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Dublin, Ireland – October 25, 2018 – Shire plc (Shire) (LSE: SHP, NASDAQ: SHPG), the leading global biotechnology company focused on rare diseases, today announced that it has filed its second submission to the United States Food and Drug Administration (FDA) for its new plasma manufacturing facility near Covington, Georgia.

This second submission is for the manufacturing of FLEXBUMIN 25% [Albumin (Human)], USP, 25% Solution, a treatment primarily used as plasma-volume replacement therapy in immune disorders, trauma and other critical conditions. The Georgia facility received its first FDA approval, to manufacture GAMMAGARD LIQUID [Immune Globulin Infusion (Human)] 10% Solution.

“We are very pleased to file this second submission for our state-of-the-art manufacturing facility in Georgia, after the facility received FDA approval earlier this year,” said Matt Walker, Head of Technical Operations for Shire. “Expanding our capacity for manufacturing FLEXBUMIN will allow us to better meet the increasing global demand for plasma protein therapies and further supports our growing immunoglobulin and bio-therapeutics portfolio by enabling us to deliver these important treatments to our patients.”

Shire's Immunology franchise has seen strong demand, with product sales increasing +13% in the second quarter of 2018 versus the prior year.

The Georgia site currently employs approximately 900 full-time colleagues and contract employees. Since the beginning of 2018, Shire has ramped up hiring to fill roles in manufacturing, quality, engineering, maintenance, utilities, warehouse, and various support and facility roles.

Shire also plans to continue expanding its plasma collection network in Georgia and throughout the United States through its subsidiary, BioLife Plasma Services. BioLife collects the human plasma used in the manufacturing process for immunology products at the Georgia facility.

GAMMAGARD LIQUID [Immune Globulin Infusion (Human)] 10% Solution

INDICATION

GAMMAGARD LIQUID is indicated as replacement therapy for primary humoral immunodeficiency (PI) in adult and pediatric patients ≥2 years. 

Important US Safety Information 

WARNING: THROMBOSIS, RENAL DYSFUNCTION, and ACUTE RENAL FAILURE

• Thrombosis may occur with immune globulin (IG) products, including GAMMAGARD LIQUID. Risk factors may include advanced age, prolonged immobilization, hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, indwelling vascular catheters, hyperviscosity, and cardiovascular risk factors. Thrombosis may occur in the absence of known risk factors.
• Renal dysfunction, acute renal failure, osmotic nephrosis, and death may occur in predisposed patients with immune globulin intravenous (IGIV) products. Patients predisposed to renal dysfunction include those with any degree of pre-existing renal insufficiency, diabetes mellitus, age greater than 65, volume depletion, sepsis, paraproteinemia, or patients receiving known nephrotoxic drugs. Renal dysfunction and acute renal failure occur more commonly in patients receiving IGIV products containing sucrose. GAMMAGARD LIQUID does not contain sucrose.
• For patients at risk of thrombosis, administer GAMMAGARD LIQUID at the minimum dose and infusion rate practicable. Ensure adequate hydration in patients before administration. Monitor for signs and symptoms of thrombosis and assess blood viscosity in patients at risk of hyperviscosity.

Contraindications 

• History of anaphylactic or severe systemic hypersensitivity reactions to human IG
• IgA-deficient patients with antibodies to IgA and a history of hypersensitivity to human IG. Anaphylaxis has been reported with intravenous (IV) use of GAMMAGARD LIQUID.

Warnings and Precautions

Hypersensitivity: Severe hypersensitivity reactions may occur, even in patients who have tolerated previous treatment with human IG. If a hypersensitivity reaction occurs, discontinue infusion immediately and institute appropriate treatment. IgA-deficient patients with antibodies to IgA are at greater risk of developing potentially severe hypersensitivity reactions, including anaphylaxis.

Renal Dysfunction/Failure: Acute renal dysfunction/failure, acute tubular necrosis, proximal tubular nephropathy, osmotic nephrosis, and death may occur with IV use of IG products, especially those containing sucrose. Ensure patients are not volume depleted prior to infusion. In patients at risk due to pre-existing renal insufficiency or predisposition to acute renal failure, assess renal function before initiation and throughout treatment, and use the minimum infusion rate practicable for IV administration. If renal function deteriorates, consider discontinuation.

Hyperproteinemia, increased serum viscosity, and hyponatremia may occur. It is critical to distinguish true hyponatremia from a pseudohyponatremia because certain treatments may lead to volume depletion, a further increase in serum viscosity, and a predisposition to thromboembolic events.

Thrombosis: May occur following treatment with IG products and in the absence of known risk factors. In patients at risk, administer at the minimum dose and infusion rate practicable. Ensure adequate hydration before administration. Monitor for signs and symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity.

Aseptic Meningitis Syndrome: Has been reported with use of IG and may occur more frequently in females. Conduct a thorough neurological exam on patients exhibiting signs and symptoms, to rule out other causes of meningitis. Discontinuing IG treatment has resulted in remission within several days without sequelae.

Hemolysis: GAMMAGARD LIQUID contains blood group antibodies, which may cause a positive direct antiglobulin reaction and hemolysis. Monitor patients for signs and symptoms of hemolysis and delayed hemolytic anemia and, if present, perform appropriate confirmatory lab testing.

Transfusion-Related Acute Lung Injury: Non-cardiogenic pulmonary edema may occur with IV administered IG. Monitor patients for pulmonary adverse reactions. If suspected, perform appropriate tests for presence of anti-neutrophil and anti-HLA antibodies in both product and patient serum. May be managed using oxygen therapy with adequate ventilatory support.

Transmittable Infectious Agents: Because GAMMAGARD LIQUID is made from human plasma, it may carry a risk of transmitting infectious agents (e.g., viruses, other pathogens). No confirmed cases of viral transmission or variant Creutzfeldt-Jakob disease (vCJD) have been associated with GAMMAGARD LIQUID.

Interference with Lab Tests: False positive serological test results and certain assay readings, with the potential for misleading interpretation, may occur as the result of passively transferred antibodies.

Adverse Reactions 

IV administration for PI: The serious adverse reaction seen during IV clinical studies was aseptic meningitis. The most common adverse reactions observed in ≥5% of subjects were headache, fatigue, pyrexia, nausea, chills, rigors, pain in extremity, diarrhea, migraine, dizziness, vomiting, cough, urticaria, asthma, pharyngolaryngeal pain, rash, arthralgia, myalgia, oedema peripheral, pruritus, and cardiac murmur.

Subcutaneous administration for PI: The most common adverse reactions observed in ≥5% of subjects were infusion site (local) event (rash, erythema, edema, hemorrhage, and irritation), headache, fatigue, heart rate increased, pyrexia, abdominal pain upper, nausea, vomiting, asthma, blood pressure systolic increased, diarrhea, ear pain, aphthous stomatitis, migraine, oropharyngeal pain, and pain in extremity.

Drug Interactions

Passive transfer of antibodies may transiently interfere with immune responses to live attenuated virus vaccines (e.g., measles, mumps, rubella, and varicella).

Please click for Full Prescribing Information, including Boxed Warning regarding Thrombosis, Renal Dysfunction and Acute Renal Failure.

FLEXBUMIN 25% [Albumin (Human)], USP, 25% Solution

1. What is FLEXBUMIN?

FLEXBUMIN 25% is indicated for hypovolemia, hypoalbuminemia, (burns, Adult Respiratory Distress Syndrome (ARDS), and nephrosis), cardiopulmonary bypass surgery, and hemolytic disease of the newborn (HDN). Albumin is not indicated as an intravenous nutrient

Important US Safety Information

Contraindications

• History of hypersensitivity reaction to albumin preparations or to any of the excipients (N-acetyltryptophan and sodium caprylate). Reactions have included anaphylactic shock, anaphylactic reaction, or hypersensitivity/allergic reactions
• Severe anemia or cardiac failure with normal or increased intravascular volume.

Warnings and Precautions
Hypersensitivity Reactions: have been observed (including anaphylactic reactions). If hypersensitivity reaction is suspected, discontinue administration immediately and implement appropriate standard medical treatment.

Hypervolemia/Hemodilution: Under conditions where hypervolemia and/or hemodilution may occur, adjust the dose and rate of infusion to the patient’s volume status. When administering large volumes, monitor hemodynamic parameters. Ensure adequate substitution of other blood constituents and monitor electrolyte balance. Discontinue administration at the first clinical signs of cardiovascular overload.

Hemodynamics: Closely monitor hemodynamic parameters after administration for evidence of cardiac or respiratory failure, renal failure or increasing intracranial pressure

Blood Pressure: Monitor blood pressure in trauma patients and postoperative surgery patients in order to detect re-bleeding secondary to clot disruption.

Hemolysis: Do not dilute with Sterile Water for Injection, as there is potential risk of fatal hemolysis and acute renal failure in recipients.

Transmission of Infectious Agents: Because FLEXBUMIN 25% is made from human plasma it may carry a risk of transmitting infectious agents (e.g., viruses, other pathogens). No cases of transmission of viral diseases, Creutzfeldt-Jakob disease (CJD) or variant Creutzfeldt-Jakob disease (vCJD) have ever been identified.

Adverse Reactions:
The most serious adverse reactions are hypersensitivity reaction (including anaphylactic reaction) and pulmonary edema.

Administration Caution
Do not use plastic containers in series connections. Such use could result in air embolism due to residual air being drawn from the primary container before the administration of the fluid from the secondary container is complete.

Please click for Full Prescribing Information.