Characteristics of Immunoglobulin Products Used to Treat Primary

Immunodeficiency Diseases
PRODUCT NAME Bivigam Cutaquig Cuvitru Flebogamma DIF Gammagard Liquid Gammagard S/D Gammaked Gammaplex Gamunex - C Hizentra HYQVIA3 Octagam Privigen
Biotest Pharmaceuticals
MANUFACTURER Corporation2
Octapharma Takeda Grifols Takeda Takeda Kedrion Bio Products Laboratory Grifols CSL Behring Takeda Octapharma CSL Behring

IG 10% (Human) of HYQVIA:

Cohn-Oncley fractionation,
METHOD OF Anion exchange
PRODUCTION chromatography; Precipitation
and removal of fraction III
(Including Viral of the cold ethanol process,
Inactivation) solvent/detergent treatment,
35 nm nanofiltration.
Cohn-Oncley cold ethanol
fractionation, ultrafiltration,
chromatography, solvent/
detergent treatment, low pH
incubation
Cold alcohol fractionation,
polyethylene glycol
Cohn-Oncley
precipitation, ion exchange
fractionation, ion-exhange
chromatography,
fractionation, ion-exhange
chromatograph solvent/
pH 4 treatment,
detergent treatment,
35nm nanofiltration, low
pasteurization, solvent
detergent treatment,
pH/elevated temperature
and double sequential
incubation.
nanofiltration through 35
and 20 nm filters.
Cohn-Oncley
chromatography solvent/
detergent treatment, ion-exchange chromatography, purification, cloth and depth
35nm nanofiltration,
low pH/elevated
temperature incubation.
Kistler & Nitschmann
fractionation, DEAE-
Cohn-Oncley fractionation,
Sephadex chromatography,
Cohn-Oncley fractionation, caprylate/chromatography
Solvent/detergent,
purification, cloth and depth
solvent detergent treatment. filtration, final container
CM-Sepharose
chromatography, Virus
low pH incubation.
Filration (20 nm) Terminal
low pH incubation.
Cohn-Oncley fractionation,
caprylate/chromatography
filtration, final container
low pH incubation.
fractionation, depth filtration,
Cohn-Oncley fractionation,
ion-exhange chromatography
Cold alcohol fractionation,
solvent/detergent treatment,
octanoic acid fractionation,
35nm nanofiltration, low Octanoic Acid Fractionation,
anion exchange
pH/elevated temperature Cohn-Oncley cold ethanol CH9 Filtration, pH 4.0
chromatography; pH 4
incubation recombinant fractionation, ultra-filtration, incubation, Depth filtration,
incubation, depth filtration,
nanofiltration; TSE reduction
human hyaluronidase: chromatography, solvent Chromatography,
produced from genetically detergent treatment. Nanofiltration,
steps include octanoic acid
engineered Chinese Hamster TSE Reduction Steps.
Ovary (CHO) cells containing
and virus filtration.
a DNA plasmid encoding for
a soluble fragment of human
hyaluronidase PH20.

FORM Liquid Liquid Liquid Liquid Liquid Lyophilized Liquid Liquid Liquid Liquid Liquid Liquid Liquid

24 Months
SHELF-LIFE/ (refrigerated) 12 Months (room temperature
36 Months (refrigerated) 36 Months (refrigerated)
24 Months 24 Months 24 Months (room temperature 24 Months 36 months 30 Months 3 Months4 (room 36 Months
STORAGE (refrigerated)
6 Months (room storage not to exceed
(room temperature storage) storage not to exceed (room temperature storage)
36 Months
(room temperature storage)
36 Months
(room temperature storage) temperature storage not
24 Months
(room temperature storage)
temperature up to 25°C 25°C or 77°F)
REQUIREMENT 25°C or 77°F) to exceed 25°C or 77°F)
or 77°F)

None
RECONSTITUTION None None None None None None None None None None
N/A N/A (Ready-to-use liquid
TIME (Liquid solution) (Liquid solution) (Liquid solution) (Liquid solution) (Liquid solution) (Liquid solution) (Liquid solution)
solution)
(Liquid solution) (Liquid solution) (Liquid solution)

AVAILABLE
10% 16.50% 20% 5% 10% 10% 5% 10% 10% 5% 10% 10% 20% (200 mg/mL) 10% 5% 10% 10%
CONCENTRATIONS
Up to 100 mL/hr/ all sites
combined. First 6 infusions:
≤ 20 mL/hr/site (30 mL/hr/all ≥40 kg BW:
sites combined). Subsequent 30 mL/site at
infusions: 25 mL/hr/site
MAXIMUM (Up to 100 mL/hr/all sites
First 2 Infusions: 20-30mL/hour site
Up to 25 mL/hr/injection
< 40kg BW: maximum
10 - 20 mL/hr/site 6.0 mL/kg/ 4.8 mL/kg/ 5 mL/kg/hr 4 mL/ 8 mL/ 4.8 mL/kg/ 20 mL per 4.8 mL/kg/ 20 mL per 160 mL/site <4.2 mL/kg/ <7.2 mL/kg/
RECOMMENDED 3.5 mL/kg/hour combined) Subsequent
<40 kg BW: 4.8 mL/kg/hour site (50 mL/hr for all 4.8mL/kg/hour
infusions may gradually Subsequent Infusions: hour hour (IV) kg/hour kg/hour hour (IV) hour (SC) hour (IV) hour (SC)
sites combined) > 40kg BW: maximum hour hour
INFUSION RATE increase to 50 mL, then to ≤60 mL/hr/site 20 mL/site 300 mL/site
80 mL; if well tolerated, use at 15-20 mL/
a max of 100 mL/hr/all sites hour/site (SC)
combined

35 grams for For 70 kg 2.5 hours 1.44 hours

Time will vary based upon
Time will vary based on Time will vary based on Time will vary 70kg person, person, 1 hr Time will vary Time will vary depending Time can Time can
TIME TO INFUSE patient tolerability; 146.5 Time will vary based upon Time will vary based upon Time will vary based on Variable based on
1.6 hours 1 hour tolerability and route of concentration and depending on route of 2 hrs 40 minutes 53 minutes depending on route of upon volume and vary based vary based
35 gms1 min based on recommended patient tolerability patient tolerability.
administration. tolerability. administration. if infused if infused administration. tolerability.
patient tolerability.
on patient on patient
patient tolerability.
infusion rates.
according to PI according to PI tolerability. tolerability.

5%
20 mg/ml 40 mg/ml 100 mg/ml. 90 mg/ml.
SUGAR CONTENT No added sugars 79 mg/mL Maltose No added sugars None No added sugars None D-sorbitol None None None No added sugars None
glucose glucose maltose maltose
(polyol)

8.5 mg/mL sodium chloride

8.5 mg/mL 17 mg mL in recombinant human
0.100-0.140 M 30 - 50 Trace amounts
SODIUM CONTENT sodium chloride
≤30 mmol/L No added sodium Trace amounts No added sodium sodium sodium Trace amounts
mmol/L
< 30 mM Trace amounts
(≤10 mmol/L) hyaluronidase, no added
≤30 mmol/L Trace amounts
chloride chloride
sodium in IG 10%

Typically,
OSMOLARITY/ 636 460 - 500 Isotonic
≤ 510 mOsm/kg 310-380 mOsm/kg 280-292 mOsm/kg 240-370 mOsm/kg 240 - 300 mOsm/kg 1250 mOsm/L 258 mOsm/kg 280 258 mOsm/kg 380 mOsmol/kg 240 - 300 mOsm/kg 310 - 380 mOsm/kg
OSMOLALITY mOsm/kg mOsm/kg
mOsmol/kg
(320 mOsmol/kg)

PH 4.0 - 4.6 5.0 - 5.5 4.6 - 5.1 5.0 – 6.0 4.6 – 5.1 6.8 ± 0.4 4.0 – 4.5 4.6 – 5.1 4.9 – 5.2 4.0 – 4.5 4.6 – 5.2 4.6 - 5.1 5.1 – 6.0 4.5 – 5.0 4.8

Average:
< 3 mcg/mL Specification Average of
Average: ≤ 1 µg/mL Average:
IgA CONTENT ≤ 200 µg/mL ≤0.6 mg/mL of IgA 80 µg/mL
< 3 mcg/mL
(Specification 37 µg/mL
≤ 2.2 µg/mL
N/A 46 µg/mL
<4 mcg/mL
value: 46 µg/mL ≤50 mcg/mL 37 μg/mL <100 µg/mL 106 μg/mL < or = 25mcg/mL
value: < 20 mcg/ml of IgA
< 100 mcg/mL)

APPROVED
METHOD OF Intravenous Subcutaneous Subcutaneous Intravenous Intravenous Subcutaneous Intravenous Intravenous Subcutaneous Intravenous Intravenous Subcutaneous Subcutaneous Subcutaneous Intravenous Intravenous
ADMINISTRATION

1
0.5 gm/kg for a 70 kg adult = 35 gms; 5% Concentrations: 1g = 20 mL; 10% Concentrations: 1g = 10 mL.
2
Distributed by ADMA Biologics. Immune Deficiency Foundation
3
HYQVIA is a dual vial unit containing 10% IgG (100 mg/mL) and 160 U/mL recombinant human hyaluronidase.
110 West Road, Suite 300, Towson, MD 21204
4
Shorter room temperature shelf life of HYQVIA (3 months) compared to Gammagard Liquid (24 months) is due to the recombinant human hyaluronidase component of HYQVIA.
800-296-4433 | idf@primaryimmune.org | www.primaryimmune.org
The time to infuse is based on the maximal infusion rate. Check product label for storage temperatures, which vary among immunoglobulin products. Check package insert for detailed
prescribing information. Information for each of the products listed above has been provided directly to IDF by the manufacturer of that product. Download this chart at: www.primaryimmune.org/ig-products

Table updated June 2019