Glassia

GLASSIA is a sterile, ready to use, liquid preparation of purified human alpha1 -proteinase inhibitor (Alpha1 -PI), also known as alpha1 -antitrypsin (AAT). The solution contains 2% active Alpha1 -PI in a phosphate-buffered saline solution. The specific activity of GLASSIA is ≥ 0.7 mg functional Alpha1 -PI per mg of total protein. Not less than 90% of the Alpha1 -PI in GLASSIA is of the monomeric form as measured by size-exclusion chromatography.

GLASSIA is prepared from human plasma obtained from US-licensed plasma collection centers by a modified version of the cold ethanol fractionation process and the Alpha1 -PI is then purified using chromatographic methods.

Individual plasma units used for production of GLASSIA are tested using FDA- licensed serological assays for hepatitis B surface antigen (HBsAg) and for antibodies to hepatitis C virus (HCV) and human immunodeficiency virus types 1 and 2 (HIV-1/2), as well as by FDA-licensed Nucleic Acid Testing (NAT) for HCV and HIV-1. Each plasma unit must be non-reactive (negative) in all tests. Plasma is also tested by in-process NAT procedures for parvovirus B19 and the limit for B19 DNA in the manufacturing pool is set not to exceed 10 IU per mL.

To reduce the risk of viral transmission, the manufacturing process for GLASSIA includes two steps specifically designed to remove or inactivate viruses. The first of these is nanofiltration (NF) through a 15 nm filter which can remove both enveloped and non–enveloped viral agents and the second is solvent/detergent (S/D) treatment with a mixture of tri-(n-butyl) phosphate (TNBP) and Polysorbate 80 (Tween 80) which inactivates enveloped viral agents such as HIV, HBV and HCV.

The effectiveness of the S/D treatment and nanofiltration procedures for reducing virus content has been assessed using a series of viruses with a range of physico-chemical characteristics. The results of the viral challenge studies are summarized in Table 4.

Table 4: Log10 Virus Reduction during Manufacture of GLASSIA

Dosage Forms And Strengths

GLASSIA is available as a single-use vial containing approximately 1 gram of functional Alpha1 -PI in 50 mL of ready to use solution.

Storage And Handling

Each carton of GLASSIA contains a single use vial containing approximately 1 gram of functional Alpha1 -PI in 50 mL of solution and a sterile filter needle (NDC 0944-2884-01).

• Store GLASSIA at 2°C to 8°C (36°F to 46°F). Do not freeze.
• Product may be stored at room temperatures not exceeding 25°C (77°F) for up to one month.
• Once removed from refrigeration use within one month.
• Keep vial in carton until required for use.
• Do not use after the expiration date printed on the label.
• GLASSIA contains no preservatives and no latex.

Manufactured by: Kamada Ltd. Beit Kama, MP Negev 8532500 Israel. Revised: Jun 2016

No Information Provided

GLASSIA
[Alpha1 -Proteinase Inhibitor (Human)] for Intravenous Administration

The following summarizes important information about GLASSIA (pronounced glass-see-a). Please read it carefully before using this medicine. This information does not take the place of talking with your healthcare professional, and it does not include all of the important information about GLASSIA. If you have any questions after reading this, ask your healthcare professional.

What is GLASSIA?

GLASSIA is a liquid medicine containing human Alpha1 -Proteinase Inhibitor (Alpha1 -PI) also known as alpha1 -antitrypsin (AAT), which is purified from human blood. The main purpose of infusing GLASSIA is to increase the levels of the AAT protein in your blood and lungs. AAT protein protects the lung tissue by blocking certain enzyme-caused damage. Such damage can lead to severe lung disease, such as emphysema.

Limitations of Use:

• The effects of increasing the AAT protein levels with GLASSIA or any other Alpha1 -PI product on worsening pulmonary function and progression of emphysema have not been proven in clinical trials.
• The long-term effects of AAT replacement and maintenance therapy with GLASSIA have not been studied.
• GLASSIA is not intended as a therapy in individuals with lung disease other than severe Alpha1 -PI deficiency.

Who should not take GLASSIA?

You should not use GLASSIA if you:

• Have IgA deficiency with antibodies to IgA
• Have had a severe allergic reaction to human Alpha11-PI products

What is the most important information that I should know about GLASSIA?

Severe allergic reactions can occur with GLASSIA. Your doctor will inform you about signs of allergic reactions which include hives, swelling in the mouth or throat, itching, tightness in the chest, trouble breathing, wheezing, faintness, low blood pressure, or serious allergic reaction. If you have any of these reactions, discontinue use of the product and contact your physician and/or seek immediate emergency care, depending on the severity of the reaction.

If you or your caregiver will be administering GLASSIA outside a healthcare setting, ask your doctor about an epinephrine pen and/or other supportive care for certain severe allergic reactions. Ask your doctor to make sure you receive training on how and when to use any prescribed supportive care medicine and keep it close at hand when administering GLASSIA.

How should I take GLASSIA?

• GLASSIA is given directly into the bloodstream.
• You can get GLASSIA at your healthcare professional's office, clinic, hospital, or delivered directly to your home by a healthcare professional from a limited network of specialty pharmacy providers.
• Your healthcare professional will decide if self-infusion in your home is right for you. You should be trained on how to do infusions by your healthcare professional.

What should I tell my healthcare professional before I start using GLASSIA?

Before starting GLASSIA, tell your healthcare professional if you:

• Have IgA deficiency with antibodies to IgA.
• Have a history of severe allergic reactions to Alpha11-PI products.

What are the possible or reasonably likely side effects of GLASSIA?

• A possible side effect to GLASSIA is worsening or flare-up of your chronic obstructive pulmonary disease (COPD) in which your breathing gets worse than usual.
• Call your healthcare professional or go to your emergency department right away if you get: Hives, swelling in the mouth or throat, itching, chest tightness, trouble breathing, wheezing, fainting or dizziness. These could be signs of a serious allergic reaction.
• The most common side effects are headache and upper respiratory tract infections. Other possible side effects of GLASSIA include: cough, sinus infection, chest discomfort, dizziness, increased liver enzymes, shortness of breath, nausea, and fatigue.

These are not all of the possible side effects for GLASSIA. You can ask your healthcare professional for information that is provided to healthcare professionals. Talk to your healthcare professional about any side effects that bother you or that don’t go away.

How do I store GLASSIA?

Store GLASSIA refrigerated or at room temperature.

• You can store GLASSIA in the refrigerator (36°F to 46°F [2°C to 8°C]). Do not freeze.
• You can store GLASSIA at room temperature (up to 77°F [25°C]) for up to one month. You must use GLASSIA within one month once you remove it from the refrigerator. Do not re-refrigerate GLASSIA once the product has been stored at room temperature.
• Keep the GLASSIA vial in the box until you are ready to administer the product.

Check the expiration date on the carton and vial label. Do not use GLASSIA after the expiration date.

INSTRUCTIONS FOR USE

GLASSIA
[Alpha1 -Proteinase Inhibitor (Human)]

For intravenous use only

Do not attempt to do an infusion to yourself unless you or your caregiver have been taught how by your healthcare professional.

Always follow the specific instructions given by your healthcare professional. The steps listed below are general guidelines for using GLASSIA. If you are unsure of the procedures, call your healthcare professional before using.

Prepare a clean flat surface and gather all the materials you will need for the infusion. Check the expiration date, and let the vial of GLASSIA warm up to room temperature. Do not apply heat, place in hot water, or microwave. Wash your hands and put on clean exam gloves. If you are infusing yourself at home, the use of gloves is optional.

1. Check the vial(s) of GLASSIA:
   • Do not use if the protective cap is missing or broken.
   • Look at the color: it should be clear and colorless to yellow-green.
   • Do not use if the solution is cloudy.
   • It may contain a few (protein) particles.
   • Do not shake the vial(s).
2. Gather all supplies
   • Gather all supplies: vial(s) of GLASSIA as prescribed and infusion supplies: tourniquet, alcohol swabs, intravenous needle set, vented transfer device(s), 5 micron in-line filter (not provided) and 60 mL sterile syringe(s), 5 micron sterile filter needle (provided for each vial of product), sterile intravenous infusion container (bag) (if necessary), administration infusion set, extension set (if necessary), bandage, tape, sterile gauze, sharps container, IV pole or hook, clean gloves (if necessary) and infusion log.
   • If your doctor has prescribed epinephrine pen and/or other supportive care for certain severe allergic symptoms, keep it close at hand during your infusion. Carefully follow your doctor's instructions and training if you have to administer the prescribed medicine for a severe allergic reaction.
   • Wash your hands and allow them to dry.
   • Apply gloves as directed by your healthcare professional. Open supplies as shown by your healthcare professional.
3. Prepare the vials (s) for infusion as directed by your healthcare professional:
   • Remove the protective cap from the vial.
   • Wipe the stoppers of each vial that you will need for your dose with a sterile alcohol swab and allow the stopper to dry.
   • As directed by your healthcare professional, you may infuse directly from the vial or pool the recommended number of vials of GLASSIA into an empty, sterile container (bag) for intravenous infusion. Use the product within 3 hours of entering the vial(s) or pooling into a sterile container (bag).

If you are pooling into a sterile container (bag):

• Attach a vented spike to a sterile syringe.
• Insert the vented spike into the center of the GLASSIA vial.
• Turn the vial upside down and pull back on the plunger to pull the GLASSIA solution into the syringe(s).
• Remove the syringe from the vented spike.
• Point the syringe tip up and gently push the plunger of the syringe to remove the air.
• Attach a 5-micron filter needle (supplied in each box) to the filled syringe.
• Wipe the injection port on the empty sterile container (bag) with an alcohol swab.
• Remove protective cover of needle and insert the needle into the injection port and fill the empty bag.
• Repeat these steps, if using multiple vials to achieve the desired dose as directed by your healthcare professional, using a new filter needle with each vial.
4. Prepare the infusion set:
   • Close the roller clamp on the IV infusion set.
   • Attach an in-line 5 micron filter to the end of the IV infusion set.
   • Attach an extension set (if necessary).
   • Remove cap from the IV infusion set spike and insert spike into the infusion port on the bag containing GLASSIA.
   • Hang the pooling bag from an IV pole or hook.
   • Squeeze the drip chamber until it is half-full and fill the IV infusion set as directed by your healthcare professional.
5. Prepare the infusion site(s):
   • Select an infusion site as directed by your healthcare professional.
   • Rotate infusion sites as directed.
   • Apply a tourniquet and get the injection site ready by wiping the skin well with an alcohol swab (or other suitable solution suggested by your healthcare provider) and wait for the skin to dry.
6. Insert and secure the intravenous needle set as directed by your healthcare professional.
   • Release the tourniquet and flush the intravenous needle set (butterfly) with normal saline to check needle placement is correct. If not successful repeat steps as directed by your healthcare professional.
   • Remove the saline flush syringe and attach the IV infusion set filled with GLASSIA solution.
7. Follow your healthcare professional's instructions for infusing GLASSIA:
   • Open the roller clamp and administer GLASSIA solution at room temperature at a rate as directed by your healthcare professional. The maximum recommended infusion rate for GLASSIA is 0.2 milliliter per kilogram body weight per minute which will take approximately 15 minutes to infuse.
   • Check infusion site occasionally throughout the infusion.
   • When the infusion is complete, take the needle out of the vein and use sterile gauze to put pressure on the infusion site for several minutes and then apply a sterile bandage.
   • Do not recap the intravenous needle set. Place the needle in a hard-walled sharps container for proper disposal. Do not dispose of these supplies in ordinary household trash.
8. Record the infusion:
   • Write down the product lot number and expiration date in your treatment record/infusion log.
   • Write down the date, time (start and end), dose, site(s) of infusion (to assist in rotating sites) and any reactions after each infusion. Report all reactions to your healthcare professional.
   • Throw away all open vials, and any unused solution into a sharps container, as recommended by your healthcare professional.

Call your doctor for instructions if you miss a dose of alpha 1-proteinase inhibitor.

There may be other drugs that can interact with alpha 1-proteinase inhibitor. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Alpha-1 proteinase inhibitor injection, also called alpha 1-PI, is used to treat a certain type of emphysema (a lung condition). The emphysema is caused by the lack of a protein called alpha 1-antitrypsin (AAT) in the body. This medicine replaces the protein when the body does not produce enough.

This medicine is to be given only by or under the immediate supervision of your doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache.
• Signs of a common cold.
• Sinus pain.
• Dizziness.
• Feeling tired or weak.
• Muscle pain.
• Upset stomach.
• Runny nose.
• Irritation where this medicine is used.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Two serious adverse reactions observed on two separate occasions during clinical studies with Glassia were cholangitis and exacerbation of chronic obstructive pulmonary disease (COPD).

The most common drug-related adverse reactions considered by the investigator to be at least possibly related to Glassia administration observed at a rate of >3% in subjects receiving Glassia were headache and dizziness.

Clinical Studies Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

A total of 65 subjects have received treatment with intravenous Glassia in two clinical studies, both performed in the US. Three subjects participated in both studies. However, because of the large temporal difference between studies (> 5 years) and major difference in study designs, each study was analyzed separately without excluding these three subjects who participated in both trials from either study analysis.  Thus, safety and efficacy of Glassia are reported on all 18 subjects in a Phase I study and all 50 subjects who received Glassia in a Phase II/III study, for a total of 68 subjects, representing 65 unique subjects.

In an open label, Phase I non-parallel, dose-escalation study, 18 subjects received a single infusion of Glassia at dosages of 30, 60 or 120 mg/kg.

In a randomized, Phase II/III double-blind, active-control study, 50 subjects were scheduled to receive weekly infusions of Glassia or the comparator Alpha1-PI product, Prolastin, at a dosage of 60 mg/kg for a total of 12 doses after which all subjects remaining in the study were treated for another 12 weeks with Glassia only. Overall, 17 subjects received 12 doses and 21 subjects received 24 doses of Glassia during the study. Eleven subjects received either 22 or 23 doses and one subject did not receive any treatment with Glassia during the last 12 weeks of the study.

The population treated with Glassia in these two studies was 40-74 years old, 54% male, 100% Caucasian and had congenital Alpha1-PI deficiency with clinical evidence of emphysema.

Table 1 compares the adverse events reported during the initial 12 weeks (double-blind portion) of the Phase II/III study occurring in all subjects treated with Glassia with events in the concurrent Prolastin control group.

During the 12-week double blind portion of the Phase II/III trial, 4 subjects (12%) had a total of 7 exacerbations of chronic obstructive pulmonary disease (COPD) during Glassia treatment and 5 subjects (29%) had a total of 6 exacerbations of COPD during Prolastin treatment. Seventeen additional exacerbations in 14 subjects (28%) occurred during the 12-week open-label treatment period with Glassia. The overall rate of pulmonary exacerbations during treatment with either product was 1.3 exacerbations per subject per year.

Most adverse events were mild to moderate in severity, although two episodes of headache and one episode of cholangitis were severe. Two subjects experienced treatment emergent serious adverse events (cholangitis and infective exacerbation of COPD), both of which were considered by the investigator to be unrelated to treatment with Glassia.

Out of 68 subjects treated with Glassia during clinical studies, 14 (21%) experienced one or more adverse events that were assessed by the investigator as possibly or probably related to treatment (Table 5).

A total of 3 subjects (approximately 5%) receiving Glassia reported urticaria, irrespective of the investigator's opinion of cause.

Testing for viral markers for HBV, HCV, HIV-1 and HIV-2 showed no seroconversions during either study.

Post-Marketing Experience

No spontaneous adverse event reports have been received.

1. WHO. "α1-Antitrypsin deficiency." Memorandum from a WHO meeting. 1997;75: 397-415.
2. Stoller JK, et al. Augmentation therapy with α1-antitrypsin: patterns of use and adverse events. Chest 2003;123:1425-34.
3. Cox DW. α1-Antitrypsin Deficiency. In: Scriver C, Sly W, eds. The Metabolic and Molecular Bases of Inherited Disease. New York: McGraw Hill; 2002:5559-78.
4. Crystal RG, et al. The alpha1-antitrypsin gene and its mutations. Clinical consequences and strategies for therapy. Chest 1989;95:196-208.
5. Crystal RG. α1-Antitrypsin deficiency: pathogenesis and treatment. Hosp Pract (Off Ed) 1991;26:81-4, 8-9, 93-4.
6. Turino GM, et al. Clinical features of individuals with PI*SZ phenotype of α1-antitrypsin deficiency. Am J Respir Crit Care Med 1996;154:1718-25.

Glassia 50 mL unit carton

ALPHA-1 PROTEINASE INHIBITOR (HUMAN)

GlassiaTM

Injection Solution

For Intravenous Administration Only

50 mL

NDC 0944-2884-01

KAMADA

Glassia 50 mL vial label

ALPHA-1 PROTEINASE INHIBITOR (HUMAN)

GlassiaTM

For Intravenous Administration Only

Injection Solution

50 mL