**10. Conclusion**

*Medical Isotopes*

Ph. Eur. [68Ga]Ga-DOTA-TOC is provided [59]. It has to be noted, that monograph #2464 is currently under revision which can lead to different limits in feature

**WHAT? HOW? LIMITS** Appearance Visual inspection Clear, colorless solution

pH pH indicator strips < 2 Radionuclide identity Half-life determination 62 to 74 min

Radiochemical purity TLC >91%

Chemical purity ICP-AES/ICP-MS <10 μg/GBq Fe

Bacterial endotoxins LAL test ≤175 EU/total volume Sterility Direct inoculation sterile

*Quality control specifications [68Ga]Ga-DOTA-TOC as given by the Ph. Eur. For generator-produced* 

Radionuclidic purity γ-spectrometry <0.1% long living impurities

γ-spectrometry 511, (1022), 1077, (18,839 keV

TLC <3% [68Ga]Ga in colloidal form

HPLC <50 μg/V DOTA-TOC and metal complexes of

GC <10% V/V and <2.5 g per administration

HPLC <2% [68Ga]Ga3+

TLC <200 μg/V HEPES

<0.001% germanium-68

<10 μg/GBq Zn

DOTA-TOC

The quality control for a certain 68Ga-radiopharmaceutical depends on the production route of gallium-68, the synthesis route of the radiopharmaceutical as

As descripted in Section 7.2, the respective production route leads to different radionuclidic impurities (germanium-68 vs. gallium-66 & gallium-67) that need to take into account for the final product specifications. However, this is not yet implemented in the pharmacopeias but is in part already in progress. For example, the monograph for [68Ga]Ga-DOTA-TOC (#2464) of the Ph. Eur. is currently in revision to take into account the cyclotron production of gallium-68 [68].

In general, the quality of the final radiopharmaceutical needs to fulfill all specifications given by the relevant legislation or pharmacopeia independent from the synthesis route. Nevertheless, it may be possible to dispense individual tests given, for example, for licensed kit preparations. For example, the Ph. Eur. states in its general notices "An article is not of Pharmacopoeia quality unless it complies with all the requirements stated in the monograph. This does not imply that performance of all the tests in a monograph is necessarily a prerequisite for a manufacturer in assessing compliance with the Pharmacopoeia before release of a product. The manufacturer may obtain assurance that a product is of Pharmacopoeia quality on the basis of its design, together with its control strategy and data derived, for example, from

**9. Regulatory aspects: the most important at the end**

**36**

(**Table 6**).

**Table 6.**

well as of the relevant legislation.

*gallium-68 (monograph #2464) [59].*

Gallium-68 is a well-researched radionuclide with growing importance for clinical practice triggered by the development of new tracers expanding its application and the increasing demand for theranostic patient care.

Its availability via radionuclide generator in combination with comparably easy coordination chemistry enables a patient care even in places where the cyclotronproduced PET-radionuclides are unavailable and, in the case of NETs, enables patient care where no 18F-alternative exists.
