Endoglycosidase

Antigen Neutralization

Human Immunoglobulin G

Extravasation of Diagnostic and Therapeutic Materials

Immunologic Deficiency Syndromes

<section class="Section" data-sectioncode="34089-3"><a name="S11"></a><a name="section-9"></a><h1>11 DESCRIPTION</h1>HYQVIA is a dual vial unit with one vial of Immune Globulin Infusion 10% (Human) and one vial of rHuPH20.The Immune Globulin Infusion 10% (Human) of HYQVIA is a ready-for-use, sterile, liquid preparation of highly purified and concentrated IgG antibodies. The distribution of the IgG subclasses is similar to that of normal plasma. The Fc and Fab functions are maintained in the primary component. Pre-kallikrein activator activity is not detectable. The Immune Globulin Infusion 10% (Human) of HYQVIA contains 100 mg/mL protein. At least 98% of the protein is IgG, average immunoglobulin A (IgA) concentration is 37µg/mL, and immunoglobulin M (IgM) is present in trace amounts. The Immune Globulin Infusion 10% (Human) of HYQVIA contains a broad spectrum of IgG antibodies against bacterial and viral agents. Glycine (0.25M) serves as a stabilizing and buffering agent. There is no added sugar, sodium, or preservatives. The pH is 4.6 to 5.1. The osmolality is 240 to 300 mOsmol/kg.The Immune Globulin Infusion 10% (Human) of HYQVIA 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 the Immune Globulin Infusion 10% (Human) of HYQVIA 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).To further improve the margin of safety, three dedicated, independent and effective virus inactivation/removal steps have been integrated into the manufacturing and formulation processes, namely solvent/detergent (S/D) treatment, 35 nm nanofiltration, and a low pH incubation at elevated temperature. 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.7In 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, these 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 the Immune Globulin Infusion 10% (Human) of HYQVIA performed in accordance with good laboratory practices (<a href="#table12">Table 12</a>) have demonstrated that:<ul class="Disc"><li>S/D treatment inactivates the lipid-enveloped viruses investigated to below detection limits within minutes.</li><li>35 nm nanofiltration removes lipid-enveloped viruses to below detection limits and reduces the nonlipid enveloped viruses HAV and B19V. As determined by a polymerase chain reaction assay, nanofiltration reduced B19V by a mean log10 reduction factor of 4.8 genome equivalents.</li><li>Treatment with low pH at elevated temperature of 30°C to 32°C inactivates lipid-enveloped viruses and encephalomyocarditis virus (EMCV, model for HAV) to below detection limits, and reduces mice minute virus (MMV, model for B19V).</li></ul><a name="table12"></a><table width="90%"><caption>Table 12: Three Dedicated Independent Virus Inactivation/Removal Steps Mean Log10 Reduction Factors<a class="Sup" href="#footnote-13" name="footnote-reference-13">*</a> (RFs) For Each Virus and Manufacturing Step</caption><col align="left" valign="middle" width="17%"/><col align="left" valign="middle" width="15%"/><col align="left" valign="middle" width="9%"/><col align="left" valign="middle" width="8%"/><col align="left" valign="middle" width="15%"/><col align="left" valign="middle" width="7%"/><col align="left" valign="middle" width="12%"/><col align="left" valign="middle" width="17%"/><thead><tr class="Botrule First"><th align="left" class="Lrule Rrule">Virus type</th><th align="left" class="Rrule" colspan="3">Enveloped RNA</th><th align="left" class="Rrule">Enveloped DNA</th><th align="left" class="Rrule" colspan="2">Non-enveloped RNA</th><th align="left" class="Rrule">Non-enveloped DNA</th></tr><tr class="Botrule"><th align="left" class="Lrule Rrule">Family</th><th align="left" class="Rrule">Retroviridae</th><th align="left" class="Rrule" colspan="2">Flaviviridae</th><th align="left" class="Rrule">Herpesviridae</th><th align="left" class="Rrule" colspan="2">Picornaviridae</th><th align="left" class="Rrule">Parvoviridae</th></tr><tr class="Last"><th align="left" class="Lrule Rrule">Virus</th><th align="left" class="Rrule">HIV-1</th><th align="left" class="Rrule">BVDV</th><th align="left" class="Rrule">WNV</th><th align="left" class="Rrule">PRV</th><th align="left" class="Rrule">HAV</th><th align="left" class="Rrule">EMCV</th><th align="left" class="Rrule">MMV</th></tr></thead><tfoot><tr class="First Last"><td align="left" colspan="8">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-13" name="footnote-13">*</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-14" name="footnote-14">†</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><tr class="Botrule First"><td align="left" class="Lrule Rrule">SD treatment</td><td align="left" class="Rrule">&gt;4.5</td><td align="left" class="Rrule">&gt;6.2</td><td align="left" class="Rrule">n.a.</td><td align="left" class="Rrule">&gt;4.8</td><td align="left" class="Rrule">n.d.</td><td align="left" class="Rrule">n.d.</td><td align="left" class="Rrule">n.d.</td></tr><tr class="Botrule"><td align="left" class="Lrule Rrule">35 nm nanofiltration</td><td align="left" class="Rrule">&gt;4.5</td><td align="left" class="Rrule">&gt;5.1</td><td align="left" class="Rrule">&gt;6.2</td><td align="left" class="Rrule">&gt;5.6</td><td align="left" class="Rrule">5.7</td><td align="left" class="Rrule">1.4</td><td align="left" class="Rrule">2.0</td></tr><tr class="Botrule"><td align="left" class="Lrule Rrule">Low pH treatment</td><td align="left" class="Rrule">&gt;5.8</td><td align="left" class="Rrule">&gt;5.5</td><td align="left" class="Rrule">&gt;6.0</td><td align="left" class="Rrule">&gt;6.5</td><td align="left" class="Rrule">n.d.<a class="Sup" href="#footnote-14" name="footnote-reference-14">†</a></td><td align="left" class="Rrule">&gt;6.3</td><td align="left" class="Rrule">3.1</td></tr><tr class="Last"><td align="left" class="Lrule Rrule">Overall log reduction factor (ORF)</td><td align="left" class="Rrule">&gt;14.8</td><td align="left" class="Rrule">&gt;16.8</td><td align="left" class="Rrule">&gt;12.2</td><td align="left" class="Rrule">&gt;16.9</td><td align="left" class="Rrule">5.7<a class="Sup" href="#footnote-14">†</a></td><td align="left" class="Rrule">&gt;7.7</td><td align="left" class="Rrule">5.1</td></tr></tbody></table>The rHuPH20 of HYQVIA is produced from genetically engineered Chinese Hamster Ovary (CHO) cells containing a DNA plasmid encoding for a soluble fragment of human hyaluronidase PH20. The purified hyaluronidase glycoprotein contains 447 amino acids with an approximate molecular weight of 61,000 Daltons [see <a href="#S12.1">Clinical Pharmacology (12.1)</a>]. This component is supplied as a sterile, clear, colorless, ready-for-use solution and has an approximate pH of 7.4 and an osmolality of 290 to 350 mOsm. Each vial contains 160 U/mL of rHuPH20 with 8.5 mg/mL sodium chloride, 1.78 mg/mL sodium phosphate dibasic dihydrate, 1.0 mg/mL human albumin, 1.0 mg/mL edentate disodium dihydrate, 0.40 mg/mL calcium chloride dihydrate, and 0.17 mg/mL sodium hydroxide added for pH adjustment. It does not contain preservatives.Due to comprehensive virus testing at the Master Cell Bank, Working Cell Bank and bulk harvest stage, effective virus reduction during the purification process and use of pharmaceutical grade human albumin as an excipient with no other materials of human or animal origin involved in the manufacturing process, rHuPH20 provides for high margins of safety with respect to viruses.</section>

HYQVIA

hyaluronidase, human recombinant

immunoglobulin G, human

50 ML immunoglobulin G, human 100 MG/ML Injection

100 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

1.25 ML hyaluronidase, human recombinant 160 UNT/ML Injection

10 ML hyaluronidase, human recombinant 160 UNT/ML Injection

15 ML hyaluronidase, human recombinant 160 UNT/ML Injection

300 ML immunoglobulin G, human 100 MG/ML Injection

2.5 ML hyaluronidase, human recombinant 160 UNT/ML Injection

5 ML hyaluronidase, human recombinant 160 UNT/ML Injection

hyaluronidase

immunoglobulin G

Psoriasis (PsO)

Psoriatic Arthritis (PsA)

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Taltz

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Cosentyx

Siliq

Tremfya

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Verzenio

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