Alpha1-Proteinase Inhibitor

Name: Alpha1-Proteinase Inhibitor

Description

ARALAST NP contains approximately 2% Alpha1-PI with truncated C-terminal lysine (removal of Lys394), whereas ARALAST contains approximately 67% Alpha1-PI with the C-terminal lysine truncation.8 No known data suggest influence of these structural modifications on the functional activity and immunogenicity of Alpha1-PI.9

ARALAST NP is a sterile, lyophilized preparation of purified human alpha1-proteinase inhibitor (Alpha1-PI), also known as alpha1-antitrypsin (AAT). ARALAST NP is a similar product to ARALAST, containing the same active components of plasma Alpha1-PI with identical formulations.

ARALAST NP is prepared from large pools of human plasma by using the cold ethanol fractionation process, followed by purification steps including polyethylene glycol and zinc chloride precipitations and ion exchange chromatography.

To reduce the risk of viral transmission, the manufacturing process includes treatment with a solvent detergent (S/D) mixture [tri-n-butyl phosphate and polysorbate 80] to inactivate enveloped viral agents such as human immunodeficiency virus (HIV), hepatitis B (HBV), and hepatitis C (HCV). In addition, a nanofiltration step is incorporated into the manufacturing process to reduce the risk of transmission of enveloped and non-enveloped viral agents. Based on in vitro studies, the process used to produce ARALAST NP has been shown to inactivate and/or partition various viruses as shown in Table 3 below.

Table 3 : Virus Log Reduction in ARALAST NP Manufacturing Process

Processing Step Virus Log Reduction Factors
HIV-1 BVDV PRV HAV MMV
Cold ethanol fractionation 4.6 1.4 2.1 1.4 ≤ 1.0a
Solvent Detergent-treatment > 5.8 > 6.0 > 5.5 N/A N/A
15 N nanofiltration > 5.3 > 6.0 > 5.6 > 5.1 4.9
Overall reduction factor > 15.7 > 13.4 > 13.2 > 6.5 4.9
aHIV-1: Human Immunodeficiency Virus-1; BVDV: Bovine Viral Diarrhea Virus, model for Hepatitis C Virus and other lipid enveloped RNA viruses; PRV: Pseudorabies Virus, model for lipid-enveloped DNA viruses, to which Hepatitis B also belongs; HAV: Hepatitis A Virus; MMV: Mice Minute Virus, model for small non-lipid-enveloped DNA viruses

Reduction factors < 1.0 are not used for calculation of the overall reduction factor

N/A - Not applicable; study did not test for virus indicated

The unreconstituted, lyophilized cake should be white or off-white to slightly yellow-green or yellow in color. When reconstituted as directed, the concentration of functionally active Alpha1-PI is ≥ 16 mg/mL and the specific activity is ≥ 0.55 mg active Alpha1-PI/mg total protein. The composition of the reconstituted product is as follows:

Component Quantity/mL
Elastase Inhibitory Activity ≥ 400 mg Active Alpha1-PI/0.5 g viala ≥ 800 mg Active Alpha1-PI/1.0 g vialb
Albumin ≤ 5 mg/mL
Polyethylene Glycol ≤ 112 mcg/mL
Polysorbate 80 ≤ 50 mcg/mL
Sodium ≤ 230 micromol/mL
Tri-n-butyl Phosphate ≤ 1.0 mcg/mL
Zinc ≤ 3 mg/L
aReconstitution volume: 25 mL/0.5 g vial
bReconstitution volume: 50 mL/1.0 g vial

Each vial of ARALAST NP has the functional activity, as determined by inhibition of porcine pancreatic elastase, stated on the label. The formulation contains no preservative. The pH of the solution ranges from 7.2 to 7.8. Product must only be administered intravenously.

Warnings

Included as part of the PRECAUTIONS section.

Overdose

No information provided.

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Intravenous [preservative free]:

Glassia: 1000 mg/50 mL (1 ea) [latex free]

Solution Reconstituted, Intravenous [preservative free]:

Aralast NP: 400 mg (1 ea [DSC]); 500 mg (1 ea); 800 mg (1 ea [DSC]); 1000 mg (1 ea) [contains polyethylene glycol, polysorbate 80]

Prolastin-C: 1000 mg (1 ea)

Zemaira: 1000 mg (1 ea)

Pharmacologic Category

  • Antitrypsin Deficiency Agent
  • Blood Product Derivative

Pharmacology

Alpha1-antitrypsin (AAT) is the principle protease inhibitor in serum. Its major physiologic role is to render proteolytic enzymes (secreted during inflammation) inactive. A decrease in AAT, as seen in congenital AAT deficiency, leads to increased elastic damage in the lung, causing emphysema.

Distribution

Vd: ~3.5 L

Time to Peak

Serum: ~1 hour; threshold levels achieved after 3 weeks

Half-Life Elimination

Metabolic: ~5-6 days

Dosing Adult

Alpha1-antitrypsin deficiency: IV: 60 mg/kg once weekly

Reconstitution

Reconstitute lyophilized powder with provided diluent (SWFI). Allow product and diluent to reach room temperature (if refrigerated) prior to reconstitution. Filtering requirements during preparation vary by product; consult manufacturer recommendations. May pool vial contents by transferring into a sterile container for IV infusion. To mix, swirl; do not shake. Administer within 3 hours of preparation or within 3 hours of entering the vial (Glassia); products do not contain a preservative.

Aralast NP: Each 500 mg and 1,000 mg vial should be diluted with 25 mL and 50 mL of diluent, respectively

Prolastin-C: Each 1,000 mg vial should be diluted with 20 mL of diluent

Zemaira: Each 1,000 mg vial should be diluted with 20 mL of diluent

Pregnancy Risk Factor C Pregnancy Considerations

Animal reproduction studies have not been conducted.

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