Antigen Neutralization

Human Immunoglobulin G

Immunologic Deficiency Syndromes

<section class="Section" data-sectioncode="34089-3"><a name="ID_7cfcb57c-d341-4a22-9798-54aee404a98a"></a><a name="section-10"></a><h1>11 DESCRIPTION</h1>GAMMAGARD LIQUID is a ready-for-use sterile, liquid preparation of highly purified and concentrated immunoglobulin G (IgG) antibodies. The distribution of the IgG subclasses is similar to that of normal plasma. The Fc and Fab functions are maintained in GAMMAGARD LIQUID. Pre-kallikrein activator activity is not detectable. GAMMAGARD LIQUID contains 100 mg/mL protein. At least 98% of the protein is immune globulin, the average immunoglobulin A (IgA) concentration is 37 µg/mL, and immunoglobulin M is present in trace amounts. GAMMAGARD LIQUID contains a broad spectrum of IgG antibodies against bacterial and viral agents. Glycine (0.25M) serves as a stabilizing and buffering agent. There are no added sugars, sodium or preservatives. The pH is 4.6 to 5.1. The osmolality is 240 to 300 mOsmol/kg, which is similar to physiological osmolality (285 to 295 mOsmol/kg). GAMMAGARD LIQUID is manufactured from large pools of human plasma. IgG preparations are purified from plasma pools using a modified Cohn-Oncley cold ethanol fractionation process, as well as cation and anion exchange chromatography.Screening against potentially infectious agents begins with the donor selection process and continues throughout plasma collection and plasma preparation. Each individual plasma donation used in the manufacture of GAMMAGARD LIQUID is collected only at FDA approved blood establishments and is tested by FDA licensed serological tests for Hepatitis B Surface Antigen (HBsAg), and for antibodies to Human Immunodeficiency Virus (HIV-1/HIV-2) and Hepatitis C Virus (HCV) in accordance with U.S. regulatory requirements. As an additional safety measure, mini-pools of the plasma are tested for the presence of HIV-1 and HCV by FDA licensed Nucleic Acid Testing (NAT) and found to be negative. To further improve the margin of safety, validated virus inactivation/removal steps have been integrated into the manufacturing and formulation processes, namely solvent/detergent (S/D) treatment,10 35 nm nanofiltration, and a low pH incubation at elevated temperature (30 C to 32 C). The S/D process includes treatment with an organic mixture of tri-n-butyl phosphate, octoxynol 9 and polysorbate 80 at 18 C to 25 C for a minimum of 60 minutes. S/D treatment inactivates the lipid-enveloped viruses investigated to below detection limits within minutes.12In vitro virus spiking studies have been used to validate the capability of the manufacturing process to inactivate and remove viruses. To establish the minimum applicable virus clearance capacity of the manufacturing process, virus clearance studies were performed under extreme conditions (e.g., at minimum S/D concentrations, incubation time and temperature for the S/D treatment). Virus clearance studies for GAMMAGARD LIQUID performed in accordance with good laboratory practices are summarized in <a href="#_Ref464557146">Table 12</a>.<a name="_Ref464557146"></a><table width="100%"><caption>Table 12: Three Dedicated Independent Virus Inactivation/Removal Steps Mean Log10 Reduction Factors<a class="Sup" href="#footnote-2" name="footnote-reference-2">*</a> (RFs) For Each Virus and Manufacturing Step</caption><col width="14%"/><col width="15%"/><col width="11%"/><col width="10%"/><col width="15%"/><col width="9%"/><col width="10%"/><col width="16%"/><tfoot><tr class="First Last"><td align="left" colspan="8" valign="top">Abbreviations: HIV-1, Human Immunodeficiency Virus Type 1; BVDV, Bovine Viral Diarrhea Virus (model for Hepatitis C Virus and other lipid enveloped RNA viruses); WNV, West Nile Virus; PRV, Pseudorabies Virus (model for lipid enveloped DNA viruses, including Hepatitis B Virus); EMCV, Encephalomyocarditis Virus (model for non-lipid enveloped RNA viruses, including Hepatitis A virus [HAV]); MMV, Mice Minute Virus (model for non-lipid enveloped DNA viruses, including B19 virus [B19V]); n.d. (not done), n.a. (not applicable).</td></tr><tr><td align="left" colspan="8"><dl class="Footnote"><dt><a href="#footnote-reference-2" name="footnote-2">*</a></dt><dd>For the calculation of these RF data from virus clearance study reports, applicable manufacturing conditions were used. Log10 RFs on the order of 4 or more are considered effective for virus clearance in accordance with the Committee for Medicinal Products for Human Use (CHMP, formerly CPMP) guidelines.</dd><dt><a href="#footnote-reference-3" name="footnote-3">†</a></dt><dd>No RF obtained due to immediate neutralization of HAV by the anti-HAV antibodies present in the product.</dd></dl></td></tr></tfoot><tbody class="Headless"><tr class="First"><td class="Botrule Lrule Rrule Toprule" valign="middle">Virus type</td><td class="Botrule Lrule Rrule Toprule" colspan="3" valign="middle">Enveloped RNA</td><td class="Botrule Lrule Rrule Toprule" valign="middle">Enveloped DNA</td><td class="Botrule Lrule Rrule Toprule" colspan="2" valign="top">Non-enveloped RNA</td><td class="Botrule Lrule Rrule Toprule" valign="top">Non-enveloped DNA</td></tr><tr><td class="Botrule Lrule Rrule Toprule" valign="top">Family</td><td class="Botrule Lrule Rrule Toprule" valign="top">Retroviridae</td><td class="Botrule Lrule Rrule Toprule" colspan="2" valign="top">Flaviviridae</td><td class="Botrule Lrule Rrule Toprule" valign="top">Herpesviridae</td><td class="Botrule Lrule Rrule Toprule" colspan="2" valign="top">Picornaviridae</td><td class="Botrule Lrule Rrule Toprule" valign="top">Parvoviridae</td></tr><tr><td class="Botrule Lrule Rrule Toprule" valign="top">Virus</td><td class="Botrule Lrule Rrule Toprule" valign="top">HIV-1</td><td class="Botrule Lrule Rrule Toprule" valign="top">BVDV</td><td class="Botrule Lrule Rrule Toprule" valign="top">WNV</td><td class="Botrule Lrule Rrule Toprule" valign="top">PRV</td><td class="Botrule Lrule Rrule Toprule" valign="top">HAV</td><td class="Botrule Lrule Rrule Toprule" valign="top">EMCV</td><td class="Botrule Lrule Rrule Toprule" valign="top">MMV</td></tr><tr><td class="Botrule Lrule Rrule Toprule" valign="top"> SD treatment </td><td class="Botrule Lrule Rrule Toprule" valign="top">&gt;4.5</td><td class="Botrule Lrule Rrule Toprule" valign="top">&gt;6.2</td><td class="Botrule Lrule Rrule Toprule" valign="top">n.a.</td><td class="Botrule Lrule Rrule Toprule" valign="top">&gt;4.8</td><td class="Botrule Lrule Rrule Toprule" valign="top">n.d.</td><td class="Botrule Lrule Rrule Toprule" valign="top">n.d.</td><td class="Botrule Lrule Rrule Toprule" valign="top">n.d</td></tr><tr><td class="Botrule Lrule Rrule Toprule" valign="top"> 35 nm nanofiltration </td><td class="Botrule Lrule Rrule Toprule" valign="top">&gt;4.5</td><td class="Botrule Lrule Rrule Toprule" valign="top">&gt;5.1</td><td class="Botrule Lrule Rrule Toprule" valign="top">&gt;6.2</td><td class="Botrule Lrule Rrule Toprule" valign="top">&gt;5.6</td><td class="Botrule Lrule Rrule Toprule" valign="top">5.7</td><td class="Botrule Lrule Rrule Toprule" valign="top">1.4</td><td class="Botrule Lrule Rrule Toprule" valign="top">2.0</td></tr><tr><td class="Botrule Lrule Rrule Toprule" valign="top"> Low pH treatment </td><td class="Botrule Lrule Rrule Toprule" valign="top">&gt;5.8</td><td class="Botrule Lrule Rrule Toprule" valign="top">&gt;5.5</td><td class="Botrule Lrule Rrule Toprule" valign="top">&gt;6.0</td><td class="Botrule Lrule Rrule Toprule" valign="top">&gt;6.5</td><td class="Botrule Lrule Rrule Toprule" valign="top">n.d.<a class="Sup" href="#footnote-3" name="footnote-reference-3">†</a></td><td class="Botrule Lrule Rrule Toprule" valign="top">&gt;6.3</td><td class="Botrule Lrule Rrule Toprule" valign="top">3.1</td></tr><tr class="Last"><td class="Botrule Lrule Rrule Toprule" valign="top">Overall log reduction factor (ORF)</td><td class="Botrule Lrule Rrule Toprule" valign="middle">&gt;14.8</td><td class="Botrule Lrule Rrule Toprule" valign="middle">&gt;16.8</td><td class="Botrule Lrule Rrule Toprule" valign="middle">&gt;12.2</td><td class="Botrule Lrule Rrule Toprule" valign="middle">&gt;16.9</td><td class="Botrule Lrule Rrule Toprule" valign="middle">5.7<a class="Sup" href="#footnote-3">†</a></td><td class="Botrule Lrule Rrule Toprule" valign="middle">&gt;7.7</td><td class="Botrule Lrule Rrule Toprule" valign="middle">5.1</td></tr></tbody></table></section>

GAMMAGARD Liquid

immunoglobulin G, human

50 ML immunoglobulin G, human 100 MG/ML Injection

100 ML immunoglobulin G, human 100 MG/ML Injection

10 ML immunoglobulin G, human 100 MG/ML Injection

25 ML immunoglobulin G, human 100 MG/ML Injection

200 ML immunoglobulin G, human 100 MG/ML Injection

300 ML immunoglobulin G, human 100 MG/ML Injection

10 ML immunoglobulin G, human 100 MG/ML Injection [Gammagard]

25 ML immunoglobulin G, human 100 MG/ML Injection [Gammagard]

50 ML immunoglobulin G, human 100 MG/ML Injection [Gammagard]

100 ML immunoglobulin G, human 100 MG/ML Injection [Gammagard]

200 ML immunoglobulin G, human 100 MG/ML Injection [Gammagard]

300 ML immunoglobulin G, human 100 MG/ML Injection [Gammagard]

Gammagard

immunoglobulin G

Psoriasis (PsO)

Psoriatic Arthritis (PsA)

Ankylosing Spondylitis (AS)

Nonradiographic Axial Spondyloarthritis

Taltz

Juvenile Idiopathic Arthritis

Hidradenitis Suppurativa (HS)

Cosentyx

Siliq

Tremfya

Crohn's Disease (CD)

Ulcerative Colitis (UC)

Stelara

Skyrizi

Ilumya

Migraine

Cluster Headache

Migraine Prevention

Emgality

Qulipta

Acute Migraine

Ubrelvy

Nurtec ODT

Vyepti

Aimovig

Ajovy

Breast Cancer: HR+ (HER2-)

Verzenio

Ibrance

Kisqali

Atopic Dermatitis (Eczema)

Cibinqo

Eucrisa

Asthma (injectable)

Asthma OCS Dependent

Nasal Polyposis

Eosinophilic Esophagitis (EoE)

Prurigo Nodularis

Dupixent

Opzelura

Adbry

NSCLC ALK+ OR ROS1+ Disease

Lorbrena

Alecensa

Alunbrig

NSCLC cMET Mutation

Xalkori

Rheumatoid Arthritis (RA)

Xeljanz

Uveitis

Graft Versus Host Disease (GVHD)

Orencia

COVID-19 Treatment

Alopecia Areata

Olumiant

Multiple Sclerosis (MS)

Secondary Progressive Multiple Sclerosis

Zeposia

Rinvoq

Entyvio

Report Adverse Event 

Prescribing Information

Medication Guide 

Submit MSL Request

Pharmacy List 

Reimbursement Information 

Billing Guide 

Coverage Authorization Request 

Coverage Authorization Appeals 

Gammagard Liquid Start Form

Enroll in Patient Savings Program 

Other HCP Resources: Primary Immunodeficiency (PI)

Other HCP Resources: Multifocal Motor Neuropathy (MMN)

About Gammagard Liquid: Primary Immunodeficiency (PI)

Side Effects: Primary Immunodeficiency (PI)

Gammagard Liquid Start Guide: Primary Immunodeficiency (PI)

Patient Resources: Primary Immunodeficiency (PI)

Patient Brochure: Primary Immunodeficiency (PI)

Takeda Patient Support 

About Gammagard Liquid: Multifocal Motor Neuropathy (MMN)

Side Effects: Multifocal Motor Neuropathy (MMN)

Gammagard Liquid Start Guide: Multifocal Motor Neuropathy (MMN

Doctor Discussion Guide: Multifocal Motor Neuropathy (MMN)

Patient Resources: Multifocal Motor Neuropathy (MMN)

Patient Brochure: Multifocal Motor Neuropathy (MMN)

Instructions for Use: Primary Immunodeficiency (PI)

Instructions for Use: Multifocal Motor Neuropathy (MMN)