CPDM Presents at SNMMI’s 2021 Annual Meeting

Posted on June 25, 2021 by carenas24

On June 14, 2021, CPDM presented during SNMMI’s virtual annual meeting. Presently, the recording of the CE session is unavailable. The presentation slides are posted below.

Coalition of PET Drug Manufacturers: A New Trade Association?

Industry Perspective on the Impact of COVID-19 on FDA Inspections and Regulation of PET Drug Manufacturers

Academic Perspective on the Impact of COVID-19 on FDA Inspections and Regulation of PET Drug Manufacturers

PET Community Hosts FDA Workshop

Posted on February 18, 2020 by Dalton Clark

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

USP Opens Call for Volunteers to Serve on Expert Committees

Posted on August 6, 2018 by C. Kubler

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.

Coalition for PET Drugs Meeting Presentation Available

Posted on July 5, 2018 by C. Kubler

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>.

USP Presentations from SNMMI Annual Meeting Available

Posted on June 29, 2018 by C. Kubler

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:

Coalition for PET Drugs Sponsors Three Sessions at SNMMI Annual Meeting

Posted on July 11, 2017 by C. Kubler

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:

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:

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:

SNMMI Comments to FDA on Compounding

Posted on May 5, 2017 by C. Kubler

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 Develops USP Recommendations for Compounded Sterile Radiopharmaceuticals

Posted on January 26, 2017 by C. Kubler

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 »

FDA Issues Draft Guidances on Compounding and Repackaging Radiopharmaceuticals

Posted on January 26, 2017 by C. Kubler

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.

FDA Releases SBIA Summary of eCTD Requirements

Posted on October 27, 2016 by C. Kubler

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 »

NRC Licensing Guidance for Eckert and Ziegler Ge-68/Ga-68 Generator

Posted on October 20, 2016 by C. Kubler

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 »

Coalition Comments on PET GMP Recordkeeping Burden

Posted on March 1, 2016 by C. Kubler

On February 29, 2016, the Coalition submitted comments to the FDA on the burdens associated with the PET drug Good Manufacturing Practice (GMP) regulations at 21 CFR part 212. As previously reported, the FDA issued a Federal Notice on December 29, 2015. FDA included in their notice estimates of the recordkeeping and third-party disclosure burdens that are required to comply with the PET GMPs. The notice also describes some of the methodology that the FDA used to develop these estimates. The notice is in response to the Paperwork Reduction Act of 1995, which requires the FDA to estimate the recordkeeping burden required to comply with the PET GMPs.

The Coalition submitted comments on three areas of importance:

Whether the proposed collection of information is necessary for the proper performance of FDA’s functions, including whether the information will have practical utility
The accuracy of FDA’s estimate of the burden of the proposed collection of information, including the validity of the methodology and assumptions used
Ways to enhance the quality, utility, and clarity of the information to be collected

View the Coalition comment letter

Public Comments for PET GMP Recordkeeping Burden

Posted on January 15, 2016 by C. Kubler

The Coalition would like to make PET drug manufacturers aware of an announcement from the FDA that appeared in the December 29, 2015, issue of the Federal Register. The notice announces the opportunity for public comment on the annual recordkeeping and third-party disclosure burdens associated with the PET drug Good Manufacturing Practice (GMP) regulations at 21 CFR part 212. The notice is in response to the Paperwork Reduction Act of 1995, which requires the FDA to estimate the recordkeeping burden required to comply with the PET GMPs.

The notice contains the FDA’s estimates of the recordkeeping and third-party disclosure burdens that are required to comply with the PET GMPs. In addition, the notice describes some of the methodology that the FDA used to develop these estimates. Through the notice, the FDA invites comments on the following specific topics:

Whether the proposed collection of information is necessary for the proper performance of FDA’s functions, including whether the information will have practical utility;
the accuracy of FDA’s estimate of the burden of the proposed collection of information, including the validity of the methodology and assumptions used;
ways to enhance the quality, utility, and clarity of the information to be collected; and
ways to minimize the burden of the collection of information on respondents, including through the use of automated collection techniques, when appropriate, and other forms of information technology.

The comment period is open until February 29, 2016. The Coalition is considering options in response to this notice and will update this website as appropriate. Individuals, PET drug manufacturers, and any other stakeholder may submit comments. The notice is available at this URL: https://www.federalregister.gov/articles/2015/12/29/2015-32685/agency-information-collection-activities-proposed-collection-comment-request-current-good

USP Seeking Comments on General Chapter Revisions. Deadline approaching!

Posted on November 11, 2015 by C. Kubler

The US Pharmacopeia (USP) is currently in the process of revising several general chapters that are important to the nuclear medicine community. The USP sets public standards that serve patients, academia, industry, regulators, healthcare professionals, and other stakeholders. As a long-standing part of the revision process, the USP seeks public comments on revisions before adopting final resolutions. Comments from the public play an important role in the USP standards setting process!

Chapter <821> Radioactivity describes requirements for instrumentation used in radioactivity measurements. The Expert Committee responsible for this chapter has revised <821> to update, clarify, and simplify the chapter. In addition, the Committee has created a new informational chapter <1821> to complement <821>. Once finalized, <821> will serve as an enforceable chapter with requirements for instruments used in radioactivity measurements and <1821> will serve as a source of educational information relevant to radioactivity measurements.

Simultaneously with changes to chapters <821> and <1821>, the USP is also introducing a new informational chapter <1823>, which is a source of educational information relevant to PET drugs. These chapters are available on the USP Key Issues page. In addition to the Key Issues page, the USP Quality Matters blog contains more information about these revisions. See: http://qualitymatters.usp.org/updating-quality-standards-nuclear-medicine-and-radioactive-materials.

Stakeholders are encouraged to participate in the standard setting process by commenting on these revisions. Stakeholders include radiopharmaceutical manufacturers and other entities that make radioactivity measurements according to USP standards. The USP is accepting public comments on these revisions until November 30, 2015.

Reminder: Two-year post approval inspections

Posted on November 5, 2015 by C. Kubler

The Coalition would like to share some important reminders with PET Drug manufacturers that may be coming up on their two-year post approval inspection. Below is a list of items FDA inspectors recently asked for in one of the current inspections. This serves as a reminder to make sure you have all of your GMP documentation and reports up to date and ready for your FDA inspection.

Organizational Chart
Position/job description for each personnel in the facility
Bill of lading (interstate shipment document; 18O-H2O)
Table of contents for all SOPs
Out of specification investigations and follow-up for the past 24 months
Floor layout with air specification labeled for each room
SOP-LAFW qualification report (Vendor annual qualifications and reports)
SOP-equipment qualification and maintenance of main instruments involved with production + analytical procedures
SOP- Environmental, Personnel
SOP-Personnel training and aseptic technique training records
SOP-ISO 5 cleaning area
SOP-Media Fill and qualification of personnel records
SOP-Vendor qualification
SOP-Microbiological media qualification
SOP-Manufacture batch/QC records for the past 24 months
SOP-Stability test
SOP-Document Change records
SOP- Out of Specification
SOP- Manufacture and QC methods
SOP- Procedure for actions taken for any sterility failures.

Important Change to NDA 021870

Posted on August 11, 2015 by C. Kubler

The Coalition would like to make PET drug manufacturers aware of a change to an FDA-approved application for Fludeoxyglucose F 18 Injection (FDG). This modification involves the radioactivity concentration (strength) for FDG described in new drug application (NDA) 021870, which is held by the Feinstein Institute for Medical Research. This change only applies to NDA 021870 and became effective on July 9, 2015. Specifically, the change was to increase the maximum radioactivity concentration from 300 mCi/mL to 400 mCi/mL.

While the modification may not seem significant at first glance, it raises the question of the potential impact on abbreviated new drug applications (ANDAs) that reference NDA 021870. To address this question, members of the PET community have contacted the FDA Office of Generic Drugs (OGD) for clarification. In response, OGD stated that it is not necessary to change the radioactivity concentration in ANDAs that reference NDA 021870. Consequently, no revisions to the product label are required for these ANDAs, nor is it necessary to perform new stability studies.

However, the change allows for an increase in the concentration of FDG up to 400 mCi/mL for ANDAs that reference NDA 021870. If an ANDA holder elects to change the concentration of the product described in their application, applicants are advised that changes to their specific product would require new stability studies, as well as an updated label that is revised as part of a prior approval supplement. In the communication from OGD, they noted that a suitability petition is not required to support a concentration up to 400mCi/mL.

Thanks to Dan Yokell at Massachusetts General Hospital and Bob Wolfangel at Certis International for bringing this information to the attention of the Coalition. The Coalition will share further information on this topic as necessary.

More information on NDA 021870 may be found on the FDA’s “Drugs@FDA” website at this URL. In the search window, type 021870 to access the NDA.

More information on prior approval supplements may be found in the post entitled, “Sponsored Session from SNMMI Annual Meeting: Current Topics in FDA Reviews and Inspections of PET Drug Manufacturers,” that appeared on the Coalition’s website on June 25, 2015 (see below).

Coalition Comments on Generic Drug User Fee Act

Posted on July 14, 2015 by C. Kubler

The Coalition for PET Drugs submitted comments to the U.S. Food and Drug Administration (FDA) on the reauthorization of Generic Drug User Fee Act (GDUFA). In general, the Coalition supports GDUFA and believes that user fees have successfully provided the FDA with the resources necessary for timely review of applications for typical generic drug products.

View the entire letter here »

Slide Presentations from “FDA: Imaging Drug Development – Regulatory Issues” CE Session

Posted on June 30, 2015 by C. Kubler

The Coalition is following up on a message that we posted on May 29. In that posting, we highlighted a session at the recent SNMMI annual meeting entitled “FDA: Imaging Drug Development – Regulatory Issues.” The session was sponsored by the Health Policy and Regulatory Affairs group at SNMMI. For more information about the session, take a look at the May 29 posting.

Today, the Coalition would like to make you aware that the presentations from this session are now available on the FDA website. So, in case you missed the session or would like to review the presentations, here is the URL:

http://www.fda.gov/Drugs/ScienceResearch/ResearchAreas/
Oncology/ucm093322.htm#presentations

Important Upcoming Events at SNMMI Annual Meeting in Baltimore

Posted on May 29, 2015 by C. Kubler

The Coalition would like to make you aware of some important events at the upcoming SNMMI annual meeting in Baltimore. We hope you can attend!

On Friday, June 5 from 9 to 10 am in the room Ruth in the Baltimore Hilton Hotel, the Coalition, led by Sally Schwarz, R.Ph. and Henry VanBrocklin, Ph.D., will hold a public meeting to review activities over the last year and to discuss future directions.

The Coalition is co-sponsoring a CE session with the Radiopharmaceutical Sciences Council (RPSC) on Monday, June 8, in Room 317 of the Baltimore Convention Center. The title of this session is “Current Topics in FDA Reviews and Inspections of PET Drug Manufacturers.” The session runs from 4:45 to 6:15 pm and includes the following presentations:

Current topics in FDA reviews and inspections from the perspective of a small entity, Steve Mattmuller, MS, RPh, BCNP
Current topics in FDA reviews and inspections from the commercial perspective, David Wilson, BS, RPh
Reporting changes to an approved NDA or ANDA, Michael Nazerias, M.S.
Overview of a sterility assurance program for PET drugs, Eric Webster

An additional session has recently been added to the program. The additional session is entitled “Update on Current Topics at the USP” and takes place immediately after the previous session on Monday, June 8, in Room 317 of the Baltimore Convention Center. The goal of the new session is to provide an update on the latest activities at the USP related to PET drug monographs and the revision of general chapters for PET drugs and radioactivity. In addition, information will be provided for the next revision cycle and future directions at the USP. The session runs from 6:20 pm to 6:50 pm and includes the following presentations:

Brief update on USP monographs for PET drugs, Steve Zigler, Ph.D.
Progress on general chapters pertinent to nuclear medicine, Steve Zigler, Ph.D.
Update on new revision cycle 2015-2020, Ravi Ravichandran, Ph.D.

Finally, a session entitled “FDA: Imaging Drug Development – Regulatory Issues” takes place on Tuesday, June 9, from 10:00 am to 11:30 am in Room 318-319 of the Baltimore Convention Center. This session is sponsored by the Health Policy and Regulatory Affairs group at SNMMI and includes the following presentations:

Chemistry, manufacturing, and control (CMC) issues in applications, Ravi Kasliwal, Ph.D.
Nonclinical requirements for low dose diagnostic agents: past, present, and envisioning the future, Adebayo Laniyonu, Ph.D.
Efficacy considerations for imaging product approval, Louis Marzella, MD, Ph.D.
Statistical aspects of evaluating diagnostics, Thomas Gwise, Ph.D.
PET products: case histories and inspectional updates, Krishna Gosh, Ph.D.
Ge-68/Ga-68 Generators – FDA perspective, John Amartey, Ph.D.

Coalition Sponsors Session on FDA Topics

Posted on June 24, 2014 by C. Kubler

The Coalition for PET Drug Approval recently sponsored a session focused on FDA topics for PET drug manufacturers. The session was held at the 2014 annual meeting of the Society of Nuclear Medicine and Molecular Imaging (SNMMI) in St. Louis. The session drew more than 100 attendees, representing academic PET drug manufacturers, commercial PET drug manufacturers, FDA representatives, and others. Five speakers covered a range of topics including Coalition activities, ANDA/NDA submission considerations, how to handle FDA inspections, and post-approval commitments for NDA and ANDA holders. The presentations generated numerous questions from the audience, including discussions of next steps and potential sessions at next year’s annual meeting of the SNMMI.

In case you missed the session, the presentations are available here:

A Passion for Policy

Posted on May 15, 2014 by C. Kubler

By: Ashley Mishoe, PharmD

Brenda Uratani. To those of us in the positron emission tomography (PET) community, this is a name associated with dedication to PET, a spirit of guidance, and a passion for safety. At the recent SNMMI Mid-Winter Meeting, Brenda announced her retirement from the United States Food and Drug Administration (FDA) and pursuit of new opportunities in the private sector. I am excited to share her story because of her key role in shaping the PET drug community we have today.

Dr. Uratani first began her career with the FDA as a review microbiologist in the Office for New Drug Chemistry within the Center for Drug Evaluation and Research (CDER). Her primary focus in this position was reviewing new drug applications (NDAs) and abbreviated new drug applications (ANDAs) and critically evaluating investigations and validation studies regarding sterile drugs. She tells me that her background in experimental design and her studies in microbiology became quite helpful in understanding the types of contaminants possible, pinpointing the origins of potential contaminants, and determining appropriate end-product testing.

Enter 1999 and a decade that would completely change Brenda’s career (not to mention add a lot more pages to her curriculum vitae). That year, Dr. Uratani was assigned to the FDA’s mandate of developing good manufacturing practices (GMPs) and guidance documents for a new (and vastly different) area—PET drug manufacturing. She tells me that when she was first assigned to this project, she knew nothing about PET drugs or the PET community. However, Brenda made it her goal to become more familiar with the processes and the inherent issues involved in PET drug manufacturing. She visited more than ten manufacturing facilities in her first year (including those in research, commercial, and academic settings), and she spent countless hours studying the processes involved and asking questions along the way. As the draft GMPs started to take form, Dr. Uratani led FDA-initiated public meetings, where she acted as a key liaison between the FDA and the PET community.

I know what you’re thinking. Creating GMPs for one country is definitely a big enough goal to fill a person’s career. For the average person, you are probably right. But not for her; no, not for Brenda. Why take on one country, when you could tackle two? And by “two,” I mean she also conquered China. From 2009 to 2011, Dr. Uratani was appointed as the Assistant Country Director for the FDA’s analysis of the China FDA (SFDA). In this position, she served as the FDA’s liaison in China, where she influenced the Chinese government as they were revising and developing new GMPs for sterile drug products and also screened drugs to be exported. While Brenda enjoyed her experiences abroad, after two years, she was ready to return to the States. She didn’t return empty-handed, though; she brought with her a newfound knowledge of international trade and a better understanding of foreign policy and drug manufacturing abroad.

Skills. Brenda obviously has them, and I wanted to know what she thought were the most crucial skills when formulating new policies. Her answer was not surprising, and it was one that should be applied to all aspects of life. “Active listening and teamwork,” Brenda explains, “are critical in policy development.” Some of the experiences that taught her the most were listening carefully to the concerns of stakeholders in the PET community, understanding the paradigm shift the leaders were facing, and fully grasping the inherent safety concerns surrounding PET drugs. Brenda says that the most cherished part of her job was overcoming the challenges that arose when working with the PET community, and she adds that she is most gratified by the outcome of the PET regulations.

Because of her dedication to the field of PET, I was also anxious to hear Dr. Uratani’s thoughts for the future of PET drug manufacturing. Fortunately, she thinks that it is very bright, and she tells me that it is gratifying to reflect on how far the standards have come since the draft GMPs. I can hear the pride in her voice as she admits that she considers PET her “baby” and that she has enjoyed watching the PET community grow and develop into the relatively mature field it is today.

Although she is passionate about policy formation, Dr. Uratani recently left her career at the FDA to pursue new goals. She now works for Genentech Roche as a Senior Principal Tech Advisor. Brenda has fond memories of her days with the FDA; however, she is also excited to be starting something new.

Ultimately, the PET community is grateful for her contributions to the field, her dedication to quality standards, and for her unwavering support. She may not be with the FDA any longer, but she leaves behind a legacy as their expert in PET GMPs—a legacy that will always be remembered.

Her heart, her passion, her effort—it was GMPs, it was ensuring the safety of PET drugs for patients, and it was fighting for appropriate PET drug manufacturing standards. Brenda’s mission was creating policies that would simultaneously protect patients while enabling the growth of a new industry, and this mission resulted in an unparalleled set of quality standards for PET drug manufacturing. For these things, and in the name of patients who benefit from PET drugs every day, we are thankful and are fortunate to have had such a strong, dedicated person like Brenda. Good luck, Brenda!

My name is Ashley Mishoe. I am a PET nuclear pharmacist, a follower of all things GMP, and I am thankful for the work of Brenda.

Coalition Submits Comments on ANDA Draft Guidance

Posted on April 4, 2014 by C. Kubler

The Coalition for PET Drug Approval submitted comments to the FDA on March 24 to address Improving the Quality of Abbreviated New Drug Application Submissions.

FDA announces Q&A guidance on Oversight of PET Drug Products

Posted on December 4, 2012 by C. Kubler

On Tuesday, December 4, 2012, the Food and Drug Administration announced the availability of a guidance entitled, “FDA Oversight of PET Drug Products- Questions and Answers.” The Q &A’s cover almost all areas of the FDA approval and surveillance processes, including applications submissions, review, and compliance with good manufacturing practices, inspections, registrations/listing and user fees.

For the complete Federal Register notice, please click on the following:
http://www.gpo.gov/fdsys/pkg/FR-2012-12-04/html/2012-29157.htm

FDA announces availability of IND applications for PET Drugs

Posted on December 4, 2012 by C. Kubler

On Tuesday, December 4, 2012, the Food and Drug Administration announced the availability of a guidance entitled, “Investigational New Drug Applications for Positron Emission Tomography (PET) Drugs.” This guidance will support manufacturers of PET drugs in submitting investigational new drug applications (INDs).

For the complete Federal Register notice, please click on the following:
http://www.gpo.gov/fdsys/pkg/FR-2012-12-04/html/2012-29163.htm

FDA Approves Choline C11 Injection for Prostate Cancer Detection

Posted on September 13, 2012 by C. Kubler

The U.S. Food and Drug Administration (FDA) announced today the approval for the production and use of Choline C 11 Injection, a PET imaging agent used to help in the detection of prostate cancer.

Choline C 11 Injection is administered intravenously to produce an image that helps to locate specific body sites for follow-up tissue sampling and testing in men with recurrent prostate cancer.

The Mayo Clinic is the first facility approved to manufacture Choline C 11 Injection. The agent is manufactured and distributed by the Mayo Clinic PET Radiochemistry Facility in Rochester, Minn.

To read the full FDA press release, visit: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm319201.htm

NORTH SHORE/LIJ HEALTH SYSTEM RECEIVES EXPANDED ACCESS IND

Posted on July 10, 2012 by C. Kubler

North Shore/LIJ Health System has recently received FDA approval of an expanded access IND for Fluorodopa F-18 PET for Parkinsonian diseases.

FDA also approved the facility’s request to seek payment for the studies, however CMS approval must be granted for Medicare reimbursement. In the FDA –approved Expanded Access IND, 18F-dopa with PET is indicated to detect loss or no loss of dopaminergic neurons in the striatum in patients with parkinsonian syndromes. These two conditions are visually detected using a Fluorodopa F-18 PET scan.

Dr. Thomas Chaly has indicated willingness to share the IND for use as reference by other facilities seeking to submit similar applications. According to Dr. Chaly,

“Fluorodopa PET technology is superior to SPECT and the images are easy to interpret. The Striatal Occipital Ratio quantification (SOR) available with the PET technology will help to avoid false positives and negatives. Fluorodopa F 18 PET will reduces the scanning time for patients considerably. There are many advantages to Fluorodopa F 18 PET imaging. I am excited and many Medical centers will be very happy to have this.”

Facilities interested in the expanded access IND for Fluorodopa F-18 PET for Parkinsonian diseases can contact Dr. Chaly directly:

Thomas Chaly, PhD, FAIC
Chief, Radiochemistry/Cyclotron
The Feinstein Institute for Medical Research
Associate Professor
North Shore/LIJ Health System
350 Community Drive
Manhasset, New York, 11030
(516)562-1042
tchaly@nshs.edu

COALITION SUBMITS COMMENTS ON DRAFT GUIDANCE

Posted on May 30, 2012 by C. Kubler

The Coalition for PET Drug Approval submitted comments to the FDA on the draft guidance entitled “Investigational New Drug Applications for Positron Emission Tomography (PET) Drugs”.

The draft guidance document is intended to assist manufacturers of PET drugs in submitting investigational new drug applications (INDs). The draft guidance summarizes the IND process for PET drugs, makes recommendations for how to submit an IND, provides advice on expanded access options for investigational PET drugs, and describes the process for requesting permission to charge for an investigational PET drug.

The Coalition comments focus on the limits to the number of patients and the amount of time that the expanded access IND may be held by the physician investigators. To view the comment letter, CLICK HERE.

FDA ISSUES GUIDANCE ON MEDIA FILLS FOR VALIDATION OF ASEPTIC PREPARATIONS FOR PET DRUGS

Posted on April 11, 2012 by C. Kubler

The FDA has released the final Guidance on Media Fills for Validation of Aseptic Preparations for Positron Emission Tomography Drugs.

This guidance is being issued consistent with FDA’s good guidance practices regulation. The guidance represents the Agency’s current thinking on media fills and process simulations for PET drugs. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. An alternative approach may be used if such approach satisfies the requirements of the applicable statutes and regulations.

To view the guidance: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM273766.pdf

FDA ISSUES DRAFT GUIDANCE ON INDS FOR PET DRUGS

Posted on February 14, 2012 by C. Kubler

The FDA has announced the availability of a draft guidance document entitled, “Investigational New Drug Applications for Positron Emission Tomography (PET) Drugs”.

The draft guidance is intended to assist manufacturers of PET drugs in submitting investigational new drug applications (INDs). The draft guidance summarizes the IND process for PET drugs, makes recommendations for how to submit an IND, provides advice on expanded access options for investigational PET drugs, and describes the process for requesting permission to charge for an investigational PET drug.

Comments will be accepted until May 14, 2012 and may be submitted in writing or electronically through http://www.regulations.gov (Search Docket No. FDA-2012-D-0081).

To view the draft guidance: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM291573.pdf

FDA TO OFFER WEBINAR ON SPL FOR PET MANUFACTURERS

Posted on February 3, 2012 by C. Kubler

FDA has scheduled a webinar to assist PET drug manufacturers prepare their SPL files prior to the new deadline. The webinar will be offered on April 23, 2012.

For more information: http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/ucm155705.htm

Please Note: While registration is free, pre-registration is required.

To register, please submit the following information via e-mail to spl@fda.hhs.gov:

1. Attendee’s first and last name
2. Name of your organization
3. Session name and date of training session(s) for which you are registering.

You will be limited to one phone/web conference line per company.

FDA ISSUES FAQ GUIDANCE FOR CGMP FOR PET DRUGS

Posted on February 2, 2012 by C. Kubler

UPDATE: FDA has posted new draft guidance – FDA Oversight of PET Drug Products, Questions and Answers.

FDA has published a revised version of the FAQ guidance initially published on the agency’s website on February 2, 2012. The guidance is intended to help producers of PET drugs meet the requirements for FDA’s drug approval process. This guidance provides questions and answers that address nearly all aspects of the drug regulatory process, including application, submission, review, compliance with CGMPs, inspections, registration and listing and user fees.

The guidance is available at: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/
Guidances/UCM290024.pdf

Comments and suggestions regarding this draft document should be submitted either electronically or written documents by May 29, 2012.

FDA TO OFFER WEBINAR ON CGMP FOR PET DRUGS

Posted on December 21, 2011 by C. Kubler

The Food and Drug Administration (FDA) has announced a webinar on CGMP for PET drugs.

The FDA will offer a webinar on CGPM for PET drugs on Thursday, January 19, 2012, from 1:00pm – 3:00pm Eastern Standard Time.

At this time, there is no detail on the agenda items. Any additional information provided by FDA will be added here.

For more information on viewing the webinar or participating via conference line, please visit http://www.fda.gov/Drugs/DevelopmentApprovalProcess/Manufacturing/ucm284352.htm?source=govdelivery

FDA ANNOUNCES MEETING ON GENERIC DRUG USER FEE ACT

Posted on December 8, 2011 by C. Kubler

The FDA has announced a public meeting to discuss the proposed Generic Drug User Fee Act.

The Food and Drug Administration (FDA) has announced it will hold a public meeting to discuss the proposed recommendations for the Generic Drug User Fee Act (GDUFA), which will authorize FDA to collect fees and use them for the process for the review of human generic drug applications and associated Type II Active Pharmaceutical ingredient Drug Master Files (DMFs) and for conducting associated inspections for fiscal years 2013-2117.

The meeting will be held at the FDA’s White Oak Campus, Silver Spring, MD, on Monday, December 19th from 8:00am to 5:00pm ET. Registration is required to attend and must be received by December 12, 2011. The meeting will also be webcast.

For more information, please view the Federal Register announcement: http://www.gpo.gov/fdsys/pkg/FR-2011-12-08/html/2011-31630.htm

ADDITIONAL INFORMATION PROVIDED BY FDA

Posted on December 7, 2011 by C. Kubler

In response to an inquiry, the Food and Drug Administration (FDA) has answered several remaining questions.

In response to an inquiry from the Coalition for PET Drug Approval, Elizabeth Giaquinto of the FDA has answered the following lingering questions:

Has the deadline for filing an ANDA/NDA for N-13 Ammonia been extended? If so, what is the Agency’s new deadline? What should a site do if they are unable to submit a completed deadline by the December 12th deadline?

In response to both of these questions, FDA has decided that for the next six months, until June 12, 2012, FDA does not intend to take enforcement action against a PET facility currently producing any PET drugs for clinical use for failure to submit a new or amended drug application by December 12, 2011, provided that the facility complies with all other FDA requirements, including CGMPs.

FDA will not exercise enforcement discretion after June 12, 2012. Therefore, if a facility wishes to continue to produce PET drugs for clinical use after June 12, 2012, they must have submitted an NDA or ANDA by that data, or be producing drugs under an IND. PET facilities who are unable to submit an NDA or ANDA by June 12, 2012 or operate under an IND must find a new supplier who has submitted an NDA or ANDA. This policy is applicable to all PET drugs, including N-13 Ammonia.

Is the electronic Common Technical Document (eCTD) format required for submission?

FDA does recommend that electronic submissions (which are preferable because they facilitate FDA’s review of the application) follow the CTD format. Paper submissions must be organized in the CTD format.

How would an entity expand into a new location (or add a new production module) after the filing deadline?

Please refer to the chart for current thinking on this issue: FDA Current Thinking on Changes to Facilities or Equipment

FDA ISSUES NEW GUIDANCE FOR PET CGMP INSPECTIONS

Posted on November 10, 2011 by C. Kubler

The Food and Drug Administration (FDA) has posted new guidance for compliance with PET CGMP inspections.

The FDA posted the Compliance Program Guidance Manual for PET CGMP Drug Inspections. FDA’s Compliance Programs provide instructions to FDA personnel for inspecting facilities, sampling and analyzing FDA-regulated products, and initiating and implementing regulatory follow-up, when appropriate. FDA personnel who will be involved in evaluation PET production facilities are being trained to use the PET Compliance Program, to know the PET CGMP regulations and guidance, and to understand the unique aspects of PET production.

FDA has indicated it will offer webinars to the PET community to explain this program and provide general information about FDA inspection practices beginning in 2012. Information about the webinars will be posted as it is received.

To view the compliance manual, visit: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/UCM277416.pdf

FDA WEBINAR ON DRUG MASTER FILES

Posted on November 10, 2011 by C. Kubler

The Food and Drug Administration (FDA) will offer a webinar entitled “Introduction to the Drug Master File (DMF)”.

On Monday, November 14, 2011, at 11:00am ET, the FDA Center for Drug Evaluation and Research (CDER) Small Business Assistance Program will present a webinar entitled Introduction to the Drug Master File (DMF) which will discuss all aspects of filing a DMF, including when and why to submit a DMF; requirements and recommendations for formatting and submitting original DMFs and subsequent submissions; how DMFs are reviewed and common problems.

Registration is required to view the webinar. To register, please visit the website: https://collaboration.fda.gov/dmf/event/registration.html

To participate in listen-only mode, please dial:
Domestic: 800-857-0171
International: 517-319-9290
Password: 2718839

FDA POSITION ON INDS FOR PET DRUGS IN CLINICAL TRIALS

Posted on October 27, 2011 by C. Kubler

Recent questions posed to the FDA regarding the requirement for INDs for PET drugs used in clinical trials has drawn a clarifying response from the FDA on its position.

In response to questions posed regarding the requirement for INDs for PET drugs used in clinical trials, the FDA issued a clarifying statement:

“FDA has received several inquiries about the continued use of PET drugs (fludeoxyglucose F18 injection, sodium fluoride F18 injection, and ammonia N13 injection) in ongoing clinical trials for new uses of these products or to support clinical trials of therapeutics, and many have expressed concerns that if INDs are required at this time for these drugs, hundreds of ongoing clinical trials and certain proposed trials may be disrupted or delayed. As a result of these inquiries and concerns, we think it is necessary to clarify our position regarding these trials.

FDA’s position is:

• If the PET drug used in the clinical trial is being made at a facility for which manufacturing data have been submitted in an NDA or ANDA for the PET drug, then FDA will not object to use of the PET drug without an IND until December 12, 2015, if this and the other requirements in 21 CFR 312.2 are met (see 21 CFR 312.2(b)).
• However, if significant manufacturing deficiencies are found during the NDA/ANDA review, or during inspection of the facility the PET drug is sourced from, FDA may notify the sponsor that the PET drug should no longer be used in clinical trials.

After December 12, 2015, investigational use of a PET drug must be covered by an IND unless it is exempt from all of the IND requirements.

We were also asked about what documentation must be provided to support an IND that is already in effect for a therapeutic drug which relies on a PET diagnostic drug to monitor disease progression or otherwise evaluate the efficacy of the therapeutic drug. For this scenario, before December 12, 2015, no CMC documentation for the PET drug needs to be submitted to the IND for the therapeutic drug as long as the PET drug is manufactured at a facility for which supportive manufacturing information has been submitted in an NDA/ANDA. After December 12, 2015, for PET drugs manufactured at facilities that are not named in an approved NDA or ANDA, CMC documentation for the PET drug will need to be submitted to the IND for the therapeutic drug.

Sponsors have asked other questions such as how an investigator will know whether an NDA/ANDA has been submitted and what records should be submitted to document that the PET drug was sourced from a facility named in a submitted NDA/ANDA. Documentation should be maintained at the trial site where the investigation is being conducted that indicates the number of the NDA/ANDA that contains the CMC data for the facility from which the drug is sourced. Over the next several months, clinical investigators should make sure this documentation is in place for the PET drugs used in their investigations.

We will be addressing these issues in guidance on investigational drugs as well as in a guidance responding to numerous questions we have received over the past several months. These guidances will be published in draft, and we will look forward to receiving comments from affected parties and making necessary revisions to the guidance as appropriate.”

FDA ISSUES DRAFT GUIDANCE ON MEDIA FILLS OF ASEPTIC PREPARATIONS FOR PET DRUGS

Posted on October 6, 2011 by C. Kubler

The Food and Drug Administration (FDA) has issued a draft guidance entitled “Media Fills for Validation of Aseptic Preparations for Positron Emission Tomography (PET) Drugs”.

The draft guidance is intended to help manufacturers of PET drugs meet the requirements for the Agency’s current good manufacturing practice regulations of PET drugs. The draft guidance, once finalized, will represent the Agency’s current thinking on media fills and process simulations for PET drugs.

Interested persons should submit comments through http://www.regulations.gov, Docket No. FDA-2011-D-0691, by December 29, 2011.

To view the draft guidance, please visit: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM273766.pdf

FDA TO HOLD ANNUAL INSPECTIONS SUMMIT

Posted on September 19, 2011 by C. Kubler

The U.S. Food and Drug Administration (FDA) announced its Sixth Annual Inspections Summit to be held October 4 – 6, 2011.

The Sixth Annual FDA Inspections Summit will be held at the Hyatt Regency, Bethesda, MD, October 4-6, 2011. The rate FDA issues 483s and warning letters is going up, up, up. The agency has already issued 874 letters in fiscal 2011, compared with 673 for all of last year. FDA’s emphasis on enforcement has led to more, better-educated FDA investigators and more inspections this year.

Who Should Attend:

•Executive Management
•Regulatory Affairs
•Quality Assurance/Quality Control
•Legal and Compliance Officers
•Clinical Research Directors
•Consultants/Service Providers

For more information, please visit: http://www.fdanews.com/conference/detail?display=0&eventId=3042&hittrk=119QRN

FDA ISSUES GUIDANCE FOR FILING PET NDAs AND ANDAs

Posted on September 1, 2011 by C. Kubler

The Food and Drug Administration (FDA) issued guidance for industry entitled “PET Drug Applications – Content and Format for NDAs and ANDAs.”

The guidance is intended to assist the manufacturers of certain PET drugs – FDG, ammonia N 13, and sodium fluoride F 18 – in submitting NDAs and ANDAs in accordance with FDA regulations. In order to continue to market PET drugs for clinical use, manufacturers must submit NDAs or ANDAs by December 12, 2011.

In addition to the guidance for filing the applications, FDA has provided sample formats for the Chemistry, Manufacturing, and Controls (CMS) section.

To view the final guidance, please visit: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM078738.pdf

To view the sample formats for the CMC section, please visit: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM078740.pdf

Update: Q & A from FDA Meeting on March 2, 2011

Posted on August 16, 2011 by C. Kubler

The Coalition for PET Drug Approval has compiled questions and answers that were posed during the FDA Public Meeting on March 2, 2011.

We continue to develop answers to the questions posed by Coalition representatives during the FDA meeting. Please check back regularly to see additions to the Q & A. Questions are sorted by area of most relevance.

Acceptability of Filing an ANDA:

Q: When we submit our ANDA, do we need to submit all of the method validation data, or will that be reviewed at the time of the FDA inspection (after submission of the ANDA)?

Dr. Kasliwas of the FDA stated that validation data, the analytical validation data and other validation data has to be submitted in the application, and it’s part of the review process. During inspection, the inspector may look at the source data.

Administrative:

Q: The guidance provides reference to and advice to format an application in the CTD format. The attachments to the guidance which provides sample format are not formatted according to CTD format. As a result, the discussions and suggestions regarding the formatting of the application are inconsistent and confusing. What is the correct format for the application?

Dr. Shimmer of the FDA stated that the Electronic Technical Document (eCTD) format is the preferred format. Recognizing that most are going to be submitting…a few ANDAs, it may not make sense to invest monetarily to submit via…the eCTD format. So there are other options, and these other options are these hybrid electronic submissions, which amount to scanned electronic copied organized in the CTD format.

They can be submitted via the Gateway or they can be submitted on physical media. So by physical media, I mean CDs or DVDs…you are required to use hyperlinks.

Q:The guidance provides that paper applications are acceptable. Discussion is provided regarding an electronic submission. The way the information is presented does not make a clear differentiation between submitting an application “electronically” on media, such as a pdf file on CD-ROM, versus an electronic submission of an e-CTD (which is an xml formatted file) through an established FDA electronic portal. Please advise as to how to submit a CD-ROM copy with a paper submission. It is our understanding that this has become an expectation of the FDA which is not mentioned.

Dr. Shimmer stated that FDA will take them, will review them… but applicants must submit multiple copies…and also submit a red chemistry or review copy and a maroon copy to the field. If you submit in paper, you have to submit a copy to your local field to facilitate the inspection. Even if you make a paper submission, labeling is still required to be submitted electronically.

Compliance and Inspections:

Q: Can the initial FDA inspection for an academic setting be scheduled in advance since academic sites don’t have a corporate QA office that can jump on a plane and guide the consumer safety officer through the facility and associated paperwork (and instead have patients each day to serve)?

Mr. Hasselbalch of the FDA noted a tradition of pre-scheduling or scheduling preapproval inspections. So it’s not unknown to FDA to call in advance and make arrangements for the time we’ll arrive. FDA is encouraging that now.

FDA will continue to do so and perhaps consider specifying, in particular, academic sites more lead time so they can be better prepared and have the appropriate people on site for that inspection.

You need to be prepared, that part, 212.110, says that records should be readily available for review and coying by FDA employees….we understand these are small facilities and you may need help, but you also should be organized such that you should have enough resources, given the appropriate schedule, to be able to handle an inspection.

Q: The FD&C Act specifies that inspections will be made upon drug producers once every two years. However, in the Q&A for the proposed 21 CFR Part 212, the statement is made that the FDA will continue to perform surveillance inspections of a number of PET facilities each year. Please clarify the inspection profile.

Does this mean that each PET facility, producing commercial materials, will be inspected within the two years beginning December 12, 2011?

Mr. Hasselbalch indicated that these are fairly standard objectives. FDA thinks they apply just as well to PET production facilities as they do to other types of facilities….FDA does these inspections to verify readiness for production and GMP compliance…and understands that PET drugs are now generally in commercial production…this year there are a lot more inspections due to submission of ANDA and NDA applications.

Q: Will PET facilities submitting ANDA/NDA and registering in accordance with section 510 of the FD&C Act be inspected prior to the approval of their ANDA/NDA? If so, under what timeframe and against what checklist/inspection criteria?

There is currently no PET Production Inspection Guidance available. The FDA is in process of writing this Guidance, but it will hopefully be available later this year.

Q:Inspections have raised the issue on the requirement of mandatory standard for cyclotron maintenance including target rebuilds. Can the FDA comment on the relevance of the request (given the nature of performance of the cyclotron and final product testing)?

This question was not directly discussed during the public meeting. Dr. Kasliwal did mention that the information regarding the cyclotron that the FDA will want to see as part of the process are parameters such as beam current, bombardment times and information on the type of target body material and target windows.

Environmental Monitoring and Aseptic Processing:

Q: What is the FDA position on growth promotion testing for solid media? Currently, there have been differing responses from FDA inspectors, depending on the area of the country where the inspections are occurring. If we need to perform these tests, can we test 3 lots of material to validate our source of media from a specific manufacturer, and then perform the test on an annual basis? Or will the FDA require growth promotion testing on every lot of media?

Dr. Parella stated, for PET drugs, growth promotion testing is not a requirement for solid media for environmental monitoring. You don’t need to do growth promotion, but it is an incoming component. So you need to quality the vendor. You really need to have some identity to make sure that, in fact, it’s a reliable supplier and that the transportation doesn’t compromise the media. But as long as all of that is okay, then growth promotion is not required.

Q: Is growth promotion testing required on liquid media? How frequently is the testing required? Can 3 consecutive lots of media be tested to validate the manufacturer’s process and shipping; with single lot testing annually thereafter?

When media are purchased “ready-to-use” from a commercial vendor, the first three batches should be tested for growth promotion as part of the vendor qualification. Commercially prepared media used in the sterility test should be used within the label’s shelf life, stored according to the label’s recommendations, and one batch should be tested for growth promotion periodically (e.g. quarterly).

The periodic growth promotion testing could be performed in conjunction with an operator qualification as long as their timing is close. If this is the case, a positive control should be prepared by inoculating a separate vial from te same batch of media used for the media fill. This will also serve as a growth promotion test. The microbiology department within your hospital is an acceptable laboratory to perform this testing.

INDs for Investigational Use of PET Drugs:

Q: Will an IND need to be submitted by the December 12, 2011 deadline to support the use of an investigational PET drug in the situation where the investigational use has been ongoing without an IND?

FDA does not plan for sponsors to stop the ongoing PET drug investigational use in patients/subjects while the newly submitted IND is under 30 day FDA review. Instead, the investigational use of the PET drug can continue during the 30 day review. If FDA becomes aware of special concerns during or at the conclusion fo the review, FDA will contac the sponsors.

Q: Will FDA publish guidance on expanded access INDs?

FDA is developing guidance on expanded access INDs and anticipates this will be made available in Spetember 2011. FDA does expect thtat expanded access INDs will be an option for continued clinical use of certain PET drugs.

Production:

Q: System suitability requirements in USP 823 suggest that the tailing factor and resolution (or column efficiency, as appropriate) are to be determined on a daily basis. This frequency is too often; these should be included with other chromographic parameters that are to be determined on a more reasonable basis (e.g., six months). What is the FDA’s view on this for manufacturing under ?

Dr. Kasliwal and Dr. Duffy of the FDA stated that it is acceptable to have a different procedure than outlined in USP for determining system suitability, but that any differences must be justified based on specific circumstances and the FDA will evaluate the strength of the justification and make a ruling during the review of the NDA/ANDA applicaton. Dr. Perrella of the FDA stated that system suitability still needs to be performed on a daily basis.

Q: 212.50(f) Would an NDA/ANDA submission be deemed adequate with the inclusion of the production and stability of a single batch if a full testing is always performed?

This question was not asked during the public meeting. Dr. Kasliwal mentioned in his presentation that the FDA expects to see stability data for three batches at the upper range of the proposed radioactive concentration as part of the application.

Q: Is identity testing on Mannose Triflate required (other than the ‘test’ in which Mannose Triflate can be used to produce FDG)?

Dr. Kasliwal mentioned in his presentation that a specific identity test is not required for mannose triflate because of the final product analysis, but there must be specifications for the mannose triflate that have to be met so that it can be released for the FDG production process.

Q: Expectations on handling invalid tests and sample size for repeat testing?

Dr. Perrella of the FDA stated that if a test is invalidated due to a technical issue and you can document the issue and the root cause, it is allowable to repeat the test. Both Dr. Duffy and Dr. Perrella of the FDA stated that the number of repeat tests needed depends on the nature of the test and the nature of the out-of-specification investigation.

Q: When is it necessary to dilute final product to meet the concentration specification? Is there a preference to use sterile water, normal saline or half normal saline?

This question was not directly discussed during the public meeting. In his presentation Dr. Kasliwal did mention that the diluting solution must be compatible with the drug product.

New FDA cGMP Guidance for Small Businesses Available

Posted on August 5, 2011 by SNMMI

The Food and Drug Administration (FDA) has announced the availability of a guidance for small business entities entitled “PET Drugs— Current Good Manufacturing Practice(CGMP); Small Entity Compliance Guide.” The guideline is intended to help small businesses better understand FDA’s thinking on compliance with the positron emission tomography drugs (PET) CGMP regulations, including appropriate resources, procedures, and documentation for PET drug production facilities.

← FDA ISSUES CHECKLIST FOR ANDAs

New FDA cGMP Guidance for Small Businesses Available →

FDA MEETING ON GENERIC DRUG USER FEE PROGRAM

Posted on July 22, 2011 by C. Kubler

The FDA has issued notice of an upcoming public meeting on a proposed generic drug user fee program.

The FDA announced a public meeting to provide an update and gather additional stakeholder input on the development of a generic drug user fee program. The program could provide needed resources to facilitate a more timely review of generic drug applications by the FDA.

The meeting will be held on August 25, 2011 from 2:00 – 3:30pm ET at the FDA White Oak Campus, Silver Spring, MD. Stakeholders may request to give an oral presentation; time allowed for presentations will be dependent upon the number of requests received.

To register for the meeting and/or request to present at the meeting, email GDUFA_Meeting3@fda.hhs.gov.

To view the Federal Register notice of the meeting: http://www.gpo.gov/fdsys/pkg/FR-2011-07-22/html/2011-18591.htm

FDA ISSUES CHECKLIST FOR ANDAs

Posted on June 28, 2011 by C. Kubler

The FDA CDER recently issued a checklist for filing ANDAs to ensure completeness and acceptability of an application.

To view the FDA issued checklist, CLICK HERE. Additionally, to prevent confusion among PET manufacturers who may be submitting an ANDA for the first time, we have simplified this checklist. To view the shortened checklist, CLICK HERE.

All of the items listed (except form 3674) are detailed in the Guidance PET Drug Applications Content and Format for NDAs and ANDAs Feb 2011: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM078738.pdf

Form 356h and 3674 may also be downloaded from the FDA website: http://www.fda.gov/AboutFDA/ReportsManualsForms/Forms/default.htm

FDA LABEL INFORMATION AVAILABLE THROUGH DAILYMED WEBSITE

Posted on May 31, 2011 by C. Kubler

DailyMed provides high quality information about marketed drugs including information about FDA labels (package inserts).

The DailyMed website provides health information providers and the public with a standard, comprehensive, up-to-date, look-up and download resource of medication content and labeling as found in medication package inserts. The National Library of Medicine (NLM) provides this as a public service and does not accept advertisements.

Visit the DailyMed website: http://dailymed.nlm.nih.gov/dailymed/about.cfm

Other information about drugs may also be available. NLM regularly processes data files uploaded from FDA’s system and provides and maintains this Web site for the public to use in accessing the information. Additional information about medicines is available on NLM’s MedlinePlus Web site http://www.nlm.nih.gov/medlineplus/medicines.html.

REQUIREMENT FOR SUBMISSION OF CERTIFICATION FORM (FDA 3674)

Posted on May 24, 2011 by C. Kubler

FDA will require applicants to include an additional certification form not mentioned during the public meeting on March 2, 2011.

We wish to call your attention to a requirement for submittal of a certification form to FDA with drug applications which was not mentioned at the March 2, 2011 FDA meeting or elsewhere in guidance FDA has provided on PET applications, nor on the application check list. Thanks to Jim Slater at UCSF for calling this to our attention. Jim learned of this requirement in a conversation with Martin Shimer at OGD.

View the certification form (FDA 3674) and an FDA guidance which describes what types of applications require this certification form to accompany the submission.

PRESENTATIONS AND TRANSCRIPT FROM FDA MEETING NOW AVAILABLE

Posted on May 24, 2011 by C. Kubler

The Food and Drug Administration (FDA) has made the materials from the March 2, 2011 public meeting available on their website.

FDA held a public meeting on March 2, 2011, to assist applicants in preparing NDAs or ANDAs for fludeoxyglucose (FDG) 18 injection, ammonia N 13 injection, and sodium fluoride F 18 injection used in PET imaging. By December 12, 2011, FDA expects all producers of PET drugs in commercial clinical use will begin submitting applications for marketing approval. FDA recognizes that many PET producers are unfamiliar with the drug approval process. Accordingly, FDA offered the meeting to discuss the drug approval process including drug registration and listing for PET producers and the general inspection process.

CLICK HERE to visit the FDA webpage with the meeting presentations.

CLICK HERE to view the meeting transcript.

EDUCATIONAL SESSIONS ON FDA REGULATIONS OFFERED AT SNM ANNUAL MEETING

Posted on May 20, 2011 by C. Kubler

The Society of Nuclear Medicine will hold its Annual Meeting in San Antonio, TX, in June 2011. Educational sessions offered during the meeting will include information on FDA regulations.

On Saturday, June 4, 2011, the SNM Clinical Trials will host a categorical session titled Molecular Imaging in Clinical Trials, Part I. This session will run from 7:30am to 11:30 am and include topics such as FDA inspections and audits and submitting an IND under .

Also on Saturday, June 4th, the FDA will host a session titled FDA: Drug, Device, and Biologic Regulatory Issues.This session will include speakers from the FDA and information on regulations that specifically cover PET radiopharmaceuticals.

For more information on these education sessions, please visit the SNM Annual Meeting Website.

FDA HOLDS PUBLIC MEETING ON GENERIC DRUG USER FEE PROGRAM

Posted on May 19, 2011 by C. Kubler

On Tuesday, May 10, 2011, the FDA hosted a public meeting to gather stakeholder input regarding a proposed generic drug user fee program. A user fee program could provide necessary supplemental funding, in addition to current Congressional appropriations, to facilitate the timely review of human generic drug applications by FDA, and FDA is currently in negotiations with the regulated industry aimed at providing a consensus proposal for congressional consideration.

FDA has reopened the docket at Regulations.gov (link no longer available) through which stakeholders can provide comment. The docket number is FDA-2010-N-0381.

To view a summary of the meeting: http://www.fda.gov/downloads/Drugs/NewsEvents/UCM255187.pdf

To view the slide presentation from the meeting: http://www.fda.gov/downloads/Drugs/NewsEvents/UCM255189.pdf

ANSWERS TO YOUR QUESTIONS

Posted on April 12, 2011 by C. Kubler

The Coalition for PET Drug Approval continues to pose questions to the FDA regarding compliance with 21 CFR 212. When feedback is received, those questions and answers will be posted here.

Below are questions with responses developed based on feedback received from the FDA:

1. USP Sterility mentions the use of several microbes and fungi to be tested under aerobic and anaerobic conditions. In a recent webinar offered through the FDA, during the question and answer session, the use of just one microbe was mentioned. If this is correct, which microbe would it be, i.e., E. Coli or something else? What exactly is an anaerobic incubator? After inoculation of our FTM and TSB Hungate media tubes, the environment inside the tube is considered anaerobic. In that case, how does one make a sealed Hungate tube aerobic? In the past, all tubes were inoculated and either stored at room temperature or placed in the incubator for the 14 day period. Are we going to be required to do something different?

For ready to use media from a qualified commercial supplier, the use of one of the aerobic species for TSB and one of the anaerobic species fro FTM is recommended. Species listed in USP Sterility Tests may be used. An anaerobic incubator is unnecessary if the FTM is handled properly. FTM should remain anoxic below the surface of the medium. USP recommends FTM is incubated at 30-35*C, and that TSB is incubated at 20-25*C. The incubation practices should conform to USP .

2. The intention of the promotion testing and/or operator simulation is to prove that the media being used actually grows organisms or replicates the operator qualification for manipulation of sterile products by using a positive control. It was mentioned on one of the slides that once vendor qualification was accomplished by completing three batches, that the sterility test or environmental monitoring media test could be done periodically. The sterility test must be done for each batch of PET drug product, it is unclear what was meant by “sterility test” on that slide. Furthermore, the same slide mentioned to test one batch “periodically” (e.g. quarterly) to see that you actually get a positive growth test.

Could the quarterly test be done in conjunction with an operator qualification if it just happens that both fall close to each other (within a couple of weeks) on the calendar? Is it acceptable if the Microbiology Department in the hospital completese this testing on our behalf? In this case, the Microbiology Department is equipped to handle inoculation of organisms into our sterile media and they have these microorganisms on hand and it is not desireable to introduce these microorganisms into the Radiopharmacy.

3. If, for example, the next quarter arrivesm, and you still have the same lots of FTM and TSB in your inventory, is it still necessary to replicate the test on the existing lot or can you wait until your existing lot is consumed, a new vendor lot arrives, and you proceed to test the new lot?

Only the first batch/lot fo the medium that arrives in the next quarter needs to be growth promotion tested, unless last quarter’s medium has not been stored according to the manufacturer’s recommendations. If the previous quarter’s medium has been stored according to the manufacturer’s recommendation and hasn’t reached expiry, that batch/lot may continue to be used.

4. Does the 100 mol bulk vial of TSB that we use in our operator qualifications for sterile manipulation also have to be tested for growth promotion. If it does, could we only do this procedure when we get a new vendor lot in inventory?

A positive control should be included in each media fill, prepared by inoculationga separate vial from the same batch/lot of medium used for the media fill. This will aslo serve as a growth promotion test for that lot of medium. If the medium used to prepare the media fill’s positive control provides acceptable growth promotion test results, then this may also serve to fulfill the requirement of periodic (e.g., quarterly) growth promotion testing.

COALITION FOR PET DRUG APPROVAL SEEKS COMMUNITY INPUT

Posted on March 29, 2011 by C. Kubler

The Coalition is seeking feedback on issues of concern or outstanding questions regarding the 21 CFR Part 212 regulation.

The purpose of the coalition is to help our community understand requirements related to the implementation of 21 CFR part 212 and the submission process for PET NDAs or ANDAs, and to make a positive impact on the overall implementation process through interaction with the FDA.

To fulfill this mission, the Coalition is asking PET manufacturers to submit questions that remain unanswered or concerns regarding the implementation and compliance with the CGMP for PET drugs. The Coalition will include these in communications with the FDA or order to benefit the community. To submit a question, please email Coalitionforpetdrugapproval@snm.org.

COALITION FOR PET DRUG APPROVAL FORMULATES QUESTIONS FOR FDA, SERIES #2

Posted on March 4, 2011 by C. Kubler

The Coalition for PET Drug Approval has compiled questions which they will be seeking answers to from the FDA. The answers will be posted for public review. At the present time these are the questions that have been compiled by the coalition.

Facility Question

Segregation of manufacturing and pharmacy activities: What are the FDAs filing and compliance expectations for how to delineate the separation of manufacturing and pharmacy activities?

In some sites, the drug product is synthesized and transferred into a dispensing cell in the radiopharmacy at which time the QC sample, sterility sample, and retention sample are extracted just prior to drawing the finished unit dose for administration. How would the FDA like to see the segregation of manufacturing activities from pharmacy practice activities?

Administrative Questions

1. Can the FDA open a docket so information could be accessible to the community?

2. Fees:

a. Application fees

b. Establishment fees

c. Product fees

3. Full prescribing information (package insert) must be developed against the RLD (reference listed drug) labeling. Considering that PET drugs are distributed outside the normal channels of distribution for drugs, it would be useful for the FDA to provide:

a. Guidance on the responsibility of academic PET drug producers for printing and distributing a package insert for PET drugs under an approved application.

b. Guidance for the commercial sector as the batch vial does not enter the ordinary channels of distribution, but rather the product is delivered to the prescribing physician in the form of a dispensed prescription from a pharmacy.

Environmental Monitoring and Aseptic Processing

1. Please specifically clarify the environmental air quality expectations/requirements for different areas within a PET manufacturing site.

2. In general, what are the minimal environmental air quality monitoring requirements?

Production Questions

1. Will the FDA accept the use of materials meeting other agency’s compendia requirements, (e.g., European pharmacopeia, and assuming these materials would be declared in an ANDA/NDA filing, and would be sourced and managed using the local quality management system (QMS))?

2. System suitability requirements in USP 823 suggest that the tailing factor and resolution (or column efficiency, as appropriate) are to be determined on a daily basis. This frequency is too often; these should be included with other chromatographic parameters that are to be determined on a more reasonable basis, e.g., six months. What is the FDA’s view on this for manufacturing under 212?

3. Given the scale of the typical PET manufacturing facility we are faced with a more rapid “equipment turnover” than a very large commercial manufacturing facility. If a facility submits an NDA/ANDA for FDG prior to 12/12/11 and the facility wants to (or needs to – due to equipment failure or other due cause) upgrade their FDG production method, which may require the purchase of another module that utilizes a different process:

a. Can the facility purchase the module, validate the process, and amend the ANDA prior to the initial inspection of the facility by the FDA since this FDA inspection may take several years to complete?

b. What is the process for notifying the FDA of this change as the inspector will be looking for the MX box during the ANDA approval inspection?

4. 212.50(f) – Would an NDA/ANDA submission be deemed adequate with the inclusion of the production and stability of a single batch if full testing is always performed?

5. Does the FDA have any guidance on what level of reduced testing would be acceptable once a product has undergone process verification?

6. Is identity testing on mannose triflate REQUIRED (other than the “test” in which mannose triflate can be used to produce FDG)?

7. Expectations on handling invalid tests and sample size for repeat testing?

Acceptability of Filing an ANDA

1. When we submit our ANDA do we need to submit all of the method validation data, or will that be reviewed at the time of the FDA inspection (after submission of the ANDA)?

2. Sample labeling is provided only for one RLD (reference listed drug) and one of the specific RLD strength. Guidance states that if labeling is different you must do a side-by-side. Will the FDA provide an example of all the RLD labeling? For clarity, a statement should be provided in the guidance that makes it clear that the reference to any of the RLD formations/labeling selected to use as a RLD for filing an ANDA should be provided.

Compliance and Inspections

1. Can the initial FDA inspection for an academic setting be scheduled in advance since academic sites don’t have a corporate QA office that can jump on a plane and guide the consumer safety officer through the facility and associated paperwork (and instead have patients each day to serve)?

2. The Food, Drug, and Cosmetic Act (FD&C Act) specifies that inspections will be made upon drug producers once every two years. However, in the questions and answers for the proposed 21 CFR 212, the statement is made that the FDA will continue to perform surveillance inspections of a number of PET facilities each year. Please clarify the expected inspection profile. Does this mean that each PET facility producing commercial materials will be inspected within the two years beginning December 12, 2011?

3. Forced degradation studies: Will we be required to perform forced degradation studies with short “shelf life” drugs.

4. What is the FDA position on growth promotion testing for solid media? Currently there have been differing responses from FDA inspectors, depending on the area of the country where the inspections are occurring. If we need to perform these tests, can we take three lots of material to validate our source of media from a specific manufacturer, and then perform the test on an annual basis? Or will the FDA require growth promotion testing on every lot of media?

5. Inspections have raised the issue on the requirement of mandatory standards for cyclotron maintenance including target rebuilds. Can the FDA comment on the relevance of the request (given the nature of performance of the cyclotron and final product testing)?

General Question

Will the FDA provide greater clarity on expectations around Quality-by-Design applicability to PET products?

COALITION FOR PET DRUG APPROVAL FORMULATES QUESTIONS FOR FDA, SERIES #1

Posted on February 23, 2011 by C. Kubler

Facility Questions

1. Air, ceiling, floor, and wall materials: The radiosynthesis is processed in the hot cell; however, some operation is performed in the laboratory, such as HPLC operation, buffer preparation, weighing raw materials on a scale. Is there any specified quality for the ceiling and floor (for example, shall we use seamless, washable material)?

2. Segregation of manufacturing and pharmacy activities:

a. Can the PET radiopharmaceutical manufacturing activities be conducted in the same room as the PET dose dispensing?

b. Can the QC samples be drawn from the vial in the same hot cell where the PET doses are dispensed (pharmacy operation)?

ANDA/NDA Filing Questions

What does paper application mean for the ANDA?

a. Does this mean the entire document is submitted in paper, or is it required to save the sections as PDF files on a CD?

b. Is the PDF index required to be linked to the various sections in the document?

c. Are there any other links that need to be inserted?

Administrative Questions

1. Fees:

a. What is the process for requesting “fee waivers”?

b. What fees have the potential to be waived?

c. Will academic sites preparing PET drugs for their internal patients (e.g., not distributing to others) be required to pay the fees?

2. The guidance provides reference to and advice to format an application in the CTD format. The attachments to this guidance which provides sample format are not formatted according to the CTD. As a result, the discussions and suggestions regarding the formatting of the application are inconsistent and confusing. What is the correct format for the CTD?

3. The guidance provides that paper applications are acceptable. Discussion is provided regarding an electronic submission. The way the information is presented does not make a clear differentiation between submitting an application “electronically” on media, such as a PDF file on CD-ROM, versus an electronic submission on an e-CTD (which is an XML formatted file), through an established FDA electronic portal. Please advise as to how to submit a CD-ROM copy with a paper submission. It is our understanding that this has become an expectation of the FDA which is not mentioned.

Environmental Monitoring and Aseptic Processing

1. Is there any specified air quality for the general (non-aseptic processing) areas of the laboratory?

2. Is there any specified air quality requirements for the hot cells?

3. Is it acceptable to use settling plates for environmental monitoring or will there be a requirement to use an active air sampling system?

4. Is growth promotion testing required for the contact plates (solid media) used in an ISO class 5 hood? How frequently?

5. Is growth promotion testing required on liquid media? How frequently is the testing required? Can 3 consecutive lots of media be tested to validate the manufacturer’s process and shipping, with single lot testing annually thereafter?

Production Questions

1. Is it required to check the osmolality for every batch of FDG prepared?

2. Would the FDA consider an application for a concentration greater than 300 mCi/mL for FDG perhaps as high as 500 mCi/mL?

3. When is it necessary to dilute the final product to meet the concentration specification? Is there a preference to use sterile water, normal saline, or half normal saline?

4. In order for a site to apply for a concentration higher than 37.5 mCi/mL for N-13 is it better to file a petition or file a 505 (b) 2 NDA?

a. What is the current wait time for the petition?

b. In case the NDA approval is not received before the deadline, it is assumed the laboratory can continue producing PET drugs in a continuation mode until FDA approval is received. Is that correct?

5. Assuming that product stability is demonstrated during validation testing, is there any limit to expiration time of the product?

6. Is a type V DMF required for the chemical synthesis units? If a manufacturer does not file a type V DMF, how should the community proceed? What information do we need to file in the ANDA or NDA?

7. The new draft guidance states that the QC needs to be done for 3 qualification batches at the highest concentration allowed. Is it correct that a stability study is required for only 1 of these batches?

8. Which analytical techniques, if any, require validation?

Acceptability of Filing an ANDA

1. Pages 9 and 10 discuss the parameters considered in making a determination of a generic being identical and bioequivalent to a RLD. The requirement is to assess whether differences in inactive ingredients do or do not have an effect on viscosity and specific gravity of the proposed PET drug product. This seems totally irrelevant to PET drug products and without scientific merit. Please state the regulation where this requirement resides and clarify why the expectation to make this assessment exists.

2. The statement at the bottom of page 39 that discusses Q1 and Q2 ingredient differences is vague and could be very subjective. Can the FDA please clarify and give examples for inclusion in the guidance and for discussion at the meeting?

a. Please clarify if one must demonstrate by objective scientific evidence (data), or by presenting a sound scientific discussion, whether such differences will not affect the chemical or physical properties.

b. If the former, must a laboratory comparison between the RLD and the proposed drug be done?

3. If the proposed drug differs from the RLD in strength, route of administration, or dosage form, an ANDA may still be submitted, but the sponsor first must obtain FDA approval of a suitability petition. Among these attributes, only a change in strength is likely to be relevant for a PET drug. The guidance states that a change in mCi/mL at end of synthesis (EOS), total drug content, or amount of active ingredient are considered a change in strength which will require approval of a suitability petition before the ANDA may be filed. We ask the agency to discuss the merit for PET drugs, because the total content of the vial and the total amount of radioactivity are irrelevant to the safety and effectiveness of a PET drug, and rapidly changes naturally. Indeed, on January 26, 2011, the FDA approved an NDA submitted by NIH for sodium fluoride F 18, for which the labeling states that the total volume and total radioactivity per vial are variable. A change in activity concentration (mCi/mL) at EOS should be the only relevant consideration in determining whether a suitability petition needs to be submitted because of a change in strength from the RLD. Please clarify.

Compliance and Inspection

The commercial PET sector has experienced many routine PET establishment and pre-approval inspections. Their experience shows that most inspectors have not performed PET establishment inspections nor are they familiar with USP <823> prior to inspection. As a result, a disturbing trend has evolved where the industry has experienced the equivalent of “regulation by inspection” where inspectors rely on their previous experience with Part 211 to issue observations on inspections rather than rely on the specific provisions of USP Chapter 823 Part 212 and the unique nature of PET drugs, their manufacture, and the establishment. Precedent-setting 483 observations are being made which have no foundation in the USP general chapters, chapter 823, monographs, or the PET GMP Part 212, and associated guidance, or in traditional radiopharmaceutical industry practices at large. As the result of one inspector’s findings such observations could have industry-wide repercussions, which can be linked to a lack of understanding of the nature of PET and the tremendous disparity between the nature of a large industrial pharmaceutical establishment and the special nature of PET drugs and their manufacturing environment. The coalition will provide specific examples of “regulation by inspection” that the industry has experienced within the next week for discussion at the public meeting.

General Notations Regarding the Guidance Document

Formulation information is provided on pages 6-8 for 3 FDG RLDs, 2 NaF RLDs, and 1 ammonia RLD. Some of the information provided is not accurate or complete:

The 12/06 resided labeling for NDA 21-768 is not available on Drugs@FDA.
Fludeoxyglucose F 18 injection (NDA 21-768) and Fludeoxyglucose F 18 injection (NDA 21-870); labeling revision in 12/06 is inconsistent with the information provided.
Table lists as isotonic; labeling does not state isotonic.
Citrate content: labeling states the concentration of the active and inactive ingredients “in citrate buffer.”
NDA 21-870: 20-300 mCi/mL correct pH on the label is 4.5-7.5, not 5.5-7.5, as listed.
NDA 21-870: also original RLD strength is 20-200 mCi/mL, pH = 5.5-7.5. This information is not provided. The table on page 37, under generic drug fails to include the 20-300 mCi/mL strength. The table under RLD fails to list the 20-200 mCi/mL strength.
Page 40, table under RLD, 20-200 mCi/mL should be included.
Page 9, C-General recommendations, 3. Sodium Fluoride Injection: the statement that NDA 22-494 is listed as discontinued in the Orange Book is in error.
Page 26 discusses the field copy and includes a statement that it should contain the technical section, application form, and summary. The suggested format for an application as provided in the appendix of the draft guidance does not discuss a summary section. Please clarify if a summary should be included. In addition, the appendix refers to the “CMC” section; module 3 in a CTD format is called the “Quality” section. The inconsistencies in the appendix, as a guide for formatting the application and the discussion of the CTD format, create confusion about the expectations of the content of an application.

SPL TRAINING SESSION – POSITRON EMISSION TOMOGRAPHY (PET) DRUG SPL

Posted on February 22, 2011 by C. Kubler

FDA’s Office of Critical Path has created a web-based training session to help applicants use SPL. The first registration session is being offered on March 8. Please click on this link for more information:

http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/ucm241316.htm

Positron Emission Tomography (PET) Drug SPL

SPL (Structured Product Labeling) Training Session – Positron Emission Tomography (PET) Drug SPL

Date: Tuesday, March 8, 2011
Time: 1:00 – 2:30 p.m., ET

Registration Information

There is no registration fee for the training sessions but pre-registration is required because of limited connections for the webinars. To register, please submit the following information via e-mail to spl@fda.hhs.gov:

Attendee’s first and last name
Name of your organization

WHAT IS A PET SCAN?

Posted on February 16, 2011 by C. Kubler

The Coalition for PET Drug Approval is working with members of the medical community to make sure that drugs used when performing a PET scan are licensed by the FDA. In order to do a PET scan you must use a PET drug. If you are not sure what a PET scan really is we are providing information that will help you better understand. Our objective is to help the medical community to be able to continue to offer this very valuable diagnostic tool by helping manufacturers who produce the PET drugs to be able to continue to do so. For information about what a PET scan is please click here of paste this URL in your Web brower: http://www.drugs.com/health-guide/positron-emission-tomography-pet-scan.html

PET DRUGS PROPOSED CGMP RULE AND DRAFT GUIDANCE Q&As

Posted on February 16, 2011 by C. Kubler

The FDA recently published a series of questions and answers related to PET drugs and the CGMP rule and draft guidance. The Coalition for PET Drug Approval is making the information published by the FDA available to stakeholders in an effort to address all issues related to the process and to assist the community in being able to meet the deadline for the licensure application process of December 12, 2011. To view the FDA publication please click here or paste the URL into your Web browser: http://www.fda.gov/Drugs/DevelopmentApprovalProcess/Manufacturing/ucm085803.htm

CPDM Presents at SNMMI’s 2021 Annual Meeting

PET Community Hosts FDA Workshop

USP Opens Call for Volunteers to Serve on Expert Committees

Coalition for PET Drugs Meeting Presentation Available

USP Presentations from SNMMI Annual Meeting Available

Coalition for PET Drugs Sponsors Three Sessions at SNMMI Annual Meeting

SNMMI Comments to FDA on Compounding

SNMMI Develops USP Recommendations for Compounded Sterile Radiopharmaceuticals

FDA Issues Draft Guidances on Compounding and Repackaging Radiopharmaceuticals

FDA Releases SBIA Summary of eCTD Requirements

NRC Licensing Guidance for Eckert and Ziegler Ge-68/Ga-68 Generator

Sponsored Session from SNMMI Annual Meeting:PET Drug Manufacturing: Living in an FDA-Regulated World

Coalition Comments on PET GMP Recordkeeping Burden

Public Comments for PET GMP Recordkeeping Burden

USP Seeking Comments on General Chapter Revisions. Deadline approaching!

Reminder: Two-year post approval inspections

Important Change to NDA 021870

Coalition Comments on Generic Drug User Fee Act

Slide Presentations from “FDA: Imaging Drug Development – Regulatory Issues” CE Session

Sponsored Session from SNMMI Annual Meeting: Current Topics in FDA Reviews and Inspections of PET Drug Manufacturers

Important Upcoming Events at SNMMI Annual Meeting in Baltimore

Coalition Sponsors Session on FDA Topics

A Passion for Policy

Coalition Submits Comments on ANDA Draft Guidance

FDA announces Q&A guidance on Oversight of PET Drug Products

FDA announces availability of IND applications for PET Drugs

FDA Approves Choline C11 Injection for Prostate Cancer Detection

NORTH SHORE/LIJ HEALTH SYSTEM RECEIVES EXPANDED ACCESS IND

COALITION SUBMITS COMMENTS ON DRAFT GUIDANCE

FDA ISSUES GUIDANCE ON MEDIA FILLS FOR VALIDATION OF ASEPTIC PREPARATIONS FOR PET DRUGS

FDA ISSUES DRAFT GUIDANCE ON INDS FOR PET DRUGS

FDA TO OFFER WEBINAR ON SPL FOR PET MANUFACTURERS

FDA ISSUES FAQ GUIDANCE FOR CGMP FOR PET DRUGS

FDA TO OFFER WEBINAR ON CGMP FOR PET DRUGS

FDA ANNOUNCES MEETING ON GENERIC DRUG USER FEE ACT

ADDITIONAL INFORMATION PROVIDED BY FDA

FDA ISSUES NEW GUIDANCE FOR PET CGMP INSPECTIONS

FDA WEBINAR ON DRUG MASTER FILES

FDA POSITION ON INDS FOR PET DRUGS IN CLINICAL TRIALS

FDA ISSUES DRAFT GUIDANCE ON MEDIA FILLS OF ASEPTIC PREPARATIONS FOR PET DRUGS

FDA TO HOLD ANNUAL INSPECTIONS SUMMIT

FDA ISSUES GUIDANCE FOR FILING PET NDAs AND ANDAs

Update: Q & A from FDA Meeting on March 2, 2011

New FDA cGMP Guidance for Small Businesses Available

FDA MEETING ON GENERIC DRUG USER FEE PROGRAM

FDA ISSUES CHECKLIST FOR ANDAs

FDA LABEL INFORMATION AVAILABLE THROUGH DAILYMED WEBSITE

REQUIREMENT FOR SUBMISSION OF CERTIFICATION FORM (FDA 3674)

PRESENTATIONS AND TRANSCRIPT FROM FDA MEETING NOW AVAILABLE

EDUCATIONAL SESSIONS ON FDA REGULATIONS OFFERED AT SNM ANNUAL MEETING

FDA HOLDS PUBLIC MEETING ON GENERIC DRUG USER FEE PROGRAM

ANSWERS TO YOUR QUESTIONS

COALITION FOR PET DRUG APPROVAL SEEKS COMMUNITY INPUT

COALITION FOR PET DRUG APPROVAL FORMULATES QUESTIONS FOR FDA, SERIES #2

COALITION FOR PET DRUG APPROVAL FORMULATES QUESTIONS FOR FDA, SERIES #1

SPL TRAINING SESSION – POSITRON EMISSION TOMOGRAPHY (PET) DRUG SPL

WHAT IS A PET SCAN?

PET DRUGS PROPOSED CGMP RULE AND DRAFT GUIDANCE Q&As

Coalition of PET Drug Manufacturers