Guidance for Additional Considerations to Support Conformity Assessment of In Vitro Companion Diagnostic Medical Devices in South Korea

1. What this guidance is and why it matters

South Korea’s Ministry of Food and Drug Safety (MFDS) published a harmonized guidance (GHWP/WG2/F001:2023) describing additional considerations for conformity assessment of in vitro companion diagnostics (IVD-CDx). The guidance is presented by MFDS as a regulatory reference in its English “Regulations” listing. Source: Guidance (Final Document) (PDF) , MFDS Regulations listing (English) ([MFDS][1])

The motivation is practical: because an IVD-CDx result is used to decide whether a patient can safely and effectively receive a corresponding therapy, the test’s analytical performance, clinical performance, and labelling alignment with the therapeutic product must be clear and defensible. Source: Guidance (Final Document) (PDF)

2. Scope: what is considered an IVD-CDx

The guidance defines an IVD-CDx as an IVD medical device that provides information essential to the safe and effective use of a corresponding therapeutic product and is used to:

1. identify patients most likely to benefit,
2. identify patients at increased risk of serious adverse reactions,
3. monitor response to adjust dose/continuation, or
4. identify patients where a product is safe/effective only in a specific sub-population. Source: Guidance (Final Document) (PDF)

The scope note clarifies that tests used only to match donors/recipients are generally outside IVD-CDx scope, while some HLA-related tests may still function as IVD-CDx depending on the therapeutic context. Source: Guidance (Final Document) (PDF)

3. Development situations covered

The guidance distinguishes three common situations:

• Novel IVD-CDx: newly developed for a therapeutic product.
• Follow-on IVD-CDx: developed after an initial IVD-CDx exists for the same therapy/biomarker.
• Changes/additions: changes to an approved IVD-CDx (e.g., adding specimen types) or adding a new therapeutic product to the labelling. Source: Guidance (Final Document) (PDF)

4. Key definitions you should align on early

• Cut-off: a level/value/grade used to classify results (e.g., positive vs. negative) and support the treatment decision. Source: Guidance (Final Document) (PDF)
• Liquid biopsy: non-invasive acquisition of tumour/genetic information via blood or other body fluids (including plasma/serum, exosomes, circulating tumour cells, and circulating tumour DNA). Source: Guidance (Final Document) (PDF)
• Specific group/class of therapeutic products: a labelling approach where an IVD-CDx claims use with a therapeutic group/class (often oncology), requiring clear scientific justification and labelling boundaries. Source: Guidance (Final Document) (PDF) and FDA Companion Diagnostics overview ([U.S. Food and Drug Administration][2])

5. Conformity assessment: the “additional considerations” to document

The guidance assumes the baseline IVD conformity assessment principles still apply, but highlights items that are central for IVD-CDx:

5.1 Intended use must bind the test to the therapy

In the intended use, identify the corresponding therapeutic product by trade name and active ingredient, and specify the biomarker/parameter and its clinical role (selection, risk, monitoring, etc.). Source: Guidance (Final Document) (PDF)

5.2 Be explicit about what is measured and how results are interpreted

Clarify the target (e.g., gene/protein/clone for mAb-based assays), the measurement type, and how reported results map to treatment decisions—especially the cut-off and any “grey zone.” Source: Guidance (Final Document) (PDF)

5.3 Evidence must be fit for the therapeutic claim

Analytical and clinical performance evidence should support the medical decision tied to the therapy. When bridging/concordance approaches are used, specimen selection and comparators should reflect the clinical context of the therapeutic product trials (e.g., eligibility criteria). Source: Guidance (Final Document) (PDF)

6. Special cases: what reviewers will look for

6.1 Follow-on IVD-CDx

A follow-on IVD-CDx is generally expected to demonstrate equivalence to an approved comparator IVD-CDx, especially around the decision threshold. The guidance highlights the need to justify specimen selection/quality and to compare performance under clinically relevant conditions. Source: Guidance (Final Document) (PDF)

6.2 Adding specimen types (including liquid biopsy)

When adding a specimen type, additional validation should show the test remains reliable and clinically meaningful in the new matrix, and that pre-analytical variables are controlled. Source: Guidance (Final Document) (PDF)

6.3 Claiming a specific group/class of oncology therapies

If an IVD-CDx intends to cover a therapeutic group/class, the guidance provides questions and a checklist to ensure the biomarker relationship, evidence base, and labelling boundaries are sound. Source: Guidance (Final Document) (PDF) and FDA Companion Diagnostics overview ([U.S. Food and Drug Administration][2])

7. Labelling: minimum elements to align with the therapeutic product

The IVD-CDx labelling should clearly state it is a companion diagnostic and describe the biomarker, specimen type(s), cut-off, corresponding therapeutic product(s), the decision role, and key limitations/precautions. Source: Guidance (Final Document) (PDF)

8. Dossier: present a coherent intended use → evidence → decision story

The guidance also outlines three assessment categories—novel, follow-on, and changes/additions—and expects the dossier to connect intended use, analytical performance, clinical performance, and labelling consistency for the therapeutic decision. Source: Guidance (Final Document) (PDF)

9. Practical takeaways

• Align IVD-CDx and therapeutic product teams early (biomarker definition, cut-off rationale, specimen handling).
• For follow-on tests, design an equivalence strategy with clinically representative specimens.
• Treat group/class claims as a higher bar: document rationale, performance boundaries, and precise labelling language.
• Ensure IFU and therapeutic product label are mutually consistent on who gets tested, how results are interpreted, and what action follows.

Public reference links

• MFDS Regulations listing (English): MFDS Regulations listing (English) ([MFDS][1])
• FDA Companion Diagnostics overview: Companion Diagnostics (FDA) ([U.S. Food and Drug Administration][2])
• FDA guidance page (Aug 2014): In Vitro Companion Diagnostic Devices (FDA) ([U.S. Food and Drug Administration][3])