On July 29th, 2020, two new Brazilian pharmacovigilance regulations, the resolution RDC 406/2020 and normative instruction IN 63/2020, were published by Anvisa as part of the agency’s effort to harmonize the regulations with ICH and with EMA guidelines.

The RDC 406/2020 provides information about Good Pharmacovigilance Practices and establishes the requirements, responsibilities and work standards to be observed by all Marketing Authorization Holders (MAHs) in Brazil. The new rules under this directive are effective from October 27th, 2020. This regulation is not applied to Clinical trials.

The IN 63/2020 provides information regarding Periodic Benefit-Risk Evaluation Report (PBRER) to be submitted to Anvisa by the MAHs. These guidelines are effective from October 27th, 2020.

The most significant changes brought by these two new documents are to the structure of risk management plan (RMP), to the PBRER schedule, reporting of individual case safety reports (ICSR) and to the outsourcing and delegation of the local pharmacovigilance activities.

RMP content

When required by the risk-benefit profile of the product, the Risk Minimization Plan must be prepared and submitted to Anvisa as part of the Risk Management Plan when there are important identified risks with additional actions. The RMP describes how the risks in question are to be managed. The Risk Minimization Plan now includes the routine actions of the pharmacovigilance plan and additional measures.

The risk minimization plan can be requested by Anvisa in case it has not been provided previously. The Risk Minimization Plan can be submitted at the time of registration, or at any time, in cases where the drug has already been authorized.

Anvisa has not published their own template for the RMP. For most of the MAHs this update should not create much of a challenge as they have probably already been providing a similar document in other markets.

PBRER schedule

There are changes to the procedure for submitting PBRERs and to the review procedure by Anvisa. The PBRERs are no longer associated with the date of registration of the product in Brazil and will be linked to the date of the international registration of a drug or combination of drugs (international birth date).

The frequency of the PBRERs will follow the schedule published on the Anvisa Portal. The schedule is based on the list proposed by the EMA. The schedule is not available at the time of writing this.

The PBRER shall be submitted to Anvisa, respecting the periodicity made available on the Anvisa Portal. The interval between the closing date of the database and the submission of the PBRER is set as follows:

I – 70 (seventy) days, for PBRER with a periodicity of up to 12 (twelve) months;

II – 90 (ninety) days, for PBRER with a period exceeding 12 (twelve) months; and

III – 90 (ninety) days, for exceptional PBRER, unless another period is determined by Anvisa.

The frequency of the reports for each drug or combination will be determined by the risk analysis associated with its use.

Anvisa has communicated that this change should reduce the number of reports, increase the amount of data shared between countries and speed up their review process.

ICSR submission

The ICSRs shall be reported through the VigiMed database. Anvisa is performing the database migration from NOTIVISA to VigiMed gradually, company by company during late October. The MAH shall appoint a manager for VigiMed who is responsible for adding and managing the system accesses for other users of their company.

For Brazilian ICSRs only, the following is required: all serious AEs should be reported regardless of the reporter source (consumer, health professional, spontaneous, requested, etc.) within 15 calendar days.

MedDRA coding of adverse events shall be used. Those MAHs that are still using WHO-ART to code the events, should replace it with MedDRA.

QPPV employment

The Brazilian QPPV and their deputy can no longer be outsourced to a subcontractor. They shall be employees of the MAH.

However, the MAH may delegate to third parties the performance of any other pharmacovigilance activities (f.e. screening of non-indexed local language journals), as long as the responsibilities are clearly and descriptively documented. The contractual documentation shall define who is involved in each pharmacovigilance activity.