Direct-to-Patient Shipment

For decades, the collection, storage, and transport of human biological specimens has formed an integral part of pharmacological trials, medical treatments, and epidemiological research. However, in recent years, cell and gene therapies (CGT) and vaccination programs have increased the demand for ultra-low or cryogenic shipping conditions and end-to-end monitoring.

At the same time, the regulations relating to the management and transport of specimens, vaccines, and temperature-sensitive pharma products have taken on particular importance. Around the globe, guidelines now set out recommended protocols and approved practices in the growing area of bioscience.

Below, we discuss the implications for logistics and transportation. Firstly, you will find an overview of the types of biosamples before we consider packaging, kit level monitoring, and the challenges involved. We also cover Direct-to-Patient applications and its associated practicalities.

01 Temperature Monitoring of Biological Samples

Given that regulations require the transport and storage of biological samples under strict environmental guidelines, end-to-end monitoring is indispensable. Sample viability and usability depend on qualified supply chains and adherence to standards.

As the maxim has it, laboratory results can only be as good as the quality of the specimen(s). Therefore, from collection to delivery, biological samples must stay within the specified conditions.

Types of Sample

The type of sample depends on the purpose of each test. For instance, blood glucose tests diagnose and monitor diabetes. In contrast, urinalysis for glucose content is usually to confirm urinary tract infections and kidney disorders.

Medical sample types include:

  • Blood (the most frequently requested).

  • Saliva.

  • Sputum.

  • Urine.

  • Feces.

  • Semen.

  • Plasma.

  • Bodily tissue, such as biopsy excisions.

Recommended storage temperatures vary in line with the sample type and preservation method. That is why constant kit level monitoring is essential. Some samples are susceptible to slight temperature fluctuations and, as a result, quickly degrade and lose their integrity.

The interior of a refrigerator, typically between 0ºC and 4ºC, is adequate for processing fresh specimens. However, short-term DNA stability requires sub-zero temperatures from -0.5ºC down to -27ºC.

For DNA/RNA stability over the medium to long term, colder conditions between -40ºC and -80ºC are necessary. Tissue storage calls for liquid nitrogen and super-chilling to the -130ºC to -150ºC range to preserve cellular viability. Finally, the storage of living cells requires cryogenic temperatures of -196ºC.

Challenges in Handling Laboratory Samples

Complete blood count (CBC) tube sample storage should be at room temperature and transported within 24 hours. Also known as EDTA tubes, a term which refers to their chelating agent, these samples should remain at around 20ºC to minimize the risk of platelet and cell clumping.

Blood cultures also require room temperature conditions; some bacterial pathogens are not viable when refrigerated. Therefore, couriers should use different containers if necessary and adjust their procedures for the summer and winter months.

Additionally, some types of samples require storage in certain positions. Specifically, spun blood tubes should be upright to promote clot formation if no additive is present. This vertical positioning prevents contamination from prolonged contact with the stopper and aerosol formation when uncapping the tube.

Adhering to temperature limits is usually relatively straightforward within hospitals. However, healthcare providers with multiple locations and outreach programs at a considerable distance from laboratories tend to experience practical challenges, especially in keeping samples and products at viable temperatures while awaiting pickup or during delivery delays.

In such scenarios, rigorous control measures must be in place to prevent inadequate procedures or oversights from causing problems. At worst, unsatisfactory end-to-end monitoring of cold chains can scupper entire investigations or treatment programs.

Direct-to-Patient Application

This term means the delivery of drug medication or CGT to patients at home. Depending on the treatment or medical trial, patients may take medicines themselves or receive clinical support from a home care nurse or caregiver.

Similarly, biological samples or biopsies are taken and collected while the patient is at home. Direct-to-Patient models work well for commercial therapies, such as chronic illnesses and lifesaving treatment.

Importantly, this approach addresses two recurrent problems in clinical trials: patient recruitment and retention. Also, pharma companies can access a broader population instead of focusing on patients near medical centers, investigation hubs, or treatment clinics.

Although patients may need to visit a hospital initially to assess suitability and safety, they travel less during most of the trial. As a result, costs are lower, while sponsors can expedite timelines and market the product(s) that much sooner.

Although the Direct-to-Patient approach offers benefits for patients, manufacturers, and healthcare providers, it also presents challenges:

  • Varying country regulations based on global good distribution practice (GDP) and other guidance.

  • Delivery and pick-up required within predetermined – often narrow – time limits.

  • Integrity of the cold chain.

Even one single temperature excursion or delay in delivery could pose health risks.

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02 How to Monitor the Temperature of Samples

 

Chemical Indicators

Chemical temperature indicator strips, also known as high temperature ascending (HTA) labels, are relatively inexpensive for monitoring temperatures to confirm product integrity during transit and storage. The stickers enable personnel to verify that the consignment has not exceeded the set maximum. When attached to each box at the factory or laboratory, staff can confirm its correct condition at every transfer point from the medical laboratory to the operating room, doctor's office, or patient's home.

While chemical indicator strips are inexpensive and easy to use, they show relatively little information. Their response is quite slow, so they may not record a visible trace of temperature spikes of a short duration. Also, they are not as accurate as electronic devices.

Electronic Temperature Indicators

For better end-to-end monitoring, electronic indicators record more data and provide downloadable statistical reports via cloud storage. Examples such as the LIBERO ITS are cost-effective over their typical service life of four years.

Available in cool room, no-freeze, WHO, and customizable temperature profiles, the LIBERO ITS is GAMP 5-validated and individually traceable.

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03 Kit Level Monitoring and Shipping Requirements

For effective cold chain management and temperature-controlled shipping, it is helpful to ask yourself: what would a regulatory body or audit inspector want to know? Essentially, your company's technical experts should check the quality and completeness of verifiable, scientific knowledge of products, as well as the environments they pass through to reach the end-user.

To ensure that the shipping of samples and pharmaceutical products adheres to the correct conditions, companies should check the following:

  • Transport company involved: credentials, approvals, reliable operating capacity and standard procedures.

  • Shipping method: air-conditioned or refrigerated truck, cryo container, etc.

  • Product packaging: as early as possible, adapt kit designs to fit with ease inside cold-chain shippers.

  • Temperature monitoring and verification method(s).

  • Volume, frequency, and timing of shipments.

Pragmatic principles apply. Although separating high-value products into multiple shipments might increase overheads, it mitigates the risk of loss if temperature excursions occur during distribution.

Interoperability

To streamline your pharmaceutical supply chain and sample transportation, look for:

  • Good visibility of temperature indicators on the packaging.

  • Fast, straightforward evaluation and intuitive functionality, to reduce human error.

  • Automated communication through smartphones, tablets, or other electronic devices.

  • Easy access to recorded data every time the delivery arrives at a destination or changes transport company.

 

Depending on the model, today's best data indicators and loggers can address these needs. They can monitor temperature, humidity, position, and impact.

 

Challenges of 2023 Drug Supply Chain Security Act (DSCSA)

The DSCSA became part of US law in 2013. When Section 203 takes effect on November 27, 2023, it will extend the requirements within pharmaceutical supply chains. Drugs and medical products must be traceable to package level for maximum safety and security during distribution and transport.

What are the consequences for temperature monitoring of drugs in 2023?

Currently, the logistics sector uses barcodes to scan a few sample cases on pallets. However, the final section of the DSCSA requires each case on every pallet to be scannable, thus ensuring the accuracy of a transaction. Without this substantive checking, companies run the risk of costly, time-consuming, and potentially catastrophic delays

So, in November 2023, pharma supply chains must capture shipment or pallet aggregation data electronically. As a result, companies and laboratories will have to record and exchange transaction information at a systems level, including product and numerical identifiers. Furthermore, they must share advanced shipping notices (ASN) with trading partners using GS1 standard file (EPCIS) format.

 

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