KCENTRA Powder for solution for infusion, lyophilized Ref.[50986] Active ingredients: Coagulation factor IX complex Protein C Protein S

Source: FDA, National Drug Code (US) Revision Year: 2023

Product description

KCENTRA is a purified, heat-treated, nanofiltered and lyophilized non-activated four-factor Prothrombin Complex Concentrate (Human) prepared from human U.S. Source Plasma (21 CFR 640.60). It contains the Vitamin K dependent Coagulation Factors II, VII, IX and X, and the antithrombotic Proteins C and S. Factor IX is the lead factor for the potency of the preparation as stated on the vial label. The excipients are human antithrombin III, heparin, human albumin, sodium chloride, and sodium citrate. KCENTRA is sterile, pyrogen-free, and does not contain preservatives.

The product contents are shown in Table 6 and listed as ranges for the blood coagulation factors.

Table 6. Composition per Vial of KCENTRA*:

Ingredient	Potency Range for 500 units	Potency Range for 1000 units
Total protein	120–280 mg	240–560 mg
Factor II	380–800 units	760–1600 units
Factor VII	200–500 units	400–1000 units
Factor IX	400–620 units	800–1240 units
Factor X	500–1020 units	1000–2040 units
Protein C	420–820 units	840–1640 units
Protein S	240–680 units	480–1360 units
Heparin	8–40 units	16–80 units
Antithrombin III	4–30 units	8–60 units
Human albumin	40–80 mg	80–160 mg
Sodium chloride	60–120 mg	120–240 mg
Sodium citrate	40–80 mg	80–160 mg
HCl	Small amounts	Small amounts
NaOH	Small amounts	Small amounts

^* Exact potency of coagulant and antithrombotic proteins are listed on the carton

All plasma used in the manufacture of KCENTRA is obtained from US donors and is tested using serological assays for hepatitis B surface antigen and antibodies to HIV-1/2 and HCV. The plasma is tested with Nucleic Acid Testing (NAT) for HCV, HIV-1, HAV, and HBV, and found to be non-reactive (negative), and the plasma is also tested by NAT for human parvovirus B19 (B19V) in order to exclude donations with high titers. The limit for B19V in the fractionation pool is set not to exceed 10 ⁴ units of B19V DNA per mL. Only plasma that passed virus screening is used for production.

The KCENTRA manufacturing process includes various steps, which contribute towards the reduction/inactivation of viruses. KCENTRA is manufactured from cryo-depleted plasma that is adsorbed via ion exchange chromatography, heat treated in aqueous solution for 10 hours at 60°C, precipitated, adsorbed to calcium phosphate, virus filtered, and lyophilized.

Manufacturing steps were independently validated in a series of in vitro experiments for their virus inactivation / reduction capacity for both enveloped and non-enveloped viruses. Table 7 shows the virus clearance during the manufacturing process for KCENTRA, expressed as the mean log₁₀ reduction factor.

Table 7. Mean Virus Reduction Factors [log₁₀] of KCENTRA:

Virus Studied	Manufacturing Steps
Virus Studied	Heat treatment (“Pasteurization”)	Ammonium sulphate precipitation followed by Ca Phosphate adsorption	2 × 20 nm Virus Filtration	Overall Virus Reduction [log₁₀]
Enveloped Viruses
HIV	≥5.9	≥5.9	≥6.6	≥18.4
BVDV	≥8.5	2.2	≥6.0	≥16.7
PRV	3.8	7.2	≥6.6	≥17.6
WNV	≥7.4	n.d.	≥8.1	≥15.5
Non-Enveloped Viruses
HAV	4.0	1.8	≥6.1	≥11.9
CPV	[0.5]*	1.5	6.5	8.0

HIV Human immunodeficiency virus, a model for HIV-1 and HIV-2
BVDV Bovine viral diarrhea virus, model for HCV
PRV Pseudorabies virus, a model for large enveloped DNA viruses
WNV West Nile virus
HAV Hepatitis A virus
CPV Canine parvovirus, model for B19V
n.d. not determined
^* Reduction factor below 1 log was not considered in calculating the overall virus reduction. Studies using human parvovirus B19, which are considered experimental in nature, have demonstrated a virus reduction factor of 3.5 log by heat treatment.

Dosage Forms and Strengths
KCENTRA is available as a white or slightly colored lyophilized concentrate in a single-dose vial containing coagulation Factors II, VII, IX and X, and antithrombotic Proteins C and S. KCENTRA potency (units) is defined by Factor IX content. The actual potency for 500 unit vial ranges from 400-620 Factor IX units/vial. The actual potency for 1000 unit vial ranges from 800-1240 Factor IX units/vial. The actual content of Factor IX as measured in units of potency for the vial before reconstitution is stated by the expiration date. When reconstituted, the final concentration of drug product in Factor IX units will be in a range from 20–31 units/mL. The actual units of potency for each coagulation factor (Factors II, VII, IX and X), and Proteins C and S are stated on the carton.

How Supplied

KCENTRA is supplied in a single-dose vial.
The actual units of potency of all coagulation factors (Factors II, VII, IX and X), Proteins C and S in units are stated on each KCENTRA carton.
The KCENTRA packaging components are not made with natural rubber latex.

Table 17. How Supplied:

Each kit consists of the following:

Carton NDC Number	Components
63833-386-02	• Nominal potency 500 (range 400-620) units KCENTRA in a single-dose vial [NDC 63833-396-01] • 20 mL vial of Sterile Water for Injection, USP [NDC 63833-761-20] • Mix2Vial filter transfer set • Alcohol swab
63833-387-02	• Nominal potency 1000 (range 800-1240) units KCENTRA in a single-dose vial [NDC 63833-397-01] • 40 mL vial of Sterile Water for Injection, USP [NDC 63833-761-40] • Mix2Vial filter transfer set • Alcohol swab

Manufactured by: CSL Behring GmbH, 35041 Marburg Germany, US License No. 1765

Distributed by: CSL Behring LLC, Kankakee, IL 60901 USA

Drugs

Drug	Countries
KCENTRA	Japan, United States

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