Cold Chain Management: A Critical Component in Temperature-Sensitive Clinical Trial Drugs

The rising disease burden, an increase in an aging population, and dwindling product pipeline of older frequently prescribed drugs are propelling the pharmaceutical and biotechnology industries to offer new chemical entities and marketing new drugs at an increasing rate.

These products cannot be released without the proper clinical trials, which are conducted on a global scale, with different populations, and in some cases in locations with less-than-optimal or developing logistics infrastructures.

In the clinical supply chain, every single segment is critical to the integrity, efficacy and safety of trial drugs, from Active Pharmaceutical Ingredients (API) and drug manufacturing through delivery to the patient. This is especially true for temperature-sensitive and time-sensitive drugs used in clinical trials.

Without the appropriate compliance during the manufacturing, storage and distribution of these drugs, patients are at risk of getting unsafe or compromised products. In addition, clinical trials could be delayed, produce inconsistent results, or even fail.

This is where cold chain management comes into play, as proper controls are needed to help assure that the highest quality standards are in place. Without these, the potential impact of temperature excursions on the integrity of temperature-sensitive products can be devastating.

Learn how Sensitech cold chain products and services offer solutions to your regulatory and supply chain challenges.

Why proper cold chain management is vital

The optimal maintenance of the cold chain is becoming increasingly important as companies deal with increasing regulatory concerns, expansive market growth of biologics and vaccines, and rising logistics costs. Underlying each of these trends is, of course, the goal to ensure the utmost in patient safety.

In a study conducted by SCORR Marketing and Applied Clinical Trials, respondents from a variety of types of companies involved in clinical trials provided some insights on cold chain management. Here are a few highlights:

• Almost half (49%) of the people surveyed noted that reliability is the top influence in the clinical supply cold chain decisions.
• Over 65% say that trends in regulations have a somewhat to a very significant impact on cold chain distribution. In addition, for over 60% of respondents, growth in biologics and vaccines was key, while over 50% cited logistics costs as an important factor.
• For better management, temperature surveillance is the top technology solution, with 63% of the respondents relying on it.

Best practices and protocols are key

To meet the challenges of cold chain management, companies look for documented protocols and best practices that adhere to Good Cold Chain Management Practices (GCCMP) and help them to comply with industry and government regulations. These practices are particularly important in cold chain management for temperature-sensitive drugs for clinical trials.

To ensure proper temperature management of trial therapies, a recommended source is the March 2015 EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use (Annex 15: Qualification and Validation). This document describes the principles of qualification and validation, which are applicable to the facilities, equipment, utilities and processes used for the manufacture of medicinal products. It can also be used as supplementary optional guidance for active substances.

There is increased regulatory pressure to both establish technical quality agreements with down-stream supply chain partners, and audit suppliers with an aim toward continuous improvement. In the study mentioned above, 57% of the companies surveyed outsource their clinical supply cold chain management. In these cases, training on best practices for appropriate storage, handling and distribution may be needed.

The EU Guidelines outline a quality risk management approach and defined processes that should be applied throughout the lifecycle of a medicinal product. Additionally, it provides insights into what a quality risk management system should provide, such as justification for the scope and extent of qualification and validation covering the facilities, equipment, utilities and processes.

Transportation is also a key area that is covered in the EU Guidelines. Here are some specifics:

• Finished medicinal products, investigational medicinal products, bulk product and samples should be transported from manufacturing sites in accordance with the conditions defined in the marketing authorization, the approved label, product specification file or as justified by the manufacturer.
• It is recognized that verification of transportation may be challenging due to the variable factors involved; however, transportation routes should be clearly defined. Seasonal and other variations should also be considered during verification of transport.
• A risk assessment should be performed to consider the impact of variables in the transportation process other than those conditions that are continuously controlled or monitored. This includes delays during transportation, failure of monitoring devices, product susceptibility and any other relevant factors.
• Due to the variable conditions expected during pharmaceutical transportation, continuous monitoring and recording of any critical environmental conditions to which the product may be subjected should be performed.

Sensitech Professional Services will conduct a temperature-sensitive supply chain assessment and will assess, evaluate, and document internal and external practices as they relate to the EU Guidelines. Each assessment is customized to meet the specific needs and objectives of each customer, with the goal of identifying thermal compliance gaps and opportunities for improvement. For instance, an assessment can include the overall evaluation of global supply chains over multiple seasons, or it could be tailored to evaluate a specific trade lane, product, or other variable.

Another key step that is required by regulatory agencies is good electronic record keeping. This relates back to the fact that a majority of the people surveyed above use temperature surveillance technology. Included in this is typically a secure and comprehensive data management system for viewing, storing, retrieving and analyzing time-and-temperature data for temperature sensitive shipments. The data management system should be designed and built to comply with FDA 21 CFR Part 11 guidance and EC Annex 11 (Data Management). Use of this technology demonstrates control, and provides companies with alerts that may launch investigations, which also must be documented.