Aligning new interventions with developing country health systems: Target product profiles, presentation, and clinical trial design

Figures & data

Figure 1.  Target product profile template.

Table 1. Target product profile (TPP) template definitions: structural elements.

Structural elements	Definitions
Product class	Category of product. e.g., Blood-stage malaria vaccine
Product name	How product will be known publicly. To be completed once product approaches phase 2b
Date of TPP endorsement	Date TPP formally adopted by organisation
Date of TPP revisions	Means of tracking changes over time
Desired target	Optimal characteristics
Minimally acceptable target	Minimal characteristics that would allow product to continue development
Product profile target	Characteristics specific to a product in late development (e.g., phase 2b), which should fall between desired and minimal targets
Rationale	Identifies data and publications to justify each target, or at minimum the reasoning behind each target

Table 2. Target product profile (TPP) template definitions: characteristic categories.

Categories	Definitions
Indication	Intended use against a measurable outcome. e.g., Prevention of uncomplicated malaria.
Expected efficacy	Anticipated efficacy level for the indication, measured in a clinical trial. e.g., 80%.
Target population(s)	Ages, parts of the world, and/or defining characteristics of those who could receive the intervention. e.g., Children under five years of age in malaria-endemic countries.
Route of administration	For example, Oral; intra-muscular injection.
Formulation and presentation	Formulation, e.g., Liquid or lyophilised (a dried powder) which needs to be reconstituted (mixed with a liquid) before injection; presence of a preservative; and volume of each injection. Presentation, e.g., Size and type of vial; vial labelling.
Dosage schedule	How many doses, at what intervals. e.g., Three doses at one month intervals.
Safety profile	Anticipated or acceptable levels of adverse events; populations or individuals who should not receive the product, or receive it with caution. e.g., Safety allows for use in the target population, or comparable to similar interventions used in the target population.
Co-administration	Other interventions that can be administered at the same health visit. e.g., Hepatitis B vaccine.
Shelf-life and storage	Shelf-life relates to how long the product can be stored after it leaves the manufacturer, and storage indicates packaging requirements and temperature at which it needs to be maintained. e.g., Two years at 2–8° Celsius.
Manufacturability	Scalability of the production process to quantities anticipated for the developing world. e.g., Up to 100 million doses/year; more than two suppliers.
Price	Absolute or cost-effectiveness relative to peer interventions. e.g., See Table 3.
Product registration and WHO pre-qualification	Rigour of the regulatory bodies anticipated to register the product, and expectations for pre-qualification. e.g., Licensure by WHO-evaluated fully-functional regulatory agency. Pre-qualified by WHO.

Table 3. Public sector preferences for RTS,S vial size.

Vial size	Public sector preference
Mono-dose vial	A mono-dose RTS,S presentation is not recommended at any of the costs per purchased dose that were investigated. The advantage of the low opened-vial wastage rate associated with mono-dose vials is offset by the need to approximately double the volume of refrigerated storage required as compared with a basic schedule of vaccines. In addition, reconstituting mono-dose vials would have an excessive impact on health worker workload.
2-dose vial	The current 2-dose presentation appears to offer the best compromise between volume-per-dose, cost per-dose, and wastage in routine immunisation settings at a price point greater than around US$2.50 per purchased dose.
3-dose vial	A 3-dose vial appears to offer the best compromise for routine use at a cost per purchased dose below the US$2.50 price point.
5-dose vial	A 5-dose vial looks unlikely to be viable at any price point unless it can be supplied in compact, purpose-made vials at a cost per administered dose that is competitive with 3-dose.
10-dose vial	A 10-dose presentation would be welcomed by countries but would only be economical at the lower price points (around US$1.00 per dose) as a supplementary presentation for use in larger urban and campaign settings, where opened-vial wastage levels can be assured to be around 10% or less.