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Evaluation of biosimilars
The evaluation of biosimilars
General process and data requirements
Applications to register biosimilars are:
- managed through the Prescription Medicines Registration Process
- to be submitted in Common Technical Document (CTD) format.
Related information and guidance
- Pre-Submission Planning Form (PPF)
- Information for sponsors completing the PPF
- Mandatory requirements for an effective application
- General submission dossier requirements
- CTD module 1
- CTD modules 2,3, 4 and 5
- Risk management plan guideline
Related European Guidelines
The TGA has adopted a number of EU guidelines outlining data requirements specific to biosimilars as well as an ICH guideline on the assessment of comparability:
- CHMP/437/04: Guideline on similar biological medicinal products
- EMEA/CHMP/BWP/49348/2005: Guideline on similar biological medicinal products containing Biotechnology-Derived Proteins as Active Substance: Quality Issues
- CPMP/ICH/5721/03 ICH Topic Q 5 E: Comparability of Biotechnological/Biological Products Note for Guidance on Biotechnological/Biological Products Subject to Changes in their Manufacturing Process
- EMEA/CHMP/BMWP/42832/2005: Guideline on similar biological medicinal products Containing Biotechnology-Derived Proteins as Active Substances: Non-Clinical and Clinical Issues
- CHMP/BMWP/101695/2006: Guideline on Comparability of Biotechnology-Derived Medicinal Products after a change in the Manufacturing Process - Non-Clinical and Clinical Issues
- EMEA/CHMP/BMWP/14327/2006: Guideline on Immunogenicity Assessment of Biotechnology-Derived Therapeutic Proteins
- Product-specific guidelines detailing the clinical and safety data requirements
What to include in the application to register a biosimilar
- Provide the results of the studies outlined by the relevant guidelines above.
Provide:
- chemistry, manufacturing and quality control data (Module 3)
- preclinical data (Module 4)
- clinical data (Module 5)
- a Risk Management Plan.
Include the details of these in a PPF, and ensure that the SBMP box on the PPF is ticked.
Pre-submission meeting
If desired, it is possible to arrange a pre-submission meeting to discuss proposed biosimilar application with the relevant clinical evaluation unit of OMA prior to lodging the application.
The evaluation process for biosimilars
Once the PPF is accepted by the TGA, milestones are set by the TGA for the submission, evaluation, feedback and decision.
Evaluation of the CTD Modules
Modules 1-5 are evaluated simultaneously.
If reduced Module 4 and 5 datasets are submitted evaluation will commence on the assumption that the Module 3 data will demonstrate sufficient comparability of the proposed biosimilar to the reference product
If the Module 3 evaluation fails to demonstrate that the proposed biosimilar is sufficiently comparable to the reference product, the application may be:
- withdrawn, and
- resubmitted as a New Biological Entity (NBE) with full clinical and pre-clinical datasets.
If it is not withdrawn it is probable that the application will be rejected.
Note
Application and evaluation fees for the biosimilar will not be refunded if the application is withdrawn after completion of the first round evaluation.
Advisory committee advice about biosimilars
During the evaluation of a biosimilar application, the TGA may refer the application to the following advisory committees for advice:
- the Advisory Committee on Prescription Medicines (ACPM)
- the Pharmaceutical Subcommittee (PSC)
- the Advisory Committee on the Safety of Medicines (ACSOM).
Flowchart outlining possible outcomes of a biological medicine submission
Possible outcomes of a submission to register a biological medicine
This is a text only description of the flowchart image above.
When the sponsor applies for registration, if they elect to not use the biosimilar process, it is processed as a novel biological medicine or stand-alone. A full data set is submitted and evaluated and on the basis of that evaluation, the biological medicine is either approved or rejected.
If the sponsor elects to use the biosimilar process, an abridged submission with a comparability study is made and evaluated. The product may be approved or rejected as a biosimilar on the basis of the evaluation of the abridged data set.
If the comparability study is evaluated to show the biosimilar is not sufficiently comparable to the reference product, the sponsor may elect to withdraw the submission, lose the submission and evaluation fees and resubmit with a full data set as a novel biological medicine.