1. Technical Note about Biological Products
October 19, 2011
Due to the recent end of several patents for innovative biotechnological
products, the interest in producing and selling copies of these products has
been growing in Brazil and in the world.
In Brazil, domestic producers have great interest in this market and have been
investing heavily.
Biotechnological products are included in different government programs and
since they are high value added and high cost products, they consume a
significant portion of the health budget. Thus, the Brazilian government has
great interest in making biotechnological products increasingly more available in
the market so the access can be expanded, always aware of efficacy and safety
issues.
In this sense, since 2009 several issues related to biotechnological products,
whether innovative or not, and the increase in domestic production capacity for
them, have been discussed in the Executive Group of the Health Industrial
Complex (GECIS).
The diverse needs pointed out in this group include the need for review of the
regulatory framework to register the biological products, the category in which
biotechnological products are classified in Brazil.
Thus, since 2009, review of the RDC 315/05, the regulatory framework for
registering biological products in Brazil at the time, began to be discussed within
the ambit of the GECIS and internally at ANVISA.
Based on this study, Public Consultation 49/2010 was published in May 2010
with the proposal to review the regulatory framework for registering
biotechnological products. The Public Consultation process extended to
December 2010 with broad participation by the national production sector,
including holding a technical meeting to discuss the contributions made during
the public consultation process. The meeting of the Collegiate Board for
deliberating on norm publication also included the presence of representatives
from the national production sector.
RDC no. 55/2010 was published in December 2010. It is currently the regulatory
framework for registering biological products, whether innovative or not.
In order to elaborate RDC 55/10, regulatory frameworks and guidelines from
different agencies in the world were considered, such as Health Canada
(Canada), EMA (Europe), CECMED (Cuba), KFDA (Korea) and the guideline

2. published by the World Health Organization (WHO) specifically for registering
similar biotherapeutic products (WHO SBP guideline).
According to the RDC 55/2010, there are two biological and biotechnological
products in Brazil. The innovative products are called new biological products
and the copies are called biological products.
New biological products should be registered through the classical regulatory
manner, with presentation of a complete report, with all production and quality
control data and complete nonclinical and clinical data (Phase I, II and III).
For biological products, that is, non-innovative products, there are two possible
regulatory paths for registration: the development copy for comparison path and
Individual development copy path. In these two paths, it is possible to present a
registration report with reduced information.
In the individual development path, the product is compared to the biological
product used for comparison (new biological product registered based on a
complete report), including its cellular origin, production process, quality
parameters and nonclinical and clinical studies. In this case, data for
comparison are presented between the biological product intended for
registration and the biological product used for comparison, and based on the
results, the nonclinical and clinical development paths can be simplified. Use of
the development copy by comparison path also enables extrapolation of
therapeutic indications. The development copy by comparison path permitted
internalizing guidelines found in the WHO SBP Guideline.
For non-innovative products, based on already existing and successful
experiences in Brazil, there is a second regulatory path, the individual
development copy, used in cases where there are differences between the
biological product intended for registration and the biological product for
comparison which do not permit using the classical path for checking
comparability. In this case, the producer can carry out the technological
development of its product with production data, quality control and nonclinical
and clinical Phase I and II studies on a non-comparison basis and their
extension can be increased or decreased according to the molecule’s
complexity and specific characteristics. In the development copy by comparison
path it will be necessary to conduct a Phase III Study of comparison of
equivalence or non-inferiority with the biological product used for comparison
and the extrapolation of therapeutic indications is not conducted.
We believe the new regulation proposed for registering biological products in
Brazil, RDC55/10, will provide the legal and scientific guidelines needed for
developing copies of biological products in Brazil and will close some previously
existing regulatory loopholes since it contains specific regulatory paths for
registering non-innovative biological products.

3. Throughout 2011, ANVISA’s Biological Product Registration and Clinical
Research Offices have conducted several meetings with different domestic
industries to monitor nonclinical and clinical development of biological products.
Additional regulatory needs were detected during this monitoring program.
Thus, in order to improve technical and regulatory frameworks, CPBIH/ANVISA
elaborated four specific technical guidelines: GUIDELINE FOR EXERCISING
COMPARABILITY STUDIES FOR REGISTERING BIOLOGICAL PRODUCTS;
GUIDELINE FOR ELABORATING CLINICAL STUDY REPORTS FOR
REGISTRATION PURPOSES AND/OR FOR POST-REGISTRATION
AMENDMENTS OF BIOLOGICAL PRODUCTS; GUIDELINE FOR
REGISTERING HEPARINS USING THE COMPARISON PATH; GUIDELINE
FOR REGISTERING ALPHA INTERFERON USING THE COMPARISON
PATH. The guidelines are available on the ANVISA website, clicking on the
biological products link. Another important action was to provide a complete
regulatory framework for registering biological products, including the RDC
55/10 registration and RDC 49/2011 post-registration norms, among other
RDCs needed for registration and post-registration of biological products.
Publication of the legal bases for registering biological products was conducted
in partnership with ABDI and will also be available in electronic format on the
ANVISA website, on the biological products link.
Another important initiative will be the creation of the Technical Chamber for
Biological Products (CATEBIO), in accordance with the resolution approved at a
meeting of the Anvisa Collegiate Board on October 19, 2011. The resolution will
be published in the Official Federal Gazette. CATEBIO is a collegiate board of
an advisory nature technically tied to the Biological Product and Registration
Office (CPBIH), of the Efficacy and Safety Evaluation Office (GESEF) and the
General Management of Medications (GGMED), comprised of specialists with
renowned knowledge in the clinical and biotechnological area, free of any
conflict of interest. At CATEBIO, specific themes such as the development and
registration of biological products as well as broader issues such as establishing
guidelines and elaborating guidelines by product category will be discussed.
Over recent months, Anvisa’s major focus in the biological product area has
been to monitor the development of copies of monoclonal antibodies by national
and international industries. Thus, publication of a specific guideline on the
theme is projected for 2012.