FDA not too long ago issued a draft steerage, Analysis of Thermal Results of Medical Units that Produce Tissue Heating and/or Cooling (link), which describes data to incorporate in a advertising and marketing software to help the analysis of thermal results of medical gadgets that produce native, regional, and/or systemic adjustments in tissue temperature as a consequence of their use, both by heating or cooling.
The draft steerage applies to medical gadgets that warmth or cool tissue as an meant or unintended consequence of system use. Examples of such gadgets embrace gadgets that ship types of electromagnetic power; gadgets that ship ultrasound; electroporation gadgets; gadgets that produce temperature adjustments by contact; and gadgets with elements corresponding to batteries, turbines, chargers, leads, and electrode contacts that may probably warmth surrounding tissue throughout use.
To guage the thermal results of a tool, the draft steerage recommends that bench testing precede analysis of thermal results. Bench testing needs to be performed first to confirm the system meets its specs and to show that the next information generated are consultant of the ultimate completed system’s efficiency.
An analysis of thermal results ought to embrace an evaluation of tissue results (e.g., thermal injury, tissue look, tissue/organ operate) and associated unfold of thermal power within the tissue. These assessments could also be carried out experimentally (i.e., utilizing phantoms, ex vivo animal tissue fashions, and/or in vivo animal testing), computationally, and/or clinically. To find out which sort of tissue analysis is acceptable, the draft steerage recommends the magnitude and distribution of the heating and/or cooling supplied by the system be thought of along with the provision of the suitable experimental mannequin, noting that use of a phantom mannequin or ex vivo animal tissue mannequin could also be acceptable for gadgets with native tissue temperature adjustments, however is probably not appropriate for gadgets with regional or systemic results, the place affect of blood circulate on the event of tissue results must be accounted for.
For ex vivo tissue or in vivo animal testing, the steerage contains dialogue of the number of tissue and check strategies, noting that testing needs to be carried out such that the tissue is uncovered to the minimal, common, and worst-case temperature-time historical past. The draft steerage discusses number of tissues, tissue check strategies, and strategies for assessing the thermally affected tissue area(s), together with thermal power unfold. For measuring the thermally affected tissue area(s), the draft steerage recommends use of histological strategies or strategies evaluating adjustments in properties, corresponding to electrical, mechanical, and optical properties or properties associated to imaging. For measuring thermal power unfold, the draft steerage discusses probe-based and image-based thermometry.
When in vivo animal testing is required, assessments ought to observe good laboratory practices and the animal mannequin needs to be consultant of the meant scientific software. For instance, aesthetic gadgets meant to create fractional results, the place the technical parameters of the topic system are considerably completely different from the comparator system, needs to be examined utilizing an animal mannequin. Notably, this identical instance is used for a scenario by which information from a research in people could also be wanted. The draft steerage notes that histological information from use of the system in tissues of curiosity in people or an acceptable animal mannequin needs to be supplied. Whereas histological information is frequent in research of animal fashions, it isn’t clear how human histological information needs to be obtained in a research of an aesthetic system and the draft steerage offers no dialogue of this level.
The draft steerage additionally discusses use of computational analysis of tissue results and thermal power unfold, recommending that such evaluations ought to use computational fashions of related tissues, impose clinically related boundary situations, and be validated to foretell tissue results and thermal power unfold within the meant tissue of curiosity for the complete vary of spatio-temporal temperature distribution.
Given the complexity of those research and the dearth of element relating to the applicability of the steerage to particular gadgets, in search of a pre-submission could also be helpful to sponsors. The draft steerage recommends in search of steerage by the pre-submission course of to deal with questions of:
- Using phantoms, ex vivo tissue, or in vivo animal fashions.
- Collection of acceptable mannequin parameters for the meant scientific software.
- The induced spatial temperature distribution over time (i.e., “temperature-time historical past”) wanted to help a claimed tissue impact.
- Design of scientific research, when wanted, to help the system’s indications to be used.
- Eventualities the place the suggestions within the steerage might not apply.
- Analysis of gadgets that induce reversible or irreversible electroporation results, as electroporation-based ablation has been related to induction of cardiac arrhythmias.
The draft steerage notes that the suggestions replicate present evaluation practices. Whereas corporations that already market gadgets that produce tissue heating and/or cooling might already be aware of FDA’s expectations, availability of the steerage ought to assist these with new gadgets keep away from surprises throughout evaluation of their advertising and marketing purposes.