The Coalition’s Latest Efforts
USP Opens Call for Volunteers to Serve on Expert Committees
December 9, 2024 - The Coalition would like to make the PET 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 and Expert Panels. The Call for Candidates opened is open until March 2025 and may be found on the USP’s website (https://callforcandidates.usp.org/). 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 application process is quite simple and potential applicants are encouraged to apply as soon as possible. If you have any questions, please contact Charles Metzger [cmetzger(at)petdrugmanufacturers.org].
Coalition announces Board of Director ballot results
October 4, 2024 - Following a high level of membership voting participation (over 75%), we are pleased to announce that the following individuals will begin their terms as voting members of the board:
David Dick, PhD / University of Iowa
Sharon Lee, PhD / University of Pennsylvania
The board extends sincere appreciation to all candidates for their commitment and readiness to contribute to our shared goals and they look forward to working together with them in upcoming Coalition projects. With David and Sharon's election, the composition of the board is now three voting members from commercial entities and four from academic institutions. Review the newly reconfigured leadership team here.
Coalition releases position paper on stability studies
July 23, 2024 - During our 2023 FDA PET Drugs Workshop, one topic that garnered much attention was stability testing performed on PET drugs and the FDA’s recent policy changes in this area. The position paper discusses these changes, which, if implemented, will have a profound impact on the supply of PET drugs in the USA.
Beginning in 2023, some FDA inspections highlighted the requirement for PET manufacturers to perform stability testing at every manufacturing facility on an annual basis. Initially, this appeared to be erroneous since the inspections occurred at facilities listed in approved applications with a stability protocol that described the “one stability, one facility” approach. The PET community was further surprised during the November 2023 FDA workshop when the agency repeatedly noted the need to clarify the PET GMPs and stressed that the regulations require stability testing at each facility annually. However, in fact, careful examination of the PET GMP regulations, PET guidance documents, and the general regulations for drug marketing reveals that this requirement does not appear to be explicitly stated. To download the paper in its entirety, click here.
Announcing a CMS OPPS proposed rule that will result in improved patient access to diagnostic radiopharmaceuticals
On July 12, CMS released its fiscal year 2025 proposed rule on the Medicare hospital Outpatient Prospective Payment System (OPPS), and it included adjustments to an existing packaging policy for diagnostic radiopharmaceuticals established in 2008. CMS stated, “We propose to pay separately for diagnostic radiopharmaceuticals with per day costs above a threshold of $630, which is approximately two times the volume weighted average cost amount currently associated with diagnostic radiopharmaceuticals. We also propose to update the $630 threshold in CY 2026 and subsequent years by the Producer Price Index (PPI) for Pharmaceutical Preparations.”
Along with many organizations, universities, hospitals and industry partners, the Coalition enthusiastically supports this change to the current OPPS bundling system. CMS’ reimbursement of higher-priced diagnostic radiopharmaceuticals with per-day costs above a $630 threshold will allow patients access to new, more advanced diagnostic nuclear medicine procedures. The change will also align CMS’ radiopharmaceutical reimbursement policy with those for many other drugs included in the OPPS.
This would replace a system wherein diagnostic radiopharmaceuticals are treated as “supplies” and reimbursed through a packaged payment system. The methodology averages the higher cost of these specialized products with more general and widely used lower-cost radiopharmaceuticals, thus overpaying for the low-cost products and underpaying for the higher-cost products. This results in healthcare institutions not being able to provide these services. creating a significant barrier to patient access to the newer, more precise generation of diagnostic nuclear imaging drugs.
The proposed rule is published annually and will have a 60-day comment period, which will end on September 9, 2024. The final rule will be issued in early November and will take effect January 1, 2025. For more information (including how to comment), browse https://www.federalregister.gov/public-inspection/2024-15087/medicare-and-medicaid-programs-hospital-outpatient-prospective-payment-and-ambulatory-surgical.
Coalition Leadership Holds Open Board Meeting at SNMMI 2024 Conference
June 10, 2024 - Over 40 PET drug manufacturing stakeholders joined the Coalition’s open board meeting as did three representatives of the FDA. Our agenda was as follows:
7:00 a.m. Welcome and Introductions
7:05 a.m. Treasurer’s Report
7:10 a.m. Coalition Update and Latest Developments
7:25 a.m. FDA Refusal to Receive (RTR) for PET Submissions
7:40 a.m. Update on November 2023 FDA Workshop
7:45 a.m. Closing Thoughts and Q&A
Stream the YouTube video of the open board meeting
Please note that due to some AV/Zoom complexities, you will observe some slide irregularities about 11.5 minutes into the video (for about 10 minutes).
Visit a page devoted to sharing hyperlinks to the “regulatory pointers” documents. Also included on this page is an ANDA checklist referred to by the FDA’s Ravi Kasliwal.
Coalition Leadership Wishes Everyone a Happy National Positron Emission Tomography Day
May 11, 2024 (5/11) - Each year, the Coalition celebrates 5/11 as national Positron Emission Tomography (PET) Day.[i] Currently, there is no official designation for 5/11, but if May the 4th is Star Wars Day, then 5/11 is a good day to celebrate the power of PET scans to provide patients with answers that no other imaging modality offers!
The Coalition strongly believes that the potential for PET scans to provide early disease detection and staging is critical for certain patient populations. In the US alone, PET scans provide answers to approximately 2.5 million patients each year.[ii]
Perhaps one day everyone will celebrate 5/11 and possibly even use the month of May as awareness month for patients who have undergone a PET scan. Until then, the Coalition would like to thank you for your support. The Coalition is nothing without its members! Together, the Coalition will continue to make a difference in the lives of millions of patients each year!
[i] In case an explanation is necessary, the reference to 5/11 is based on the 511 keV gamma emissions produced by a PET drug. These emissions form the basis for all PET imaging techniques.
[ii] Source: IMV 2023 PET Imaging Market Summary Report.
Coalition Schedules Open Business Meeting for June 10 in Toronto
April 30, 2024 - Coalition leaders are preparing to host our annual business meeting at the Metro Toronto Convention Centre (Room 206CD in the North Building) on Monday, June 10, 7:00 a.m. - 8:00 a.m. Our preliminary agenda includes:
7:00 a.m. Welcome and Introductions
7:05 a.m. Treasurer’s Report
7:10 a.m. Coalition Update and Latest Developments
7:25 a.m. FDA Refusal to Receive (RTR) for PET Submissions
7:40 a.m. Update on November 2023 FDA Workshop
7:45 a.m. Closing Thoughts and Q&A
We intend to offer Zoom/remote access to the meeting. More details to follow.
Coalition Completes Development of Bylaws
Apr 22, 2024 - Motivated by the desire to ensure that the Coalition flourishes long after they have completed their leadership terms, the Coalition’s Board of Directors finished and approved the organization’s bylaws. You may download the bylaws here. Leadership spent countless careful hours (generating at least 16 versions!) before approving the bylaws. Future amendments to the bylaws will require a 2/3 majority vote of the membership at any regular or special meeting.
Coalition Submits Comments regarding FDA’s Draft Report and Plan on Best Practice for Guidance
Feb 26, 2024 - The Coalition's comments the FDA’s draft report were developed by a working group over the course of a month and were discussed, slightly modified and approved by the Board. You can download the comments here. A key excerpt from the cover letter follows:
“Upon careful considerations of the evolving nature of the regulatory and compliance landscape of diagnostic radiopharmaceuticals, the Coalition does not support automatic implementation of Level 1 and 2 Guidance that can impact the manufacturing and/or regulatory submission of PET/diagnostic drugs at this time. Instead, the Coalition requests continuing engagement through Guidance review cycles and the use of comment periods.”
“The community has demonstrated its commitment to meeting review cycles over the last decade, and it is committed to maintaining timely and effective processes that will support the continued development of diagnostic radiopharmaceutical that are safe, effective and available to providers and patients.”
FDA Working Group members involved in the comment process include: Cristen Brown, Giuseppe Carlucci, Marianna Dakanali, Christopher Ignace, Hilary Lee, Ashley Mishoe, Michael Nazerias, Michael Nickels, Reiko Oyama, Jill Wilson, and Charles Metzger. These individuals and the Coalition Board devoted this time and energy on behalf of all USA PET drug manufacturers.
Coalition Submits Comments regarding the Proposed Revision to USP Chapter 823
Jan 30, 2024 - The Coalition's comments regarding USP <823> were developed by a working group over the course of a few months, submitted to constituents for their suggested modifications, and finally discussed, modified and approved by the Board. You can download the comments and cover letter here. A key excerpt from the cover letter follows:
“The Coalition supports the removal of “compounding” from <823>. Beyond that, the Coalition believes many of the proposed revisions of <823> are a major departure from the currently official chapter. The Coalition further believes the proposed revisions lack justification based on the existing track record, the low risk level, and the current regulatory framework for PET drugs. The proposed revision of <823> affects all PET drug manufacturers, especially those involved in new product development. Consequently, the Coalition believes the adoption of the proposed revisions would substantially impede innovation and jeopardize the future growth of PET drugs and PET imaging.”
USP <823> Working Group Members include: Keith Bowen, Marianna Dakanali, Brian Hockley, Sharon Lee, Steve Mattmuller, Charles Metzger, Reiko Oyama, Peter Scott, and Eric Webster. We appreciate the time, energy and expertise of the dedicated volunteers!
Joint Workshop on PET Drug Regulations with FDA, Coalition of PET Drug Manufacturers, MITA, and SNMMI
Silver Spring, MD – The Coalition of PET Drug Manufacturers (the Coalition), Medical Imaging & Technology Alliance (MITA), and the Society of Nuclear Medicine and Molecular Imaging (SNMMI), the leading collective voices of PET drug manufacturers, recently co-hosted a workshop on Positron Emission Tomography (PET) Drugs: Product Quality Regulatory Submissions, Facility Inspections, and Benefit-Risk Considerations with the U.S. Food and Drug Administration (FDA).
The supply chain of PET drugs in the US is a unique combination of academic and commercial manufacturing facilities, and we are pleased to have the opportunity to bring these stakeholders together with the FDA. Not only did this event provide a forum for bringing better understanding to PET drug regulations, but it also allowed for nuanced consideration of challenges and possible solutions. The sustainable supply of PET drugs is critical for patient care now and in the future and this event set the stage for the continued evolution of the regulatory environment in this area.
The event, held on November 13 and 14, has become a recurring event and had the highest level of attendance to date, confirming the importance of periodically assessing the state of PET drug manufacturing to ensure continued patient access to life saving imaging exams. It provided a forum for stakeholders to discuss regulatory considerations on a wide range of topics, including facility inspections and compliance, product quality considerations and regulatory applications, control and safety issues and risk management as well as broader trends impacting PET drug regulation.
The Coalition, MITA, and SNMMI represent the interests of more than 150 PET drug manufacturing facilities in the US consisting of academic self-producers and commercial suppliers delivering just-in-time manufactured PET drugs to patients. In addition, the three groups support numerous organizations and institutions involved in research and innovation to guide new radiopharmaceutical diagnostics and therapeutics through the FDA market approval process. Select this link to access presentation videos and PDFs.
Coalition Finalizes FDA PET Drugs Workshop Agenda
With the help of many volunteers from academia and industry, and through efficient collaboration with the FDA, the PET Drugs Workshop agenda is now complete. New for this year’s meeting will be final, half-day, extended Q&A session. Questions for the FDA were gathered from Coalition members and non-member constituents and submitted to the FDA.
Already over 150 have registered to attend in person; over 500 have registered to attend virtually. The workshop will take place November 13-14, 2023. There is still actual and virtual space for more attendees. Select this link to learn more.
Leadership Team Awards and Accomplishments in 2023
Henry VanBrocklin, PhD was named the 2023 recipient of the prestigious Paul C. Aebersold Award for outstanding achievement in basic science applied to nuclear medicine. VanBrocklin is a professor in the Department of Radiology and Biomedical Imaging and director of the Radiopharmaceutical Research Program in the Center for Molecular and Functional Imaging at the University of California, San Francisco. Henry is a founding member of the Coalition and currently serves as co-chair.
Sally Schwarz, MS, RPh, BCNP was named the 2023 recipient of the Michael J. Welch Award for outstanding contribution to the field of radiopharmaceutical sciences. Schwarz is professor in the Department of Radiology in the Division of Research Imaging Facilities at Washington University in St. Louis, Missouri. Sally is also a founding member of the Coalition and currently serves as board member. She is also a former president of the SNMMI.
Peter J. H. Scott, PhD was named the 2023 recipient of the Sam Gambhir Trailblazer Award for excellence in transformative research and exceptional mentorship. Scott is associate professor of radiology and pharmacology, division director of nuclear medicine, and director of the PET Center at the University of Michigan in Ann Arbor, Michigan. Peter serves as a Coalition board member.
Cathy S. Cutler, PhD was named as president-elect for the SNMMI, having been elected by membership as vice president-elect in 2022. Cutler has long been an active leader at SNMMI and is currently director of the medical isotope research and production program at Brookhaven National Laboratory in Upton, New York. Cathy serves as a Coalition board member.
Coalition Held June 26 Business Meeting during SNMMI Meeting in Chicago
Our business meeting was open to all and was held on Monday, June 26, 2023, from 7:00 a.m. to 8:00 a.m. in the Lakeside Building at McCormick Place. Over 50 people attended in-person, and over 15 attended via Zoom. To view a YouTube video of the entire meeting, browse https://youtu.be/Ug3nbjOaFIs.
Our agenda:
A. Welcome and Introductions
B. Coalition Update and Latest Developments
C. Introduction to Online Member Forum
D. Update on 2nd FDA Workshop on Inspections Management and Regulatory Considerations
E. Treasurer’s Report and Next Steps
F. Closing Thoughts and Q&A
Announcing an Advocacy Opportunity – Support the FIND Act
The nuclear medicine community is busy advocating on Capitol Hill for the Facilitating Innovative Nuclear Diagnostics (FIND) Act on Capitol Hill. HR 1199 establishes appropriate payment for diagnostic radiopharmaceuticals under the Medicare hospital outpatient setting. Please feel free to use either of the following grassroots tools to easily send a letter of support to your Member of Congress. If you want additional information regarding the FIND Act Coalition efforts, please contact Sue Bunning [sbunning(at)medicalimaging.org] or Julia Bellinger [JBellinger(at)snmmi.org].
Right Scan Right Time Grassroots Tool
SNMMI Support the FIND Act Tool
March 13, 2023 Coalition Open Board Meeting Details Latest Efforts, including an FDA Workshop Update
During our March 13 Open Board Meeting, we devoted most of our time to:
Update regarding holding an FDA Workshop and cooperation with the FDA, SNMMI, MITA, and the WMIS (Steve Zigler)
A) The Coalition (in collaboration with the SNMMI, MITA, and the WMIS) sent a proposed agenda to the FDA.
B) After our meeting, the FDA indicated that they would like to organize a workshop on November 13, 2023.
C) This is great news, and the Coalition is moving forward with planning.
E) Henry VanBrocklin and Steve Zigler will be gathering data on PET drug safety for the meeting and for writing a white paper.Working group updates:
A) Effective Communication Working Group (Nick Freiburger) - testing of our online forum will begin soon
B) FDA Intelligence Working Group (Peter Scott) - this survey will be completed soon
C) Regulatory Pathways Working Group (Steve Mattmuller) - based on feedback, this survey requires further modification
To download one-page minutes of the meeting, click here.
November 14, 2022 Coalition Open Board Meeting Details Latest Efforts, including Working Group Updates
During our November 14 Open Board Meeting, we devoted most of our time to:
Update regarding FDA and cooperation with the Coalition and MITA (Chris Ignace)
Working group updates:
A) Remote Regulatory Assessment Response Working Group (Chris Ignace)
B) Effective Communication Working Group (Nick Freiburger)
C) FDA Intelligence Working Group (Peter Scott)
D) Regulatory Pathways Working Group (Steve Mattmuller)
To access a YouTube video of the meeting (with detailed slides), browse https://youtu.be/F5-JpOrVATs.
After Gaining Constituents' Input, the Coalition Submitted Comments to the FDA Draft Guidance to Expand Remote Regulatory Assessments
In a federal register notification on July 25th, 2022 (https://www.govinfo.gov/content/pkg/FR-2022-07-25/pdf/2022-15812.pdf) and reported by Thompson FDA here (click this link), the FDA announced that they will be expanding their remote regulatory assessment program “across all FDA-regulated products beyond the current COVID-19 public health emergency,”. Docket FDA-2022-D-810 (https://www.regulations.gov/docket/FDA-2022-D-0810)
The agency released a draft guidance “Conducting Remote Regulatory Assessments Questions and Answers Draft Guidance for Industry” (https://www.regulations.gov/document/FDA-2022-D-0810-0002) that is open for review and comments. Comments are due to the FDA by September 23, 2022.
The Coalition sought comments from members and non-members to submit on behalf of PET drug manufacturers. To that end:
We created a Google Form to collect your comments/input. That form was closed on August 31.
Coalition leaders considered all input provided by August 31 and created a preliminary draft letter to submit to the FDA.
We uploaded to this page a preliminary draft of our letter to the FDA and asked Coalition constituents to provide any suggestions for improvement through a Google Form by September 20.
Coalition leadership reviewed these inputs and submitted the final letter on September 21, 2022.
Coalition Held Its First Open Board Meeting on August 15, 2022
On Monday, August 15, at 3:00 p.m. US CDT, the Coalition Board held its first open session. This was a practice suggested by attendees of our meeting in Vancouver, and leadership thought it was a great idea. We chose to hold this first Open Board Session as a Zoom Webinar. This meant that attendees were muted and unable to share their cameras during the meeting, but – when the time came – we asked people to raise their hands and then enabled them to ask audible questions.
Agenda (condensed) for Open Board Meeting - Download the Minutes (Word file) or Access the Video Recording via YouTube
Welcome and introduction (Henry VanBrocklin; Steve Zigler)
Working groups based on our project needs (Peter Scott; Steve Zigler)
Seeking additional volunteers for these workgroups by (Peter Scott; Steve Zigler)
Opening the meeting up to general attendee input (Steve Mattmuller)
Other business (Henry VanBrocklin)
Next open meeting November 14, 2022 (3:00 PM US CT)
Close meeting (Henry VanBrocklin)
Coalition of PET Drug Manufacturers Comments on FDA Recordkeeping Burden
On June 6, 2022, the Coalition submitted comments to the FDA on the recordkeeping burden associated with the PET Good Manufacturing Practice (GMP) regulations at 21 CFR part 212. The comments were in response to a Federal Notice on April 7, 2022, wherein the FDA requested comments under the Paperwork Reduction Act of 1995. In the Notice, the FDA included estimates of the recordkeeping and third-party disclosure burdens that are required to comply with the PET GMP regulations. The notice also describes some of the methodology that the FDA used to develop these estimates.
The Coalition submitted comments on numerous areas of importance:
In the Notice, the FDA referred to “high-risk” component manufacturers and stated that the Agency performs risk assessments of each manufacturer. However, the Coalition is not aware of a science-based risk profile based on the intrinsic characteristics of PET drugs and the manufacturing processes used in their preparation. In the absence of a publicly available risk assessment for PET drugs, the application of risk-based decisions for PET drugs can only be characterized as a subjective exercise in perceived risk. To correct this deficiency, the Coalition proposed that FDA work with PET manufacturers to develop a science-based risk profile for PET drugs. Further, the Coalition suggested that the risk analysis consider the intrinsic safety factors of PET drug products, such as the mass of the active radiopharmaceutical ingredient, the likelihood of a pharmacological response, radioactivity levels, potential for repeat uses, manufacturing methods, sterility assurance, etc. Until the completion of a risk assessment for PET drugs, the Coalition recommends that the FDA refrain from subjective classifications such as “high risk.”
The Coalition supports the collection of recordkeeping information by the FDA and believes it is necessary for the proper performance of FDA’s functions. The Coalition believes that accurate assessments of the documentation and recordkeeping requirements are especially important for the FDA to fully understand the impact of these activities on PET drug manufacturers due to the small number of personnel at PET manufacturing facilities. Consequently, the recordkeeping burden disproportionately impacts PET drug manufacturers to a greater extent than traditional pharmaceutical manufacturers.
Based on the estimates in the Notice, the Coalition believes the actual recordkeeping burden is a factor of at least 10 times or more than the estimates in the Notice. The Notice does not explicitly state if the FDA estimates account for differences in paper-based and electronic systems. The Coalition believes it is important to make this distinction and to include the effort required to develop and maintain paper-based and electronic systems. In other words, documentation and recordkeeping are more than the completion of forms. The effort required to develop and maintain these systems should be included in FDA assessments.
To enhance the quality, utility, and clarity of the information, the Coalition believes the estimates will be improved if the FDA works with the Coalition to obtain the appropriate data through surveys or questionnaires. The Coalition proposed that the FDA and the Coalition jointly develop a survey to obtain recordkeeping estimates directly from PET drug manufacturers. The Coalition could distribute the surveys, then collect and compile the data for use by the FDA and the PET community.
Finally, the Coalition suggests that the FDA provide details about how the Agency uses the collected information to define regulatory tactics for PET drug manufacturing. For example, does the FDA use this information to define inspectional strategies, expectations compliance activities, or for other purposes?
Coalition Holds Business Meeting at SNMMI Annual Meeting in Vancouver
On Monday, June 13, 2022, the Coalition of PET Drug Manufacturers held a business meeting during the annual meeting of the SNMMI in Vancouver. Approximately 40 attendees participated in person in addition to an on-line audience. The agenda is below, and a YouTube recording of the meeting is available here.
To download a 17-page PDF transcript of the meeting, click here.
7:00 am: Welcome and Introductions
Steve Mattmuller, R.Ph., BCNP
7:05-7:12 am: Coalition History and the Creation of a New Trade Association
Sally Schwarz, R.Ph., and Henry VanBrocklin, Ph.D.
7:12-7:20 am: Mission, Goals, and Latest Developments
Sally Schwarz, R.Ph., and Henry VanBrocklin, Ph.D.
7:20-7:30 am: Highlights: “Proceedings: PET Drugs: A Workshop on Inspections Management and Regulatory Considerations”
Steve Zigler, Ph.D.
7:30-7:40 am: Going Forward
Peter Scott, Ph.D.
7:40-7:55 am: Q&A
7:55-8:00 am: Closing
Coalition Publishes Proceedings of February 2020 Workshop
The Coalition’s latest work is the publication of the proceedings of a workshop that the Coalition organized in February 2020. The workshop was entitled “PET Drugs: A Workshop on Inspections Management and Regulatory Considerations” and was attended by radiopharmaceutical scientists, nuclear pharmacists, regulatory affairs professionals, and compliance specialists with expertise in PET drug manufacturing. Attendees represented academic institutions, commercial suppliers, contract manufacturers, and innovators involved in the development of new PET drugs. Many representatives from the FDA also attended. Approximately 150 attendees participated in-person and numerous participants joined in a live video broadcast of the event. The presentations and a recording of the workshop are currently available on the FDA’s website.
Four predominant needs emerged from the workshop, which are summarized here as follows:
The uniformity in the review of PET drug applications and the inspection of PET manufacturing facilities.
A science-based risk profile for PET drugs.
Improvements to training for FDA investigators and the regulated community
Continued dialog between the FDA and the PET community.
Coalition leadership members Sue Bunning, Steve Zigler, Sally Schwarz, and Steve Mattmuller at a PET Drugs Workshop in February 2020. (Leadership members not pictured: Henry VanBrocklin, Peter Scott, Christopher Ignace.)
Uniformity in the review of PET drug applications and the inspection of PET manufacturing facilities. The FDA has received numerous NDAs and ANDAs for PET drugs. The reviews of these applications frequently result in different questions and different requirements placed upon applicants. This is further complicated by the fact that different FDA offices are responsible for the review of NDAs and ANDAs. In addition, once a PET drug is approved, the FDA must perform inspections at approximately 150 different manufacturing facilities for PET drugs. These inspections often result in different observations and different requirements placed on manufacturing facilities. What may be a significant finding at one facility may not even be noticed at another. This is also complicated by the fact that different FDA offices perform various types of inspections, and it is not possible to determine the level of coordination and alignment of the various offices involved in the inspection of PET manufacturing facilities. This variability creates confusion among PET drug manufacturers and ultimately undermines the intent of FDAMA and the PET GMP regulations; if left unaddressed, this could undermine the uniformity of the PET drug supply that all stakeholders desire to achieve. Therefore, the Coalition calls on the FDA to improve the uniformity of FDA inspections at PET manufacturing facilities. One FDA speaker at the workshop conceded that “the variability of FDA inspections is inevitable.” However, the FDA can minimize, if not eliminate, variability in PET inspections by implementing several relatively simple steps .
A science-based risk profile for PET drugs. As with all medical procedures, inherent risk factors are associated with the use of PET drugs. Several FDA speakers during the workshop described the importance of risk-based approaches for both the review of applications for PET drugs and in the execution of inspections of PET manufacturers. This approach is consistent with pharmaceutical quality initiatives implemented by the FDA in 2002. However, the Coalition is not aware of a science-based risk profile that is based on the intrinsic properties of PET drugs and the manufacturing processes used in their preparation. Further, the little information that exists in this area is not uniformly understood within the FDA or across the PET community. Thus, the application of the risk-based approach to PET drugs can only be characterized as a subjective exercise in perceived risk by applicants, individual reviewers and investigators. To correct this deficiency, the Coalition calls on the FDA to work with PET manufacturers to develop a science-based risk profile for PET drugs. The evaluation of risk factors, rates of occurrence, and mitigating strategies should be evaluated based on the characteristics of PET drugs. The risk analysis should consider the intrinsic safety factors of PET drugs that have been described elsewhere, such as the mass of the active radiopharmaceutical ingredient, the likelihood of a pharmacological response, radioactivity levels, potential for repeat uses, etc. The analysis should be published and openly available to the regulated community. By working together with PET manufacturers, the results of this exercise will provide transparency to the regulated community and will better inform FDA review practices and inspectional policies.
Improvements to training for FDA investigators and the regulated community. Over time, FDA personnel change and new people become involved in the review of PET drug applications and in the inspection of PET drug manufacturing facilities. Consequently, there is a continual need for educational resources for new entrants in this field.
During the workshop, the FDA noted the need to improve training programs for investigators. Few educational programs exist to address the technology of PET drug manufacturing. The FDA should continue to work with the Coalition to develop and adopt educational resources from the PET community. Like all continuing education materials, the FDA’s training program for investigators should be regularly reviewed, updated, and administered on an ongoing basis.
Continued dialog between the FDA and PET manufacturing community. The workshop provided an invaluable forum for the FDA and PET drug stakeholders to exchange ideas, issues, and challenges associated with the regulation of PET drugs. The workshop was only a start: the PET GMP regulations are less than 10 years old and the experiences with the Agency and the PET community will continue to evolve. The long-term sustainable implementation of new regulations requires time and a routine dialog. It is critical for the FDA and the PET community to share information outside formal channels associated with the review of an application or an inspection. To that end, the FDA and the PET community should commit to holding this workshop in alternating years for the foreseeable future. Interim informational meetings should continue to take place between the FDA and PET stakeholders during the SNMMI annual meeting to address new and ongoing issues associated with the approval and regulation of PET drugs.