Advate

Main information

  • Trade name:
  • Advate 2000 IU Injection with diluent
  • Dosage:
  • 2000 IU
  • Pharmaceutical form:
  • Injection with diluent
  • Units in package:
  • Combination pack, 1 vial of active + 1 vial of diluent + 1 BaxJect II, 5 mL
  • Class:
  • General sale
  • Prescription type:
  • General sale
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug
  • Manufactured by:
  • Baxalta Manufacturing Sarl

Documents

Localization

  • Available in:
  • Advate 2000 IU Injection with diluent
    New Zealand
  • Language:
  • English

Therapeutic information

  • Therapeutic indications:
  • ADVATE is indicated for use in haemophilia A for prevention and control of haemorrhagic episodes. Patients with haemophilia A may be treated with ADVATE as perioperative management. ADVATE is not indicated in von Willebrand's disease.

Other information

Status

  • Source:
  • Medsafe - Medicines Safety Authority - New Zealand
  • Authorization number:
  • 13224
  • Authorization date:
  • 09-07-2007
  • Last update:
  • 09-05-2018

Summary of Product characteristics: dosage,interactions,side effects

NEW ZEALAND DATA SHEET

ADVATE Data Sheet 24 August 2017

Page 1 of 16

Baxalta New Zealand Ltd

1 ADVATE powder and diluent for solution for injection

Advate is available in the following strengths:

250IU

500IU

1000IU

1500IU

2000IU

3000IU &

4000IU.

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Octacog alfa (rch), Recombinant Coagulation Factor VIII (rVIII).

Laboratory code

Recombinant Antihaemophilic FVIII Plasma/Albumin‐Free Method (rAHF‐PFM).

Powder for intravenous injection, after reconstitution with Water for Injection to 2mL (for potencies

250IU, 500IU, 1000IU and 1500IU) or 5mL (across all potencies).

Unit Formulation

ADVATE

250IU

500IU

1000IU

1500IU

2000IU

3000IU

4000IU

Active ingredient:

Octocog alfa

[Recombinant

Coagulation

FVIII (rch)]

250IU

500IU

1000IU

1500IU

2000IU

3000IU

4000IU

The amounts of the inactive ingredients are constant in all strengths.

For the full list of excipients, see section 6.1.

Biological origin of the active substance

Advate is produced from a genetically engineered Chinese Hamster Ovary (CHO) cell‐line under

conditions, which are free from the use of animal derived protein. Advate (rAHF‐PFM) is presented in

a glass vial accompanied by a vial containing either 5mL (across all potencies) or 2mL (for potencies

250IU, 500IU, 1000IU and 1500IU) sterile Water for Injection (see section 4.2). The reconstituted

product is clear, a colourless solution for intravenous (IV) injection.

Trehalose, a disaccharide of two glucose molecules linked by an α, α, glucopyranose of glycoside bond

has been used as a stabiliser in the formulation, instead of human albumin as shown in the table

above. The active ingredient, rAHF‐PFM, has been manufactured by a method that is free from the

use of animal or human derived proteins. This

manufacturing process provides a low risk of

transmission of blood‐borne viruses derived from exogenous human and animal origins.

The molecular integrity and biological activity of rAHF‐PFM is indistinguishable from that of the first

generation of recombinant Antihaemophilic Factor VIII (rAHF). They differ on the culture media used

during the manufacturing process and the cell lines. In the first generation of rAHF production, the

cell lines are grown in a culture medium containing animal/human derived proteins, whereas in the

rAHF‐PFM production, the cell lines are adapted to grow without using animal/human components.

NEW ZEALAND DATA SHEET

ADVATE Data Sheet 24 August 2017

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Baxalta New Zealand Ltd

The CHO cells transfected with factor VIII gene, express factor VIII within the cell as a glycosylated

protein, rAHF‐PFM, which is subsequently secreted into the culture medium. The isolation and

purification of the rAHF‐PFM from

the culture medium is basically the same as in the first generation,

rAHF, using a series of immunoaffinity chromatography column. In this process, the purification

matrix packed into the column was produced by immobilisation of monoclonal antibodies directed to

factor VIII to a carrier, which selectively binds the rAHF‐PFM. It is followed by the elution of the

bound rAHF‐PFM from the matrix and subsequently the eluate is subjected to a series of ion‐

exchange column chromatography procedures to remove the buffer components.

The potency (IU) is determined using the one‐stage clotting assay or by chromogenic method (EP),

against

an in‐house standard that is referenced to the FDA/US Mega I Standard. The latter was

calibrated against the third WHO standard. The specific activity is approximately 4,000 ‐ 10,000IU/mg

protein.

3 PHARMACEUTICAL FORM

Injection with diluent.

Advate is formulated as a sterile, non‐pyrogenic, white to off‐white, lyophilised powder preparation of

Recombinant Antihaemophilic Factor VIII.

4 CLINICAL PARTICULARS

Therapeutic indications

Advate is indicated for use in haemophilia A for prevention and control of haemorrhagic episodes.

Patients with haemophilia A may be treated with Advate as perioperative management.

Advate is not indicated in von Willebrand's disease.

Dose and method of administration

Treatment should be initiated under the supervision of a physician experienced in the treatment of

haemophilia.

Dosage

The dosage and duration of the substitution therapy depend on the severity of factor VIII deficiency,

the location and the extent of the bleeding and on the patient's clinical condition. The dose of factor

VIII administered is expressed in International Unit (IU), which is related to the WHO standard for

factor VIII products. Factor VIII activity in plasma is expressed either as a percentage (relative to

normal human plasma) or in IUs (relative to the international Standard for factor VIII in plasma).

One IU of factor VIII activity is equivalent to that quantity of factor VIII in one mL of normal human

plasma. The calculation of the required dosage of factor VIII is based on the empirical finding that 1IU

factor VIII per kg body weight raises the plasma factor VIII activity by 2IU/dL. The dose is determined

using the following formula and following table.

Formula: Required units (IU) = body weight (kg) x desired factor VIII rise (%) x 0.5

NEW ZEALAND DATA SHEET

ADVATE Data Sheet 24 August 2017

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Baxalta New Zealand Ltd

Degree of haemorrhage/

Type of surgical procedure

Factor VIII level

required

(% or IU/dL)

Frequency of doses (hours)/

duration of therapy (days)

Haemorrhage

Early haemarthosis, muscle

bleeding or oral bleeding

20 ‐ 40

Repeat infusions every 12 to 24 hours for at

least 1 day, until the bleeding episode, as

indicated by pain, is resolved or healing is

achieved.

More extensive haemarthosis,

muscle bleeding or

haematoma

30 ‐ 60

Repeat infusions every 12 to 24 hours for 3 to 4

days or more until pain and acute disability are

resolved.

Life threatening haemorrhages

60 ‐ 100

Repeat infusions every 8 to 24 hours until

threat is resolved.

Surgery

Minor, including tooth

extraction

30 ‐ 60

Every 12 hours, at least 1 day, until healing is

achieved.

Major

80 ‐ 100

(pre‐ and

postoperative)

Repeat infusions every 8 to 24 hours until

adequate wound healing, then continue

therapy for at least another 7 days to maintain

a factor VIII activity of 30% to 60 % (IU/dL)

In cases of the haemorrhagic events as shown in the above table, the factor VIII activity should not fall

below the given plasma activity level (in % normal or IU/dL) in the corresponding period. The above

table can be used to guide dosing in bleeding episodes and surgery.

The amount and frequency of administration should be adapted to the clinical effectiveness of the

product in the individual case. Under certain circumstances (presence of a low responder inhibitor)

doses larger than the calculated doses may be necessary.

Careful control of replacement therapy is especially important in cases of major surgery or life

threatening haemorrhages. During the course of treatment, appropriate determination of plasma

factor VIII levels is advised to guide the dose to be administered and the frequency of repeated

infusions. In the case of major surgical interventions in particular, precise monitoring of the

substitution therapy by means of plasma factor VIII activity assay is indispensable. Individual patients

may vary in their response to factor VIII, achieving different levels of in vivo recovery and

demonstrating different half‐lives.

For long‐term prophylaxis against bleeding in patients with severe haemophilia A, the usual doses are

20 to 40IU of factor VIII per kg body weight at intervals of 2 to 3 days. In some cases, especially in

younger patients, shorter dose intervals or higher doses may be necessary. There are data on 13

paediatric patients collected on the use of Advate.

Patients with inhibitors

Patients should be evaluated for the development of factor VIII inhibitors, if the expected plasma

factor VIII activity levels are not attained, or if bleeding is not controlled with an appropriate dose. In

patients with high levels of inhibitor, factor VIII therapy may not be effective and other therapeutic

options should be considered. Management of such patients should be directed by physicians with

experience in the care of patients with haemophilia A (see section 4.4/Anti‐bodies against Mouse or

Hamster (CHO) Proteins).

NEW ZEALAND DATA SHEET

ADVATE Data Sheet 24 August 2017

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Baxalta New Zealand Ltd

Laboratory tests

Although dosage can be estimated by the calculations as described above, it is strongly recommended

that, whenever possible, appropriate laboratory tests including serial AHF assays be performed on the

patient's plasma at suitable intervals to ensure that adequate AHF levels have been reached and

maintained.

If bleeding is not controlled with the recommended dose, the plasma level of Factor VIII should be

determined and a sufficient dose of Advate should be administered to achieve a satisfactory clinical

response.

If the patient's plasma factor VIII fails to reach the expected levels or if bleeding is not controlled after

adequate dosage, the presence of inhibitor should be suspected. By performing appropriate

laboratory investigations, the presence of an inhibitor can be demonstrated and quantified in terms

of IU factor VIII neutralised by each mL of plasma. If the inhibitor is present at a level of less than

10BU/mL, administration of additional factor VIII may neutralise the inhibitor. Thereafter, the

administration of additional factor VIII should elicit the predicted response. The control of factor VIII

and inhibitor levels by laboratory assays is necessary in this situation. Inhibitor titres above 10BU/mL

may make haemostatic control with factor VIII either impossible or impractical because of the large

dose required. In addition, the inhibitor titre may rise following AHF infusion because of an

anamnestic response to factor VIII.

Nature and contents of container

Advate powder comes in single‐dose 5mL vials. Each vial is labelled for potency in IU, and is packaged

together with either a 2mL or 5mL sWFI vial, 1 BaxJect II device for reconstitution, 1 mini‐infusion set,

1 10mL sterile disposable syringe for administration, 2 alcohol swabs and 2 plasters.

Please refer to the table below for details of the Advate and diluent vials, and the suitable potencies

for each diluent volume:

ADVATE 5mL (extractable volume)

sWFI

ADVATE 2mL (extractable volume)

sWFI

ADVATE vial type

single‐dose 5mL vials of neutral

borosilicate glass hydrolytic type I

single‐dose 5mL vials of neutral

borosilicate glass hydrolytic type I

ADVATE vial stopper

teflon coated butyl rubber

teflon coated butyl rubber

Suitable potencies (IU)

250, 500, 1000, 1500,

2000, 3000, 4000

250, 500, 1000, 1500

sWFI (diluent) vial type

neutral borosilicate glass hydrolytic

type I

neutral borosilicate glass hydrolytic

type I

sWFI vial cap colour

grey

clear, colourless

Instructions for use, handling and disposal

The preparation is to be administered intravenously after reconstitution with the provided sterilised

water for injection. Do not use after the expiry date printed on the label. Use within 3 hours after

reconstitution. Do not refrigerate the preparation after reconstitution.

Discard any unused preparation appropriately, see section 6.6.

NEW ZEALAND DATA SHEET

ADVATE Data Sheet 24 August 2017

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Baxalta New Zealand Ltd

Reconstitution using the BaxJect II device: use aseptic technique

Bring the Advate (dry factor concentrate) and Sterile Water for injection (diluent) to room

temperature (25°C).

Remove caps from the factor concentrate and diluent vials.

Cleanse stoppers with a germicidal solution, and allow to dry prior to use. Place the vials on a flat

surface.

Open the BaxJect II device package by peeling away the lid, without touching the inside (Figure

A). Do not remove the device from the package.

Turn the package over. Press straight down to fully insert the clear plastic spike through the

diluents vial stopper (Figure B).

Grip the BaxJect II package at its edge and pull the package off the device (Figure C). Do not

remove the blue cap from the BaxJect II device. Do not touch the exposed white plastic spike.

Turn the system over, so that the diluent vial is on top. Quickly insert the white plastic spike fully

into the Advate vial stopper by pushing straight down (Figure D). The vacuum will draw the

diluent into the Advate vial.

Swirl gently until Advate is completely dissolved.

NOTE: do not refrigerate

after reconstitution.

Administration: use aseptic technique

Parenteral drug products should be inspected for particulate matter and discoloration prior to

administration, whenever solution and container permit. A colourless appearance is acceptable for

Advate. Advate should be administered at room temperature not more than 3 hours after

reconstitution. Plastic syringes must be used with this product, since proteins such as Advate tend to

stick to the surface of glass syringes.

Remove the blue cap from the BaxJect II device. Connect the syringe to the BaxJect II device

(Figure E). DO NOT INJECT AIR.

Turn the system upside down (factor concentrate vial now on top). Draw the factor concentrate

into the syringe by pulling the plunger back slowly (Figure F).

Disconnect the syringe; attach a suitable needle and inject intravenously as instructed under

Administration by Bolus Infusion.

If a patient is to receive more than one vial of Advate, the contents of multiple vials may be drawn

into the same syringe. Please note that the BaxJect II reconstitution device is intended for use

with a single vial of Advate and Sterile Water for Injection only, therefore reconstituting and

withdrawing a second vial into the syringe requires a second BaxJect II reconstitution device.

Administration by bolus infusion

A dose of Advate should be administered over a period of ≤ 5 minutes (maximum infusion rate

10mL/min). The pulse rate should be determined before and during administration of Advate. Should

a significant increase in pulse rate occur, reducing the rate of administration or temporarily halting

the injection usually allows the symptoms to disappear promptly.

NEW ZEALAND DATA SHEET

ADVATE Data Sheet 24 August 2017

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Baxalta New Zealand Ltd

Figure A

Figure B

Figure E

Figure F

Administration by continuous infusion

The 1500, 1000 and 500IU/vial nominal potency of Advate are suitable for use in a continuous

infusion mode of administration. Continuous infusion of Advate must employ either a syringe pump

running at a rate of greater than or equal to 0.4mL/hour, or a CADD‐1 type infusion pump running at a

rate of 1.5mL/hour. In vitro studies employing a syringe pump or CADD‐1 pump have demonstrated

> 80% of the hour 0 potency of Advate for up to 48 hours of continuous infusion. For sterility

assurance purposes, a fresh supply of reconstituted Advate for continuous infusion (prepared under

laminar air flow conditions) should be replaced at bedside no less frequently than every 12 hours.

The post‐reconstitution photostability of Advate is acceptable under the conditions of visible and

ultra‐violet light exposure in a clinical setting. It is highly recommended that factor VIII levels be

checked within 3 to 6 hours after the initiation of continuous infusion in order to document that the

desired factor VIII levels are being maintained.

Rates of infusion should be modified based on the levels of plasma factor VIII activity measured at

least once per day thereafter and based on the desired level of factor VIII.

Contraindications

Known hypersensitivity to any component or to mouse or hamster proteins.

Special warnings and precautions for use

Hypersensitivity reactions

Allergic‐type hypersensitivity reactions, including anaphylaxis, have been reported with Advate and

have been manifested by dizziness, paresthesias, rash, flushing, face swelling, urticaria, and pruritis.

Patients should be informed of the

signs of hypersensitivity reactions (including hives, generalized

urticaria, tightness of the chest, wheezing, hypotension and anaphylaxis). If these symptoms occur,

they should be advised to discontinue use of the product immediately and contact their physicians. In

the case of anaphylactic shock, the current medical standards for shock treatment should be

implemented.

Inhibitor formation

The formation of neutralising antibodies (inhibitors) to factor VIII is a known complication in the

management of individuals with haemophilia A. In particular when the subject has not been treated

with antihaemophilic factor VIII previously, the chance of antibodies formation is high. These

NEW ZEALAND DATA SHEET

ADVATE Data Sheet 24 August 2017

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Baxalta New Zealand Ltd

inhibitors are usually IgG immunoglobulins directed against factor VIII procoagulant activity, which are

quantified in Bethesda Units (BU) per mL of plasma using the modified Bethesda assay.

The risk of developing inhibitors is correlated to the extent

of exposure to the factor VIII, the risk is

being highest within the first 20 exposure days. Rarely, inhibitors may develop after the first 100

exposure days. Patients treated with Advate should be carefully monitored for the development of

inhibitors by appropriate clinical observations and laboratory tests. Inhibitors have predominantly

been reported in previously untreated patients.

The risk for inhibitor development depends on a number of factors relating to the characteristics of

the patient, e.g. type of the Factor VIII gene mutation, family history, ethnicity, which are believed to

represent the most significant risk factors for inhibitor formation.

Among 136 treated subjects greater or equal to 10 years of age, all of whom had > 150 exposure days

to Factor VIII at study entry, 102 had at least 75 exposure days to Advate rAHF‐PFM. None of these

subjects developed an inhibitor. One subject who had < 50 exposure days to Advate (rAHF‐PFM)

while on the study developed an inhibitor. This subject manifested a low titer inhibitor (2.0BU by the

Bethesda assay) after 26 exposure days with Advate (rAHF‐PFM).

Antibodies against mouse or hamster (CHO) proteins

Advate (rAHF‐PFM) contains trace amounts of mouse immunoglobulin G (MuIgG); maximum level of

0.1ng/IU and hamster (CHO) proteins (maximum levels of 1.5ng/IU). As such, there exists a remote

possibility that patients treated with this product may develop hypersensitivity to these non‐human

derived proteins.

In the Phase 2/3 pivotal study of Advate (rAHF‐PFM), serum samples were tested by enzyme

immunoassays at base line and after every 15 ± 2 days for the presence of antibodies to CHO proteins

and MuIgG. Four study subjects showed a statistically significant increasing trend in the levels of anti‐

CHO (n = 1) or anti‐MuIgG (n = 3) antibody levels over the course of the study. A fifth study subject

showed a marked increase in anti‐MuIgG antibodies coincident with the 60 and 75 day interval study

visits. None of these subjects exhibited adverse experiences (AEs) or other study findings consistent

with an allergic or hypersensitivity response.

Interaction with other medicines and other forms of interaction

No interactions of Advate with other medicinal products are currently known, based upon the

absence of data from clinical trials, current medical/scientific literature, and post marketing safety

reports.

Fertility, pregnancy and lactation

Effects on fertility

Mutagenity studies and long‐term studies in animals to evaluate carcinogenic potential of Advate

have not been performed. Animal studies examining the effects of Advate on fertility have not been

conducted.

Use in pregnancy (Category B2)

Factor VIII deficiency is an X‐chromosome linked (male) congenital disease. The safety of Advate for

use in pregnant women has not been established. Physicians should balance the potential risks and

only prescribe if clearly needed. Animal reproduction studies with recombinant factor VIII,

including

ADVATE, have not been conducted.

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Baxalta New Zealand Ltd

Use in lactation

It is not known if Advate or its metabolites are excreted in human milk. The safety of Advate for use in

lactating women has not been established. Breastfeeding is not recommended in women being

treated with Advate. Physicians should carefully consider the potential risks and benefits for each

specific patient before prescribing Advate.

Effects on ability to drive and use machines

There is no information on the effects of Advate on the ability to drive or operate an automobile or

other heavy machinery.

Undesirable effects

Although hypersensitivity or allergic reactions were not observed in any subjects participating in the

clinical trials with Advate, such reactions are theoretically possible. Patients should be informed of

the early signs of hypersensitivity reactions, which may include nausea, vomiting, rash, urticaria,

dizziness, shortness of breath, hypotension and syncope. Patients should be advised to contact their

physician if these symptoms occur.

Across all clinical studies, a total of 1304 adverse reactions were reported among 128 of the 150

subjects who received at least 1 infusion of Advate rAHF‐PFM. Of the 1304 adverse events, 696 were

reported among 85 subjects

> 16 years of age and 608 were reported among 43 subjects ≤ 16 years of

age. All adverse events (product related and unrelated) reported by at least 10% of subjects are

shown in the following table.

Summary of all Adverse Reactions (product related and unrelated) that occurred in

greater or equal to 10% of study subjects.

MedDRA System Organ Class

MedDRA Preferred Term

Number

of Events

Number of

subjects

% of evaluable

subjects*

GASTROINTESTINAL

Pharyngolaryngeal

pain

11.3

GENERAL DISORDER AND

ADMINISTRATION SITE

CONDITIONS

Fall

12.7

Pyrexia

16.7

INFECTIONS AND INFESTATIONS

Nasopharyngitis

14.7

INJURY, POISONING, AND

PROCEDURAL COMPLICATIONS

Accident numbers

17.3

Limb injury numbers

34.7

MUSCULOSKELETAL AND

CONNECTIVE TISSUE DISORDER

Arthralgia

23.3

NERVOUS SYSTEM DISORDER

Headache numbers

29.3

RESPIRATORY, THORACIC,

MEDIASTINAL DISORDER

Cough

15.3

Note: Percentage relative to 150, the total number of subjects across all the studies who received at least one infusion of

ADVATE rAHF‐PFM

Eighteen of the 1304 adverse events were regarded as serious; none were related to the study

medication. There was no death. Among the 1286 non‐serious adverse events, only 28 in 12 subjects

were judged by the investigator to be related to the study drug. Severity ratings among the 28 events

were mild in 8 cases, moderate in 16 cases, and severe in 4 cases as shown in the following table.

The unexpected decreased coagulation factor VIII levels occurred in one subject during continuous

infusion of rAHF‐ PFM following surgery (postoperative Days 10 – 14). Haemostasis was maintained

at all times during this period and both plasma FVIII levels and clearance rates returned to

appropriate levels by postoperative Day 15. Factor VIII inhibitor assays performed after completion of

NEW ZEALAND DATA SHEET

ADVATE Data Sheet 24 August 2017

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Baxalta New Zealand Ltd

continuous infusion and at study termination were negative. Factor VIII inhibitor testing was

performed throughout all the studies in the rAHF‐PFM clinical program. Among 136 treated subjects

10 years of age, all of whom had

150 exposure days to Factor VIII products at the study entry, 102

had at least 75 exposure days to Advate rAHF‐PFM. None of these subjects developed an inhibitor.

One subject who had < 50 exposure days to Advate rAHF‐PFM while on study developed an inhibitor.

This subject manifested a low titer inhibitor (2.0BU by the Bethesda assay) after 26 Advate rAHF‐PFM

exposure days. Eight weeks later the inhibitor was no longer detectable, and in vivo recovery was

normal at 1 and 3 hours after infusion of Recombinate rAHF. For the group comprising all subjects

with at least 75 exposure days to Advate rAHF‐PFM and the single subject who developed an inhibitor,

the 95% confidence interval (Poisson distribution) for the risk of developing an inhibitor to Factor VIII

was 0.02 to 5.4%.

Summary of Non‐Serious, Study‐Drug Related Adverse Events

Severity

MedDRA Preferred Term

Number of Events

Mild

Dysgeusia

Pruritus

Dizziness

Catheter‐related infection

Rigors

Headaches

Total

8

Moderate

Dysgeusia

Dizziness

Headache numbers

Hot flushes

Diarrhoea numbers

Oedema lower limb

Sweating increased

Nausea

Dyspnoea numbers

Abdominal pain upper

Chest pain

Bleeding tendency*

Haematocrit decreased

Joint swelling

Total

16

Severe

Headache

Pyrexia

Haematoma numbers

Coagulation factor VIII decreased

Total

4

*Recorded as a prolonged bleeding after postoperative drain removal on the case report form.

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In addition to the adverse reactions noted above, the following adverse reactions have been reported

in clinical trials:

BLOOD AND LYMPHATIC SYSTEM DISORDERS: Factor VIII inhibition, Lymphangitis.

CARDIAC DISORDERS: Palpitations

EYE DISORDERS: Eye inflammation.

GASTROINTESTINAL DISORDERS: Abdominal

pain upper, Diarrhoea, Nausea, Vomiting.

GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS: Pyrexia, Chest discomfort, Chest pain,

Chills, Feeling abnormal, Peripheral oedema, Vessel puncture site haematoma.

INFECTIONS AND INFESTATIONS: Influenza, Laryngitis.

INJURY, POISONING AND PROCEDURAL COMPLICATIONS: Post procedural complication, Post

procedural haemorrhage, Procedural site reaction.

INVESTIGATIONS: Coagulation factor VIII level decreased, Haematocrit decreased, Laboratory test

abnormal, Monocyte count increased.

NERVOUS SYSTEM DISORDERS: Headache, Dizziness, Dysgeusia, Memory impairment, Migraine,

Syncope, Tremor.

RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS: Dyspnoea.

SKIN AND SUBCUTANEOUS TISSUE DISORDERS: Hyperhidrosis, Pruritus, Rash, Urticaria.

VASCULAR DISORDERS: Hematoma, Hot flush, Pallor.

Post‐Marketing Adverse Reactions

In addition to the adverse reactions noted in clinical trials, the following adverse reactions have been

reported in the post‐marketing experience. These adverse reactions are listed by preferred MedDRA

(Version 15.1) term in order of severity:

IMMUNE SYSTEM DISORDERS: Anaphylactic reaction, Hypersensitivity.

BLOOD AND LYMPHATIC SYSTEM DISORDERS: Factor VIII inhibition.

GENERAL AND ADMINISTRATION SITE CONDITIONS: Injection site reaction, Fatigue, Malaise.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows

continued monitoring of the benefit/risk balance of the medicine. Healthcare professionals are asked

to report any suspected adverse reactions https://nzphvc.otago.ac.nz/reporting/

Overdose

There has been no reported clinical adverse experience that could be associated with overdosage.

advice on the management of overdose please contact the National Poisons Centre on phone

number: 0800 764 766 [0800 POISON] in New Zealand (or the Poison Information Centre on 131126

in Australia).

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5 PHARMACOLOGICAL PROPERTIES

Pharmacodynamic properties

Pharmacotherapeutic group: Blood Coagulation Factor VIII

ATC Code: B02BD02.

Under normal physiological conditions, factor VIII is essential for blood clotting and haemostasis. The

activated factor VIII (FVIIIa) acts as a cofactor for activating factor IX to IXa cascading to activate factor

X to Xa. By the actions of the activated factors Va and Xa, circulating pro‐thrombin is converted into

thrombin. Subsequently, thrombin converts fibrinogen to fibrin monomer cascading to formation of

linear fibrin polymer. By the action of factor XIII the fibrin monomer is cross‐linked to form fibrin clots

leading to the arrest of bleeding episodes.

In patients with haemophilia A (classical haemophilia), a sex‐linked hereditary disorder of blood

coagulation, the level of circulating factor VIII is decreased, leading to profuse bleeding into joints,

muscles or internal organs, either spontaneously or as a result of accidental or surgical trauma. The

use of plasma‐derived or recombinant derived factor VIII has been shown successfully to correct this

deficiency. Thus, plasma derived and recombinant derived factor VIII have the same pharmacological

actions.

Chemical structure

The chemical structure of rAHF‐PFM is that of a dimeric glycoprotein, which has been shown to have

a similar amino acid sequence with that of the human plasma derived factor VIII. Amino acid analysis

of the purified glycosylated protein demonstrated that it constitutes 2332 amino acids with a

molecular mass of approximately 280kDa. Thus, the rAHF‐PFM is a full length factor VIII.

Pharmacokinetic properties

A randomized, crossover pharmacokinetic comparison of Advate (rAHF‐PFM) and Recombinate (rAHF)

was conducted in the context of a pivotal Phase 2/3 study. Pharmacokinetic parameters area under

the plasma curve versus time (AUC), C

, mean residence time (MRT) and volume distribution in

steady state [V

] were calculated from Factor VIII activity measurements in blood samples obtained

immediately before and at standardized time intervals up to 48 hours following each infusion. The

results are shown in the following table.

Pharmacokinetic Parameters for ADVATE (rAHF‐PFM) and RECOMBINATE (rAHF)

Parameters

RECOMBINATE (rAHF)

ADVATE (rAHF‐PFM)

N

Mean ± sd

N

Mean ± sd

AUC(

0 ‐ 48h

) (IU

·h/dL)

1530 ± 380

1534 ± 436

In vivo recovery (IU/dL/kg)

2.59 ± 0.52

2.41 ± 0.50

Half‐life (t

½

)

11.24 ± 2.53

11.98 ± 4.28

C

max

(IU/dL)

129 ± 27

120 ± 26

MRT (h)

14.52 ± 3.81

15.68 ± 6.21

V

SS

(dL/kg)

0.46 ± 0.10

0.47 ± 0.10

C

L

(dL/kg/hr)

0.03 ± 0.01

0.03 ± 0.01

For the pharmacokinetic parameters AUC(

0 ‐ 48h

) and the in vivo recovery, the 90% confidence

intervals for the ratios of the mean values for the test and control articles were within the pre‐

established bioequivalence limits of 0.80 and 1.25 for the per‐protocol (n = 30) study population. This

was also true in the intent‐to‐treat study (n = 50) population for the total AUC and in vivo recovery. In

addition, in vivo recovery at the onset of treatment and after 75 exposure days was compared for 62

NEW ZEALAND DATA SHEET

ADVATE Data Sheet 24 August 2017

Page 12 of 16

Baxalta New Zealand Ltd

subjects. Results indicated no significant change in the in vivo recovery at the onset of treatment and

after 75 exposure days.

Clinical trials

In the phase 2/3 pivotal study, a global assessment of efficacy was rendered either by the

subject (for

home treatment) or study site investigator (for treatment under medical supervision) using an ordinal

scale of excellent, good, fair, or none, based on the quality of haemostasis achieved with Advate

(rAHF‐PFM). A total of 510 bleeding episodes were reported, with a mean (± SD) of 6.1 ± 8.2 bleeding

episodes per subject. Of the 510 new bleeding episodes treated with Advate (rAHF‐PFM), 439 (86%)

were rated excellent or good in their response to treatment, 61 (12%) were rated fair, 1 (0.2%) was

rated as having no response, and for 9 (2%), the response to the treatment was unknown. A total of

411 (81%) new bleeding episodes were managed with a single infusion, 62 (12%) required 2 infusions,

15 (3%) required 3 infusions, and 22 (4%) received 4 or more infusions of Advate (rAHF‐PFM) for

satisfactory resolution. A total of 162 (32%) new bleeding episodes occurred spontaneously, 228

(45%) were the result of antecedent trauma, and for 120 (24%) bleeding episodes the etiology was

unknown.

The rate of new bleeding episodes during the protocol‐mandated minimum of 75 exposure day

prophylactic regimen (≥ 25IU/kg body weight 3 – 4 times per week) was calculated as a function of

the bleeding episodes for 107 evaluable subjects (n = 274) new bleeding episodes. These rates are

presented in the following table.

Rate of New Bleeding Episodes During Prophylaxis

Bleeding Episode Etiology

Mean (± SD) New Bleeding Episodes/Subjects/Month

Spontaneous

0.34 ± 0.49

Post Traumatic

0.39 ± 0.46

Unknown*

0.33 ± 0.34

Overall

0.52 ± 0.71

Etiology was indeterminate

In a post‐hoc analysis, the overall rate of bleeding was correlated with the degree of compliance with

the prescribed prophylactic regimen. Subjects who infused less than 25IU Advate (rAHF‐PFM) per kg

per dose for more than 20% of prophylactic infusions or administered less than 3 infusions per week

more than 20% of study weeks (n = 37) experienced a 2.3‐fold higher rate of bleeding in

comparison with subjects who complied with prescribed prophylactic regimen at least 80% of the

time and at ≥ 80% of the prescribed dose (n = 70).

The phase 2/3 continuation study involved subjects previously treated in the pivotal Phase 2/3 study

and provided additional data on Advate (rAHF‐PFM). An interim analysis of efficacy was conducted

for 27 of 82 enrolled subjects who self‐administered Advate (rAHF‐PFM) on routine prophylactic

regimen during a minimum period of 50 exposures days to Advate (rAHF‐PFM). As in the pivotal

Phase 2/3 study, new bleeding episodes were treated with Advate (rAHF‐PFM) and the outcome of

the treatment was rated as excellent, good, fair, or none, based on the quality of haemostasis

achieved. A total of 51 new bleeding episodes occurred in 13 of the 27 subjects being treated with

Advate (rAHF‐PFM). By etiology, 53% of these bleeding events resulted from trauma and 27%

occurred spontaneously; the remaining 20% had an undetermined etiology. The response to

treatment with Advate (rAHF‐PFM) for the majority (63%) of all new bleeding episodes was rated as

excellent or good. In addition, 86% of the bleeding episodes resolved with only 1 infusion and an

NEW ZEALAND DATA SHEET

ADVATE Data Sheet 24 August 2017

Page 13 of 16

Baxalta New Zealand Ltd

additional 6% were resolved by a second infusion. Thus, 92% of the bleeding episodes required 1 or 2

infusions of study product.

An interim analysis of the haemostatic efficacy of Advate (rAHF‐PFM) during the perioperative

management

of subjects undergoing surgical procedures was conducted for 10 of 25 planned

subjects. Ten subjects underwent 10 surgical procedures while receiving Advate (rAHF‐PFM). Eight

subjects received the test product by intermittent bolus infusion and 2 subjects received a

combination of continuous and intermittent bolus infusion. Nine of 10 subjects completed the study.

Six of the surgical procedures were classified as major, and 4 were minor. Of the 6 major surgeries, 5

were for orthopaedic complications of haemophilia. A brief description of each surgical procedure,

along with study duration and study medication exposure, is presented in the following table.

Surgical Procedures, Study Duration, and Study Medication Exposure

Surgery Type

Days of

Study

ADVATE (rAHF‐PFM)

Exposure Days

Cumulative ADVATE (rAHF‐

PFM) Exposure (IU)

Total hip replacement

61,600

Knee joint replacement

76,060

Knee Arthrodesis

66,080

Transposition of the left ulnar

nerve

14,560

Insertion of Mediport

46,893

Dental Extraction

16,599

Left elbow synovectomy

102,180

Teeth Extraction

10,350

Right knee arthroscopy,

chondroplasty, and synovectomy

32,334

Wisdom teeth Extraction

15,357

* Advate (rAHF‐PFM) was administered by continuous infusion for the first 48 hours post‐operatively,

followed by bolus infusions for the remainder of study treatment.

For each of the 10 subjects, intra‐ and post‐operative quality of haemostasis with Advate (rAHF‐PFM)

was assessed by operating surgeon and study site investigator, respectively, using ordinal scale of

excellent, good, fair, or none. The same rating scale was used to evaluate control of haemorrhage

from a surgical drain placed at the incision site in one subject. The quality of haemostasis achieved

with Advate (rAHF‐PFM) was rated as excellent or good for all assessments.

Smaller diluent vial (2mL sWFI) for potencies up to 1500IU inclusive (from 5mL sWFI to 2mL sWFI).

An open label, randomized, crossover clinical study was conducted in 35 evaluable subjects diagnosed

with severe haemophilia A (factor VIII [FVIII] activity ≤ 1% of normal) to investigate the PK parameters

and safety of a single dose of Advate (50IU/kg

100IU) reconstituted in two different volumes of

sterilised water for injections (sWFI, 2mL or 5mL). Subjects were randomized (1 : 1) to receive an

infusion with Advate reconstituted in 2mL followed by an infusion with Advate reconstituted in 5mL

sWFI or vice versa.

Results of this clinical study are summarized in the following table.

NEW ZEALAND DATA SHEET

ADVATE Data Sheet 24 August 2017

Page 14 of 16

Baxalta New Zealand Ltd

PK Parameters for Adolescent/Adult Cohort (Study 060702: PP Dataset)

Parameter

2mL infusion

5mL infusion

Mean (geometric

mean) value for

2mL infusion

SD (2mL)

Mean (geometric

mean) value for

5mL infusion

SD (5mL)

AUC(

0 ‐ 48h

) (IU

·h/dL)

1298.67

380.60

1363.56

487.57

C

max

(IU/dL)

104.42

19.35

107.89

17.95

Adjusted in vivo IR

1

(IU/dL : IU/kg)

1.93

0.35

2.00

0.36

Half‐life (h)

12.54

3.80

12.50

2.89

C

L

(mL/(kg/h))

3.85

0.95

3.81

1.20

MRT (h)

14.79

5.24

14.34

4.27

V

ss

(dL/kg)

0.54

0.13

0.51

0.13

Abbreviations: PP = per‐protocol, SD = standard deviation

Mean adjusted in vivo incremental recovery (IR) values were computed using C

Preclinical safety data

Mutagenity studies and long‐term studies in animals to evaluate carcinogenic potential of Advate

have not been performed. Animal studies examining the effects of Advate on fertility have not been

conducted.

6 PHARMACEUTICAL PARTICULARS

List of excipients

The amounts of the inactive ingredients are constant in all strengths.

Unit Formulation

ADVATE

250IU

500IU

1000IU

1500IU

2000IU

3000IU

4000IU

Active ingredient:

Octocog alfa

[Recombinant

Coagulation

FVIII (rch)]

250IU

500IU

1000IU

1500IU

2000IU

3000IU

4000IU

Inactive

ingredient:

Trehalose

(mg)

40.0

(mg)

40.0

(mg)

40.0

(mg)

40.0

(mg)

40.0

(mg)

40.0

(mg)

40.0

Histidine

Trometamol

Sodium

Chloride

26.5

26.5

26.5

26.5

26.5

26.5

26.5

Calcium

Chloride

Glutathione

(reduced)

Polysorbate 80

Mannitol

160.0

160.0

160.0

160.0

160.0

160.0

160.0

NEW ZEALAND DATA SHEET

ADVATE Data Sheet 24 August 2017

Page 15 of 16

Baxalta New Zealand Ltd

Incompatibilities

Not applicable.

Shelf life

Two years. The product is stable for the duration of the specified shelf life when stored in the

specified temperature storage condition. Advate should be administered at room temperature not

more than 3 hours after reconstitution. For single use only.

Special precautions for storage

Advate should be stored at 2°C ‐ 8°C for the duration of its shelf life. Do not freeze. In the case of a

need for ambulatory use, Advate may be kept at or below 25°C (room temperature) for a single

period of up to 6 months and then discarded. After Advate has been stored at room temperature, it

should not be re‐refrigerated. Do not use beyond the expiration date printed on the label. Protect

from light.

Nature and contents of container

Advate is formulated as a sterile, nonpyrogenic, off‐white, lyophilized powder, for intravenous

injection. It is supplied in single‐dose glass vials containing nominally 250, 500, 1000, 1500, 2000,

3000 or 4000IU per vial and a diluent (Sterile Water for Injection or sWFI) for reconstitution.

Advate with 5mL of sWFI is available as a lyophilized powder in single‐use glass vials containing

nominally 250, 500, 1000, 1500, 2000, 3000 or 4000 International Units (IU). Advate with 2mL of

Sterile Water for Injection is available as a lyophilized powder in single‐use glass vials containing

nominally 250, 500, 1000 or 1500IU.

Please see section 4.2/Nature and

contents of container for the table showing details of the Advate

and diluent vials, and the suitable potencies for each diluent volume.

Not all pack sizes may be marketed.

Needleless transfer device (BAXJECT)

The product is accompanied by a needleless transfer device designed for transferring and mixing

medicines contained in two vials (product and diluent). Each Needleless Transfer Device has a two‐

vial holder, a two‐sided siliconised piercing plastic spike for penetration into the rubber stoppers of

the two vials, a stopcock with an embedded/filter, and a female port designed for connection to a

syringe (see Fig A – F in section 4.2).

Special precautions for disposal

Discard any unused portion of the product appropriately.

Any unused product or waste material should be disposed of in accordance with local requirements.

7 MEDICINE SCHEDULE

General Sale Medicine.

NEW ZEALAND DATA SHEET

ADVATE Data Sheet 24 August 2017

Page 16 of 16

Baxalta New Zealand Ltd

8 SPONSOR

Advate is distributed in New Zealand by:

Baxalta New Zealand Ltd

33 Vestey Drive

Mt Wellington

Auckland 1060

Baxalta New Zealand Ltd

PO Box 14 062

Panmure

Auckland 1741

Phone (09) 574 2400.

Advate is distributed in Australia by:

Baxalta Australia Pty Ltd

1 Baxter Drive

Old Toongabbie, NSW 2146.

9 DATE OF FIRST APPROVAL

Date of publication in the New Zealand Gazette of consent to distribute the medicine:

Advate 250IU, 25/01/2007

Advate 500IU, 25/01/2007

Advate 1000IU, 25/01/2007

Advate 1500IU, 25/01/2007

Advate 2000IU, 21/04/2009

Advate 3000IU, 16/04/2009

Advate 4000IU, 09/07/2015.

10 DATE OF REVISION OF THE TEXT

24 August 2017.

SUMMARY TABLE OF CHANGES

Section changed

Summary of new information

Entire document reformatted to new standard format based on the European

Summary of Product Characteristics (SPC).

Date of Revision of Text updated.

Based on Australian PI approved 7 November 2008, most recent amendment 01 October 2013; and

CCDS20120130514.

Please refer to the Medsafe website (www.medsafe.govt.nz) for most recent data sheet.

Baxalta, Advate, BaxJect II and Recombinate are trademarks of Baxalta Incorporated.

14-1-2019

Germany Black Ant 2000mg tablets (Zhansheng Weige Chaoyue Xilishi)

Germany Black Ant 2000mg tablets (Zhansheng Weige Chaoyue Xilishi)

These tablets pose a serious risk to your health and should not be taken

Therapeutic Goods Administration - Australia

20-12-2018

Pest categorisation of Gymnosporangium spp. (non‐EU)

Pest categorisation of Gymnosporangium spp. (non‐EU)

Published on: Wed, 19 Dec 2018 Following a request from the European Commission, the EFSA Panel on Plant Health performed a pest categorisation of Gymnosporangium spp. (non‐EU), a well‐defined and distinguishable group of fungal plant pathogens of the family Pucciniaceae affecting woody species. Many different Gymnosporangium species are recognised, of which at least 14 species are considered not to be native in the European Union. All the non‐EU Gymnosporangium species are not known to be present in th...

Europe - EFSA - European Food Safety Authority EFSA Journal

20-12-2018

Pest categorisation of Grapholita inopinata

Pest categorisation of Grapholita inopinata

Published on: Wed, 19 Dec 2018 The EFSA Panel on Plant Health (PLH) performed a pest categorisation of Grapholita inopinata, (Lepidoptera: Tortricidae), the Manchurian fruit moth, for the territory of the EU. G. inopinata is a well‐defined species that is recognised as a major pest of Malus spp. in Far East Russia, Eastern Siberia and northern China. G. inopinata is less common in Japan where it is not a serious pest. G. inopinata is not known to occur in the EU. G. inopinata is listed in Annex IIAI of ...

Europe - EFSA - European Food Safety Authority EFSA Journal

20-12-2018

Pest categorisation of Cronartium spp. (non‐EU)

Pest categorisation of Cronartium spp. (non‐EU)

Published on: Wed, 19 Dec 2018 Following a request from the European Commission, the EFSA Panel on Plant Health performed a pest categorisation of Cronartium spp. (non‐EU), a well‐defined and distinguishable group of fungal pathogens of the family Cronartiaceae. There are at least 40 species described within the Cronartium genus, of which two are considered native to the EU (C. gentianeum and C. pini) and one has been introduced in the 19th century (C. ribicola) and is now widespread in the EU – these t...

Europe - EFSA - European Food Safety Authority EFSA Journal

19-12-2018

Pest categorisation of Phyllosticta solitaria

Pest categorisation of Phyllosticta solitaria

Published on: Tue, 18 Dec 2018 The European Commission requested EFSA to conduct a pest categorisation of Grapholita prunivora (Lepidoptera: Tortricidae), an oligophagous moth whose larvae feed mostly on leaves and fruit of different Rosaceae including cultivated apples, plums, cherries and pecans. It overwinters in soil and bark crevices of its host plants. G. prunivora has reliable identification methods, both for adults and immature stages. It occurs in North America, where it can impact pome and sto...

Europe - EFSA - European Food Safety Authority EFSA Journal

19-12-2018

Pest categorisation of Grapholita prunivora

Pest categorisation of Grapholita prunivora

Published on: Tue, 18 Dec 2018 The European Commission requested EFSA to conduct a pest categorisation of Grapholita prunivora (Lepidoptera: Tortricidae), an oligophagous moth whose larvae feed mostly on leaves and fruit of different Rosaceae including cultivated apples, plums, cherries and pecans. It overwinters in soil and bark crevices of its host plants. G. prunivora has reliable identification methods, both for adults and immature stages. It occurs in North America, where it can impact pome and sto...

Europe - EFSA - European Food Safety Authority EFSA Journal

18-12-2018

Pest categorisation of Carposina sasakii

Pest categorisation of Carposina sasakii

Published on: Mon, 17 Dec 2018 The EFSA Panel on Plant Health performed a pest categorisation of the peach fruit moth, Carposina sasakii Matsumura (Lepidoptera: Carposinidae) for the EU. C. sasakii is not currently regulated in the EU although C. niponensis, a valid species of no economic significance that was previously mistakenly synonymised with C. sasakii, is regulated in Annex IIAI of 2000/29 EC. C. sasakii is a well‐defined species that is recognised as a major pest of apples, peaches and pears in...

Europe - EFSA - European Food Safety Authority Publications

13-12-2018

Pest categorisation of Septoria malagutii

Pest categorisation of Septoria malagutii

Published on: Wed, 12 Dec 2018 The Panel on Plant Health performed a pest categorisation of Septoria malagutii, the causal agent of annular leaf spot of potato, for the EU. The pest is a well‐defined fungal species and reliable methods exist for its detection and identification. S. malagutii is present in Bolivia, Ecuador, Peru and Venezuela. The pest is not known to occur in the EU and is listed as Septoria lycopersici var. malagutii in Annex IAI of Directive 2000/29/EC, meaning its introduction into t...

Europe - EFSA - European Food Safety Authority Publications

20-11-2018

Pest categorisation of non‐EU Monochamus spp.

Pest categorisation of non‐EU Monochamus spp.

Published on: Mon, 19 Nov 2018 The Panel on Plant Health performed a pest categorisation of non‐EU Monochamus spp., a well‐defined insect genus in the family Cerambycidae (Insecta: Coleoptera). Species can be identified using taxonomic keys at national and regional level, and DNA barcoding. Two online world catalogues exist for the genus. The genus includes about one hundred species and many subspecies colonising conifers and non‐conifer trees in many areas in the world. The non‐EU species are listed in...

Europe - EFSA - European Food Safety Authority Publications

10-11-2018

Pest categorisation of Popillia japonica

Pest categorisation of Popillia japonica

Published on: Thu, 08 Nov 2018 00:00:00 +0100 The Panel on Plant Health performed a pest categorisation of Popillia japonica(Coleoptera: Scarabaeidae) for the EU. P. japonica is a distinguishable species listed in Annex IAII of Council Directive 2000/29/EC. It is native to Japan but established in the USA in the early 20th century. It spreads from New Jersey to most US states east of the Mississippi, some to the west and north into Canada. P. japonica feeds on over 700 plant species. Adults attack folia...

Europe - EFSA - European Food Safety Authority Publications

1-11-2018

Pest categorisation of Conotrachelus nenuphar

Pest categorisation of Conotrachelus nenuphar

Published on: Wed, 31 Oct 2018 00:00:00 +0100 The EFSA Panel on Plant Health performed a pest categorisation of Conotrachelus nenuphar (Herbst) (Coleoptera: Curculionidae), for the EU. C. nenuphar is a well‐defined species, recognised as a serious pest of stone and pome fruit in the USA and Canada where it also feeds on a range of other hosts including soft fruit (e.g. Ribes,Fragaria) and wild plants (e.g. Crataegus). Adults, which are not good flyers, feed on tender twigs, flower buds and leaves. Femal...

Europe - EFSA - European Food Safety Authority Publications

1-11-2018

Pest categorisation of Acrobasis pirivorella

Pest categorisation of Acrobasis pirivorella

Published on: Wed, 31 Oct 2018 00:00:00 +0100 The European Commission requested EFSA to conduct a pest categorisation of Acrobasis pirivorella (Lepidoptera: Pyralidae), a monophagous moth whose larvae exclusively feed on developing buds, flowers, and fruits of cultivated and wild Pyrus spp. A. pirivorella is a species with reliable methods available for identification. A. pirivorellaoccurs in north‐east Asia only, causing significant damage in cultivated pears. It is regulated in the EU by Council Direc...

Europe - EFSA - European Food Safety Authority Publications

30-10-2018

Pest categorisation of Sternochetus mangiferae

Pest categorisation of Sternochetus mangiferae

Published on: Mon, 29 Oct 2018 00:00:00 +0100 The European Commission requested EFSA to conduct a pest categorisation of Sternochetus mangiferae (Coleoptera: Curculionidae), a monophagous pest weevil whose larvae exclusively feed on mango seeds, whereas adults feed on mango foliage. S. mangiferae is a species with reliable methods available for identification. It is regulated in the EU by Council Directive 2000/29/EC where it is listed in Annex IIB as a harmful organism whose introduction into EU Protec...

Europe - EFSA - European Food Safety Authority Publications

30-10-2018

Pest categorisation of Aleurocanthus spp.

Pest categorisation of Aleurocanthus spp.

Published on: Mon, 29 Oct 2018 00:00:00 +0100 The Panel on Plant Health performed a pest categorisation of Aleurocanthus spp., a well‐defined insect genus of the whitefly family Aleyrodidae (Arthropoda: Hemiptera). Difficulties within the taxonomy of the genus give doubt about the ability to accurately identify some members to species level. Nevertheless, the genus is thought to currently include about ninety species mainly reported from tropical and subtropical areas. The genus is listed in Council Dir...

Europe - EFSA - European Food Safety Authority Publications

17-10-2018

Pest categorisation of Stagonosporopsis andigena

Pest categorisation of Stagonosporopsis andigena

Published on: Tue, 16 Oct 2018 00:00:00 +0200 The Panel on Plant Health performed a pest categorisation of Stagonosporopsis andigena, the causal agent of black blight of potato, for the EU. The pest is a well‐defined fungal species and reliable methods exist for its detection and identification. S. andigena is present in Bolivia and Peru. The pest is not known to occur in the EU and is listed in Annex IAI of Directive 2000/29/EC as Phoma andina, meaning its introduction into the EU is prohibited. The ma...

Europe - EFSA - European Food Safety Authority Publications

17-10-2018

Pest categorisation of Thecaphora solani

Pest categorisation of Thecaphora solani

Published on: Tue, 16 Oct 2018 00:00:00 +0200 The Panel on Plant Health performed a pest categorisation of the fungus Thecaphora solani, the causal agent of smut of potato, for the EU. The identity of the pest is well established and reliable methods exist for its detection and identification. T. solaniis present in Bolivia, Chile, Colombia, Ecuador, Mexico, Panama, Peru and Venezuela. The pathogen is not known to occur in the EU and is listed in Annex IAI of Directive 2000/29/EC, meaning its introducti...

Europe - EFSA - European Food Safety Authority Publications

16-10-2018

Pest categorisation of Cronartium harknessii, Cronartium kurilense and Cronartium sahoanum

Pest categorisation of Cronartium harknessii, Cronartium kurilense and Cronartium sahoanum

Published on: Mon, 15 Oct 2018 00:00:00 +0200 Following a request from the European Commission, the EFSA Panel on Plant Health performed a pest categorisation of Cronartium harknessii, Cronartium kurilense and Cronartium sahoanum, which are well‐defined and distinguishable tree fungal pathogens of the family Cronartiaceae. In 2018, these species were moved from the genus Endocronartium to the genus Cronartium. These pathogens are not known to be present in the EU and are regulated in Council Directive 2...

Europe - EFSA - European Food Safety Authority Publications

16-10-2018

Pest categorisation of Melampsora farlowii

Pest categorisation of Melampsora farlowii

Published on: Mon, 15 Oct 2018 00:00:00 +0200 Following a request from the European Commission, the EFSA Panel on Plant Health performed a pest categorisation of Melampsora farlowii, a well‐defined and distinguishable fungus of the family Melampsoraceae. M. farlowii is the causal agent of a leaf and twig rust of hemlocks (Tsuga spp.) in eastern North America. The pathogen is regulated in Council Directive 2000/29/EC (Annex IAI) as a harmful organism whose introduction into the EU is banned. M. farlowii ...

Europe - EFSA - European Food Safety Authority Publications

21-9-2018

Pending EC decision:  Jivi, damoctocog alfa pegol, Opinion date: 20-Sep-2018

Pending EC decision: Jivi, damoctocog alfa pegol, Opinion date: 20-Sep-2018

Europe - EMA - European Medicines Agency

7-9-2018

Orphan designation:  Recombinant human beta-glucuronidase (vestronidase alfa),  for the: Treatment of mucopolysaccharidosis type VII (Sly syndrome)

Orphan designation: Recombinant human beta-glucuronidase (vestronidase alfa), for the: Treatment of mucopolysaccharidosis type VII (Sly syndrome)

On 21 March 2012, orphan designation (EU/3/12/973) was granted by the European Commission to NDA Regulatory Science Ltd, United Kingdom, for recombinant human beta-glucuronidase for the treatment of mucopolysaccharidosis type VII (Sly syndrome).

Europe - EMA - European Medicines Agency

27-7-2018

Pending EC decision:  Abseamed, epoetin alfa, Opinion date: 26-Jul-2018

Pending EC decision: Abseamed, epoetin alfa, Opinion date: 26-Jul-2018

Europe - EMA - European Medicines Agency

27-7-2018

Pending EC decision:  Binocrit, epoetin alfa, Opinion date: 26-Jul-2018

Pending EC decision: Binocrit, epoetin alfa, Opinion date: 26-Jul-2018

Europe - EMA - European Medicines Agency

24-7-2018

Opinion/decision on a Paediatric investigation plan (PIP):    -, Andexanet alfa, Therapeutic area: Other

Opinion/decision on a Paediatric investigation plan (PIP): -, Andexanet alfa, Therapeutic area: Other

Europe - EFSA - European Food Safety Authority EFSA Journal

14-12-2018


Summary of opinion: Besremi,ropeginterferon alfa-2b,  13/12/2018,  Positive

Summary of opinion: Besremi,ropeginterferon alfa-2b, 13/12/2018, Positive

Summary of opinion: Besremi,ropeginterferon alfa-2b, 13/12/2018, Positive

Europe - EMA - European Medicines Agency

12-12-2018

Elocta (Swedish Orphan Biovitrum AB (publ))

Elocta (Swedish Orphan Biovitrum AB (publ))

Elocta (Active substance: efmoroctocog alfa) - Centralised - Variation - Commission Decision (2018)8678 of Wed, 12 Dec 2018 European Medicines Agency (EMA) procedure number: EMEA/H/C/3964/X/21

Europe -DG Health and Food Safety

28-11-2018


Opinion/decision on a Paediatric investigation plan (PIP): vonicog alfa, decision type: , therapeutic area: , PIP number: P/0225/2018

Opinion/decision on a Paediatric investigation plan (PIP): vonicog alfa, decision type: , therapeutic area: , PIP number: P/0225/2018

Opinion/decision on a Paediatric investigation plan (PIP): vonicog alfa, decision type: , therapeutic area: , PIP number: P/0225/2018

Europe - EMA - European Medicines Agency

26-11-2018

Jivi (Bayer AG)

Jivi (Bayer AG)

Jivi (Active substance: damoctocog alfa pegol) - Centralised - Authorisation - Commission Decision (2018)7987 of Mon, 26 Nov 2018 European Medicines Agency (EMA) procedure number: EMEA/H/C/004054/0000

Europe -DG Health and Food Safety

22-11-2018

Brineura (BioMarin International Limited)

Brineura (BioMarin International Limited)

Brineura (Active substance: cerliponase alfa) - Centralised - Yearly update - Commission Decision (2018)7885 of Thu, 22 Nov 2018

Europe -DG Health and Food Safety

22-11-2018

NovoSeven (Novo Nordisk A/S)

NovoSeven (Novo Nordisk A/S)

NovoSeven (Active substance: Eptacog alfa (activated)) - Centralised - 2-Monthly update - Commission Decision (2018)7877 of Thu, 22 Nov 2018 European Medicines Agency (EMA) procedure number: EMEA/H/C/000074/II/0104

Europe -DG Health and Food Safety

14-11-2018

Caring for a loved one? Be prepared for any situation. 4 tips to help you keep you loved one safe:  http://www.fda.gov/caregivertips  #NationalFamilyCaregiversMonthpic.twitter.com/DpNpz8NCDe

Caring for a loved one? Be prepared for any situation. 4 tips to help you keep you loved one safe: http://www.fda.gov/caregivertips  #NationalFamilyCaregiversMonthpic.twitter.com/DpNpz8NCDe

Caring for a loved one? Be prepared for any situation. 4 tips to help you keep you loved one safe: http://www.fda.gov/caregivertips  #NationalFamilyCaregiversMonth pic.twitter.com/DpNpz8NCDe

FDA - U.S. Food and Drug Administration

12-11-2018

Ruconest (Pharming Group N.V.)

Ruconest (Pharming Group N.V.)

Ruconest (Active substance: Conestat alfa) - Centralised - Yearly update - Commission Decision (2018)7548 of Mon, 12 Nov 2018

Europe -DG Health and Food Safety

29-10-2018

Replagal (Shire Human Genetic Therapies AB)

Replagal (Shire Human Genetic Therapies AB)

Replagal (Active substance: Agalsidase alfa) - Centralised - Yearly update - Commission Decision (2018)7250 of Mon, 29 Oct 2018

Europe -DG Health and Food Safety

2-10-2018

PegIntron (Merck Sharp and Dohme B.V.)

PegIntron (Merck Sharp and Dohme B.V.)

PegIntron (Active substance: Peginterferon alfa-2b) - Centralised - Transfer Marketing Authorisation Holder - Commission Decision (2018)6484 of Tue, 02 Oct 2018 European Medicines Agency (EMA) procedure number: EMEA/H/C/280/T/135

Europe -DG Health and Food Safety

2-10-2018

Vimizim (BioMarin International Limited)

Vimizim (BioMarin International Limited)

Vimizim (Active substance: elosulfase alfa) - Centralised - Transfer Marketing Authorisation Holder - Commission Decision (2018)6491 of Tue, 02 Oct 2018 European Medicines Agency (EMA) procedure number: EMEA/H/C/002779/T/0026

Europe -DG Health and Food Safety

2-10-2018

ViraferonPeg (Merck Sharp and Dohme B.V.)

ViraferonPeg (Merck Sharp and Dohme B.V.)

ViraferonPeg (Active substance: Peginterferon alfa-2b) - Centralised - Transfer Marketing Authorisation Holder - Commission Decision (2018)6477 of Tue, 02 Oct 2018 European Medicines Agency (EMA) procedure number: EMEA/H/C/329/T/128

Europe -DG Health and Food Safety

2-10-2018

IntronA (Merck Sharp and Dohme B.V.)

IntronA (Merck Sharp and Dohme B.V.)

IntronA (Active substance: Interferon alfa-2b) - Centralised - Transfer Marketing Authorisation Holder - Commission Decision (2018)6487 of Tue, 02 Oct 2018 European Medicines Agency (EMA) procedure number: EMEA/H/C/281/T/116

Europe -DG Health and Food Safety

24-9-2018

Kanuma (Alexion Europe SAS)

Kanuma (Alexion Europe SAS)

Kanuma (Active substance: sebelipase alfa) - Centralised - Yearly update - Commission Decision (2018)6245 of Mon, 24 Sep 2018

Europe -DG Health and Food Safety

24-9-2018

Ovitrelle (Merck Europe B.V.)

Ovitrelle (Merck Europe B.V.)

Ovitrelle (Active substance: Choriogonadotrophin alfa) - Centralised - Transfer Marketing Authorisation Holder - Commission Decision (2018)6220 of Mon, 24 Sep 2018 European Medicines Agency (EMA) procedure number: EMEA/H/C/320/T/75

Europe -DG Health and Food Safety

4-9-2018

Epoetin alfa Hexal (Hexal AG)

Epoetin alfa Hexal (Hexal AG)

Epoetin alfa Hexal (Active substance: epoetin alfa) - Centralised - 2-Monthly update - Commission Decision (2018)5857 of Tue, 04 Sep 2018 European Medicines Agency (EMA) procedure number: EMEA/H/C/726/II/WS/1406

Europe -DG Health and Food Safety

4-9-2018

Binocrit (Sandoz GmbH)

Binocrit (Sandoz GmbH)

Binocrit (Active substance: epoetin alfa) - Centralised - 2-Monthly update - Commission Decision (2018)5856 of Tue, 04 Sep 2018 European Medicines Agency (EMA) procedure number: EMEA/H/C/725/II/WS/1406

Europe -DG Health and Food Safety

4-9-2018

Abseamed (Medice Arzneimittel PUtter GmbH and Co KG)

Abseamed (Medice Arzneimittel PUtter GmbH and Co KG)

Abseamed (Active substance: epoetin alfa) - Centralised - 2-Monthly update - Commission Decision (2018)5860 of Tue, 04 Sep 2018 European Medicines Agency (EMA) procedure number: EMEA/H/C/727/WS/1406

Europe -DG Health and Food Safety

4-9-2018

VEYVONDI (Baxalta Innovations GmbH)

VEYVONDI (Baxalta Innovations GmbH)

VEYVONDI (Active substance: vonicog alfa) - Centralised - Authorisation - Commission Decision (2018)5866 of Tue, 04 Sep 2018 European Medicines Agency (EMA) procedure number: EMEA/H/C/4454

Europe -DG Health and Food Safety

27-8-2018

Mepsevii (Ultragenyx Germany GmbH)

Mepsevii (Ultragenyx Germany GmbH)

Mepsevii (Active substance: vestronidase alfa) - Centralised - Authorisation - Commission Decision (2018)5714 of Mon, 27 Aug 2018 European Medicines Agency (EMA) procedure number: EMEA/H/C/4438

Europe -DG Health and Food Safety

27-8-2018

Beromun (BELPHARMA s.a.)

Beromun (BELPHARMA s.a.)

Beromun (Active substance: Tasonermin (Tumor Necrosis Factor alfa-1a)) - Centralised - Transfer Marketing Authorisation Holder - Commission Decision (2018)5699 of Mon, 27 Aug 2018 European Medicines Agency (EMA) procedure number: EMEA/H/C/206/T/40

Europe -DG Health and Food Safety

27-8-2018

Aranesp (Amgen Europe B.V.)

Aranesp (Amgen Europe B.V.)

Aranesp (Active substance: darbepoetin alfa) - Centralised - Yearly update - Commission Decision (2018)5707 of Mon, 27 Aug 2018

Europe -DG Health and Food Safety

22-8-2018

Luveris (Merck Europe B.V.)

Luveris (Merck Europe B.V.)

Luveris (Active substance: Lutropin alfa) - Centralised - Transfer Marketing Authorisation Holder - Commission Decision (2018)5631 of Wed, 22 Aug 2018 European Medicines Agency (EMA) procedure number: EMEA/H/C/000292/T/0077

Europe -DG Health and Food Safety

22-8-2018

Pergoveris (Merck Europe B.V.)

Pergoveris (Merck Europe B.V.)

Pergoveris (Active substance: follitropin alfa / lutropin alfa) - Centralised - Transfer Marketing Authorisation Holder - Commission Decision (2018)5629 of Wed, 22 Aug 2018 European Medicines Agency (EMA) procedure number: EMEA/H/C/000714/T/0059

Europe -DG Health and Food Safety

8-8-2018

GONAL-f (Merck Europe B.V.)

GONAL-f (Merck Europe B.V.)

GONAL-f (Active substance: Follitropin alfa) - Centralised - Transfer Marketing Authorisation Holder - Commission Decision (2018)5445 of Wed, 08 Aug 2018 European Medicines Agency (EMA) procedure number: EMEA/H/C/71/T/140

Europe -DG Health and Food Safety

6-8-2018

ReFacto AF (Pfizer Europe MA EEIG)

ReFacto AF (Pfizer Europe MA EEIG)

ReFacto AF (Active substance: Moroctocog alfa ) - Centralised - Transfer Marketing Authorisation Holder - Commission Decision (2018)5374 of Mon, 06 Aug 2018 European Medicines Agency (EMA) procedure number: EMEA/H/C/232/T/146

Europe -DG Health and Food Safety

2-8-2018

EU/3/18/2046 (Italfarmaco S.p.A.)

EU/3/18/2046 (Italfarmaco S.p.A.)

EU/3/18/2046 (Active substance: Givinostat) - Orphan designation - Commission Decision (2018)5278 of Thu, 02 Aug 2018 European Medicines Agency (EMA) procedure number: EMA/OD/062/18

Europe -DG Health and Food Safety

30-7-2018

NovoEight (Novo Nordisk A/S)

NovoEight (Novo Nordisk A/S)

NovoEight (Active substance: turoctocog alfa) - Centralised - 2-Monthly update - Commission Decision (2018)5093 of Mon, 30 Jul 2018 European Medicines Agency (EMA) procedure number: EMEA/H/C/2719/II/23

Europe -DG Health and Food Safety

25-7-2018

Bemfola (Gedeon Richter Plc.)

Bemfola (Gedeon Richter Plc.)

Bemfola (Active substance: follitropin alfa) - Centralised - Yearly update - Commission Decision (2018)4989 of Wed, 25 Jul 2018

Europe -DG Health and Food Safety