Table 3. Characteristics of anti-COVID-19 hyperimmune immunoglobulin.

Characteristic	Specification†	Average of 10 batches‡
Transparency	Optical density of not more than 0.05	Meet criteria
Color intensity	Optical density of not more than 0.05	Meet criteria
pH	4.5–5.5	4.82 ± 0.12
Protein concentration	80–120 mg/ml	98.1 ± 6.5 mg/ml
Purity	≥95% of the total protein content	97.6 ± 0.7%
Distribution of molecular size of IgG	≤3% polymeric ≥90% monomeric/dimeric IgG	0.17 ± 0.08% 99.82 ± 0.08%
IgA content	<1 mg/ml	0.18 ± 0.05 mg/ml
Heat stability	No jelling	Meet criteria
Glycine content	21.0–29.0 mg/ml	Meet criteria
Virus inactivating agents	Tween-80 ≤1.0 μg/ml Tri-n-butylphosphate ≤5.0 μg/ml	≤1.0 μg/ml ≤5.0 μg/ml
Osmolality	≥240 mOsmol/kg	344.0 ± 19.4 mOsmol/kg
Sterility	Should be sterile	Meet criteria
Pyrogens	Should be nonpyrogenic	Meet criteria
Abnormal toxicity	Should be nontoxic	Meet criteria
Anti-COVID-19 IgG (concentration factor)	≥6 × starting plasma pool	(9.4 ± 1.4) × starting plasma pool
Anticomplementary activity	<1 CH50/mg IgG	<1 CH50/mg IgG
Hemagglutinins anti-A and anti-B	1/64 diluted solution shows no agglutination	1/64 diluted solution shows no agglutination
Anti-D	Anti-D content no more than that of the positive standard sample	Anti-D content less than that of a positive standard sample
IgG subclass distribution	IgG distribution corresponding to normal human serum	IgG1 – 62.0 ± 4.0 IgG2 – 26.3 ± 4.8 IgG3 – 7.7 ± 2.0 IgG4 – 4.0 ± 0.7
Fc function	≥60% of intravenous immunoglobulin reference preparation	134.6 ± 5.5%
PKA activity	≤35 IU/ml	4.5 ± 0.3 IU/ml
Thrombogenic potential	No thrombus formation should be observed	Meet criteria
Yield		4.25 ± 0.24 g IgG/l plasma

^†The characteristics of anti-COVID-19 hyperimmune immunoglobulin satisfy the requirements of the European Pharmacopoeia and State Pharmacopoeia of the Russian Federation.

^‡One batch produced from 350 l of human plasma.

CH50: Complement, total.