Australia's Therapeutic Goods Administration (TGA) has released guidelines for biosimilar drug applications, with data requirements based on European Medicines Agency (EMA) and International Conference on Harmonization standards. The guidance is issued in addition to the existing EMA guidelines on biosimilars evaluation that have been used by the TGA for biosimilar applications since 2008.
IHS Global Insight perspective | |
Significance | The TGA's biosimilars guidelines, released on 30 July, provide a definition of biosimilars, data requirements for comparability studies, rules on extrapolation, post-registration and pharmacovigilance rules, as well as naming conventions for biosimilar products. |
Implications | The guidelines remain closely based on the EMA's pathway, and include a number of the latter's guidelines verbatim. |
Outlook | With the EMA's guidance already the basis for the TGA's review of biosimilars, the release will not have any immediate effect on drug registration, but provides a clearly defined Australian pathway with the government likely to encourage greater use of biosimilars in the future. |
Australia's Therapeutic Goods Administration (TGA) has released a guidance document on the data requirements for the registration of biosimilars, referring to all products containing biotechnology-derived proteins as the active substance, as well as vaccines, monoclonal antibodies (mAbs), and polysaccharides, such as low molecular-weight heparins. It provides an outline of the scientific and regulatory principles to be applied. The TGA had previously adopted the European Medicines Agency (EMA)'s biosimilars pathway rules in 2008, and the current guidance is issued in addition to those rules.
Biosimilar definition, comparability study requirements
The TGA adopts the term "similar biological medicinal product" (SBMP) from the European Union guidelines, and defines a biosimilar as imitating an already registered biological medicine that "has a demonstrable similarity in physicochemical, biological and immunological characteristics, efficacy and safety, based on comprehensive comparability studies", and "has been evaluated by the TGA according to this guideline and other relevant EU guidelines adopted by the TGA".
The reference product must be registered in Australia and marketed for a "suitable duration and have a volume of marketed use so that there is likely to be a substantial body of acceptable data regarding the safety and efficacy". For reference products registered in Australia but manufactured overseas, a bridging comparability study between the Australian-sourced product and all batches of the reference product is required. The data requirements for comparability studies follow EU and International Conference on Harmonization (ICH) guidelines verbatim. Where a registration fails to prove comparability, the application can be withdrawn, or re-filed as a novel biologic entity.
EU rules on extrapolation adopted
The guidance adopts the same standards on extrapolation as the EU, stating that, in cases where the reference product is approved for more than one indication, the biosimilar must prove safety and efficacy in each of those indications. However, it does allow for extrapolation of therapeutic similarity across indications "in certain cases", depending on "clinical experience, available literature data, whether or not the same mechanisms of action or the same receptor(s) are involved in all indications" (see Europe: 11 June 2013: EMA issues revised guideline on biosimilars containing biotechnology-derived proteins for consultation).
Post-registration and pharmacovigilance
The guidance also outlines requirements related to post-registration regulations and pharmacovigilance, which are the same as those applied to novel biologics. This means that biosimilars are placed on batch release as a condition of registration, meaning that all batches are tested by the TGA until consistency has been demonstrated.
In terms of pharmacovigilance, drug companies must develop a comprehensive Risk Management Plan outlining procedures that will be in place to meet Australian and EU guidelines, including reporting of safety updates and adverse events to the TGA.
Biosimilar naming conventions
The guidance sets out conventions for naming biosimilars registered in Australia. A biosimilar's Australia Biological Name (ABN) must include the reference product's active ingredient, along with a biosimilar identifier: the prefix "sim-" plus a three-letter code issued by the World Health Organization (WHO) International Non-proprietary Name (INN) Committee. The product's trade name must be clearly distinguishable from the reference and other biosimilar products. For a link to the TGA's page on data requirements, see here, and for the biosimilars guidance home page, see here.
Outlook and implications
The Australian government has a low level of data protection for novel biologics in place relative to OECD peers, with only five years' exclusivity compared with 10 in Europe and 12 in the United States. Nevertheless, relatively few biosimilars have been approved in Australia, with only one epoetin alpha and three filgrastim biosimilars passed by the TGA – a factor of the relatively small market.
The TGA's release of guidelines puts in place a more clearly defined biosimilars pathway, the agency having relied since 2008 on a number of the EMA's biosimilars guidelines. The rules on extrapolation are particularly relevant for mAb biosimilar products, with Australia following Europe's lead. The EU's first approval for a mAb biogeneric earlier this year – for Celltrion (South Korea)'s Remsima (inflixmab) and Hospira (US)'s Inflectra, copies of Johnson & Johnson (US)'s Remicade – included extrapolation to all of the reference product's indications (see Europe: 1 July 2013: EMA's CHMP recommends 10 drugs for MAA, positive opinion granted to first two biosimilar mAbs).
The TGA's naming conventions for biosimilars may potentially slow uptake, as the demand for differentiated INN for biosimilars prevents pharmacists from freely substituting. This means that prescribing physicians in Australia must specifically name a biosimilar, and are therefore responsible for increased biosimilars prescribing. It should be noted that three of the filgrastim biosimilars have been permitted identical INNs due to the absence of glycosylation and an identical amino acid sequence, and therefore can be freely substituted.