4. Regulatory Authority (RA)/ Competent Authority (CA)

4.1 Provide a list of documents needed to be submitted for RA/CA review and approval including the number of copies and/or translations as relevant. 

Preclinical and clinical trial protocol requirements are set forth in MoH Regulation No. 1480/2011 and ANMAT Regulation No. 6677/2010. The protocols must be approved by ANMAT and by the relevant Ethics Committee.

According to national laws and regulations, the protocol must mainly comply with the following requirements:

• General Information: (a) full title of the study, including the phase of clinical development; (b) version number and date thereof; (c) name of the sponsor; (d) summary of the protocol; and (e) schedule of visits and procedures.
• Background and justification: (a) description of the problem to be investigated and current state of knowledge; (b) product information under investigation, including summary of the data of efficacy, pharmacokinetics, tolerance, and toxicity obtained in clinical and preclinical studies; (c) purpose and relevance of the proposed research; and (d) basis for the development phase proposed for the study.
• Objectives: description of the primary and secondary objectives.
• Study design: (a) study design and justification of the choice; (b) random assignment method, if applicable; and (c) other methods to reduce bias.
• Population under study: (a) expected number of participants; (b) inclusion and exclusion criteria of participants; and (c) criteria for withdrawal of participants.
• Statistical analysis: (a) study hypothesis, specifying the null and alternative hypothesis; (b) specification of descriptive methods and statistical tests for variables; (c) criteria for the management of missing, excluded, and spurious data; (d) criteria for inclusion or exclusion of participants in the analysis; (e) computer tools to be used; (f) criteria for the processing of security information; and (g) intermediate analysis schedule, if applicable.
• Efficacy evaluation: (a) parameters of effectiveness to be measured, including instruments and methods of measurement; and (b) effectiveness criteria.
• Products under investigation: (a) description of the products under investigation, indicating active pharmaceutical ingredient, formulation, dosage, way of administration, frequency, and duration of treatment and follow-up; (b) allowed and non-allowed medications; (c) criteria for suspension of treatment; and (d) planned rescue treatment and follow-up in cases of failure or events adverse.
• Adverse events: procedures for registering and reporting adverse events.
• Ethical aspects: (a) specification that the investigation will be reviewed by an Independent Ethics Committee (IEC); (b) procedures for obtaining informed consent; (c) protection of the confidential information and the identity of the participants; (d) details of coverage and compensation for damages available to participants; (e) justification of payments or compensation for expenses available to the participants; (f) anticipation of access at the end of the trial to the intervention identified as beneficial in the trial or to an appropriate alternative or other suitable benefit; (g) justification for the use of placebo, if used; (h) justification for carrying out the investigation in a vulnerable group, if applicable; and (i) possible conflicts of interest.
• Administrative aspects and others: (a) procedures for the conservation and storage of products under investigation; (b) registration and communication of clinical data;(c) handling of the trial documents; (d) monitoring and audit procedures; (e) criteria for the cancellation of the trial; and (f) plan for publication of the results.

4.2 Time required for RA/CA review and approval process and turnaround time if any query is raised during the review process. 

The evaluation process is expected to take 60 working days (for technical evaluation) + 10 working days (for administrative aspects): 70 working days in total for clinical research studies.

Studies evaluated and approved/ongoing in countries with high vigilance standards will be approved in 45 working days (to provide technical reports) + 10 administrative working days (to issue final approval letter): 55 working days in total.

4.3 Does the regulation support electronic submission?

Yes.

4.4 Does the regulation require the applicant to be a Principal Investigator (PI)/Chief Investigator (CI)?

The Sponsor must be the applicant.

4.5 Please describe the process of RA/CA submission for clinical trial approval. 

Clinical trial applications are regulated by ANMAT. The documents required as per ANMAT Disposition 969/97 are listed below.

The Sponsor must submit the clinical study protocol, prepared by the Principal Investigator, and containing the following information: 

Information general

1. Project title.
2. Name of the responsible investigator(s).
3. Name(s) of the Centre(s) where the study will be carried out.
4. Name and profession of the persons who will collaborate with the study (doctor, bioengineer, biochemist, pharmacist, chemist, nurse, statistician, or other health professionals).
5. Name of sponsor.

Justification and Objectives

1. Objectives of the study.
2. Reasons for its execution.
3. Background and essential information, with the respective bibliographic references.

Ethical aspects

1. General ethical considerations on the study, from the point of view of the rights of the persons under study.
2. Description of how healthy or sick persons subject to study will be informed and model informed consent form.
3. In all informed consent forms used in a clinical trial (including the consent form for minors), the following text shall be included in red, in capital letters, squared, Times New Roman 11 or equivalent: 

BY SIGNING THIS FORM YOU ARE AGREEING TO PARTICIPATE IN MEDICAL RESEARCH IN CLINICAL PHARMACOLOGY OR EXPERIMENTAL MEDICAL TECHNOLOGY AUTHORIZED BY THE NATIONAL ADMINISTRATION OF DRUGS, FOOD AND MEDICAL TECHNOLOGY (ANMAT). IF YOU HAVE ANY QUESTIONS ABOUT WHAT YOUR DOCTOR OR THE ETHICS COMMITTEE HAS EXPLAINED TO YOU, BEFORE SIGNING KNOW THAT YOU CAN CONSULT "ANMAT RESPONDE", TOLL-FREE LINE 0800 333 1234 OR 011 4340 0800 FROM MONDAY TO FRIDAY FROM 8 A.M. TO 5 P.M. (Subsection incorporated by Article 8 of Provision No. 6550/2008 of the National Administration of Drugs, Food and Medical Technology B.O. 7/11/2008. See art. 9° of the same standard) 

Work schedule

1. Description of the work schedule with specification of the stages, duration of the same, and time of completion.
2. Justification of the schedule: Time evolution of the disease, expected duration of treatment, and other parameters that are related to time. 

Study design

1. Validation of the equipment, device, apparatus, or instrument to be used. Where the equipment, apparatus, device, or instrument uses an innovative technique, it shall be validated with one or more other systems capable of assessing its mechanism of action, safety, and effectiveness. 
2. Specification of the type of study.
3. Description of the randomization method.
4. Description of study design.
5. Specification of bias reduction factors.

Selection criteria 

1. Specification of the sample, including age ranges, sex, ethnicity, prognostic factors, etc. 
2. Detailed description of the criteria for inclusion and exclusion in the study.  
3. Description of criteria for withdrawing persons included in the study.  

Treatments

1. In case of using medicinal product or medicinal products: Clear description of the product(s) to be used (active ingredients, excipients, pharmaceutical form(s), concentrations). 
2. Description of the treatments or procedures to be carried out to the groups (treated, control, etc.). 
3. Description of the periods in which each treatment or procedure will be administered to the groups (treated, control, etc.). 
4. Description of form/s of use. 
5. Rules of use of concomitant treatments or procedures (if applicable). 
6. Description of the measures to be implemented to ensure the safe use of the medical device(s). 
7. Description of measures to promote and control strict compliance with the instructions. 

Evaluation of effectiveness and safety

1. Specification of the variables to be evaluated, according to the organ, apparatus, or system on which the device or apparatus that is the subject of the study acts, as well as its actions on the cardiovascular, respiratory, central nervous system, neuromuscular system, urinary system, and endocrine system. 
2. Description of the methods/s of measurement and recording of the effects produced by the medical device(s) under study. 
3. Description of the analyses and special procedures to be used (clinical, laboratory, imaging, etc.). 

Adverse events 

1. Methods of recording adverse events. 
2. Behaviors to follow if complications are verified. 
3. Specification of the place where the study codes will be located and the procedures for its opening in case of emergency. 
4. Information on the notification of adverse events, including by whom and to whom they should be raised and the deadline for delivery and notification form. 

Practical application

1. Failed medical device replacement procedures (if applicable).
2. Specifications and instructions for possible deviations from the clinical study protocol. 
3. Specification of the distribution of duties and responsibilities within the investigation team, as well as their coordination. 
4. Address, telephone, facsimile, email, etc. that allow permanent contact with the research group. 
5. Where necessary, considerations of confidentiality issues. 

Records of the information obtained

1. Procedures for the archiving of information of persons incorporated into the general study and special lists of patients. The records should allow easy identification of each volunteer (healthy or sick). You must include a model of the Individual Registration Form. 
2. Procedures for the treatment and processing of adverse event records with the medical device(s) under study. 

Evaluation of the information obtained and statistical methodology

1. Specific description of how the results obtained will be evaluated. 
2. Computer Methods 
3. Detailed description of the statistical methods to be used.
4. Description of the statistical method(s) in the treatment of information arising from the people withdrawn from the study. 
5. Rationale for the choice of sample size and its clinical justification
6. Level of statistical significance to be used.
7. Rules for completion of the study. 

Bibliography

The bibliographic references used for the preparation of the clinical study protocol will be attached. 

4.6 Does the RA/CA provide written acknowledgment of the submitted application? If not, describe how the application is tracked.

The submission is tracked within the ANMAT portal.

4.7 What is the relevant RA/CA fee in local currency/USD? Please provide as much information as possible (e.g. if the fee is different for notification/approval, initial submission, amendment, study with IMPD and study without IMPD, etc.)

The cost of a clinical trial application is 251000 Argentinian Pesos (equivalent to around 1135 USD).

4.8 Does RA/CA accept checks or can payment be made electronically? Please provide details on (1) A/C number; (2) A/C Name; (3) Sort Code; (4) Swift Code; (5) Bank address, etc. Where can remittance advice notices be sent?

Payment must be made electronically via the ANMAT payment system (the link below requires the user to first log in before they are able to access payment information). 

https://extranet.anmat.gov.ar/pagoelectronico/

4.9 Is there any guidance tool available for making an electronic application? If yes, provide the link and/or step-by-step instructions.

Once a sponsor logs into the system, guidance is provided on the process for making payment. This information is in Spanish.

4.10 Does RA/CA require any screenshots/mock screens for participant-facing materials?

Yes. Where patient-facing materials are provided electronically, screenshots should be provided.