Radiopharmaceuticals (RPs) are at the forefront of many diagnostic and therapeutic advancements, but the regulations surrounding their development and approval are extensive. Because RPs are appreciably different from standard pharmaceuticals, their regulatory process is unique and often lacking in specific guidance.
This can lead to confusion as these novel products scramble to conform to the documented parameters of non-radioactive drugs, as well as to the additional chemical, radiochemical, and pharmaceutical requirements that must be met. This article will highlight some of the most prevalent regulatory guidance for RPs today, with a focus on US guidelines, governing institutions, and the approval process.
Overview
Working with radioactive material is an inherently complex undertaking. These materials present numerous complications due to their short half-lives, overexposure risks, and transportation standards, all of which necessitate appropriate precautions. As radioactive material, RPs must comply with both pharmaceutical and nuclear regulations, which adds to the difficulty of handling them.
Because RPs must abide by many governing entities, it’s essential to understand the guidelines, steps, and governing bodies involved in the RP approval process. To help with this, FDA has issued RP industry guidance with an emphasis on therapeutic RPs. This guidance contains provisions that aim to help sponsors gain a better understanding of compliance requirements.
Development and lifecycle guidelines
The United States has straightforward guidelines for RPs throughout the development and lifecycle pipeline. These regulations are issued by several governing bodies, the most prevalent of which include the Radioactive Drug Research Committee (RDRC), and a special division of the FDA known as the Center for Drug Evaluation and Research (CDER).
Recognizing that technology and innovation would continue to advance, the FDA Modernization Act of 1997 instituted RP regulatory reforms regarding the increased use of RPs in diagnostics and therapeutics.
The substantial FDA oversight RPs face is in part due to events such as the 2004 contamination incident, in which a radiopharmaceutical kit formulation was contaminated with Hepatitis C due to improper use of materials.
Regulatory phases and requirements
The approval pathway includes complex investigations and regulatory authority clearance along the way. First, an Investigational New Drug (IND) application is filed, clinical trials follow, after which a New Drug Application (NDA) must be submitted. Once an RP has an approved NDA or Abbreviated New Drug Application (ANDA) status, it can be used clinically.
In human studies, research-based RPs require approval from the RDRC. And while approval is always the goal, there are allowances for certain drug use for patients with serious or deadly conditions in which no other effective diagnostic or treatment option exists. For example, if a PET drug is unapproved, it can still be used clinically via the IND expanded access route.
Pathway to approval in the US
In the US, there may be different pathways to RP approval depending on its intended use. The typical IND and Emergency Investigational New Drug (EIND) approval process is as follows:
- Clinical plan is investigated, noting the study goal and compound selection rationale
- Summary of all documented studies of preclinical data, clinical data, and participants
- For studies on human volunteers, trial protocols are performed
- CMC (Chemistry, Manufacturing, and Controls) documents must be filed
- Quality control for toxicity studies is performed
- Animal dosimetry is reviewed
- Institutional Review Boards (IRBs) must grant approval
- Data quality and integrity must be proven and maintained through a CRF (Case Report Form) and study performance in compliance with Good Clinical Practice (GCP)/International Council for Harmonization (ICH) guidelines
Once the IND or EIND is approved, the clinical trial process moves through its distinct phases before final approval from FDA is granted.
- Phase 0: RPs are explored in humans
- Phase 1: Studies how RPs metabolize in the body and possible side effects
- Phase 2: Data identifying dose-specific effectiveness and safety ranges are obtained for different study types
- Phase 3: Efficacy and safety are studied and compared to the current RP standard
The Pearl Pathways difference
In the lengthy radiopharmaceutical development and approval process, an experienced partner can make all the difference. Pearl’s expert consulting team has the industry knowledge needed to help successfully navigate the highly regulated life science environment by balancing risk, speed to market, and cost in order to achieve business goals.
Learn more about what partnering with Pearl could do for you. Contact us today.