Medicinal, Animal-Derived, Nanomaterial and CMR Substances

1. Key takeaways

Devices incorporating medicinal substances, human or animal tissues, nanomaterials or CMR substances do not follow an ordinary compliance path in Turkey. Each category sits in its own point of Ek I, and some categories additionally open onto dedicated national regulations. The takeaways below map each substance class to its statutory anchor so that the assessment can be planned category by category. Because the categories overlap in practice — a device may combine a medicinal substance with an animal-derived component — the mapping below should be applied to every constituent, not to the device as a whole.

• Devices with special substances have separate provision-level channels in Turkey, located in different points of Ek I, with some also leading to dedicated Turkish national regulations.
• Devices incorporating a medicinal substance and substances absorbed by the body: points 12.1–12.2 of Ek I apply, further citing the Turkish regulation on the authorisation of medicinal products for human use.
• Human-derived tissues / cells: point 13.1 of Ek I applies, citing the Regulation on Human Tissues and Cells, the Blood Law No. 5624 and the regulations on blood and blood products.
• Animal-derived tissues: point 13.2 of Ek I applies, with a further labelling-side identification requirement in point 23.2(d) of Ek I; in addition, Turkey maintains an independent dedicated regulation (see article 49 for details).
• Nanomaterials: the definition is found in the definition provisions of the Regulation, and the technical requirements fall in section 10.6 of Ek I. CMR and endocrine-disrupting substances: sections 10.4.1–10.4.2 of Ek I apply, with a threshold of 0.1% by weight.

2. Legal basis

Two instruments anchor the topic: the general Regulation, whose Ek I points allocate the substance-specific requirements, and a dedicated national regulation for devices manufactured using animal tissues, which operates alongside the general regime. Where the two instruments overlap, the table below makes the parallel visible so that neither track is planned in isolation. The table records both with their official references.

3. Expert insights

Insight one: the correct order of judgement for special substances is substance → point → whether a dedicated regulation is triggered. First identify the constituent substance, then locate the Ek I point, and then examine whether that point cites a dedicated Turkish national regulation. Skipping the second step and going straight to the dedicated regulation risks missing the general requirements of Ek I. The general points still apply in full alongside any sectoral instrument, and a file built on the sectoral instrument alone will lack the baseline evidence the reviewer expects to find. Recording the sequence in the project file also creates a review trail: whoever picks up the assessment later can see not just the conclusion but the route by which it was reached. Substance-level mapping also feeds the substance list recommended later in this article, keeping the two artefacts consistent.

Insight two: 0.1% is a threshold, not an exemption. The threshold for CMR and endocrine-disrupting substances in section 10.4 of Ek I is set at 0.1% by weight. Being below the threshold does not mean no assessment is needed — what it determines is the intensity of the burden of proof and whether a dedicated statement in the labelling or documentation is required. Substances present in trace amounts still enter the argumentation, only with a lighter documentary expectation, so the substance list must record them even when the conclusion is favourable. The same logic applies to borderline substances whose classification is uncertain: document the judgement and its basis, whatever the outcome, so the decision survives review.

Insight three: animal-derived devices are the classic case of dual-track regulation in Turkey. There are the general requirements of point 13.2 of Ek I on one side, and the 2021 dedicated regulation on the other. Where the two documents run in parallel, apply the stricter requirement — this is the safe course for risk control. A dual-track file that documents compliance under both instruments is far harder to challenge than one that optimises for only the lighter of the two, and it spares the project a second round of evidence gathering if the reviewer reads the stricter track first. Practically, this means the stricter file should be treated as the master, and the lighter obligations will then be met by construction.

4. Practical recommendations

• Maintain a substance list for every product: all constituents plus whether each is a CMR / endocrine-disrupting substance, a nanomaterial or a pharmacologically active substance.
• Where human-derived or animal-derived materials are involved, check the labelling-side requirements of point 23.2(d) of Ek I in step.
• For devices incorporating animal-derived tissues, build a separate file under the dedicated regulation of Sayı 31364 in addition to point 13.2 of Ek I.

5. Verification checklist

• □ A complete constituent substance list has been compiled, marking whether each is a controlled special substance.
• □ CMR / endocrine-disrupting substances have been assessed under sections 10.4.1–10.4.2, with a threshold of 0.1% (w/w).
• □ Nanomaterials have been assessed under section 10.6.
• □ Devices incorporating a medicinal substance have been assessed under points 12.1–12.2, and the cited provisions of the regulation on medicinal product authorisation for human use have been checked.
• □ Devices incorporating animal-derived tissues have been documented against the dedicated regulation of Sayı 31364 in parallel.

Regulatory information verified to 29 October 2026. The Ek I points and the dedicated regulation issue number listed in this article were checked against the current text and the annex on the Turkish legislative information system (MevzuatNo 38657 and 36228).

How GRZAN can help. GRZAN provides medical device and IVD registration, quality system, authorised representative and local testing support for the Turkish market. Our team prepares CE/UTS-compliant documentation, and supports post-market vigilance obligations. Business enquiries: info@grzanglobal.com