Regulatory History, Challenges, and the Role of the Coalition

PET drugs are manufactured, dispensed, and distributed in environments with overlapping areas of regulatory authority. For example, PET manufacturing is subject to requirements of any combination of the following authorities: the FDA, the USP, the NRC (or Agreement State Agency), and even the EPA. Once manufacturing is complete, PET drugs are regulated by state boards of pharmacy and/or medicine. Finally, the transportation of PET drugs must comply with DOT regulations and possibly even FAA regulations. Thus, the regulatory requirements for PET drugs are complex and often difficult to understand. Consequently, various agencies often have conflicting requirements that contradict each other.

The most important regulatory event for PET drugs was the 1997 FDA Modernization Act (FDAMA). Section 121 of FDAMA, which was entitled “Positron Emission Tomography,” established the regulatory authority of the FDA over PET drug manufacturers after the FDA completed good manufacturing practice (GMP) regulations specific to PET drug manufacturing. Prior to FDAMA, regulatory authority over PET drug manufacturing was unclear. In 2013, the FDA completed their FDAMA mandate and adopted full regulatory control of PET drugs. As such, clinical PET drugs used commercially today must be described in a New Drug Application (NDA) or Abbreviated New Drug Application (ANDA) that is approved by the FDA.

Throughout its history, the FDA’s regulatory approach for non-PET drugs has evolved around a manufacturing supply model consisting of enterprise-scaled manufacturing facilities that produce a limited number of large-scale batches each year. This supply model does not reflect PET manufacturing. Instead, due to the short half-life of PET radionuclides, the supply model for PET drugs is drastically different. For example, the nationwide supply of FDG requires more than 100,000 batches manufactured at about 150 manufacturing facilities.

The unique supply model for PET drugs demands a unique regulatory model. Prior to FDAMA, PET drug manufacturing was an unprecedented supply chain model for the FDA, which only recognized the need for specific PET regulations due to a congressional mandate. This has resulted in numerous regulatory challenges for the FDA when it comes to PET. In response to these challenges, the Coalition was formed at the behest of FDA officials in 2010 to provide a single conduit between the FDA and the community of PET manufacturers. Since its formation, the Coalition has organized numerous meetings with the FDA to discuss and provide guidance on these regulatory challenges.

Today, the Coalition is the only association dedicated to PET drug manufacturing and distribution. The power of the Coalition lies within the expertise of its members. Through workshops, publications, and other activities, the Coalition brings together academic and commercial PET drug manufacturers with regulatory agencies to exchange technical knowledge, regulatory standards, and best practices. In this manner, the Coalition advances public health by ensuring the availability of safe and effective PET drugs.