RESOLUTION – RDC N° 205, OF DECEMBER 28, 2017
Establishes special procedure for consent of clinical trials, certification of good manufacturing practices and registration of new drugs for treatment, diagnosis or prevention of rare diseases.
The Collegiate Board of Directors of the National Health Surveillance Agency, compliant with the assignment conferred to it by art. 15, III and IV, combined with art. 7th, III, and IV, of Law nº 9.782, of January 26, 1999, and art. 53, V, §§ 1st and 3rd of Bylaws approved under the terms of Annex I of the Collegiate Board Resolution – RDC n° 61, of February 3, 2016, decides to adopt the following Collegiate Board Resolution, as deliberated in meeting held on December 12, 2017, and I, Executive-Officer, determine its publication.
CHAPTER I
Initial Dispositions
Art. 1st The special procedure is approved for:
I – consent of clinical trials to be carried out in Brazil for assessment of drugs for rare diseases;
II – certification of good manufacturing practices applicable to drugs for rare diseases; and
III – sanitary registration of new drugs for rare diseases.
Art. 2nd This resolution applies to new drugs for rare diseases.
Art. 3rd For the purposes of this Resolution the following definitions will be adopted:
I – rare disease: disease that affects up to sixty five persons in each one hundred thousand individuals, as defined by the National Policy for Comprehensive Healthcare of Persons with Rare Diseases, based on official national data or, when inexistent, on data published in technical and scientific documentation;
II – new drug: drug with active pharmaceutical ingredient (API) unprecedented in the country for the new specific rare disease;
III – serious debilitating condition: disease or condition associated to irreversible morbidity or high probability of death, unless the disease evolution is interrupted; and
IV – technical and scientific documentation: documentation based on bibliographic references, indexed scientific publication, Brazilian or international, and technical publication, as those issued by sanitary and governmental authorities.
CHAPTER II
General Dispositions
Art. 4th For this resolution criteria to be used, the request for consent for clinical trials, certification of good manufacturing practices and registration of new drug must refer to drug for rare disease.
Single paragraph. Drug for rare disease will be considered as the one intended to treat, diagnose or prevent the rare disease and that:
I – is used in serious debilitating condition; and
II – is intended to significantly clinically change the evolution or to make possible the disease remission.
Art. 5th At the moment of the protocol of the application for consent for clinical trials and registration of new drug, the company must inform whether the request refers to drug for rare disease.
Art. 6th For clinical trials to be carried out in Brazil, when the application subject refers to Drug Clinical Development Dossier (DCDD), the analysis, according to this resolution criteria, applies only to applications submitted and analyzed along with the initial request.
Single paragraph. For specific dossiers of clinical trials and substantial changes per protocol inclusion, later on bound to a DCDD to be assessed according to this resolution, the company must inform whether the request refers to drug for rare disease at the moment of the protocol.
Art. 7th Applications for consent of clinical trials and registration of new drug referring to drug for rare disease must be submitted with the following documentation:
I – description of the rare disease to which the drug will be indicated;
II – relevance of the drug for treatment, diagnosis or prevention of the disease;
III – world and national data on the prevalence and incidence of the rare disease to which the drug will be indicated; and
IV – supporting document of designation of drug for rare disease by other regulatory authority, when available.
Art. 8th In case it is not confirmed during the technical analysis of applications for consent of clinical trials and registration of new drug that the request refers to a drug for rare disease, the application will be rejected.
Section I
Consent for clinical trials to be carried out in Brazil
Art. 9th The submission of drug clinical development dossier (DCDD), specific clinical trial dossier, substantial change by inclusion of protocol must be made according to specific legislation referring to execution of clinical trials with drugs in Brazil, along with documentation described in art. 7th.
Single paragraph. Consent for clinical trials to be carried out in Brazil with drug for rare disease can be granted without presentation of opinion Consubstantiated in the Committee for Ethics in Research (CEP).
Art. 10. The following procedures must be followed for purposes of consent of clinical trials to be carried out in Brazil with drugs for rare diseases:
I – request by the person interested for pre-submission meeting for presentation of DCDD, specific clinical trial dossier, or substantial change by inclusion of protocol;
II – pre-submission meeting for presentation of DCDD, specific clinical trial dossier, or substantial change by inclusion of protocol, within up to sixty days after the request by the person interested;
III – submission of DCDD, specific clinical trial dossier, or substantial change by inclusion of protocol, by the person interested, upon use of code of specific subject;
IV – assessment of DCDD, specific clinical trial dossier, or substantial change by inclusion of protocol, by Anvisa, within up to thirty days after the submission, with issue of notification of requirement or manifestation of conclusion;
V – holding of meeting in case the interested person considers necessary, for discussion of requirements;
VI – fulfillment of requirements by the person interested in up to thirty days after the notification reading; and
VII – assessment of the fulfillment of requirements, by Anvisa, in up to thirty days after submission at the agency.
Art. 11. Secondary applications, referring to DCDD, specific clinical trial dossier, or substantial change by inclusion of protocol assessed according to these resolution criteria will have the same treatment.
Section II
Certification of good manufacturing practices
Art. 12. The request for certification of good manufacturing practices must be made according to specific legislation referring to procedures for granting the certification of good manufacturing practices.
Art. 13. The following procedures must be followed for purposes of Certification of good manufacturing practices:
I – request for certification of good manufacturing practices of plants where the drug will be produced, by the person interested; and
II – publication of decision referring to the certification of good manufacturing practices by Anvisa, within up to one hundred and twenty days after submission of the request for certification.
Section III
Registration
Art. 14. The request for registration of new drug for rare disease must be made according to legislation specific to each regulatory category, added with documentation described in art. 7th.
§ 1st In case of drugs already registere
d in other countries, a technical report of assessment of the drug issued by the respective regulatory authorities must be presented, when available.
§ 2nd The submission of request for registration can be accepted with presentation of protocol of request for inspection for purposes of issuing of certificate of good manufacturing practices.
§ 3rd In the submission of request for registration, long term stability study in progress can be accepted, conducted according to temperature and humidity conditions required by specific legislations, with results available until the date of the protocol.
§ 4th Safety and efficacy reports can be accepted with presentation of phase II studies concluded and phase II studies in progress, or without presentation of phase III clinical studies, where such studies can’t be made.
§ 5th In case if imported drugs, the suppression of quality control in Brazil is allowed, as long as the quality control is made by the drug manufacturer and a summary report of the qualification of the transport system operation is presented.
§ 6th The request for registration can be instructed according to the Common Technical Document (CTD) format, provided in the M4 form of the International Conference on Harmonization (ICH).
Art. 15. The presentation of data complementation and additional proofs can be admitted after the granting of the registration upon signature of declaration of commitment between Anvisa and the company requesting the registration.
Single paragraph. The non fulfillment of the commitments assumed may imply cancelation of the drug registration.
Art. 16. In cases where the company requesting the registration does not have the full clinical development of the drug for rare disease with active pharmaceutical ingredient (API) new in the country, a clinical report can be presented containing:
I – safety and efficacy data based on bibliographic references from indexed scientific publication, Brazilian or international;
II – in vitro or in vivo comparability studies using international comparator drug;
III – relative bioequivalence/bioavailability studies using international comparator drug, where applicable;
IV – medicine label and public opinion of assessment of the international comparator drug issued by regulatory authority;
V – pharmacovigilance plan or risk minimization plan, where applicable, according to specific legislation; and
VI – updated pharmacovigilance report of the drug in case of drugs traded in other countries.
§ 1st For purposes of registration in the condition provided in the caput, Anvisa can allow the use of international drug registered at other regulatory authority when:
I – there is agreement or covenant entered into with Anvisa, and there is similarity of sanitary measures between the regulatory authority and Anvisa; and
II – the comparator drug registration is in force for at least ten years at the regulatory authority and the drug is being traded.
§ 2nd Before the registration submission, the company must consult Anvisa about the international comparator drug proposed to be used.
§ 3rd The medicine label of the drug to be registered at Anvisa must have the same indications, route of administration and posology as those of the international comparator drug, and may differ only in complementary safety information.
§ 4th The drug registered under the terms of the caput can’t be qualified as reference drug.
§ 5th The disposition in the caput does not apply to biological products.
Art. 17. Anvisa can allow the use of the international comparator drug registered in other regulatory authority under the terms provided in § 1st of art. 16 in case of request for registration of drug for rare disease with same APIs of drug already registered.
Single paragraph. Drugs that fit in the situation described in the caput will only follow these resolution criteria with regard to the possibility of use of the international comparator drug, and does not apply to the other special procedures.
Art. 18. The following procedures must be followed for purposes of registration of new drug for rare disease:
I – request by the person interested for pre-submission meeting for presentation of the product;
II – pre-submission meeting for presentation of the product within up to sixty days after the request by the person interested;
III – submission of request for registration by the person interested, upon use of code of specific subject code, within up to thirty days after the pre-submission meeting;
IV – assessment of request for drug registration, by Anvisa, within up to sixty days after the submission, with issue of notification of requirement or conclusive opinion;
V – holding of meeting in case the interested person considers necessary, for discussion of requirements;
VI – fulfillment of requirements by the person interested in up to thirty days after the notification reading; and
VII – assessment of the fulfillment of requirements, by Anvisa, in up to forty five days after submission at the agency.
§ 1st The lack of request for pre-submission meeting, under the terms of subsection I of the caput, will hinder the analysis of the request for registration according to this resolution.
§ 2nd In case of drugs of national development, the request for pre-submission meeting can be made at any time, as long as registration was not requested at other regulatory authority.
§ 3rd In case of imported drugs, the request for pre-submission meeting must be made within up to sixty days after the first request for registration at other regulatory authority, except when it is not imputable to the company interested.
§ 4th In cases where registrations of drugs for rare disease were requested or in case the drugs are already registered at other authorities before the publication of this resolution, request for pre-submission meeting as provided in subsection I of the caput will be accepted at any time.
CHAPTER II
Final and Transitory Dispositions
Art. 19. The companies that submit request for registration of new drugs according to these resolution criteria must present dossier of definition of maximum price along with the protocol of the request for registration.
Art. 20. Drugs registered with these resolution criteria will have up to three hundred and sixty five days to be traded, counted from the date of publication of the registration.
Art. 21. For requests for registration of new drugs for rare disease disposition in art. 2nd of the Collegiate Board Resolution – RDC nº 20, of April 10, 2013 does not apply.
Art. 22. Subdivision “e” of subsection IV of art. 3rd and subdivision “e” of subsection VIII of art. 38 of the Collegiate Board Resolution – RDC nº 9, of February 20, 2015 are revoked.
Art. 23. §2nd of art. 47 of the Collegiate Board Resolution – RDC nº 9, of 2015 starts to be in force with the following wording:
“Art. 47. ………………………………………………………………………………………………………
§2nd The application for substantial amendments must contain the new protocol. …………………………………………………………………………..” (NR)
Art. 24. The noncompliance with the dispositions contained in this resolution characterizes sanitary infraction under the terms of Law
nº 6.437, of August 20, 1977, without detriment to applicable civil, administrative and penal responsibilities.
Art. 25. This Resolution comes into effect 60 (sixty) days after the date of its publication.
JARBAS BARBOSA DA SILVA JR.