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Table 2 TPP for an injectable prophylactic medicine for malaria

From: Injectable anti-malarials revisited: discovery and development of new agents to protect against malaria

Parameter to be clinically evaluated for the combination Minimum essential Ideal
Antimalarial effects Blood schizonticides with at least one molecule also having causal prophylactic activity (killing hepatic schizonts) Both molecules should have causal prophylactic, blood schizonticidal and transmission-blocking activities
Mechanism of action Two partner drugs without cross resistance Two partner drugs have different modes of action, so no cross resistance
Dosing regimen Once per month, intramuscular, with an acceptable injection volume Once per 3 months, intramuscular or sub-cutaneous with an acceptable injection volume
Rate of onset of action Protection, within 72 h of initial injection Immediate protection (no lag prior to onset of action)
Clinical efficacy ≥ 80% protective efficacy ≥ 95% protective efficacy: reduction in incidence of symptomatic malaria
No drug-resistant parasites identified in volunteer infection studies still capable of transmission
Drug–drug interactions No unmanageable risk in terms of solid state or PK interactions No risks in terms of solid state or PK interactions with other co-administered PrEP or therapeutics
Safety and tolerability No drug-related SAEs; minimal drug-related AEs—i.e., not resulting in clinical study exclusion. No unacceptable pain, irritability of inflammation at injection site, especially injection abscesses Idem
Use in patients with reduced G6PD activity Testing not required as no enhanced risk in mild-moderate G6PD deficiency Testing not required as drugs not linked to haemolytic risk
Use in infants/children Use in children > 6 months old Use in infants, children and adults
Formulations Suitable for intramuscular injection with minimal preparation; maximum volume of 2 mL for adults and 0.5 mL for infants, administered with 27 gauge needle; partner drugs can be injected separately Liquid pre-filled injection device for intramuscular; maximum volume of 1 mL for adults and < 0.5 mL infants administered with 27–30 gauge needle; fixed dose combination of the drugs; or subcutaneous injection if volumes smaller than above for intramuscular injection
Cost of treatment < 5 USD per injection ≤ USD 1 for infants, USD 2 for children, USD 4 for adults
Shelf life of formulated product (ICH guidelines for zones/IVb) ≥ 2 years ≥ 3 years
  1. PK pharmacokinetic, (S)AE (severe) adverse event, ICH International Conference on Harmonization