Emerging antibody-based products for infectious diseases: Planning for metric ton manufacturing

Figures & data

Table 1. Potential indications, antibody doses and estimates of metric ton (MT) requirements (per 1 M Users)

Target*	Indication	Unmet Need	Assumptions**	Product Requirements/ 1 M Users/Yr (MT)
Respiratory Syncytial Virus	Prophylaxis (healthy infants)	140 M births/yr	50 mg dose	0.05
	Prophylaxis (adults)	600 M > 65 years old globally	10 mg/kg dose	0.6
HIV	Therapy	1.9 M with MDR HIV	Weekly 0.35 g dose	18.2
		38 M with HIV
	Prophylaxis (parenteral)	High-risk individuals; difficult to estimate	2 mAb cocktail at 1 mg/kg each and 3 doses/year	0.36
SARS-CoV-2	Therapy	> 80 M infected; >1.8 M deaths	2 Abs; 10 mg/kg	1.2
	Prophylaxis		2 Abs; 1 mg/kg	0.12
Malaria	Prophylaxis	1.1 B at high risk***	5 mg/kg; 3 times per year	0.9
Influenza	Prophylaxis	High-risk individuals; difficult to estimate	1–10 mg/kg	0.06–0.6
	Therapy	~10 M hospitalizations/yr	1–8 g/dose	1–8
Mucosal MPT (HIV, Sperm, HSV)	Prophylaxis	~140 M (for contraception)****	4 Abs (2 HIV Abs, 1 HSV antibody, 1 contraceptive antibody); 50 doses/year X 40 mg total per dose	2.0

MDR = multi-drug resistant; MPT = multipurpose prevention technology.

*emphasis on mAb product concepts that have been through a Phase 1 clinical trial.

**based on a global average weight of 60 kg.

*** https://www.who.int/data/gho/data/themes/malaria.

**** Because people are good at estimating their risk for unintended pregnancy but underestimate risk for STI acquisition, contraceptive activity is likely to be a major driver for use of a multipurpose prevention technology (MPT).

Table 2. GMP manufacturing scale of mAbs: potential annual drug substance production per single manufacturing unit

	Mammalian		Plant (transient)	Yeast/fungus
Productivity	1–10 g/L		0.1–1 g/kg of biomass	1–5 g/L
Scale of unit	2,000 L single use	20,000 L fixed	3,500 kg biomass/week	Up to 300,000 L
Yield*	2–20 kg	20–200 kg	0.35–3.5 kg	300–1500 kg
Production cycle	14 d	14 d	14 d	12 d
Assumed annual manufacturing cycles	18	14	20	20
Potential annual production	0.036–0.36 MT	0.28–2.8 MT	0.006–0.06 MT	6–30 MT

*for simplicity we assume 100% process yield in all production systems.