Vaccines and most needle-injected medicines must follow an uninterrupted temperature-controlled supply chain to remain safe and effective. The complex and costly series of handoffs from manufacturer to shipper to your arm is called the cold chain. But every year, failure to maintain specific temperatures costs billions of dollars in wasted drugs. Thermostable microneedles will cut cold chain costs, providing safe, equitable global access to vaccines and other medicines.
What Is the Pharmaceutical Cold Chain?
The pharmaceutical cold chain is the shipping and storing of vaccines and other temperature-sensitive medicines. It’s the most critical part of a drug’s journey from the lab to the last mile. To succeed, a precise series of transfers must occur within specific temperatures. But the slightest glitch can ruin an entire batch and cost millions of dollars.
An estimated 20% to 40% of pharmaceutical cold chain-dependent products are damaged before reaching the end user.
Source: ASHP
The cost of cold chain logistics for pharmaceuticals varies depending on the type of products, the distance they must travel, temperature and storage requirements, the mode of transportation, and the specific services used.
Additionally, cold chain logistics regulations vary by country and region.
Low- and middle-income countries with fundamental infrastructure challenges are the most complicated regions. Transporting and storing cold chain medicines in the areas mean higher wastage, impacting accessibility and safety.
Hot Topics in Cold Chain Management
The pharmaceutical sector's global cold chain logistics spending in 2017 was over $13 billion. Last year, BioPharm International said, “Spending on biopharma cold chain logistics has been rising steadily since 2018, and it is projected to grow by another 25% over the next three years, reaching $21.3 billion in 2024.” SupplyChainBrain calls it a 35 billion-dollar problem.
To understand better, here’s an overview of shipping and storage temperature ranges:
· Refrigerated (2 to 8 °C)
· Deep frozen (from -40 to -80 °C)
· Cryogenic (from -160 to -180 °C)
Even common vaccines have different temperature ranges.
The World Health Organization estimated that over 50% of vaccines are wasted globally annually. “Wastage in unopened vials is usually attributable to cold chain and stock management problems and can be minimized,” adding “wastage in unopened vials is avoidable and should be treated as unacceptable.” Freezing is another significant cause of wastage.
Cold chain logistics experts know they have an expensive problem to manage. Shipping giant UPS regularly surveys cold chain industry leaders. Its Eighth UPS Pain in the Chain Survey found:
63% of the executives surveyed believe that a core supply chain issue is product damage and spoilage.
47% say that increasing regulatory requirements involving cold-chain or temperature-sensitive packaging are driving up costs.
48% stated that their success in attempting to control product damage and spoilage is with thermal packaging and containers.
The Reality of Cold Chain Logistics
It’s essential to ensure the quality and safety of drugs from lab to patient. Lives depend on it. Unsurprisingly, keeping pharmaceutical products at stable temperatures is expensive.
The COVID-19 pandemic heightened our awareness of the challenges and costs. The Pfizer vaccine needed to be stored around -70C, and Moderna’s at -20C. Headlines highlighted systemic failures in developed nations, from freezer failures to syringe limitations, that left costly drugs in the bin.
The reality facing developing nations is even more challenging, where the longtail effects of cold chain logistics have a more significant impact. Less reliable infrastructures, limited access to special syringes, and a shortage of qualified healthcare specialists cause even greater dosage loss.
Vaccines and many biologics — like insulins for diabetes — are common cold chain drugs. Sofrigam says, “25% of the pharmaceutical industry's expenses are related to logistics.”
Microneedles have the potential to change the landscape.
Thermostable Microneedles for Vaccines
Vaccines reduce diseases. Incidents of smallpox, polio, yellow fever, tetanus, measles, mumps, rubella and diphtheria have decreased dramatically since their vaccines were introduced.
However, most vaccines require an unbroken cold chain. If temperature limits are breached, the vaccine loses its effect and is useless.
Microneedles will cut cold chain costs and reduce drug loss.
Research confirms the thermostability of microneedles. A long-term evaluation of microneedles for influenza vaccine “shows that influenza vaccine formulated into microneedle patches remained stable after storage for 24 months at 25°C, storage for four months at 60°C, exposure to five freeze-thaw cycles and irradiation during electron-beam sterilization.”
Vaxess recently reported its “proprietary silk fibroin as a novel biomaterial for stabilization and delivery of mRNA LNPs [Lipid Nanoparticles] can address storage and distribution limitations of current mRNA vaccines.” Studies conducted by Emory University and the Georgia Institute of Technology confirmed that “encapsulation efficiency and LNP diameter remain stable in dried silk fibroin matrices at 4°C, 25°C, and 37°C for at least two weeks.”
Thermostable microneedles could set the stage for a fundamental change in vaccine delivery.
Thermostable Microneedles to Treat Diabetes
Diabetes affects over 537 million people and is increasing. Type 2 comprises 90% of patients. Treatment with insulin is effective. But insulin depends on the cold chain and must shipped and stored between +2°C and +8°C.
Three in four adults with diabetes live in low- and middle-income countries with the most significant cold chain shipping and storage challenges. Pakistan has the highest rates, with early one-third (31%) of the population living with diabetes.
Thermostable microneedle patches to treat diabetes are getting a lot of attention, with ongoing research into microneedle technology for insulin delivery. Studies repeatedly show that “microneedles display many patient-centred benefits, such as ease of application and painless insertion.”
Last year, North Carolina State University received a US patent for a “PATCH LOADED WITH DUAL-SENSITIVE VESICLES FOR ENHANCED GLUCOSE-RESPONSIVE INSULIN DELIVERY.”
Dr. Ryan Donnelly and the Queen’s University Belfast team are discovering new methodologies using microneedles. One article notes, "Depending on the type of microneedle employed, numerous parameters can be changed to optimise the stability and activity of drugs encapsulated within a dissolving MN system.”
I asked Dr. Donnelly about insulin delivery via microneedles and potential commercial applications. His reply: “I can't see a commercialisable microneedle product for insulin being realistic due to the inability to precisely dial doses in to suit blood glucose measurement. If one makes a new glucose-responsive polymer, then this will likely constitute a novel pharmaceutical excipient and that brings with it a range of additional regulatory challenges that would be extremely expensive to overcome. Glucagon-like peptides are much better candidates for microneedle delivery due to the less precise doses required. A commercial product would benefit the 20% of patients with needle phobia, whilst eliminating sharps waste.”
Companies like Vitropep are investigating commercial peptide-based applications to treat diabetes with microneedles. Founder Christophe Tarabout, a Physical Chemist, discovered in post-doctoral research that some peptides can solidify, making them ideal candidates for microneedle applications. In 2022, Christophe started Vitropep, focused on helping people who suffer from chronic diseases like diabetes.
In a recent interview, he told me, “We want to take the pain of existing treatments out of the equation: the physical pain of hypodermic injections and the figurative pain of relying on the cold chain. In the West, we are accustomed to having refrigeration everywhere. But in low- and middle-income countries, this can be a challenge. Our hope is that a microneedle patch to treat diabetes will remove barriers and democratize access to life-saving treatment.”
Grand View Research says, “The increasing incidence of diabetes is also driving the industry demand.”
Other Benefits of Microneedles
Microneedles are small and lightweight, meaning reduced shipping and storage costs. Their thermostability can eliminate cold chains, creating a knock-on benefit in delivering medicines globally.
There are other benefits:
Simplicity: easy to self-administer for greater patient compliance
Safety: no sharps injuries or disease transmission
Painless Delivery: kids and needle phobics will rejoice
Reduced Bio-hazardous Waste: no needles or empty vials to safely dispose of
Environmental: microneedles will help reduce emissions associated with cold chain logistics and lower the carbon footprint of the pharmaceutical industry.
Resolve vaccine wastage: dose sparing
A Dutch study summed it up nicely, noting microneedle “vaccination can offer important advantages such as dose sparing, pain-free immunization and avoidance of needle-stick injuries. Furthermore, it can extend the vaccination coverage in developing countries by potentially offering improved vaccine stability, reduction of vaccine wastage and of burden on trained personnel.”
Next-Generation Vaccine Delivery
The cold chain is not going away. Keeping drugs at stable temperatures and consistently delivering them without spoilage is paramount. As new medicines and treatments emerge, improving the cold chain is essential.
In 2017, the US Food and Drug Administration (FDA) approved 57 new drugs, 23 requiring refrigeration storage and transportation within temperatures between +2°C to +8°C. With more Cell and Gene Therapy (CGT) treatments gaining approval, cold chain management systems must meet those demands.
Nonetheless, focusing on opportunities to reduce dependency on the cold chain is essential. Thermostable microneedles are a viable solution. They eliminate strict temperature controls and minimize shipping and storage costs.
Grand View Research valued the global microneedle market at USD 5.38 billion in 2022, with growth anticipated at a 7.4% compound annual growth rate (CAGR) from 2023 to 2030. The report highlights “a growing demand for microneedle drug delivery systems, owing to the availability of safer alternatives to conventional hypodermic injection, which is minimally invasive and enables pain-free administration.”
Microneedles will make vaccination and disease management programmes easier to implement and administer. Safe and easy application means less loss and more widespread, efficient delivery. Eliminating biohazardous waste has safety and environmental benefits.
More commercial microneedle products will democratize drug delivery globally.
Vaccine campaigns with microneedles will be the poster child of the future. When was the last time you saw a kid smile during inoculation? The next-generation image of vaccine delivery could be an authorized person applying a painless patch on the arms of smiling children.