Table 2.

Ebola vaccine pre- and post-licensure delivery pathways.

	Regulatory mechanisms	International expert advisory	Vaccine supply & procurement	Delivery strategies
Pre-licensure	Manufacturer and NRAs pro-vide country-specific approval for use under an investigational protocol: Clinical trial protocol Compassionate use/expanded access protocol for non-research use in high risk groups where benefit outweighs the risk Emergency use EUA from the US Food and Drug Administration Emergency approval from the European Medicines Agency.	SAGE issues recommendations EUAL: Never used previously. Established in 2015 to expedite review of available data on new vaccines or other medical countermeasures and provide recommendations to regulatory authorities allowing use in a setting that has been declared a Public Health Emergency of International Concern. EUAL can be specific to at-risk populations or countries/regions. No vaccine candidate has been granted EUAL to date.	Vaccine manufacturer supplies vaccine for investigational protocols or approved emergency use GAVI, The Vaccine Alliance support: In 2016 GAVI established a stockpile of 300,000 rVSVDG-ZEBOV-GP doses for pre-licensure investigational or compassionate use	Reactive vaccination for outbreak response (e.g., ring, geographically-targeted, mass, and reactive HCW/FLW vaccination) Vaccination of clinical trial participants
	Neither agency has issued these approvals for an Ebola vaccine.
Licensed vaccine	NRAs provide country-specific approval for Programmatic use Manufacturer Phase 4 post-licensure studies Operational research	SAGE issues recommendations WHO prequalification decision is used by international procurement agencies	Global and/or regional vaccine stockpile(s) established, managed, and monitored by the ICG EBOV Eligible at-risk countries apply for GAVI support for vaccine implementation	Reactive vaccination for outbreak response (e.g., ring, geographically-targeted, mass, and reactive HCW/FLW vaccination) Preemptive vaccination for highrisk individuals before an outbreak occurs (e.g., HCW/FLWs, international responders, laboratory personnel, contacts of EVD survivors)

Abbreviations: NRA, national regulatory authorities; EUA, Emergency Use Authorization; SAGE, Strategic Advisory Group of Experts; EUAL, WHO Emergency Use Assessment and Listing; WHO, World Health Organization; ICG EBOV, International Coordinating Group for the provision of Ebola vaccine; HCW/FLWs, healthcare and frontline workers; EVD, Ebolavirus disease.