Cold ChainSupply Chain

Understanding the Complexities of Cold Chain Logistics and FDA Compliance

COVID-19 vaccine frontrunners illustrate the need for rigorous cold chain compliance standards

Its difficult alone to make a vaccine. Its even harder to make a lot of vaccine. Then it becomes extremely complicated to get it filled into vials and distributed to the state and into the hands of doctors and nurses and administered into the patient.”

These remarks come from Dr. Rick Bright, former Director of the Biomedical Advanced Research and Development Authority (BARDA), a division of the U.S. Department of Health and Human Services. His comments followed the promising announcements from Pfizer and Moderna regarding their vaccine success rates in phase 3 clinical trials. With global coronavirus infections approaching 60 million, the world awaits widespread distribution of a vaccine. More than 54 are undergoing human clinical trials currently.

While developing a successful vaccine may seem like the races finish line, it represents just one milestone in what is more like a marathon. Emergency Use Authorizations for vaccination of the public is only the beginning of the journey. The next major hurdle is vaccine distribution, which we detailed initially in our September article: COVID-19 Therapies and the Fast-Approaching Race for Cold Chain Logistics.

The US Food and Drug Administration (FDA) and the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) provide the compliance regulations all entities within the cold chain must meet to maintain drug safety and efficacy. Careful handling of products subject to cold chain parameters is essential to ensuring long-term efficacy of perishable medicinal products such as vaccines.

Three key regulations from the FDA specifically address cold chain requirements:

 

  • 21 CFR 203.32 – Drug sample storage and handling requirements

Addresses the need for maintaining drugs under stable conditions and meeting the manufacturer’s specifications. Understanding how to interpret storage conditions at “label claim” is a vital component of successfully storing drug samples according to manufacturer requirements.

  • 21 CFR 203.36 – Fulfillment houses, shipping and mailing services, co-marketing agreements, and third-party record-keeping

This section of Title 21 outlines the responsibilities of manufacturers and authorized distributors who partner with third party distributors to deliver medicines for maintaining forms, reports, and records associated with prescription drugs. The FDA places responsibility on the manufacturer(s) and distributor(s) to maintain these records.

Outlines responsibilities for maintaining forms, reports, and records documenting requirement compliance.

  • 21 CFR 211.150 – Distribution procedures

Provides guidance on establishing written procedures for managing expiry dating and a reliable system for identifying distribution of drug samples in the event of a recall.  Manufactures and Distributors are required to distribute drug products according to “First Expiry, First Out (FEFO) standard and be able to provide comprehensive records showing where complete lots of material were shipped so they can be easily tracked for drug recall purposes.

The FDA conducts audits of the cold chain and issues any negative findings in Form 483. The process looks for scientifically sound standards, sampling plans, and testing procedures that provide assurance of pharmaceutical handling meeting all quality requirements dictated by the manufacturer.

Inspections address the four major areas of cold chain logistics operations:

  • Temperature-controlled storage
  • Temperature-controlled transport
  • Personnel training
  • Operational and management procedures

Achieving FDA and ICH standards requires rigorous temperature monitoring, extensive record-keeping, and ongoing stress testing. Without these controls, improper pharmaceutical handling can have life-threatening consequences. The standards demonstrate why cold chain logistics, especially for pharmaceuticals, is such a highly specialized field.

Temperature Control

One of the key concerns in the pharmaceutical distribution process is maintaining temperature. Advances in research and development have generated a record number of temperature-sensitive drugs. The Pfizer and Moderna vaccine frontrunners carry with them significant temperature constraints. To put it in perspective, at minus 70 degrees Celsius, Pfizers vaccine requires storage colder than winter in Antarctica. Modernas vaccine also requires frozen storage at minus 20 degrees Celsius, a standard not uncommon for frozen vaccines.

Storage and distribution conditions at less than frozen” (<0°C) present a complex challenge for companies warehousing and transporting the drugs.

Logistics providers must have pharmaceutical-grade storage units suitable for vaccines. The equipment must be capable of maintaining required temperature ranges year-round and provide ample spacing to house inventory without crowding. Storage units need back-up systems to maintain temperature integrity in the event of a power failure.

Every vaccine storage unit must have a temperature-monitoring device. The Centers for Disease Control and Prevention (CDC) recommends a continuous monitoring and recording digital data logger (DDL) with a current Certificate of Calibration Testing. DDLs provide data on all temperatures recorded at a preset interval, including when a unit goes out of range and for how long. The data should be stored for a minimum of three years and be made available for download.

In addition to digital monitoring, staff must conduct physical temperature checks a minimum of twice a day. Physical checks confirm storage units are functioning properly and doors are closed.

Beyond monitoring storage unit temperature, documentation should include ambient room temperature as well. If a unit fails, the effects of the ambient room temperature become critical in determining a vaccines viability.

When drugs are exposed to conditions outside label storage, logistics providers must contact the manufacturer immediately. Documentation of the variances cumulative time is critical in assessing overall drug efficacy.

Data Management and Stress Testing

To comply with federal regulations, logistics suppliers must provide detailed records of their operating environments. Documentation must include stability data, geographical and climatic zone data for warehousing and transport, and shipping and storage durations at each touchpoint along the cold chain. Providers also must detail contingency plans for shipping delays, out-of-range temperature variations, and other events like power failures.

The ICH recommends stress tests of documented transport and storage procedures. These are especially important for staff training and operational continuity.

The goal of data management and reporting is to show the manufacturer and the FDA that the product can reach the end consumer with its efficacy fully intact under a variety of circumstances.

Langhams Scientific Approach to Logistics

When it comes to pharmaceuticals logistics, quality is paramount and documentation is key. The vaccine cold chain is extremely complex and requires precision down to the minute and fraction of a degree, in some cases.

While many 3PLs shy away from the intensity and regulation required for life sciences and biologics logistics services, Langham specializes in it.

We meet or exceed every FDA standard. As soon as the COVID-19 vaccines are ready for distribution, we are too,” said Jeffrey James, Director of Regulated Cold Chain Services for Langham Logistics.

James joined Langham Logistics in 2019. His experience includes global supply chain distribution for temperature-sensitive medicines from drug-making giants Janssen Pharmaceuticals and Merck.

At Langham, procedural controls ensure product protection during receipt, storage, and distribution. All storage locations are validated through installation, operational, and performance qualification protocols to maintain acceptable temperature ranges. These temperature checks also extend to Langhams dedicated transport equipment and happen in real time.

Langham supports a highly sophisticated warehouse with storage locations ranging in temperature from plus 4 degrees Celsius to minus 70 degrees Celsius. The facility houses multiple drugs all with different temperature requirements simultaneously. This dedicated storage model provides clients with ultimate flexibility to expand their space requirements by temperature as needed.

We serve as a critical connector between manufacturers and their consumers. We understand FDA regulations and treat every pharmaceutical shipment for what it is—a life saver,” said James.

Learn more about Langhams Pharmaceutical and Life Sciences services by contacting our team of experts.

You might also like:

Walking the Talk: Langham Logistics Makes Diversity and Inclusion a Strategic Business Focus
UPS and FedEx’s Three Consecutive Rate Hikes Show the Need for Negotiation
Menu