Australian Public Assessment Report for purified antigen fractions of inactivated split virion A/Indonesia/05/2005 (H5N1), as03 adjuvanted

I. Introduction to product submission

Submission details

Type of submission:	New biological entity
Decision:	Withdrawn
Date of decision:	3 September 2015
Active ingredient:	Purified antigen fractions of inactivated split virion A/Indonesia/05/2005 (H5N1), AS03 adjuvanted
Product name:	Prepandrix
Sponsor’s name and address:	GlaxoSmithKline Australia Pty Ltd Level 4, 436 Johnston Street Abbotsford VIC 3067
Dose form:	Antigen as suspension and adjuvant as emulsion in separate vials
Strength:	Potency is expressed as 3.75 μg haemagglutinin (HA) per dose
Container:	One carton of Prepandrix consists three packs, including one pack containing 50 vials each with 2.5 ml antigen suspension for 10 doses and two packs of 25 vials each with 2.5 ml adjuvant emulsion for 10 doses
Pack size:	As above
Route of administration:	Intramuscular Injection preferably into the deltoid muscle or anterolateral thigh (depending on the muscle mass)
Dosage:	Primary vaccination: Two doses of 0.5 mL of the reconstituted vaccine. The second dose is administered between 3 weeks - 12 months after the first dose

Product background

This AusPAR describes the application by GlaxoSmithKline Australia Pty Ltd to register a new pandemic influenza vaccine, Prepandrix (also known as Prepandremix during the application process and in this AusPAR). Prepandemrix is a split virion influenza vaccine against a strain of influenza with pandemic potential. It contains antigen equivalent to A/Indonesia/05/2005 PR8-IBCDC-RG2 (H5N1) 3.75 micrograms (µg) adjuvanted with the GlaxoSmithKline proprietary Adjuvant System 03 (AS03) adjuvant system per 0.5 ml dose. The vaccine is presented as an emulsion and suspension which need to be mixed prior to administration.

The proposed indication is:

Prophylaxis of influenza caused by the H5N1 strain with a pandemic potential. Prepandemrix should be used in accordance with official recommendations.

Prepandemrix consists of two containers: one multidose vial containing the antigen (suspension) and a second multidose vial containing the adjuvant (emulsion). The suspension is a colourless light opalescent liquid. The emulsion is a whitish to yellowish homogeneous (milky) liquid. The submission proposes registration of multidose vials as follows:

2.5 ml suspension in a vial (type I glass) for 10 doses with a stopper (butyl rubber); pack size of 50.

2.5 ml emulsion in a vial (type I glass) for 10 doses with a stopper (butyl rubber); pack size of 25 x 2.

Prepandemrix is intended to be used according to the same dosing as the currently registered Pandemrix H5N1 (AUST R 145924). That is:

Adults from the age of 18 years will receive two doses of 0.5 mL Prepandemrix, the first administered at an elected date, the second at least three weeks and up to twelve months after the first dose for maximum efficacy. Vaccination should be carried out by intramuscular injection preferably into the deltoid muscle or anterolateral thigh (depending on the muscle mass).

Regulatory status

The sponsor has two pre pandemic H5N1 vaccines, one produced at the Dresden (Germany) manufacturing facility (D-H5N1) and the other produced at the Quebec (Canada) manufacturing facility (Q-H5N1). Both are adjuvanted with AS03.

Prepandrix (D-H5N1) is proposed for Australia. Q-H1N1 is approved for the US and Canadian markets.

At the time of this submission, Prepandrix (D-H5N1) was approved in the EU in May 2008. The initial dossier was approved with the A/Vietnam strain, with a line extension to change the strain to A/Indonesia in August 2009. The approved indication is:

Active immunisation against H5N1 subtype influenza A virus.

This indication is based on immunogenicity data from healthy subjects from the age of 18 years onwards following administration of two doses of vaccine prepared in H5N1 subtype strains.

Prepandrix should be used in accordance with official guidance.

The vaccine has also been approved in Singapore (April 2009) with the following indications:

Active immunization against H5N1 subtype of Influenza A virus.

This indication is based on immunogenicity data from healthy subjects from the age of 18 years onwards following administration of two doses of vaccine prepared with H5N1 subtype strain.

Prepandrix should be used in accordance with official guidance.

It has also been approved in Switzerland (September 2009) with the following indications:

Active immunization against H5N1 subtype of Influenza A virus. This indication is based on immunogenicity data from healthy subjects from the age of 18 years onwards following administration of two doses of vaccine prepared with H5N1 subtype strain.

Prepandrix should be used in accordance with official guidance.

The sponsor stated that the dataset in the dossier was the same as that used to support registration overseas.

Q-H5N1 has been approved in Canada (February 2013) with the following indications:

Arepanrix H5N1 is indicated for active immunization against influenza caused by the H5N1 subtype virus contained in the vaccine. This indication is based on immunological data as the vaccine has not been evaluated in efficacy trials against influenza disease (see Part II, Clinical Trials). Arepanrix H5N1 should be used according to official guidance.

Q-H5N1 has also been approved in the US (November 2013) with the following indications:

Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted is indicated for active immunization for the prevention of disease caused by the influenza A virus H5N1 subtype contained in the vaccine. Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted is approved for use in persons 18 years of age and older at increased risk of exposure to the influenza A virus H5N1 subtype contained in the vaccine.