Preclinical and Clinical Trial Requirements
Preclinical and clinical trial requirements in Argentina – a legal guide. Prepared in association with Marval, O’Farrell & Mairal, a leading global law firm, this is an extract from The Pharma Legal Handbook: Argentina, available to purchase here for USD 99.
1. Are clinical trials required to be conducted locally as a condition (stated or implicit) for marketing approval?
No. It is not a condition for marketing approval to conduct a clinical trial in Argentina (the approval of pharmaceutical products based on similarity is allowed), provided that the applicant has the necessary preclinical and clinical data when filing product application, depending the type if the drug (e.g. bioequivalence studies).
2. How are clinical trials funded?
Clinical trials may be either publicly or privately funded. Pursuant to local laws and regulations, the sponsor is the individual or legal entity responsible for the commencement, management and financing of a clinical trial (Ministry of Health Regulation No. 1,480/11 and ANMAT Regulation No. 6,677/10).
3. What are the requirements for preclinical and clinical trial protocols? Who must approve the protocols?
At a national level, clinical trials are mainly regulated by Ministry of Health (MoH) Regulation No. 1,480/11 and ANMAT Regulations No. 6,677/10, 12,792/16 and 4,008/17. Those regulations set forth the good clinical practices for conducting clinical trials in human beings in the country and are harmonized with international regulations such as the Helsinki Declaration, Nüremberg Declaration, “Operational Guidelines for Ethics Committees that review biomedical research” (WHO-World Health Organization, 2000), the “International Ethical Guidelines for Biomedical Research in Human Beings” (CIOMS – Council for International Organizations of Medical Sciences, 2002), among many others. At a regional level, each province may have its own regulations.
Preclinical and clinical trials protocol requirements are set forth in MoH Regulation No. 1,480/11 and ANMAT Regulation No. 6,770/10. The protocols must be approved by ANMAT and by the intervening Ethics Committee.
According to national laws and regulation, 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 their 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 not 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 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. What are the requirements for consent by participants in clinical trials?
The decision of an individual or his representative to participate in an investigation must be voluntary and free of undue influence, undue incentive or coercion. To take a decision, each potential participant or their legal representative must receive clear and precise information about the purpose, procedures, benefits and foreseeable risks and founding of the clinical trial, and their rights to access and rectify their data and to refuse to participate or to leave the study at any time, without any to justification and without exposing themselves to any reprisal. After verifying that the individual or his representative has understood all the information, the principal investigator must request the informed consent.
The Principal Investigator should provide an opportunity and enough time for the potential participant or his representative to consider all the options, ask the questions they want and stay satisfied with the answers, and then verify through questions that they have understood all the information received.
After the information process has been completed, the participant or his or her representative in the cases provided by law, the Principal Investigator and the witness, when appropriate, must sign and date two originals of the consent form, as a statement of having received and including the information and having taken the free and voluntary decision to participate in it. The participant or his or her representative must receive one of the originals of the consent form and a copy of the information section.
5. May participants in clinical trials be compensated?
Yes. However, such payments must not be unbalanced in order to persuade the patient to run unnecessary risks (constituting an undue incentive). The intervening Ethics Committee must review and approve any financial agreement or payment to the participants.
6. How are participants in clinical trials protected and indemnified against any harm that arises as a result of participation in the trial?
The sponsor must ensure coverage of medical care and contracting of insurance or the establishment of another type of guarantee in the country, in case of damage caused to the participants by the study (Section 3.12, Section C of Annex I of ANMAT Regulation No. 6,677/10). Likewise, sponsor must reimburse all subject injuries caused by the drug.