On Friday, February 21, SNMMI, alongside the Food and Drug Administration (FDA), members of the coalition for PET drugs, Medical Imaging Technology Alliance (MITA), and World Molecular Imaging Society (WMIS) hosted a workshop entitled “Pet Drugs: A Workshop on Inspections Management and Regulatory Issues.”
The purpose of this workshop was to provide a forum for the exchange of information and perspectives on the regulatory and compliance framework for Positron Emission Tomography (PET) drug manufacturing. Bringing all stakeholders together will improve the global understanding of regulatory and compliance topics associated with PET drug manufacturing.
You can find both slides and the webinars here.
Goals and Objectives
- Discuss regulatory compliance for the development and manufacturing of PET drugs and pathways for drug applications, application maintenance, and inspections based on Part 212.
- Share perspectives from industry, academia, investigators and regulators on inspectional findings and trends.
- Provide information on the management of Part 212 inspections and maintenance of PET NDAs and ANDAs.
Topics for Discussion
- Trends on Inspections and Compliance
- Lifecycle Management of PET Drug Applications
- Product Quality Assurance
- Changing Landscape of PET Drugs: Labeling, Electronic Submissions
The Coalition would like to make the nuclear medicine community aware of USP Volunteer Opportunities for pharmacists, chemists, practitioners, regulatory professionals, and other scientists with expertise in radiopharmaceuticals. Every five years, the USP invites qualified candidates to apply for service on Expert Committees. The Call for Candidates opened in July and may be found on the USP’s website (https://callforcandidates.usp.org/node). Interested and qualified applicants are encouraged to submit applications for Volunteer Opportunities in the areas of Chemical Medicines, Compounding, and other disciplines pertinent to radiopharmaceuticals. The deadline for application is 2020, but potential applicants are encouraged to apply as soon as possible.
Questions? Please leave a comment below.
On June 26, 2018, the Coalition for PET Drugs held a meeting at the 2018 annual meeting of the Society of Nuclear Medicine and Molecular Imaging (SNMMI) in Philadelphia. The meeting was attended by numerous members of the Coalition, as well as members of the Imaging Division at the FDA. During the meeting, a presentation was given by Krishna Ghosh, MS, Ph.D., Senior Policy Advisor at the FDA. The title of the presentation was, “PET Drug Inspections and Compliance Update.” Dr. Ghosh agreed to share the presentation on the Coalition website. It is available here:
PET Drug Inspections and Compliance Update – Krishna Ghosh, MS, Ph.D.
Other topics discussed during the meeting included: FDG labeling changes based on Pregnancy and Lactation regulatory requirements and USP updates for PET radiopharmaceutical monographs and draft chapter <825>.
On June 24, 2018, the United States Pharmacopeia (USP) and the Coalition for PET Drugs co-sponsored a session at the 2018 annual meeting of the Society of Nuclear Medicine and Molecular Imaging (SNMMI) in Philadelphia. The session was entitled “USP Radiopharmaceutical Updates.” The session focused on various topics relevant to academic and commercial PET drug manufacturers. The session was co-organized by Ravi Ravichandran, Ph.D., Sally Schwarz, R.Ph., and Steve Zigler, Ph.D. Sally Schwarz moderated the session. The session drew approximately 125 attendees representing academic PET drug manufacturers, commercial PET drug manufacturers, FDA representatives, and others.
The presentations from the session are available here:
- Overview of USP activities and How to get Involved – Ravi Ravichandran, Ph.D.
- Current and Future USP Initiatives for Radiopharmaceuticals – Steve Zigler, Ph.D.
- Introduction to USP Chapter General Chapter – Paul Mahan, R.Ph.
The Coalition for PET Drugs recently sponsored three sessions at the 2017 annual meeting of the Society of Nuclear Medicine and Molecular Imaging (SNMMI) in Denver. The sessions focused on various topics relevant to PET drug manufacturers. Each session drew approximately 100 attendees, representing academic PET drug manufacturers, commercial PET drug manufacturers, FDA representatives, and others. The three sessions covered a broad range of topics ranging from analytical methods validation to USP standards to radiopharmaceutical compounding.
The first session was a day-long Categorical Session entitled, “Best Chemistry Practices to Support the Development of PET Drugs.” The session was held on the Saturday before the official start of the annual meeting and was co-sponsored with the SNMMI’s Radiopharmaceutical Sciences Council (RPSC). This is the third year in a row that the Coalition has jointly sponsored a session with the RPSC, which demonstrates the alignment of the Coalition’s mission with that of the RPSC. The Categorical was co-organized and co-moderated by Amy Vavere, Ph.D., and Steve Zigler, Ph.D.The presentations are available here:
- Introduction to Session – Steve Zigler, Ph.D.
- Overview of FDA Regulations and Guidance Documents related to PET Drug Chemistry – Steve Zigler, Ph.D.
- F-18 and C-11 Chemistry Challenges – Peter Scott, Ph.D.
- Special Considerations for Tracers based on Proteins or Protein Fragments – Serge Lyaschenko, Ph.D.
- Field Notes #1 – Challenges behind the scenes of clinical PET tracer production – Ashley Mishoe, Pharm.D.
- Stability Studies to Support PET Drug Applications – Danny Bingham, M.S.
- Common Deficiencies in PET Drug Applications – Ravi Kasliwal, Ph.D.
- Role of USP monographs and general chapters – Steve Zigler, Ph.D.
- Characterization of Active Ingredients, By-Products, Impurities, and Standards – Jeanne Link, Ph.D.
- Field Notes #2 – Validation of a Quality Control method in a clinical PET tracer – Amy Vavere, Ph.D.
- System suitability for Analytical Methods – Mike Haka, Ph.D.
- Transfer of Technology to Multiple Facilities – Pitfalls and Best Practices – Tyler Benedum, Ph.D.
- Field Notes #3 – Experience from Inspections (CFR 212 & USP <823>) – David Dick, Ph.D.
The second session was a Continuing Education Session entitled, “USP Standards for Radiopharmaceuticals.” The session was held on Monday morning. The session was co-organized by Jim Ponto, R.Ph., Steve Zigler, Ph.D., Ravi Ravichandran, Ph.D. Dr. Ravichandran moderated the session.
The presentations are available here:
- Historical Role of the USP in Radiopharmaceuticals – Steve Zigler, Ph.D.
- Overview of USP Activities and How to Get Involved – Ravi Ravichandran, Ph.D.
- Latest Developments in USP Monographs and the Compounding of Sterile Radiopharmaceuticals – Jim Ponto, R.Ph.
The third session was a Continuing Education Session entitled, “PET Drug Manufacturing: Current Topics Related to the FDA and USP.” The session was held on Tuesday afternoon. The session was co-organized by Sally Schwarz, R.Ph. and Steve Zigler, Ph.D. Dr. Zigler moderated the session.
The presentations are available here:
- Introduction and Year in Review – Steve Zigler, Ph.D.
- FDA’s eCTD Mandate for 2017: Latest Developments – Phillip DeNoble, Pharm.D.
- Harmonizing FDA Regulation and the Practice of Pharmacy: Challenges and Opportunities – Michael Nazerias, M.S.
- Latest USP Initiatives: Monographs, General Chapters, and Compounding – Jim Ponto, R.Ph.
SNMMI submitted comments to the FDA on draft guidance “Compounding and Repackaging of Radiopharmaceuticals by State-Licensed Nuclear Pharmacies.” The guidance explains that, under current law, radiopharmaceuticals compounded or repackaged by state-licensed nuclear pharmacies and federal facilities are subject to all applicable provision of the FD&C Act related to the production of drugs. However, FDA recognizes that state-licensed pharmacies and federal facilities sometimes compound or repackage radiopharmaceuticals for patients who need them without obtaining FDA approval or meeting certain other requirements.
According to FDA, “the policies proposed in the draft guidances attempt to strike an important balance between patient access to radiopharmaceuticals compounded or repackaged by state-licensed nuclear pharmacies, federal facilities, and outsourcing facilities, and the risks that such unapproved drugs present to patients.”
SNMMI is broadly supportive of the direction of this guidance. As previously stated, SNMMI strongly recommends that FDA work with USP to develop a common understanding of activities defined and involved in the compounding of radiopharmaceuticals.
SNMMI has submitted comments on other general guidances related to compounding, but has long awaited specific guidance for radiopharmaceuticals. The society also recently provided recommendations to USP on sterile compounding of radiopharmaceuticals. SNMMI commends the FDA for the release of this guidance and encourages the FDA to support USP in the public standard setting process.
Read SNMMI’s full comment letter »
SNMMI has developed USP recommendations for compounded sterile radiopharmaceuticals. The recommendations aim to address certain common practices in the field of nuclear pharmacy that are not adequately defined by generally accepted practice standards. The society believes there is confusion in the field of nuclear pharmacy, which threatens the availability and the safe usage of radiopharmaceuticals in the U.S. The recommendations are a response to these challenges. The recommendations were developed by SNMMI’s Committee on Radiopharmaceuticals (COR) and approved by SNMMI’s Board of Directors. The COR worked with several professional organizations and trade associations in an attempt to rectify the situation. Our efforts to date have met with some success, but have still fallen short of realizing suitable standards that are generally accepted for common practices in nuclear pharmacy.
The COR believes that the USP, as the world’s leading organization for the development and maintenance of public standards, can play a critical role in the resolution of these challenges. The three recommendations from the white paper are:
- Recommendation 1. Establish an expert panel to delineate common practices that are defined as sterile compounding within the practice of nuclear pharmacy.
- Recommendation 2. Create a public standard for the preparation, compounding, and dispensing of sterile radiopharmaceuticals with the practice of nuclear pharmacy.
- Recommendation 3. Reinstate an expert committee dedicated to all standards for radiopharmaceuticals.
On September 29, SNMMI President Sally Schwarz sent the letter to the USP, where it is currently under consideration. Further details will be provided as they become available.
Access SNMMI’s full white paper »
On December 28th, the FDA issued two draft guidances that describe FDA’s proposed policies regarding the compounding and repackaging of radiopharmaceuticals for human use by state-licensed nuclear pharmacies or federal facilities, and outsourcing facilities. According to FDA, “the policies proposed in the draft guidances attempt to strike an important balance between patient access to radiopharmaceuticals compounded or repackaged by state-licensed nuclear pharmacies, federal facilities, and outsourcing facilities, and the risks that such unapproved drugs present to patients.”
The first draft guidance, “Compounding and Repackaging of Radiopharmaceuticals by State-Licensed Nuclear Pharmacies,” explains that, under current law, radiopharmaceuticals compounded or repackaged by state-licensed nuclear pharmacies and federal facilities are subject to all applicable provision of the FD&C Act related to the production of drugs. However, FDA recognizes that state-licensed pharmacies and federal facilities sometimes compound or repackage radiopharmaceuticals for patients who need them without obtaining FDA approval or meeting certain other requirements.
The second draft guidance, “Compounding and Repackaging of Radiopharmaceuticals by Outsourcing Facilities,” highlights that section 503B of the Federal Food, Drug, and Cosmetic Act applies to the compounding of radiopharmaceuticals, but not to radiopharmaceuticals that are repackaged, by outsourcing facilities. It proposes how FDA would apply the conditions of section 503B to radiopharmaceuticals compounded by outsourcing facilities. This guidance also specifies the conditions under which FDA does not intend to take action for violations of provisions of the FD&C Act regarding new drug approval requirements and labeling with adequate directions for use against an outsourcing facility that repackages radiopharmaceuticals.
The comment period for each of the draft guidances closes in 60 days. To submit your own comments, visit regulations.gov.
The U.S. Food and Drug Administration recently released a summary of the movement to require certain regulatory submissions to conform to the electronic Common Technical Document (eCTD) format.
The eCTD has been the standard format for submitting applications, amendments, supplements, and reports to the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) since 2008.
View FDA’s summary »
On September 28, 2016, the U.S. Nuclear Regulatory Commission published Licensing Guidance for Eckert and Ziegler GalliaPharm Germanium-68/Gallium-68 Pharmacy Grade Generator. All sections of this guidance apply to both medical licensee and commercial nuclear pharmacy licensee use of this generator unless otherwise specified. This guidance does not apply to licensees or applicants that will receive unit or bulk doses of Gallium-68 (Ga-68) radiopharmaceuticals rather than use the Eckert and Ziegler GalliaPharmTM generator themselves. These licensees and applicants will be regulated under Title 10 Code of Federal Regulations (10 CFR) 35.200 and, as such, authorized users (AU) must meet the requirements in 10 CFR 35.290.*
In July, NRC a memo authorizing regions to issue an exemption from decommissioning funding plan requirements (DFP) in 10 CFR 30.35(a)(1) for the possession and use of Germanium-68/Gallium-68 generators, when certain conditions are met.
*The Coalition is aware that this draft guidance applies only to Eckert and Ziegler generators and is working with the NRC to ensure that future guidance includes other generators.
Access the licensing guidance here »