In August 2022, ANVISA published the Resolution – RDC No. 741, of August 10, 2022, which provides for the general criteria for the admissibility of analysis carried out by an Equivalent Foreign Regulatory Authority (AREE – acronym from the Portuguese “Autoridade Regulatória Estrangeira Equivalente”) in health surveillance processes before ANVISA, through an optimized analysis procedure. This regulation was a result of Public Consultation No. 1039/2021, which was open to contributions between April and June 2021.

This publication initiated the new Regulatory Framework on the reliance topic at ANVISA, which can be defined as a mechanism supported by mutual trust between Authorities that allows regulatory decisions taken by an AREE to be considered for regulatory approvals in Brazil, through an optimized procedure.

Therefore, ANVISA chose to publish the RDC containing some general requirements for the admissibility of these analyses by a Foreign Authority, and each technical area will have the autonomy to define its regulatory model for the selection of an AREE, through specific normative acts.

The RDC describes what the reliance practices will be between ANVISA and the foreign authorities (unilateral, bilateral, mutual recognition, among others), which aim to cover all areas of ANVISA’s activities, considering the different regulatory contexts of each area.

It also provides some clarifications on how the optimized analysis procedure, which will be based on the regulatory documentation prepared by AREE, will be implemented. However, it is important to highlight that, regardless of the documentation that will be submitted for the optimized analysis procedure, the applicant must submit the full technical and legal documentation provided for in current health regulations, unless exempted by any specific regulatory instrument.

Therefore, in addition to the specific conditions that will be presented in a specific regulatory dossier, the optimized analysis procedure must fulfill the following requirements:

• AREE must have a transparent management system guided by good regulatory practices;
• ANVISA’s Collegiate Board decision, considering the assessment of technical opinions prepared by the technical area and the organizational unit responsible for the coordination and supervision of international affairs, per their regulatory instruments, except for the AREE defined by ANVISA whose regulatory reliance practices already are in progress before this Resolution comes into effect;
• Forecast for AREE publication by ANVISA, according to each type of regulatory process or product category;
• The conditions for maintaining the admissibility of AREE;
• Provision for monitoring and reassessment, as well as revocation of the admissibility of the AREE by ANVISA’s Collegiate Board, when the conditions set out in this Resolution and in the respective regulatory instruments are not met.

RDC 741/2022 came into force on September 1, 2022.

Access RDC 741/2022 via the link: link.

Furthermore, in August 2022, ANVISA published the Public Consultation (PC) No. 1,108, of August 18, 2022, which provides a proposal for a Normative Instruction (NI) to establish the modalities and criteria applied for the optimized analysis procedure, in which the evaluations conducted by an AREE to analyze applications for marketing authorization (MA) and variation of medicinal products and biological products, and letter of suitability for active pharmaceutical ingredients (CADIFA, acronym from the Portuguese “Carta de adequação de insumo farmacêutico ativo”), throughout Brazilian territory. This draft refers to the first regulation to present the specific requirements for the acceptability of the analysis carried out by an AREE, as provided for in RDC 741/2022.

According to the PC, the NI proposal would be applicable to medicinal products, active pharmaceutical ingredients (API), and biological products and their active substances approved by at least one AREE. The AREE initially predicted for optimized analysis purposes are presented below:

• European Medicines Agency – EMA (centralized procedure processes), applicable to medicinal products and biological products;
• Canadian Health Agency – Health Canada, applicable to medicinal products and biological products;
• World Health Organization – WHO, applicable to API and medicinal products;
• European Directorate for the Quality of Medicines & HealthCare – EDQM, applicable to API;
• Swiss Agency for Therapeutic Products – Swissmedic, applicable to medicinal products;
• Medicines and Healthcare Products Regulatory Agency – MHRA, United Kingdom: applicable to medicinal products and biological products;
• United States Food and Drug Administration – FDA: applicable to medicinal products and biological products.

The PC also included the concept of “sameness” which is considered a starting point for a given product to be eligible for the MA/variation process optimized analysis by ANVISA. According to the draft, “sameness” are attribute of the medicinal product and biological product that covers their manufacturers, qualitative and quantitative composition, strength, pharmaceutical form, therapeutic indications, contraindications, dosage, target population, route of administration, mode of use, specifications, manufacturing process and respective production plants involved, API manufacturers and quality grades of API and excipients.

After being considered eligible based on essential characteristics, the product could be classified in one of the categories below:

With the categorization, the type of analysis would be defined: verified analysis (degree of analysis 2, that is, summary verification of the dossier considering the applicability of the results of the assessment made by another authority concerning the national context) or abbreviated analysis (degree of analysis 3, that is, simplified assessment of data on quality, safety and efficacy and performance, taking into account the information available in the full AREE regulatory documentation).

The PC did not present the concepts of degrees of analysis such as considered in the definitions of verified analysis and abbreviated analysis. These are presented, however, in Technical Note No. 209/2022/SEI/GGMED/DIRE2/ANVISA, published together with the draft for PC. These levels are aligned with the WHO Good Reliance Practices Guideline – Annex X.

An important point of this draft is that specific regional conditions will always be evaluated via the regular procedure.

The PC was open for contributions from August 31 to September 15, 2022, and is available via the link.

In September 2022, ANVISA published the Resolution – RDC No. 750, of September 6, 2022, which established a temporary optimized analysis procedure, in which analyses conducted by AREE are used for the verified analysis of applications for MA and variation of medicinal products, biological products, and their active substances, and CADIFA, filed before ANVISA after the entry into force of Law No. 13,411, of December 28, 2016. This was yet another piece of legislation related to reliance in Brazil and was published to reduce the backlog of the agency’s analysis queues.

RDC 750/2022 applied to applications that were under analysis or awaiting analysis and to those that will be filed before ANVISA during the term of the Resolution, provided that they had not yet been subject to additional technical requirements.

For an application to benefit from the temporary optimized analysis procedure, in addition to sending the complete documentation established for the respective regulatory category, the following documents would need to be presented, through a specific addendum:

• Completed checklist (Annex I of the Resolution) for medicinal products or biological products;
• Completed checklist (Annex II of the Resolution) for API;
• Proof of regularization granted by the AREE, in force at the time of the application;
• List of all documents submitted in the initial application and in the specific amendment, differentiating those that were previously evaluated by AREE from those that were prepared for the Brazilian context;
• Regulatory documentation, issued by AREE, that meets the provisions of Article 8 of RDC 750/2022; and
• The report containing the evaluation of the documentation provided for in Article 8 and, additionally, demonstrating that the medicinal product or biological product and its active substances, subject to the regularization request, have essential characteristics equivalent to those approved by the AREE.

Therefore, to submit this documentation, ANVISA made the following subject codes available:

• For biological product: 12206 – GGBIO – Temporary optimized analysis procedure (RDC 750/2022);
• For API or synthetic or semi-synthetic medicinal products: 12205 – GGMED – Temporary optimized analysis procedure (RDC 750/2022).

The recognized AREE, for the temporary optimized analysis procedure, was the same as those mentioned in the PC 1,108/2022 (see above) and applications that fit the criteria established in the resolution would be subjected to analysis verified by ANVISA.

RDC 750/2022 came into force on September 19, 2022, and was valid for 6 months, that is, until March 18, 2022. However, during the ANVISA Collegiate Board Meeting, which took place on March 16, 2023, when the extension was approved, making it effective until March 31, 2024.

The new Resolution RDC No. 781, of March 16, 2023, which amended RDC 750/2022, was published on March 17, 2023, and came into force on the date of its publication.

It is important to highlight that this resolution was published temporarily and its validity was conditioned on the publication of the specific Normative Instruction on the subject, proposed by CP 1.108/2022. As soon as this is published, RDC 750/2022 will be revoked.

After a long period of public consultation, discussions with the regulated sector, and evaluation of the experiences obtained with the application of RDC 750/2022, on March 25, 2024, ANVISA published the Normative Instruction – NI No. 289, of March 20 March 2024, which establishes, under the Resolution – RDC nº 741, of August 10, 2022, the criteria applied for the optimized analysis procedure in which assessments conducted by an Equivalent Foreign Regulatory Authority (AREE) are used for the analysis of applications for MA and variation of medicinal products, biological products, vaccines and letter of the adequacy of active pharmaceutical ingredient dossier (CADIFA) in the Brazilian territory. This is the definitive regulation, the result of CP 1.108/2022. (updated on 04/01/2024)

Among the main differences identified between the draft CP 1,108/2022 and the official publication of IN 289/2024, the following may be listed:

• Inclusion of vaccines within the scope of NI.
• Exclusion of the need to carry out studies that demonstrate therapeutic equivalence in centers certified by ANVISA, if the nationally chosen reference medicine is used.
• Exclusion of categories A, B, and C and evaluation through “Abbreviated Analysis”.
• Exclusion of deadlines for ANVISA to evaluate applications submitted via the optimized analysis procedure, observing the same deadlines defined by Law 13,411 (note that this is not a priority application).
• Possibility of resubmitting applications rejected under RDC 750/2022, so that they can be reevaluated according to the new NI.
• Forecast regarding applications submitted during the validity of RDC 750/2022, which will be evaluated according to the resolution.
• Inclusion of vaccines in the scope of products approved by AREEs EMA, Health Canada, WHO, SwissMedic (also included biological products), MHRA, and FDA.
• Exclusion of the need to present checklist documentation, in the case of using the CEP (Certification of Suitability to the monographs of the European Pharmacopoeia) to request the optimized analysis procedure, issued by EDQM (European Directorate for the Quality of Medicines & HealthCare).
• Inclusion of the AREE TGA (Therapeutic Goods Administration – Australia) applicable to medicinal products, vaccines, and biological products.

IN 289/2024 came into force on April 01, 2024, while RDC 750/2022 ended its validity period on March 31, 2024.

Access IN 289/2024 via the link: ACCESS.

On April 15, 2024, ANVISA published the new application subjects and codes for MA and variation for medicinal products, biological products, vaccines, and CADIFA, using assessments conducted by an AREE.

The following application subject codes are established:

• 12275 – GGBIO – Amendment to apply for the MA-optimized analysis procedure
• 12276 – GGBIO – Amendment to apply for safety and efficacy variation optimized analysis procedure
• 12277 – GGBIO – Amendment to apply for CMC variation optimized analysis procedure
• 12278 – GGMED – Application for the optimized analysis procedure for the safety and efficacy of synthetic medicinal products
• 12279 – GGMED – Application for the optimized analysis procedure for CMC of synthetic medicines
• 12280 – GGMED – Application for the optimized analysis procedure for relative bioavailability
• 12281 – GGMED – Application for the optimized analysis procedure for Herbal, Specific or Dynamic Medicinal Products
• 12282 – GGMED – Application for the optimized analysis procedure for impurity qualification
• 12283 – CADIFA – Application for optimized analysis procedure

With this publication, previously used application subjects relating to the temporary resolution – RDC 750/2022 (codes 12205, 12206, 12223, and 12246) become inactive.

The news can be accessed via the link.