Table 1.

Key formulation attributes of a paediatric Quality Target Product Profile (pQTPP) for PQ.

Attribute	Targets	Comments
Target population (age)	Entire range 6 months–<16 years	Different dosing regimens are used, depending on the endemic area and national recommendations, based on mg per body weight or by age or weight dosing bands.
Route of administration	Oral	As per the WHO EOI requirement for prequalification [5].
Target release profile	Immediate release	As per the WHO EOI requirement for prequalification [5].
Dosage form	Tablets	At the start of DPP, the 17th WHO EOI invitation in 2019 called for PQ “tablets” only, while the latest 2023 EOI adds “(preferably dispersible for paediatric use)”. Hard tablets are suitable for use in the target population; however, the tablets would need to be scored and/or crushed to be administered to children unable to swallow them whole.
Dose and dose flexibility	Paediatric dosage strengths of primaquine base: 2.5 mg 3.75 mg 5 mg (scored) 7.5 mg (scored) 15 mg (scored)	At the start of DPP, the 17th WHO EOI invitation called for prequalification of five tablet strengths; however, the latest EOI no longer lists the 3.75 mg tablet. Five strengths will continue to be developed, providing more flexibility for clinical supplies. Scorelines allow further dosing flexibility. Dose regimens require further investigation and optimisation. Clinical trials are ongoing or planned. Dosing range recommendations are developed according to the patient’s age or weight. For fixed dose combinations, if any, the ratio of active ingredients may change across age groups.
Excipients and manufacturing	Excipients: no safety concerns for the proposed patient population. All dosage strengths are to be homothetic. Low-cost manufacturing	All excipients are Generally Recognised as Safe (GRAS) and have approval for use in pharma applications in accordance with EU and African regulations. The safety of excipients for the selected age group has been considered on a risk-benefit basis, on top of regulatory acceptance and precedence. Lower strengths will be produced proportionally to the higher strengths to get a biowaiver for prequalification (i.e., a bioequivalence study is not required for the line extension). Tablets are simple to manufacture. All prices are taken in consideration to keep the finished product low-cost.
Patient acceptability	Acceptable for the proposed patient population/caregiver, and disease state.	The flavoured tablets aim to mask the bitter taste of PQ, a key strategy to improve acceptability. Sensory evaluation has been used to guide formulation development and determine palatability. Acceptability studies of the flavoured tablets versus the basic formulation will be nested in two validation field trials conducted in Ethiopia and Burkina Faso using the ClinSearch Acceptability Score Test (CAST) [13].
Administration considerations	Ease of preparation and accurate administration with low risk of dosing errors, a minimum of manipulations (e.g., mixing with water), and no device requirements.	Easy crushing is a target criterion with the aim of using a minimum of water and avoid mixing with other vehicles. The Administration protocol will be confirmed in the following field trials. No specific dosing device is needed for the dose ranges, as the various strengths ensure ease and accuracy of dosing. This mitigates the cost of a device.