We will have limited operations from 15:00 Tuesday 24 December 2024 (AEDT) until Thursday 2 January 2025. Find out how to contact us during the holiday period.
Spikevax Bivalent Original/Omicron
Sponsor
ARTGs
389513
Device/Product name
Spikevax Bivalent Original/Omicron
Active Ingredient
Elasomeran and imelasomeran
Date of decision
Published
Submission type
New biological entity
ATC codes
J07BX03
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 was considered favourable for the therapeutic use approved.
What steps were involved in the decision process
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.
The following table summarises the key steps and dates for this application.
|
Description |
Date |
|
Determination (Provisional) |
27 April 2022 |
|
Submission dossier accepted and first round evaluation commenced |
22 June 2022 |
|
Evaluation completed |
16 August 2022 |
|
Delegate’s Overall benefit-risk assessment and request for Advisory Committee advice |
18 August 2022 |
|
Sponsor’s pre-Advisory Committee response |
19 August 2022 |
|
Advisory Committee meeting |
24 August 2022 |
|
Registration decision (Outcome) |
29 August 2022 |
|
Completion of administrative activities and registration on ARTG |
30 August 2022 |
|
Number of working days from submission dossier acceptance to registration decision* |
49 |
*Statutory timeframe for standard applications is 255 working days
Date of entry onto ARTG
Black triangle scheme
Yes. As a provisionally registered product, this medicine will remain in the Black Triangle Scheme for the duration of its provisional registration.
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
Pack sizes
10 x 5 mL multidose vials (0.1 mg/mL)
10 x 2.5 mL multidose vials (0.1 mg/mL)
10 x 2.5 mL multidose vials (0.1 mg/mL)
Routes of administration
Intramuscularly
Dosage
Individuals 18 years of age and older
Spikevax Bivalent Original/Omicron vaccine may be given at least 3 months following a primary series and /or previous booster dose with Spikevax (original) or another authorised/approved COVID-19 vaccine.
Each 0.5 mL dose of Spikevax Bivalent Original/Omicron COVID-19 vaccine 0.1 mg/mL contains 25 µg of elasomeran and 25 µg of imelasomeran embedded in lipid nanoparticles.
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.
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 (elasomeran and imelasomeran) was approved for the following therapeutic use:
Spikevax Bivalent Original/Omicron (elasomeran/imelasomeran) 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 18 years of age and older.
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
Elasomeran and imelasomeran contain mRNA encapsulated in lipid nanoparticles.
The messenger ribonucleic acid (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 COVID-19.
The messenger ribonucleic acid (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 COVID-19.
What post-market commitments will the sponsor undertake
- Spikevax Bivalent Original/Omicron COVID-19 Vaccine (elasomeran/imelasomeran) is to be included in the Black Triangle Scheme. The PI and [Consumer Medicine Information] CMI for Spikevax Bivalent Original/Omicron COVID-19 Vaccine must include the black triangle symbol and mandatory accompanying text for the product’s entire period of provisional registration.
- The Spikevax Bivalent Original/Omicron COVID-19 Vaccine EU-Risk Management Plan (version 4.2, dated 28 June 2022; DLP 27 April 2022), with Australia-Specific Annex (version 1.0, date 8 July 2022), included with submission PM-2022-02203-1, 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 (Rev 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 summary safety reports (including safety data for patients in Australia) are to be provided for the first 6 months post registration, and thereafter at intervals specified by the TGA.
Clinical Conditions
- Spikevax Bivalent Original/Omicron COVID-19 Vaccine:
- Submit the interim and final analysis of the pivotal studies P205 Part G and P205 Part F (cohort 2) and their CSR (Clinical Study Report) when available.
- Submit data on booster vaccine effectiveness of mRNA-1273.214 when available.
- Omicron BA.4/BA.5 neutralization assay validation report should be submitted when available.
- Existing conditions for Spikevax (original) 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.
Quality Conditions
- GMP clearance for listed manufacturers: All relevant manufacturing sites require approved and current GMP 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.
- Batch Release Testing and Compliance
It is a condition of registration that all independent batches of Spikevax Bivalent Original/Omicron (elasomeran and imelasomeran) 0.1 mg/mL suspension for injection vial imported into Australia are not released for sale until samples and the manufacturer’s release data have been assessed and you have 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, including all steps in production in the agreed format.
- At least 10 (ten) vials (samples) of each manufacturing batch of Spikevax Bivalent Original/Omicron (elasomeran and imelasomeran) 0.1 mg/mL suspension for injection vial 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 Original/Omicron (elasomeran and imelasomeran) 0.1 mg/mL suspension for injection vial 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-pr…]. 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.
Quality Commitments
- 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 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.