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Making COVID-19 Global Vaccine Distribution Safer and More Efficient
Dhiraj Behl
Harikesh Kalonia
Amity Institute of Pharmacy, Amity University, India

early two years have passed since we began to face the COVID-19 pandemic, and while its global consequences have been catastrophic, the situation has also catalyzed profound change in our overall health ecosystem. The progress we have experienced in drug development, transformative therapeutic innovation, and regulatory cooperation and harmonization continues to spread. Global health awareness has grown significantly, and global stakeholders continue to focus on exploring new areas of health science and technology for innovation, framing regulatory strategies and policies, and developing new leadership for this changing healthcare world.

According to a recent statement by the WHO, the pandemic is resurging in 12 African countries, mainly because the highly contagious Delta variant of the coronavirus, first recognized in India, has been detected in 14 African countries. This third wave rapidly became active—spreading faster, striking harder. We must consider who can deliver the available vaccines most quickly, and how. Is it an injection that requires a physician, or can it be properly administered by a nurse or even a pharmacist?

Each year, millions of patients choose flu vaccines delivered via the nose. The speed of vaccination can exponentially increase in intranasal vaccines, and even self-administration is a safe option.

Three COVID-19 vaccines are authorized for use in the US, each with varying storage temperature requirements. In addition, vaccines often come in multidose vials to realize efficiencies from packaging multiple doses in a single vial; however, this can also result in wastage.

Other logistical challenges include potential long lead times spent preparing, installing, and deploying sites for large-format cold storage (e.g., power access, sufficient floor space, security/access), and a lack of long-term utility for large-format cold storage (i.e., repurposing for post-COVID-19). Table 1 summarizes some of the characteristics and potential advantages/disadvantages of injectable versus inhaled intranasal vaccines.

Table 1: Advantages and disadvantages of candidate injectable and intranasal COVID-19 vaccines *tbc: To be continued (ongoing)
Table 1: Advantages and disadvantages of candidate injectable and intranasal COVID-19 vaccines. *tbc: To be continued (ongoing)
The WHO reports that more than 200 COVID-19 vaccine candidates are in the research and development pipeline and that some of these candidates, especially the messenger ribonucleic acid (mRNA) vaccine types, may require storage at ultralow temperature (ULT) to maintain potency.

It has also been observed that a high percentage of vaccines must be discarded due to failure in the cold chain (“wastage”). In a 2005 paper, the World Health Organization (WHO) reported global vaccine wastage at more than 50%, a number still cited by the United Nations Environment Programme. Recently, the French Directorate General of Health has stated that it is operating with the cautious estimate of a 30% wastage rate on COVID-19 vaccines distributed in the country.

One advantage for the intranasal route is that it can use liquid and dry powder formulations. The latter should provide clear advantages in transportation, storage, and wastage because a cold chain may no longer be required. In this respect, the superior thermostability of intranasal vaccine would be a breakthrough.

Global Accelerated Regulatory Pathways

With the advantages of intranasal vaccines seeming to outweigh the disadvantages, industry, health authorities, and regulatory agencies must align their strategies to deliver these advantages to patients in their respective jurisdictions. For example, regulatory guidance for nasal spray development has been available in the US for two decades, but similar guidance for the development of dry powder nasal spray is still not available.

Table 2 summarizes the state of accelerated or expedited regulatory approval pathways in various locations.

Table 2: Summary of accelerated or expedited regulatory approval pathways.
Table 2: Summary of accelerated or expedited regulatory approval pathways.
European Union (EU) – Regulation (EC) No 726/2004 of the European Parliament and of the Council
United States (US) – FDA Breakthrough Therapy Designation, Technical Considerations for Demonstrating Reliability of Emergency-Use Injectors Submitted under a BLA, NDA or ANDA
Canada – Health Canada Requirements for COVID-19 Drug Authorizations
India – CDSCO New Drug Clinical Trial Rules, CDSCO New Drugs and Clinical Trials FAQs
Singapore – Singapore HSA Therapeutic Products Guidance
China – China NMPA Laws and Regulations
CHMP: Committee for Medicinal Products for Human Use
DCP/MRP/NP: Decentralized/Mutual Recognition/National Procedure
# Details under Guidance for Expedited programs for serious conditions – Drugs and Biologics


Intranasal vaccination is a practical alternative because self-administration is often quite easy, it is often administered close to the site of (flu) infection, and its outcomes have been most beneficial for special populations and patients:

  • Pediatric patients: Easier to use, noninvasive
  • Elderly patients: Easier to use, noninvasive
  • HIV-infected patients: Reduced anxiety of needle stick injury or infection
  • Multimorbidity patients: Reduced number of injections and associated anxiety.

Advances in drug delivery, including connecting intranasal vaccine administration to tracking or other medical devices, may present alternatives to multiple injections and help meet patient needs during the challenging and often diverse conditions presented by COVID-19.

References available upon request.

The authors thank Janine Jamieson for support, discussions, and guidance on combination products.