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*The Coalition is aware that this draft guidance applies only to Eckert and Ziegler generators and is working with the NRC to ensure that future guidance includes other generators.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 »
The Coalition for PET Drugs recently sponsored a session focused on FDA topics relevant to PET drug manufacturers. The session was held at the 2016 annual meeting of the Society of Nuclear Medicine and Molecular Imaging (SNMMI) in San Diego. For the second year in a row, the session was co-sponsored with the Radiopharmaceutical Sciences Council (RPSC) of the SNMMI. This is an important collaboration, which demonstrates the alignment of the Coalition’s mission with that of the RPSC.
The session drew more than 100 attendees, representing academic PET drug manufacturers, commercial PET drug manufacturers, FDA representatives, and others.
In case you missed the session, the presentations are available here:
We hope the session was helpful for the PET community and we welcome your feedback. If you have any comments or questions related to the presentations or the sessions, please contact the Coalition at the link above or leave a comment below.
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
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
Questions? Please leave a comment below.
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.
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.
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).
Questions? Please leave a comment in the comments section below.