SFDA - Draft Biosimilars Guideline for Public Comment until 30 June 2024

SFDA issued a draft guide for public comment until 30 June 2024: Guideline on Quality Considerations for Development and Comparability Assessment of Biosimilars (ncc.gov.sa).

The guideline lays down the Quality/ Quality/Chemistry, Manufacturing, and Control (Quality/CMC) considerations of the regulatory requirements for new marketing authorization applications (MAA) of a biosimilar.

This guideline addresses expected steps to be performed during biosimilar process and product development, to submit complete standalone Quality/CMC data for the Drug Substance (DS) and Drug Product (DP) of the biosimilar and comparative quality exercise (CQE) in the electronic common technical document (eCTD).

Updates and Addition in the Draft Guideline

This new version of the guideline proposes to include a number of additions and updates, including the following key points:

1. The proposed updated guideline clarifies the type of biological products that fall within and out of its scope:

The guideline provides information for MAA applicants of biosimilars, highlighting regulatory considerations for the development of biosimilars and the CQE required to establish the biosimilarity against the reference product.

The guideline applies to biopharmaceutical products that can be well defined and analytically characterized, such as polypeptides and proteins produced by biotechnology-based approaches.

Parts of the principle may be applied to polysaccharides, which are considered on a case-by-case basis. Vaccines and human plasma-derived products, animal tissue-derived products are excluded from the scope of this guideline. This guideline does not address safety and efficacy considerations for regulatory approval of biosimilars.

2. Adding to the SFDA regulatory basis of review and approval a section on Biosimilar Quality/Chemistry Manufacturing Control data:

The draft guide proposes the addition of a complete standalone Quality/CMC data (eCTD Quality Overall Summary of Module 2 and Module 3) should be provided in the submitted MAA dossier, including information on the drug substance (3.2.S) and drug product (3.2.P.) sections plus the Appendices (3.2.A) is required for the drug substance and drug product of the biosimilar, as detailed in the SFDA guidance “Data Requirements for Human Drugs Submission”.

The submitted standalone Quality/CMC data should be supplemented with CQE data demonstrating the comparability of biosimilar with the reference product (eCTD Module 3; 3.2.R), as discussed in the guideline.

3. Adding to the SFDA regulatory basis of review and approval a section on Extrapolation of Indication:

For the reference product with multiple indications, the SFDA may extrapolate the approval to indications other than those investigated in comparative clinical trials to the biosimilar, under the conditions mentioned in the draft guideline.

4. Updates have been made to the "comparative quality exercise between the biosimilar and the reference product" section.

5. Updates have been made to the "definition of reference product" section, for purposes of selecting the RP for use in the CQE:

Namely, an approved biosimilar from another marketing authorization holder (MAH) cannot be used as the reference product for the development and approval of a new biosimilar. Further, the reference product should: a) have an expired patent and data exclusivity rights; and b) have been marketed for suitable duration and patient experience in clinical practice and have well established safety and efficacy profile (but for biosimilars for orphan medicines, this will be considered by SFDA on a case-by-case basis).

If a biosimilars will be locally manufactured, the selection of the reference product is determined based on the development approach of the proposed biosimilars. The biosimilars is considered locally manufactured if full or part of biomanufacturing process including upstream and downstream step(s) are conducted. The secondary packaging only shall not qualify a biosimilars to be considered a locally manufactured.

Note that a partial development of a biosimilar based on leveraging or referencing drug substance or drug product processes described in a different MAA dossier of already approved biosimilar is not accepted by SFDA because biosimilars, like all biopharmaceutical products, require complete Quality/CMC data (Module 3) on the development and control of the drug substance and drug product manufacturing processes to ensure process consistency and product quality, safety and efficacy throughout lifecycle.

6. Significant updates and additions to the "biosimilar development paradigm: stepwise tailored approach" section

Finally, the greatest number of changes have been made to this section, adding requirements related to:

1. Considerations for Biosimilar Development, such as adding details on: a) Quality Target Product Profile; b) Drug Substance of Biosimilar; c) Drug Product of Biosimilar; d) Analytical Test Methods for Biosimilar; and
2. Considerations for Comparative Quality Exercise such as adding details on: a) Comparative Stability and Degradation; b) Selection and Identification of Batches of Reference Product and the Biosimilar, including Reference Product Batches and Biosimilar Batches; c) Use of Official Biological Product Reference Standards; and d) Statistical Approaches.

Public comments are due by 30 June 2024 here: Guideline on Quality Considerations for Development and Comparability Assessment of Biosimilars (ncc.gov.sa).