2. General Questions

2.1 Name of Regulatory Authority

ANMAT is an application authority under the Argentine Ministry of Health (MH). Trials may also be subject to provincial regulations depending on where they are conducted. 

2.2 Name of Ethics Committee

There is no central Research Ethics Committee (REC) in Argentina. Trials are governed by individual ethics committees which form part of the clinical trial sites. In case a research site does not have its own REC, the study shall be evaluated by a REC belonging to another institution.

2.3 Clinical Trial Application Language

Spanish.

2.4 Is regulatory approval required from both regulatory authorities and/or EC?

Yes.

2.5 Can regulatory authority and EC submission be done in parallel?

No, REC approval must be received first.

2.6 Requirement of any import permit/license before investigational product/study product is shipped from point of origin

Products to be used in a clinical trial must first have approval from ANMAT for the trial. 

All products being imported into Argentina require a certificate of origin and consularization. Details of the other requirements and documents are provided in the following link.

Additionally, ANMAT, the regulatory equivalent of the U.S. Food and Drug Administration within the Ministry of Health, regulates and prohibits imports of certain toxic substances contained in products such as pharmaceutical products and cosmetics. 

2.7 Biological Specimen Export Requirements

As of July 1st, 2017, importers and exporters must obtain specific approval from Argentina’s Ministry of Health, ANMAT, for shipments of biologic specimens.

According to ANMAT notification No. 0004, companies involved in clinical research must apply for authorization to import/export biologic specimens by submitting the new application “Request for export/import of biological samples linked to clinical pharmacology studies.”  The application gathers information about the import/export shipment which includes:

• Name and address of clinical sponsor/investigator authorized to conduct the study
• Study protocol information (for studies taking place both in and outside of Argentina)
• Type of specimen(s)
• Information about the specimen(s)’ destination
• Information about the specimen(s)’ origin

Additionally, shipments of biologic specimens linked to studies approved in Argentina before 2013, require a certification letter from Argentina’s Drug Evaluation and Registration Directorate (DERM).

The certification letter must validate the need to continue importing/exporting biologic specimens for protocols approved five years ago or more. This new rule aims to ensure that study protocols used to authorize import/export of biological samples are still current and under proper supervision.

Companies in Argentina can apply for the DERM certification by using the new application “Request for proof of the validity of the authorization for the import/export of biological samples linked to clinical studies.” 

https://www.argentina.gob.ar/sites/default/files/importacion_de_muestras_para_investigaciones_cientificas_0.pdf

2.8 Are studies of GMOs permitted (e.g., GMOs used in vaccines/vaccine manufacture and other modified products)?

Yes. Studies of GMOs are legal in Argentina.

In Argentina, several government bodies are involved in the regulation of human cells and cellular-based therapies. The National Ministry of Health has issued regulations for cellular therapies under the Medicines Act of 1964 and the Transplant Act of 1993. More specifically, hematopoietic progenitor cell (HPC) transplantation is regulated by Instituto Nacional Central Único Coordinador de Ablación e Implante (INCUCAI) within the Ministry of Health.

2.9 Is in-country sponsor presence/representation required?

No, there are no mandatory requirements for an in-country sponsor. However, it has become a fairly widespread practice for the foreign sponsor to appoint another party to act as its local representative vis-à-vis the health authority (the principal investigator or a CRO).

2.10 Is there any mandatory requirement to identify a local PI or can a PI be based in a foreign country?

No. There is no requirement for the PI to be based in the country. However, the PI must be able to complete their responsibilities from their foreign country. These responsibilities are expressed below.

Under Argentine law, the investigator is responsible for conducting the clinical trial. Some of the duties and obligations of the investigator are: 

1. To conduct the clinical trial in accordance with the protocol. 
2. To inform the trial subjects of all relevant aspects of the study and to obtain their informed consent. 
3. To store and safeguard all the materials involved in the clinical trial. 
4. To perform record keeping and reporting obligations.
5. To make a study completion filing with the institution, the sponsor, the ethics committee, and ANMAT upon conclusion of the trial. 

2.11 Is there any mandatory requirement to identify a local chief or coordinating investigator?

No. There is no specific regulation regarding the requirement for a ‘coordinating investigator. However, the following is stated in the National Administration of Drugs, Food, and Medical Devices Regulation 6677/10:

‘The investigator may set up a team of qualified collaborators who are trained in all the applicable requirements to conduct the investigation, and may therefore, delegate some of his or her functions to them, but not his or her responsibilities. The collaborators ́ qualifications shall be documented in their updated Curricula Vitae.’

Therefore, it is up to the discretion of the principal investigator to assign roles, inclusive of a coordinating investigator if they see fit.

2.12 If the applicant is CRO or a third party, does regulatory authority need any authorization or transfer of obligations from the sponsor? Does the authorization letter need to be notarized and/or apostilled? 

According to the National Administration of Drugs, Foods and Medical Devices Regulation 6677/10, ‘The sponsor shall transfer some or all of his or her functions concerning the study to a CRO, provided that the latter is legally incorporated in Argentina and without prejudice of the legal responsibility attached to the sponsor regarding participants’ care and data integrity’.

Further to this, the tasks and functions transferred to and accepted by the CRO shall be laid down in a written agreement signed by the parties.

There is no template available, and there is also no requirement for notarization of the letter.

2.13 Is there a requirement to register clinical trials on a local registry or database?

Yes, clinical trials must be registered with the National Registry of Health Research (ReNIS).

2.14 What is the local requirement for clinical study documents archival; minimum of years for the archival, specific format followed (electronic/paper and/or both)?

According to the National Administration of Drugs, Foods and Medical Devices Regulation 6677/10, "all study documents (in any format) shall be retained for ten years after the date of the last visit of the last patient enrolled in the center".

2.15 Requirements around periodic safety reporting and timelines on SAEs/AEs/ADRs/SUSARs/DSURs.

The sponsor shall inform ANMAT of any serious and unexpected adverse drug reaction concerning the investigational product within a 10-working-day period. Serious and unexpected adverse drug reactions produced by a comparator product already registered at ANMAT to be marketed nationwide or those related to a placebo shall be reported only to the ANMAT Pharmacovigilance System.

In blinded studies, whenever the sponsor receives a report of a serious adverse event (SAE), he or she shall verify the treatment provided to the participant in order to find out whether it is the case of an unexpected and serious adverse drug reaction (ADR) but he or she shall not unmask the treatment to the investigator or persons in charge of the data analysis and discussion.

Unexpected and serious ADR reports shall include the following information:

1. The denomination of the adverse reaction.
2. Investigational product code, INN, and trademark.
3. Type of report: baseline, update (update number), or final.
4. Sponsor ́s name; the research center and the investigator ́s name.
5. ANMAT regulation authorizing the study conduct.
6. The name or title of the study.
7. Participant's code, age, and sex.
8. The date of the unexpected and serious ADR appearance, the date of the investigator's report, and the date the sponsor received it.
9. Unexpected and serious ADR seriousness criteria and unexpected and serious ADR brief description.
10. Investigational product information: daily dose, route of administration, start and suspension date, therapy duration, and indication.
11. Information on whether the reaction disappeared after treatment suspension; whether the reaction reappeared with treatment re-introduction; concomitant drugs: dosage form and start and termination date; participant's history significant for the unexpected and serious ADR.

2.16 Requirement on any periodic clinical study update, specific template, and its frequency (e.g., interim or annual progress report and final report, etc.)? 

Annual reports to the ethics committee are required.

2.17 Does the local regulation require notification of “serious breaches” of GCP or the trial protocol? 

Yes. Argentina complies with the international GCP guidelines and, therefore, follows its regulations regarding the notification of “serious breaches”.