Clinical Evaluation Dossier: Literature, Studies and Population Applicability

1. Key takeaways

Chile’s clinical evidence requirements are set in Article 21 of DS 825/1998: Class III requires supporting scientific literature plus the manufacturer’s effectiveness and safety studies; Class IV adds, on top of the Class III package, representative patient population studies, studies of all inherent risks of the device, and the manufacturer’s biological studies.

GRZAN’s assessment: what the provision demands is evidence, not a local clinical trial in Chile. The studies referred to in the text are not restricted by geography, but the applicability of foreign population data to the Chilean population must be argued — and this is one of the most frequent query points in Latin American review. A submission that anticipates the population question converts a likely deficiency into a closed issue. In practice the population argument is also where a sponsor can reuse existing evidence: epidemiological statistics, published comparability discussions and labeling differences all feed the same section.

2. Legal basis

• Regulation on the control of pharmaceutical products and medical devices | Decreto Supremo N° 825, de 1998 | August 21, 1999 | Article 21 | Class III: all Class I items plus supporting scientific literature, the manufacturer’s effectiveness and safety studies, and quality system evidence; Class IV: all Class III items plus representative patient population studies, studies of all inherent risks of the device, and the manufacturer’s biological studies.
• Same instrument | Article 2, item 14 | the intended use is that indicated by the manufacturer on the label, in the instructions for use and/or in promotional material.
• ISP technical guidance | ANDID instructivo 001 | structure of the technical file and risk management requirements for Class III and Class IV submissions.
• Law on scientific research in human beings | Ley N° 20.120 | 2006 | ethical and legal framework for research involving human subjects (relevant where studies must be conducted in Chile).

3. Expert insights

Insight one: the three evidence blocks serve different purposes and cannot substitute for one another.

Scientific literature answers what is the accepted state of knowledge for this product category; effectiveness and safety studies answer how this specific product performs; representative patient population studies answer whether the performance holds in the target population. GRZAN structures these as three independent chapters, each with its own search strategy or study methodology description. Blending them into one narrative makes the evidence structure unclear and forces the reviewer to reconstruct the logic that the sponsor should have supplied. Each chapter should open with one sentence stating what question it answers, so the reviewer can navigate without reading sequentially.

Insight two: the literature search must present a reproducible strategy.

Supporting scientific literature does not mean attaching a stack of PDFs. The submission should state: databases searched, search strings, time range, inclusion and exclusion criteria, screening counts and the final list of included publications. Reproducibility is the key to whether the literature evidence is credited. A reviewer who can re-run the search and land on the same set of papers has no reason to challenge the selection; one who cannot reproduce it has every reason to ask. The strategy should also record the date the search was run, so the list can be refreshed before filing if months have passed since the work was done.

Insight three: the population applicability statement is the passport for foreign data.

GRZAN recommends a dedicated section on population applicability covering three dimensions: differences in body size and anatomical parameters, differences in epidemiology and disease spectrum, and differences in local medical practice and use settings. The return on this section is exceptionally high — it answers in advance the questions the reviewer is most likely to raise about data generated outside Chile, and it demonstrates regulatory maturity at the same time. Where a dimension cannot be argued from data, say so and explain the mitigation — such as training or labeling — rather than staying silent on it.

Insight four: the breadth of the intended use directly determines the depth of clinical evidence.

Article 2, item 14, anchors the intended use in the manufacturer’s own indications. The wider the intended use is written, the deeper the clinical evidence must go. A pattern GRZAN sees among some manufacturers — describing an assistive capability as a diagnostic capability, or expanding an assistive claim into a diagnostic one — directly escalates the evidence requirement and can trigger deficiency letters. Writing the indication narrowly and truthfully is the lowest-cost strategy available. The intended use wording should be frozen early and propagated by template to all four document families, so later edits cannot widen it by accident.

4. Practical recommendations

1. Split the clinical evidence into three independent chapters: scientific literature, effectiveness and safety studies, and representative patient population studies.
2. Write the search strategy in full: databases, search strings, time range, inclusion and exclusion criteria, screening counts, final included list.
3. Draft a dedicated population applicability section covering body size, epidemiology and medical practice.
4. Write the intended use narrowly and factually: keep it consistent across the dossier, label, instructions for use and promotional material.
5. Keep the Class IV biological studies as a separate document; do not blend them with the biocompatibility test report.

5. Verification checklist

• □ The three clinical evidence blocks are prepared in layers against Article 21
• □ The literature search strategy is reproducible (search strings and screening counts included)
• □ A dedicated population applicability section exists (body size, epidemiology, medical practice)
• □ The intended use is consistent across the four documents and is not written broadly
• □ Class IV biological studies have been submitted as a separate document

Regulatory information verified as of October 29, 2026.

For a product-specific feasibility assessment of Chile market entry, GRZAN’s regulatory team supports manufacturers and importers with registration dossiers, conformity documentation and ISP submissions. Contact info@grzanglobal.com to discuss your project.