Harmonization of U.S., European Union, and Canadian First-in-Human Regulatory Requirements for Radiopharmaceuticals: Is This Possible?

Schwarz, Sally W.; Decristoforo, Clemens; Goodbody, Anne E.; Singhal, Nikhita; Saliba, Sarah; Ruddock, Patrick S.; Zukotynski, Katherine; Ross, Andrew

doi:10.2967/jnumed.118.209460

Cited by 20 publications

(18 citation statements)

References 6 publications

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“…Since the development of α-emitting radiopharmaceuticals is happening globally, another major issue concerning production and distribution of these novel therapies is the consideration of the local regulatory environment. A discussion of the potential for harmonization of the various international regulations has recently been published [228].…”

Section: Medicinal Chemistrymentioning

confidence: 99%

Development of Targeted Alpha Particle Therapy for Solid Tumors

et al. 2019

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Targeted alpha-particle therapy (TAT) aims to selectively deliver radionuclides emitting α-particles (cytotoxic payload) to tumors by chelation to monoclonal antibodies, peptides or small molecules that recognize tumor-associated antigens or cell-surface receptors. Because of the high linear energy transfer (LET) and short range of alpha (α) particles in tissue, cancer cells can be significantly damaged while causing minimal toxicity to surrounding healthy cells. Recent clinical studies have demonstrated the remarkable efficacy of TAT in the treatment of metastatic, castration-resistant prostate cancer. In this comprehensive review, we discuss the current consensus regarding the properties of the α-particle-emitting radionuclides that are potentially relevant for use in the clinic; the TAT-mediated mechanisms responsible for cell death; the different classes of targeting moieties and radiometal chelators available for TAT development; current approaches to calculating radiation dosimetry for TATs; and lead optimization via medicinal chemistry to improve the TAT radiopharmaceutical properties. We have also summarized the use of TATs in pre-clinical and clinical studies to date.

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Section: Medicinal Chemistrymentioning

confidence: 99%

Development of Targeted Alpha Particle Therapy for Solid Tumors

et al. 2019

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“…Human use of positron emission tomography (PET) radiotracers in a given country (or member states in the case of the European Union) is required to be conducted under appropriate governmental oversight (Schwarz and Decristoforo 2019 ; Schwarz et al 2019 ). In this paper, we focus upon clinical use of PET radiotracers in the United States, which is regulated by the Food and Drug Administration (FDA) (VanBrocklin 2008 ; Harapanhalli 2010 ; Schwarz et al 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Use of 55 PET radiotracers under approval of a Radioactive Drug Research Committee (RDRC)

Jackson

Lee

Sowa

et al. 2020

EJNMMI radiopharm. chem.

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Background In the US, EU and elsewhere, basic clinical research studies with positron emission tomography (PET) radiotracers that are generally recognized as safe and effective (GRASE) can often be conducted under institutional approval. For example, in the United States, such research is conducted under the oversight of a Radioactive Drug Research Committee (RDRC) as long as certain requirements are met. Firstly, the research must be for basic science and cannot be intended for immediate therapeutic or diagnostic purposes, or to determine the safety and effectiveness of the PET radiotracer. Secondly, the PET radiotracer must be generally recognized as safe and effective. Specifically, the mass dose to be administered must not cause any clinically detectable pharmacological effect in humans, and the radiation dose to be administered must be the smallest dose practical to perform the study and not exceed regulatory dose limits within a 1-year period. In our experience, the main barrier to using a PET radiotracer under RDRC approval is accessing the required information about mass and radioactive dosing. Results The University of Michigan (UM) has a long history of using PET radiotracers in clinical research studies. Herein we provide dosing information for 55 radiotracers that will enable other PET Centers to use them under the approval of their own RDRC committees. Conclusions The data provided herein will streamline future RDRC approval, and facilitate further basic science investigation of 55 PET radiotracers that target functionally relevant biomarkers in high impact disease states.

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“…The US pathway for submission and approval of clinical trials follows a different route with a central agency, the FDA, being responsible for reviewing. Differences between Europe and the US regarding radiopharmaceuticals have recently been addressed . However, similar documents are required to complete a clinical trial application dossier, which are addressed in the following chapters of this review.…”

Section: Current Regulatory Framework Eumentioning

confidence: 99%

“…Differences between Europe and the US regarding radiopharmaceuticals have recently been addressed. 17 However, similar documents are required to complete a clinical trial application dossier, which are addressed in the following chapters of this review.…”

Section: Current Regulatory Framework Eumentioning

confidence: 99%

Clinical translation of theranostic radiopharmaceuticals: Current regulatory status and recent examples

Peitl

Rangger

Garnuszek

et al. 2019

Labelled Comp Radiopharmac

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With the development of ever more radiopharmaceuticals suitable for theranostic applications, translation of novel compounds from the preclinical stage towards clinical application becomes a bottleneck for the advances in Nuclear Medicine. This review article summarizes the current regulatory framework for clinical trials with radiopharmaceuticals in the European Union, provides a general overview of the documentation required, and addresses quality, safety, and clinical aspects to be considered. By using a recent successful example of translating a theranostic peptide radioligand, namely 111In‐CP04, which targets receptors expressed in medullary thyroid carcinoma, the pathway from the preclinical development over establishing the required pharmaceutical documentation to designing and submitting a clinical trial is reviewed. Details regarding preclinical data, generation of the documentation, and final successful application are described. This article should provide an insight in an ever more complex process to bring innovations in the field of radiopharmaceuticals into patients.

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Harmonization of U.S., European Union, and Canadian First-in-Human Regulatory Requirements for Radiopharmaceuticals: Is This Possible?

Cited by 20 publications

References 6 publications

Development of Targeted Alpha Particle Therapy for Solid Tumors

Development of Targeted Alpha Particle Therapy for Solid Tumors

Use of 55 PET radiotracers under approval of a Radioactive Drug Research Committee (RDRC)

Clinical translation of theranostic radiopharmaceuticals: Current regulatory status and recent examples

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