Brazil - Biologics Specifics Variation Requirements

Regulations and Guidelines

Biologics Post-approval regulation

(in force since 4-Jan- 2021)

RDC n° 413/2020

Provides for post-approval changes and deregistration of biological products.

· CMC changes are classified as major, moderate, minor and without impact. Major and moderate changes require prior approval for implementation. Minor changes can be immediate implementation and should be reported in the annual report.

IN n° 65/2020

Regulates the classification of post-approval changes, conditions and technical documents necessary to support post-registration change requests and deregistration of biological products

· For changes requiring comparative data (IPC, release) please provide them as part of SUCH document of the variation package

Biologics Stability regulation

(in force since 4-Jan-2021)

RDC 412/20

Establishes the requirements and conditions for carrying out stability studies for the purposes of registration and post-registration changes of biological products

Highlights about this new regulation

1. Shelf life will be defined based on actual data from the long-term stability study. It means long-term stability study presented during the registration application must be completed. Batches can be on a commercial or pilot scale.

2. In exceptional situations, in the case of non-protein/non-polypeptide molecules, with the exception of active substances and vaccine intermediates, the determination of the expiration date can be based on the ICH Q1A (R2) and Q1E guides and their updates.

3. When data from batches on a pilot scale are used for registration purposes, a commitment that the long-term stability data of the first 3 (three) batches produced on a commercial scale must be presented to Anvisa (Annual Report).

4. All post-registration changes that require stability studies must follow RDC No. 413/20.

5. It is established conditions for the cycling study design that will be needed to support excursions during transport.

6. Stability study of the reference standard (characterized material used as a reference for evaluating batches) to support the expiration date or retest date must be provided