**8.3 68Ga-Radiopharmaceuticals**

As an example for the specifications and limitations for a 68Garadiopharmaceutical quality control as requested by the monograph #2464 of the


#### **Table 5.**

*Quality control specifications for diluted hydrochloric solutions of accelerator-produced gallium-68 as defined by a draft of a monograph for the Ph. Eur. Submitted for adoption (#3109) [67].*


#### **Table 6.**

*Quality control specifications [68Ga]Ga-DOTA-TOC as given by the Ph. Eur. For generator-produced gallium-68 (monograph #2464) [59].*

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 (**Table 6**).

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

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

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

**37**

*Gallium-68: Radiolabeling of Radiopharmaceuticals for PET Imaging - A Lot to Consider*

The implementation of a new radiopharmaceutical into the certain pharmacopeias is a protracted process. Therefore, several commonly used 68Ga-radiopharmaceuticals are not yet represented with own monographs in the pharmacopeias (e.g. [68Ga]Ga-PSMA-11). Nevertheless, such radiopharmaceuticals can be produced with consideration of the general notices, texts, monographs and along the lines of, for example, the monograph for [68Ga]Ga-DOTA-TOC. Again, in

case of doubt, the competent authorities should be consulted.

and the increasing demand for theranostic patient care.

the Russian Federation project RFMEFI60719X0301.

The authors declare no conflict of interest.

API active pharmaceutical ingredient

FDA U.S. Food and Drug Administration

HPLC high pressure liquid chromatography

ITG Isotopen Technologien Garching

ICP-AES inductively coupled plasma atomic emission spectroscopy

ICP-MS inductively coupled plasma mass spectrometry

GMP good manufacturing practice

patient care where no 18F-alternative exists.

validation studies of the manufacturing process" [59]. Further details can be found in the general chapter on extemporaneous preparation of radiopharmaceuticals (5.19) and the general monograph radiopharmaceutical preparations (#0125) [59]. Nevertheless, the competent authorities may request further quality control testing. Therefore, it is strongly recommended, especially in case of doubt, to consult

Gallium-68 is a well-researched radionuclide with growing importance for clinical practice triggered by the development of new tracers expanding its application

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

This work was supported by the Ministry of Science and Higher Education of

*DOI: http://dx.doi.org/10.5772/intechopen.90615*

the competent authorities.

**10. Conclusion**

**Acknowledgements**

**Conflict of interest**

**Abbreviations**

AEX anion-exchange

BET bacterial endotoxin test CEX cation-exchange DMF drug master file EU European Union

GC gas chromatography

HCl hydrochloric acid

#### *Gallium-68: Radiolabeling of Radiopharmaceuticals for PET Imaging - A Lot to Consider DOI: http://dx.doi.org/10.5772/intechopen.90615*

validation studies of the manufacturing process" [59]. Further details can be found in the general chapter on extemporaneous preparation of radiopharmaceuticals (5.19) and the general monograph radiopharmaceutical preparations (#0125) [59].

Nevertheless, the competent authorities may request further quality control testing. Therefore, it is strongly recommended, especially in case of doubt, to consult the competent authorities.

The implementation of a new radiopharmaceutical into the certain pharmacopeias is a protracted process. Therefore, several commonly used 68Ga-radiopharmaceuticals are not yet represented with own monographs in the pharmacopeias (e.g. [68Ga]Ga-PSMA-11). Nevertheless, such radiopharmaceuticals can be produced with consideration of the general notices, texts, monographs and along the lines of, for example, the monograph for [68Ga]Ga-DOTA-TOC. Again, in case of doubt, the competent authorities should be consulted.
