What is Cold Chain

Cold Chain is a supply chain system where product specific temperature is maintained while the it is in storage,  transportation and distribution. Temperature control is required for various reasons, such as the product safety and regulatory compliance

For many industries, such as pharmaceutical and FMCG, it is necessary to make arrangements for product delivery to their end - user with the highest standard of safety, quality and integrity. This is in addition to product manufacturing, where there are established systems to ensure product’s quality & safety. Cold Chain is such a technology that enables pharma manufacturers to protect the product after it exits the manufacturing facility.

The pharmaceutical industry is one of the users of the cold chain and is implemented where products are sensitive to the outside environment. If appropriate environmental temperatures are not maintained, it will damage the product quality and effectiveness, making it harmful and/or less effective to its users.

Pharmaceutical Cold Chain

Cold chain is becoming a necessity for the pharmaceutical industry, especially when the industry is producing next  generation vaccines, bioproducts and personalized medicines. It helps pharma manufacturers leverage the cold chain to discover new drugs, and explore new markets

Cold Chain is used by different factions of the pharma industry, such as manufacturers, distributors and healthcare providers at their respective points of discharge.

The advantages of cold chains are established and evident in pharmaceuticals. However, as the pharma cold chain continues to grow and evolve, the challenge to keep compliant is also increasing.  

Challenges, such as

● Requirement for Increased and new categories, such as controlled rooms and frozen temperatures of control temperature ranges for the pharma industry.

● Increased demand for cold chains for remote areas, where it could take days to reach its end users.

● Regulatory regulations for pharma manufacturers to make cold chain arrangements in their respective markets of jurisdiction

● The unpredictability of the supply chain due to many reasons, such as regional, regulatory and the varying requirements of the industry.

There are many ways to tackle these challenges. Examples include, Risk management, technological reliability and implementing monitoring solutions.

In this article we focus on cold chain monitoring, and how it helps pharma industry to protect the quality, safety and efficacy of the product

What is Cold Chain Monitoring

When you put your critical pharma product into the cold chain, you cannot leave without monitoring the performance of the cold chain. You have to maintain and deploy systems that would effectively monitor the temperature and relevant parameters.  

Pharma cold chain monitoring serves this purpose by utilizing different sensors and/or software solutions to monitor the container’s and surrounding different parameters. The monitoring setup is able to monitor for days

This system also keeps records of monitoring parameters for viewing later by concerned personnel for different purposes, such as analysis and validation. It can also be used for many beneficial purposes, such as improvement, process reliability and fault prevention.

How is Cold Chain Monitoring performed?

There are different methods used in cold pharma chain monitoring, selection of which depends on  many factors, such as product, technology and tracking required.

Let's briefly discuss how monitoring is performed

Data Loggers

Data loggers log different parameters at fixed time intervals automatically. They store these values in an internal memory, which allows personnel to view them later on. Typically, data loggers have enough memory to save these values for the entire distribution cycle or even more than that.

When monitoring is required, data loggers are activated and placed in the transport container. Upon activation, they start data logging. When arriving at the destination, data loggers are picked - up, and data is exported to the external media.

The main feature of the data logger is its ability to continuously store parameters that can be traced back to analyze the cold chain’s performance, such as deviations. However, data loggers lack real-time monitoring and communication with the remote systems, and can only be used as a standalone monitoring device

The logged values from data loggers can be used in variety of ways, including  

● Allowing reports to be exported into different formats, such as PDF, for viewing on compatible devices.

● USB port to directly download data on compatible devices.

● Display on the data logger for interactive viewership

● Analog values displayed on calibrated chart

There are no specific types of data loggers for the pharmaceutical cold chain. However, they must meet basic criteria for cold chain monitoring, such as

● The ability to record parameter in the required range

● The error must in acceptable range

● They must be regularly calibrated to ensure accuracy in their measurement

Chemical Indicator sensors

Chemical indicator sensors are strip-type sensors that contain specialized chemicals on their surface. These chemicals are sensitive to specific temperature and change color when a particular temperature is achieved.

The chemical sensors are used to indicate the achievement of a specific temperature, rather than a continuous monitoring mechanism. They are used to determine if the container has gone out of the acceptable threshold value during transportation.

They must be discarded after first time usage and cannot be re-used for the next or another application.

Electronic freeze indicators

These sensors indicate if it has been exposed to freezing temperatures. They are commonly used with freeze-sensitive pharma products, such as vaccines, that, if exposed to freezing temperatures, can become dangerous for their users.  

When they are exposed to freezing temperatures, it activates their internal circuitry and triggers an alarm. When activated, the alarm cannot be reversed back, and a new device must be used for the next application.

Real-time monitoring

Real-time monitoring uses the latest communication-enabled sensors to monitor the relevant parameters. The measured value is then sent to a centralized repository, usually the cloud, where authorized users, by using dedicated tools, can view these parameter, while the product is in transit.

Real-time monitoring come with unique feature, such as

● Accessing values through web-based portals

● Real-time alert system, which can generate alters if the parameter drifts from acceptance levels.

● The alerts can be generated through email, text message or a notification on the device.

● The alert can be used to immediately correct the system without waiting for the transportation to arrive at the destination.

What are some FDA guidelines related to pharma cold chain monitoring?

Some FDA guidelines related to pharma cold chain monitoring are briefed below.

21 CFR 211.150 - PART 205 -- GUIDELINES FOR STATE LICENSING OF WHOLESALE PRESCRIPTION DRUG DISTRIBUTORS

Section 205.50 of 21 CFR 211.150 mentions minimum requirements for drug storage and handling of prescription drugs. In its part “c”, the need for monitoring is described as follows.

“Appropriate manual, electromechanical, or electronic temperature and humidity recording equipment, devices, and/or logs shall be utilized to document proper storage of prescription drugs.”

Revised Guidelines on the Cold Chain Management for Pharmaceutical Products and Establishments

In 2021, the US FDA issued a circular, “Revised Guidelines on the Cold Chain Management for Pharmaceutical Products and Establishments”, which aims to provide updated guidelines on cold chain management for pharma time and temperature-sensitive products. It guarantees adherence to standards during storage and transportation to ensure quality and safe products.

According to this circular, it uses guidelines of the World Health Organization - WHO “Model guidance for the storage and transport of time- and temperature–sensitive pharmaceutical products”.

This circular applies to all the components of the pharma industry, such as manufacturers, importers, wholesalers, distributors and sellers ( warehouse or establishment) where pharma products are held. It applies to any vehicle or equipment used to transport or hold pharma products.

Section 6,  “ Transport and Delivery”,and its subpart 6.5 “Temperature and Humidity control and monitoring during transit”, describes the control technique to maintain the desired temperature.

In this section, the need for temperature monitoring is described as

● Provide air temperature monitoring systems for the vehicles used to transport time and temperature-sensitive products.

● They must have the following specifications.

● Sensors accuracy to be ±0.5°C

● Sensors for monitoring must be calibrated, as described in section 6.7 of this circular.

● Sensors must also be placed to monitor worst-case positions.

● Sensors for monitoring worst-case temperatures must remain within qualified limits.

● The record for each monitoring sensor must be maintained a minimum of six times an hour.

● The monitoring system should provide humidity monitoring systems for time and temperature-sensitive transporting products. . They must have the following acceptable specifications.

● The humidity monitoring sensors must be ±5% RH

● The humidity sensors must be calibrated, as mentioned in section 6.7.3 of this circular.

● Sensors for monitoring worst-case humidity levels must be qualified.

● The sensors' location must be selected to prevent deviations by various transients, such as door openings in the area.

● The record must be maintained for each humidity monitoring sensor, with the frequency of size timers per hour.

● All relevant documentation must accompany the humidity monitoring system.

● Active and passive shipping containers

● Chemical or electronic freeze indicators to monitor temperature and/or humidity exposure for internal and external distribution.