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Spikevax bivalent Original/Omicron BA.4-5

Device/Product name
Spikevax bivalent Original/Omicron BA.4-5
Active Ingredient
Elasomeran and davesomeran
Date of decision
Published
Submission type
New biological entity
ATC codes
07BX03
Decision
Approved for provisional registration
What was the decision based on
The decision was based on quality (chemistry and manufacturing), nonclinical (pharmacology and toxicology), clinical (pharmacology, safety and efficacy) and risk management plan information submitted by the sponsor. The benefit-risk profile of Spikevax bivalent Original/Omicron BA.4-5 COVID-19 vaccine was considered favourable for the therapeutic use approved.
What steps were involved in the decision process

Registration timeline

The following table summarises the key steps and dates for this application.

Data were provided as a rolling submission. Under normal circumstances, TGA's assessment (for both provisional and general registration) begins once all information to support registration is available. As part of the Department of Health's response to the pandemic, the TGA has agreed to accept rolling data for COVID-19 vaccines and treatments, to enable early evaluation of data as it becomes available.

Description

Date

Determination (Provisional)

28 September 2022

Submission dossier accepted and first round evaluation commenced

18 November 2022

Evaluation completed

31 January 2023

Delegate’s Overall benefit-risk assessment and request for Advisory Committee advice

2 February 2023

Sponsor’s pre-Advisory Committee response

6 February 2023

Advisory Committee meeting

9 February 2023

Registration decision (Outcome)

17 February 2023

Completion of administrative activities and registration on ARTG

20 February 2023

Number of working days from submission dossier acceptance to registration decision*

59

*Statutory timeframe for standard applications is 255 working days

Date of entry onto ARTG
Dose forms
Suspension for injection
Strength
0.1 mg/mL
Other ingredients

Heptadecan-9-yl 8-[2-hydroxyethyl-(6-oxo-6-undecoxyhexyl)amino]octanoate, cholesterol, distearoylphosphatidylcholine, 1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000, trometamol, trometamol hydrochloride, acetic acid, sodium acetate trihydrate, sucrose, water for injections

Containers
Multidose vial and pre-filled syringe

Pack sizes
10 multiple dose vials
10 pre-filled syringes
Routes of administration
Intramuscular
Dosage

Individuals 12 years of age and older

One dose of Spikevax bivalent Original/Omicron BA.4-5 (50 µg/0.5 ml) may be given at least 3 months following a primary series and/or previous booster dose with Spikevax (original), Spikevax bivalent Original/Omicron (BA.1) or another authorised/approved COVID-19 vaccine, in accordance with official recommendations.

For further information refer to the Product Information.

Pregnancy category
B1
Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed.
Studies in animals have not shown evidence of an increased occurrence of fetal damage.
The use of any medicine during pregnancy requires careful consideration of both risks and benefits by the treating health professional. This must not be used as the sole basis of decision making in the use of medicines during pregnancy. The TGA does not provide advice on the use of medicines in pregnancy for specific cases. More information is available from obstetric drug information services in your State or Territory.
What was approved

Spikevax bivalent Original/Omicron BA.4-5  (elasomeran and davesomeran) was approved for the following therapeutic use:

The provisionally approved new indication(s) for the medicine(s) are:

Spikevax bivalent Original/Omicron BA.4-5 (elasomeran and davesomeran) COVID-19 vaccine has provisional approval for the indication below:

As a booster dose for active immunisation to prevent coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 in individuals 12 years of age and older who have previously received at least a primary vaccination course against COVID-19.

The use of this vaccine should be in accordance with official recommendations.

The decision has been made on the basis of immunogenicity and short-term safety data. Continued approval depends on the evidence of longer term benefits and safety from ongoing clinical trials and post-market assessment.

What is this medicine and how does it work
Spikevax (original) (elasomeran) and Spikevax bivalent Original/Omicron (BA.1) (elasomeran/imelasomeran) both contain messenger ribonucleic acid (mRNA) encapsulated in lipid nanoparticles. The mRNA encodes for the full-length severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein modified with 2 proline substitutions within the heptad repeat 1 domain (S-2P) to stabilise the spike protein into a prefusion conformation. After intramuscular injection, cells at the injection site and the draining lymph nodes take up the lipid nanoparticle, effectively delivering the mRNA sequence into cells for translation into viral spike protein. The delivered mRNA does not enter the cellular nucleus or interact with the genome, is nonreplicating, and is expressed transiently mainly by dendritic cells and subcapsular sinus macrophages. The expressed, membrane-bound spike protein of SARS-CoV-2 is then recognised by immune cells as a foreign antigen. This elicits both T-cell and B-cell responses to generate neutralising antibodies, which may contribute to protection against coronavirus disease 2019 (COVID-19).
The nucleoside-modified mRNA in Spikevax bivalent Original/Omicron BA.4-5 (elasomeran/davesomeran) is formulated in lipid particles, which enable delivery of the nucleoside-modified mRNA into host cells to allow expression of the SARS-CoV-2 S antigen. The vaccine elicits an immune response to the S antigen, which protects against COVID-19.
What post-market commitments will the sponsor undertake
  • Spikevax bivalent Original/ Omicron BA.4-5 (elasomeran/davesomeran) is to be included in the Black Triangle Scheme. The PI [Product Information] and CMI [Consumer Medicines Information] for Spikevax bivalent Original/ Omicron BA.4-5 must include the black triangle symbol and mandatory accompanying text for five years, or the product’s entire period of provisional registration, whichever is longer.
  • Any changes to which the sponsor has agreed should be included in a revised RMP [risk management plan] and ASA [Australia specific annex]. However, irrespective of whether or not they are included in the currently available version of the RMP document, the agreed changes become part of the risk management system.

The Spikevax bivalent Original/ Omicron BA.4-5 EU [European Union]-risk management plan (RMP) (version 6.3, dated 6 December 2022, data lock point 17 September 2022), with Australia specific annex (version 1.2, dated 20 December 2022), included with Submission PM-2022-04824-1-2, and any subsequent revisions, as agreed with the TGA will be implemented in Australia.

An obligatory component of risk management plans is routine pharmacovigilance. Routine pharmacovigilance includes the submission of periodic safety update reports (PSURs).

Unless agreed separately between the supplier who is the recipient of the approval and the TGA, the first report must be submitted to TGA no later than 15 calendar months after the date of the approval letter. The subsequent reports must be submitted no less frequently than annually from the date of the first submitted report until the period covered by such reports is not less than three years from the date of the approval letter, or the entire period of provisional registration, whichever is longer.

The reports are to at least meet the requirements for PSURs as described in the European Medicines Agency’s Guideline on Good Pharmacovigilance Practices (GVP) Module VII-periodic safety update report (revision 1), Part VII.B Structures and processes. Note that submission of a PSUR does not constitute an application to vary the registration. Each report must have been prepared within ninety calendar days of the data lock point for that report

Additional to the routine submission of the routine PSURs, expedited monthly safety summary reports (including safety data for patients in Australia) are to be provided for the 6 months from the date of first supply in Australia, and thereafter at intervals specified by the TGA.

Clinical Conditions

  • Submit the interim and final analysis of the pivotal studies mRNA-1273-P205 Part H and mRNA-1273-P205 Part F (cohort 2) and their CSR (Clinical Study Report) when available.
  • Data on booster vaccine effectiveness of mRNA-1273.222 when available.
  • Existing Conditions for Spikevax remain.

Confirmatory trial data (as identified in the sponsor’s plan to submit comprehensive clinical data on the safety and efficacy of the medicine before the end of the 6 years that would start on the day that registration would commence) must be provided.

Toxicology Conditions

  • Updated reports of study MOD-045EXP and WASHU-K18-89 are to be provided by the end of April 2023.

Quality Conditions

  • GMP clearance for listed manufacturers: All relevant manufacturing sites require approved and current GMP [Good Manufacturing Practice] Clearances prior to Australian supply. A commitment is required from the sponsor that they maintain the validity of all manufacturer GMP Clearances for the duration of product supply to Australia. Additionally, that adherence to the conditions of GMP Clearance approval is upheld.
  • Post-approval stability protocol and stability commitment: The manufacturer has provided commitment to continue the ongoing stability studies presented in the stability studies protocol. Additionally, 1 batch of DP [drug product] per year for all relevant products will be placed on long-term stability program and on accelerated stability testing where significant changes are made to the manufacturing process. The manufacturer has committed to communicate any out of specifications stability test results to the TGA.
  • Batch Release Testing and Compliance

It is a condition of registration that all independent batches of Spikevax bivalent (elasomeran and davesomeran) 0.1 mg/mL suspension for injection vial and pre-filled syringe imported into Australia are not released for sale until samples and the manufacturer’s release data have been assessed and the sponsor has received notification acknowledging release from the Laboratories Branch, TGA.

For each independent batch of the product imported into Australia, the sponsor must supply the following:

    • A completed Request for Release Form, available from vaccines@health.gov.au.
    • Complete summary protocols for manufacture and QC [quality control], including all steps in production in the agreed format.
    • At least 10 (ten) vials (Samples) of each manufacturing batch of Spikevax bivalent (elasomeran and davesomeran) 0.1 mg/mL suspension for injection vial and pre-filled syringe with the Australian approved labels, PI and packaging (unless an exemption to supply these has been granted) representative of all batches of product seeking distribution in Australia.
    • At least 5 (five) vials (Samples) of any further consignments of a manufacturing batch of Spikevax bivalent (elasomeran and davesomeran) 0.1 mg/mL suspension for injection vial and pre-filled syringe with the Australian approved labels, PI and packaging (unless an exemption to supply these has been granted). Further consignments cover batches previously supplied to TGA for the purposes of batch release testing but are seeking to be supplied again.
    • If the manufacturing batch has been released in Europe or United Kingdom a copy of the EU Official Control Authority Batch Release (OCABR) certificate (or equivalent from the UK) must be provided.
    • Any reagents, reference material and standards required to undertake testing, as requested by Laboratories Branch, TGA.

Sponsors must provide all requested Samples and data in sufficient time (at least 5 business days) prior to any distribution date to allow the TGA to perform testing and review. Distribution of each batch of vaccine is conditional upon fulfilment of these conditions and receipt of a letter from the Laboratories Branch acknowledging release.

Samples and data should be forwarded to the Biotherapeutics Section, Laboratories Branch before release of each batch and with sufficient lead time to allow for Laboratories Branch testing.

The shipments (including reagents) to TGA are the responsibility of the Australian Sponsor/Agent who will be required to facilitate the import and customs clearance process.

  • Certified Product Details

An electronic copy of the Certified Product Details (CPD) as described in Guidance 7: Certified Product Details of the Australian Regulatory Guidelines for Prescription Medicines (ARGPM) https://www.tga.gov.au/guidance-7-certified-product-details should be provided upon registration of the therapeutic good. In addition, an updated CPD, for the above products incorporating the approved changes is to be provided within one (1) month of the date of approval letter. A template for preparation of CPD for biological prescription medicines and Vaccines can be obtained from the TGA website https://www.tga.gov.au/form/certified-product-details-cpd-biological-prescription-medicines]. The CPD should be sent as a single bookmarked PDF document to Vaccines@health.gov.au as soon as possible after registration/approval of the product or any subsequent changes as indicated above.

  • For all injectable products the Product Information must be included with the product as a package insert.

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