GE Healthcare Submits Application to European Medicines Agency (EMA) for Its Own Manufacturing of Optison™ 0.19 mg/ml

  GE Healthcare Submits Application to European Medicines Agency (EMA) for Its
  Own Manufacturing of Optison™ 0.19 mg/ml dispersion for injection (Human
  albumin microspheres containing perflutren)

Upon Approval, GE Healthcare’s Oslo Facility will Supply Its Own Stock to the
                                  EU Market

Business Wire

CHALFONT ST. GILES, England -- March 29, 2013

GE Healthcare today announced that it has submitted an application to amend
its European Marketing Authorisation that will allow the company to
manufacture Optison™ 0.19 mg/ml dispersion for injection within its own
facility. Upon approval, GE Healthcare will provide supply of Optison to the
EU market from its manufacturing facility in Oslo, Norway.

Optison is a transpulmonary echocardiographic contrast agent for use in
patients with suspected or established cardiovascular disease to provide
opacification of cardiac chambers, enhance left ventricular endocardial border
delineation with resulting improvement in wall motion visualisation. Optison
should only be used in patients where the study without contrast enhancement
is inconclusive.

“GE Healthcare is committed to providing safe, reliable, innovative, and
effective diagnostic products that aid in the detection of cardiovascular
diseases, and today’s filing is further evidence of our commitment,” said Ben
Newton, Global Product Leader, Ultrasound, GE Healthcare Medical
Diagnostics.“Adding our own manufacturing site for Optison has multiple
benefits, including an ability to increase capacity to meet market demands and
ensuring robust and secure stock. We look forward to serving the EU contrast
media market.”

Optison remains an important diagnostic option for patients with suboptimal
echocardiograms. Additionally, Optison offers a unique, convenient value to
clinicians and patients: It is stable at room temperature for up to 24 hours
and takes less than 60 seconds to prepare, allowing for quick access to
contrast in hospital settings like the cardiac lab or emergency room.

About GE Healthcare

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meet the demand for increased access, enhanced quality and more affordable
healthcare around the world. GE (NYSE: GE) works on things that matter - great
people and technologies taking on tough challenges. From medical imaging,
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solutions, GE Healthcare helps medical professionals deliver great healthcare
to their patients.

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PRESCRIBING INFORMATION OPTISON™ 0.19 mg/ml dispersion for injection (Human
albumin microspheres containing perflutren)

Please refer to full Summary of Product Characteristics before prescribing.

PRESENTATION Dispersion for injection supplied as 1 vial of 3 ml and 5 vials
of 3 ml. OPTISON consists of perflutren-containing microspheres of heat
treated human albumin, suspended in human albumin solution, 1%.

CONCENTRATION Perflutren-containing microspheres, 5-8 x 10 ^ 8/ml with a mean
diameter range of 2.5-4.5 µm. The approximate amount of perflutren gas in each
ml of OPTISON is 0.19 mg.

INDICATIONS This medicinal product is for diagnostic use only. OPTISON is a
transpulmonary echocardiographic contrast agent for use in patients with
suspected or established cardiovascular disease to provide opacification of
cardiac chambers, enhance left ventricular endocardial border delineation with
resulting improvement in wall motion visualisation. OPTISON should only be
used in patients where the study without contrast enhancement is inconclusive.

physicians experienced in the field of diagnostic ultrasound imaging. Before
administering OPTISON, please see Instructions for use. The product is
intended for left ventricular opacification after intravenous administration.
Ultrasound imaging must be performed during injection of OPTISON as optimal
contrast effect is obtained immediately after administration. Dosage: The
recommended dose is 0.5-3.0 ml per patient. A dose of 3.0 ml is usually
sufficient, but some patients may need higher doses. The total dose should not
exceed 8.7 ml per patient. The duration of the useful imaging time is 2.5-4.5
minutes for a dose of 0.5-3.0 ml. OPTISON could be repeatedly administered,
however, clinical experience is limited. Safety and efficacy of OPTISON in
children and adolescents below 18 years has not been established; no
recommendation on a posology can be made.

CONTRAINDICATIONS Hypersensitivity to the active substance or to any of the
excipients. Pulmonary hypertension with a systolic pulmonary artery pressure >
90 mm Hg.

reported. Care should therefore be exercised. A course of action should be
planned in advance with necessary drugs and equipment available for immediate
treatment, in case a serious reaction should occur. The experience of OPTISON
in severely ill patients is limited. There is limited clinical experience with
OPTISON in patients with certain severe states of cardiac, pulmonary, renal
and hepatic disease. Such clinical states include adult respiratory distress
syndrome, the use of artificial respiration with positive end-expiratory
pressure, severe heart failure (NYHA IV), endocarditis, acute myocardial
infarction with on-going angina or unstable angina, hearts with prosthetic
valves, acute states of systemic inflammation or sepsis, known states of
hyperactive coagulation system and/or recurrent thromboembolism, renal or
hepatic end-stage disease. OPTISON should be used in these categories of
patients only after careful consideration, and monitored closely during and
after administration. Other routes of administration not specified in section
“Dosage and method of administration” above (e.g. intracoronary injection) are
not recommended. Standard measures to prevent infections resulting from the
use of medicinal products prepared from human blood or plasma include
selection of donors, screening of individual donations and plasma pools for
specific markers of infection and the inclusion of effective manufacturing
steps for the inactivation/removal of viruses. Despite this, when medicinal
products prepared from human blood or plasma are administered, the possibility
of transmitting infective agents cannot be totally excluded. This also applies
to unknown or emerging viruses and other pathogens. There are no reports of
virus transmissions with albumin manufactured to European Pharmacopoeia
specifications by established processes. It is strongly recommended that every
time that OPTISON is administered to a patient, the name and batch number of
the product are recorded in order to maintain a link between the patient and
the batch of the product. OPTISON contrast echocardiography should be
accompanied by ECG monitoring. In animal studies, the application of
echo-contrast agents revealed biological side effects (e.g. endothelial cell
injury, capillary rupture) by interaction with the ultrasound beam. Although
these biological side effects have not been reported in humans, the use of a
low mechanical index and end-diastolic triggering is recommended. Efficacy and
safety in patients below 18 years has not been studied.

interaction studies have been performed. Use during anaesthesia with halothane
and oxygen has not been studied.

PREGNANCY AND LACTATION The safety of OPTISON for use during human pregnancy
has not been established. In pregnant rabbits exposed to daily doses of 2.5
ml/kg (approximately 15 x the maximum recommended clinical dose) during
organogenesis, maternal toxicity and embryo-foetal toxicity including a slight
to extreme dilation of ventricles in the brain of developing rabbit embryos
was observed. The clinical relevance of this finding is unknown. Therefore,
OPTISON should not be used in pregnancy unless benefit outweighs risk and it
is considered necessary by the physician. It is not known whether OPTISON is
excreted in human milk. Therefore, caution should be exercised when OPTISON is
administered to breast-feeding women.

the ability to drive and use machines have been performed.

UNDESIRABLE EFFECTS Adverse reactions to OPTISON are rare and usually of a
non-serious nature. In general, the administration of human albumin has been
associated with transient altered taste, nausea, flushing, rash, headache,
vomiting, chills and fever. Anaphylactic reactions have been associated with
the administration of human albumin products. The reported adverse events
following the use of OPTISON in Phase III human clinical studies have been
mild to moderate with subsequent full recovery. In clinical trials with
OPTISON, undesirable effects were reported as adverse events with the
following frequencies: Very common ≥1/10; Common ≥1/100 to <1/10; Uncommon
≥1/1,000 to <1/100; Rare ≥1/10,000 to <1/1,000; Very rare <1/10,000; not known
(cannot be estimated from the available data). Undesirable effects: Common:
Dysgeusia (altered taste), headache, flushing, nausea, warm sensation. :
Uncommon: Eosinophilia, dyspnoea, chest pain. Rare: Dizziness, paraesthesia,
tinnitus, ventricular tachycardia. Not Known: Visual disturbances, allergic
type symptoms (e.g. anaphylactoid reaction or -shock, facial oedema,

OVERDOSE No case of overdose has been reported. In the phase I trial, healthy
volunteers have received up to 44.0 ml of OPTISON and experienced no
significant adverse effects.

INSTRUCTIONS FOR USE AND HANDLING Like all parenteral products, the vials of
OPTISON should be inspected visually for integrity of the container. Vials are
intended for single use only. Homogenous white suspension after resuspension.
Once the rubber stopper has been penetrated, the contents should be used
within 30 minutes and any unused product discarded. OPTISON in the
non-resuspended form has a white layer of microspheres on top of the liquid
phase that requires resuspension before use. The following instructions should
be followed: • Cold solutions taken directly from the refrigerator should not
be injected. • Allow the vial to reach room temperature and inspect the liquid
phase for particulate matter or precipitates before resuspension. • Insert a
20 G plastic cannula in a large antecubital vein, preferably of the right arm.
Attach a three-way stopcock to the cannula. • The OPTISON vial must be
inverted and gently rotated for approximately three minutes to completely
resuspend the microspheres. • Complete resuspension is indicated by a
uniformly opaque white suspension and absence of any material on stopper and
vial surfaces. • OPTISON should be withdrawn with care into a syringe within 1
minute after resuspension. • Any pressure instability within the vial should
be avoided since it may cause disruption of microspheres and loss of contrast
effect. Thus, vent the vial with a sterile spike or with a sterile 18 G needle
before withdrawing the suspension into the injection syringe. Do not inject
air into the vial as this will damage the product. • Use the suspension within
30 minutes after withdrawal. • OPTISON will segregate in an undisturbed
syringe and must be resuspended before use. • Resuspend the microspheres in
the syringe immediately before injection by holding the syringe horizontally
between the palms of the hands and rolling it quickly back and forth for no
less than 10 seconds. • Inject the suspension through the plastic cannula, no
smaller than 20 G at a maximum injection rate of 1.0 ml/s. Warning: Never use
any other type of route but the open flow connection. If injected otherwise
OPTISON bubbles will be destroyed. • Immediately before injection a careful
visual inspection of the syringe is mandatory in order to ensure complete
suspension of the microspheres. • Immediately after injection of OPTISON, 10
ml of sodium chloride 9mg/ml (0.9%) solution for injection or glucose 50mg/ml
(5%) solution for injection should be injected at a rate of 1 ml/s.
Alternately, the flushing may be performed by infusion. The infusion set
should then be attached to the three-way stopcock and intravenous infusion
started at a “to keep open” (TKO) rate. Immediately after OPTISON injection
the intravenous infusion should be wide open until contrast begins to fade
from the left ventricle. The infusion should then be returned to a TKO rate.

PHARMACEUTICAL PRECAUTIONS OPTISON must not be mixed with other medicinal
products. A separate syringe should be used. OPTISON should be stored upright
between 2ºC and 8ºC. Storage at room temperature (up to 25ºC) for 1 day is
acceptable. Do not freeze. The shelf life of the product in the outer
packaging is 2 years and of finished product after rubber stopper perforation:
30 minutes.

Nydalen, N-0401 OSLO, Norway.

CLASSIFICATION FOR SUPPLY Subject to medical prescription.

MARKETING AUTHORISATION NUMBERS 1 x 3 ml: EU/1/98/065/001. 5 x 3 ml:

PRICE £286.30 for 5 x 3ml vials

Revision of text December 2010.

Adverse events should be reported. Reporting forms and information can be
found at Adverse events should also be reported to GE


GE Healthcare
Scott Lerman
609-514-6346 (office)
609-937-9352 (mobile)
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