Takeda Receives U.S. FDA Approval to Manufacture FLEXBUMIN® at New Plasma Manufacturing Facility near Covington, Georgia

March 18, 2019 Off By BusinessWire

FLEXBUMIN 25% [Albumin (Human)], USP, 25% Solution 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
Takeda received its first FDA approval for the Georgia facility, to
manufacture GAMMAGARD LIQUID® [Immune Globulin Infusion (Human)] 10%
Solution, in June 2018
This state-of the art facility supports continued growth of
Takeda’s plasma-derived therapies portfolio and further strengthens
our ability to deliver these complex therapies for patients

CAMBRIDGE, Mass.–(BUSINESS WIRE)–Takeda Pharmaceutical Company Limited (TOKYO:4502/NYSE:TAK),
(“Takeda”) today announced that the United States Food and Drug
Administration (FDA) has approved the company’s second submission for
its new plasma manufacturing facility near Covington, Georgia for the
production of FLEXBUMIN 25% [Albumin (Human)], USP, 25% Solution,
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. The Georgia facility received its
first FDA approval, to manufacture GAMMAGARD LIQUID [Immune Globulin
Infusion (Human)] 10% Solution, in June 2018.

“This latest approval is a significant milestone for the Georgia
facility, Takeda and our patients,” said Thomas Wozniewski, Global
Manufacturing & Supply Officer. “This new state-of-the-art facility is
providing much needed additional capacity for meeting increasing global
demand for plasma-derived therapies, and our team there will continue to
scale up production over the coming years.”

“Following the acquisition of Shire, Takeda created a Business Unit
dedicated to meeting the large and growing demand for plasma-derived
products, essential for treating patients with a variety of rare,
life-threatening, chronic and genetic diseases. Our strategic focus and
increased investment in plasma innovation and our world-class plasma
collection and production capabilities will enable us to expand our
broad, differentiated portfolio of medicines and serve more patients.
Our Georgia facility is a key part of these plans,” added Julie Kim,
President of Plasma-Derived Therapies at Takeda.

The Georgia facility currently employs more than 1,000 full-time and
contract employees, and continues to hire to fill additional roles in
manufacturing, quality, engineering, maintenance, utilities, warehouse,
and various support and facility roles.

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

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.

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.

About Takeda Pharmaceutical Company Limited

Takeda Pharmaceutical Company Limited (TOKYO:4502/NYSE:TAK)
is a global, values-based, R&D-driven biopharmaceutical leader
headquartered in Japan, committed to bringing Better Health and a
Brighter Future to patients by translating science into
highly-innovative medicines. Takeda focuses its R&D efforts on four
therapeutic areas: Oncology, Gastroenterology (GI), Neuroscience, and
Rare Diseases. We also make targeted R&D investments in Plasma-Derived
Therapies and Vaccines. We are focusing on developing highly innovative
medicines that contribute to making a difference in people’s lives by
advancing the frontier of new treatment options and leveraging our
enhanced collaborative R&D engine and capabilities to create a robust,
modality-diverse pipeline. Our employees are committed to improving
quality of life for patients and to working with our partners in health
care in approximately 80 countries and regions.
For more
information, visit https://www.takeda.com