Table II.

The likely considerations and potential requirements from a regulatory body that must be addressed for MNs to be accepted for clinical use. Replicated with permission from (131)

Sterility of the MN dosage form	MNs penetrate the skin surface rather than adhering to it as would a traditional transdermal patch MNs may be required to be rendered sterile depending on regulatory considerations A low bioburden may be sufficient if the system has inherent and demonstrable antimicrobial activity
Uniformity of content	Either from the system as a whole, or potentially of individual drug loaded MNs within an array, depending on the system design Likely required as is the case with all other conventional transdermal patch dosage forms
Packaging	Security of packaging, i.e., protection from water ingress Ease of removal from packaging by patients without accidental piercing of the skin prior to intended application
Potential for MN re-use	Certain MN devices may be removed intact from the skin with the potential to re-pierce the skin e.g. silicon MNs Dissolving or hydrogel-forming MNs will likely be preferred as they are self-disabling
Disposal procedures	MN materials that are not dissolvable or biodegradable may be a hazard Environmental aspects of disposal must be considered
Deposition of MN material into skin	Of particular concern with dissolving MNs and those devices which would be used for chronic conditions Product may require alternating application site Potential for short term adverse effects, such as granuloma formation or local erythema, must be stated
Ease and reliability of MN application	Patients must be able to use the product properly, without significant inconvenience
Assurance of MN insertion	Indication of correct application and delivery (particularly for vaccination applications) may be required Would be useful to assure patients they have applied the device correctly
Potential immunological effects	Repeated insult of the skin, an immunologically active site, by MNs may result in an immunological reaction Assurances regarding immunological safety will be required