory clearance at a port).
• Flexible temperature setpoints allow easy switching between ranges for shipments of different programs or products.
• Active solutions have a lower operational risk. There is reduced reliance on lane and vendor performance, external ambient conditions and exceptions, or pack-out precision.

Limitations of active solutions:

• High cost: Both rental fees and ancillary charges (powering, handling, returns) are substantial.
• Complex reverse logistics: Containers must be returned, inspected, and certified.
• Infrastructure requirements: Some airports or carriers lack the necessary charging stations or trained handling personnel.
• Potential for mechanical failure: Although rare, equipment malfunctions can compromise product if not monitored.

Passive Temperature-Controlled Solutions

Passive temperature-control shipping solutions maintain temperature using insulation materials and preconditioned refrigerants, such as phase-change materials (PCMs), gel packs, dry ice, or vacuum-insulated panels (VIPs). They do not rely on electricity or power sources.

Some key characteristics of passive temperature-control solutions include:

• Passive solutions tend to use lightweight insulated shippers and are used for parcel and pallet shipments.
• Passive solutions require accurately preconditioned PCMs or similar cooling packs. These packs are arranged in a very precise manner inside the shipper for them to maintain temperature correctly. This requires precise SOPs and operator training.
• There are single-use or reusable options depending on the customer requirements, vendor catalog, and supply chain design.
  • Single-use solutions require proper disposal and/or recycling.
  • Reusable solutions require setting up a reverse logistics process, as well as SOPs, for getting the shippers back from the consignees, checking the returned systems for integrity, and cleaning the shippers for further use.
• Passive solution performance is dependent on factors such as ambient conditions and lane validation.

Strengths of passive solutions:

• Lower cost: Passive solutions are often 30%–70% cheaper per shipment than active solutions.
• Simplified handling: No charging, powering, or diagnostics.
• Versatility across final-mile logistics: Ideal for courier, parcel, and decentralized clinical trial supply.
• Good thermal performance with modern PCMs: VIP-based solutions can maintain temperature for 72 to 144+ hours.

Limitations of passive solutions:

• Finite duration: Once the PCMs are exhausted, the temperature control protection fails.
• Pack-out variability can introduce risk: Human error in conditioning or loading can lead to excursions. This risk increases at 3PL distribution centers that have numerous customers who all require different shipping solutions.
• Sensitive to real-world deviations: Delays, extreme temperatures, or route disruptions can exceed validated duration.
• More waste: Especially with single-use kits, sustainability becomes a concern.

Common Use Cases

Active solutions are best suited for:

• global clinical programs across multiple continents
• high-value or irreplaceable batches
• temperature-sensitive biologics with narrow stability margins
• unpredictable trade corridors with frequent delays.

Passive solutions are best suited for:

• parcel-based clinical trial supply
• regional distribution
• established commercial lanes with predictable transit times
• moderate sensitivity materials or products with supportive stability data.

Cost, Risk, And Operational Strategy Comparison

Active solutions have high up-front and recurring costs (rental + handling + power + returns). Passive solutions have lower cost per shipment (which can be further reduced using reusable solutions). Single-use solutions have minimal-to-none reverse logistics costs.

Risk Management

Active solutions mitigate external ambient risk. They are better for unstable/erratic shipping lanes. Passive solutions require rigorous lane validation and precise pack-out procedures.

Infrastructure Requirements

Active solutions require charging stations, trained handlers, and sometimes airport-specific infrastructure. Passive solutions require pack-out stations and qualified refrigerated/frozen storage for PCM preconditioning . Some solutions may require pack-outs being done in refrigerated conditions.

Operational Complexity

Active solutions require scheduling coordination with carriers, monitoring hardware, and return/repositioning logistics. Passive solutions have simpler kitting and deployment requirements, can be transported by most common carriers, and usually with no hazmat declarations (dry ice is the exception). SOP training and compliance are key.

Sustainability Has Become A Major Consideration

With the pharmaceutical industry’s increasing emphasis on ESG (environmental, social, and governance) commitments, temperature-control design plays a significant role.

The pros of active solutions are they are reusable and have long life cycles. The cons are high energy consumption, emissions during transport, and repositioning/return logistics. The pros of passive solutions are some vendors offer reusable VIP/PCM solutions with circular return programs. The cons are single-use waste can be substantial if not managed properly.

Selecting the optimal solution requires a cross-functional evaluation — supply chain, quality, CMC, regulatory, and clinical operations. The evaluation team could include the CMO/warehouse/depot vendors, as they need to assess if they can support and handle your temperature-controlled solutions.

Key decision factors include accounting for:

• the product stability profile: narrow stability or high sensitivity usually requires active solutions
• lane performance or limitations: routes with limited infrastructure, high dwell times, or extreme climates favor active solutions
• budget constraints: high-volume regional programs or low cost/low margin materials may lean toward passive
• risk tolerance and business continuity: high-value material, irreplaceable material, or first-in-human doses justify active protection
• shipment duration: passive solutions must exceed the maximum validated lane duration and allow for some time for delays
• payload size: large shipments usually align better with active ULDs.

Sometimes A Hybrid Approach Is Best

Many leading biopharma companies utilize a hybrid model. They will use active for bulk API/DP shipments, global clinical distribution hubs, or high-risk lanes, while using passive for site-level distribution, regional corridors, or stable commercial products. This model balances cost efficiency with risk mitigation and operational flexibility.

The choice between active and passive temperature-controlled shipping solutions is not binary. Instead, it is a strategic supply chain decision shaped by product characteristics, clinical or commercial requirements, lane reliability, and risk tolerance. Active solutions deliver excellent thermal protection, making them indispensable for high-value, high-risk, or globally complex shipments. Passive solutions, meanwhile, offer cost-effective, flexible, and increasingly high-performing solutions ideal for many routine or regional distribution needs.

Applying this framework to inform the clinical supply temperature-control logistics strategy enables organizations to establish a robust operational baseline that can be further optimized for efficiency and cost-effectiveness across all study phases, through to and including commercial launch .

As the pharmaceutical and biopharmaceutical sectors continue to innovate, temperature-control logistics will remain a critical factor. Understanding the characteristics of active and passive solutions, and deploying them strategically, allows companies to safeguard product integrity, improve study outcomes, and optimize their global clinical supply chain performance.

About the Author:

Kevin Hickman is a veteran supply chain leader with over 25 years of experience in the pharmaceutical and biopharmaceutical industries, specializing in global logistics, cold-chain management, and end-to-end distribution. He has supported organizations ranging from emerging biotechs to global enterprises across R&D, clinical development, and commercial operations.

Most recently, Kevin served as director of global logistics at Mirati Therapeutics (a Bristol Myers Squibb company), where he oversaw global temperature-controlled logistics, GMP warehousing, distribution, and vendor management across clinical and commercial networks.

Previously, he held leadership roles at Instil Bio, Kiniksa Pharmaceuticals, Gilead Sciences, and CSL Behring, where he built and managed domestic and international cold-chain logistics programs across all temperature ranges, established GMP warehousing and 3PL distribution operations, and led strategic vendor relationships.