Frequently Asked Questions
- Centralized Imaging Biomarker INDs
- Imaging Site Registry
- Phantom Program
- International Participation
- Manufacturer's Registry
- Site Qualification
Q. Is the Clinical Trials Network solely about filing INDs for PET tracers?
A. No. The SNMMI Clinical Trials Network is dedicated to increasing the use of ALL imaging biomarkers in multicenter clinical trials of investigational therapeutics. This includes - but is not limited to - PET/CT, contrast agents for MRI, fMRI, CT and U/S, plus all optical imaging agents. Currently, we are still building our registries for PET imaging sites and radiopharmaceutical manufacturers. However, as soon as a non-PET biomarker is identified, there will be an increased effort to secure additional imaging sites and manufacturers appropriate for those trials. All groups related to any type of biomarker use are encouraged to register with the CTN at this time.
Q. Will the biomarker used under a centralized IND still have to go through Phase 2 and 3 clinical trials to obtain an approved NDA?
A. FDA has not changed its processes for New Drug Applications. The burden is still on the filer of a New Drug Application to demonstrate safety and efficacy.
Q. Is there a limit to the number of patients that can be administered under the current SNMMI-centralized IND for FLT?
A. FDA has not stipulated the total allowable number of administered doses for the F-18-FLT. For each protocol submitted within the IND, the number of patients permitted to be administered F-18 FLT has to be requested and approved.
Q. If I want to cross-reference an SNMMI-held IND, will the study information be available to others?
A. No, only FDA reviews the study data collected in any clinical trial. The CTN only collects data that is directly relevant to overseeing its IND, such as imaging-related acquisition information, compliance/QC and safety reports.
Q. Is the SNMMI-held centralized IND available for single, investigator-initiated studies?
A. No. Currently, the SNMMI-held centralized IND can only be used for multicenter clinical trials
See also Manufacturer's Registry.
Q. How do I register my imaging site in the CTN registry?
A. If you would like to join CTNs imaging site registry, click on the red "CTN Registries" button on the CTN website Home Page. The Clinical Trials Network Registries page opens with options for both Imaging Sites and Manufacturing Sites. Click on Imaging Site Registry and follow the directions to register your site in the CTN databse. Once you submit the initial information, CTN staff receives an email that you have requested access to the database. Once your request is approved, CTN will then set up your site and provide you with access to complete your site's information in the database.
Q. What if the information about my site changes after I have registered?
A. There are two ways to updagte your site's information in the CTN database. You can notify CTN staff through an email to clinicaltrials@snmmi.org. You can also go the CTN Site Registries page, click on the Imaging Site Registry link and follow the directions to update your site's information.
Q. Is there a deadline to register with the CTN?
A. No. Registration remains open indefinitely. We encourage interested imaging sites to join the CTN at any time. Registration with the CTN will NOT obligate you to participate in any specific trials. However, only sites that have registered and have met CTN qualification requirements are eligible for recommendation by the CTN to industry sponsors for a particular trial.
Q. If I register my site, will I be rquired to participate in all the clinical trials sponsored by drug developers?
A. Registration in the CTN does NOT obligate you to participate in any specific trials. You have the option to participate, or not, as each trial is being initiated and imaging sites are identified.
Q. How will sites be selected for participation in any given multicenter trial?
A. CTN recommends sites who qualify for a given trial based on the sponsor's study-specific parameters. However, final site selection is at the discretion of the sponsoring drug developer, and CTN cannot guarantee that your site will be selected.
Q. Is there a fee to register? and, if so, how much is it?
A. There is no fee to participate in the imaging or manufacturing registries at this time.
Q. What type of information is required when registering my site?
A. Imaging sites are required to complete questions that capture information on PET scanner equipment (including the dose calibrator), personnel involved in research imaging, radiopharmaceutical agents used at the site and research infrastructure. If your site plans on obtaining full CTN-qualification, all fields in the database must be completed.
Q. What is required of registered sites?
A. Imaging centers in the Clinical Trials Network imaging registry are encouraged to obtain full-CTN qualification. This includes validating your eligible PET/CT scanners and completing your site's information in the database. Remaining CTN qualified involves on-going assessment and monitoring to ensure that your site remains eligible for multicenter trial participation. This includes annual validation of your PET/CT scanners with the CTN clinical phantom, updating your site's information as circumstances or equipment changes, and adhering to all GCP and federal regulations for performing clinical research.
Q. Is it required that we have an on-site cyclotron?
A. No. Participation in the imaging site registry only requires having specific imaging capabilities. If you identify your site as an Imaging and Production site, there are additional questions to complete regarding manufacturing isues, such as having an on-site cyclotron and what radioopharmacueticals are being made. However, you do not need this to qualify as an imaging site for a study.
Q. Do we have to be a PET facility to register with the CTN?
A. CTNs mission includes the integration of ALL imaging biomarkers into clinical trials, including MR and CT imaging agents. It is possible that, in the future, the CTN may be used to drive the standardization of multicenter imaging in clinical trials even where no imaging agent is used (e.g. some MR studies). Therefore, non-PET imaging centers are encouraged to register so you continue to receive regular communications on the progress of the CTN.
Q. I note that participation of centers outside North America is encouraged. How is their participation in the phantom program being envisioned?
A. The current plans are to run the phantom program in the same way outside the US as it is being handled within the country. Essentially, the process involves shipping the CTN phantom to a site along with filling and imaging protocol instructions. The site images the phantom and returns the images to a review committee for either approval or further recommendations by the committee. Final details as to whether there will be a single review committee or others located outside the US have not been decided at this time.
Q. Is there a purchase cost, or a rental cost, for the performance phantom that is required for all registered members of the Clinical Trials Network?
A. The phantom program is made available to all sites who register for the CTN. There is no requirement to purchase the phantom. It will be provided to your site for qualification tests, and then you will return it to the CTN. The CTN now has chest phantoms available for purchase. Please contact clinicaltrials@snmmi.org for more information.
Q. Is it possible for imaging centers outside the US to participate in these trials?
A. Yes, international participation is strongly encouraged. In fact, the pharmaceutical developers who have expressed interest in using the CTN to sponsor multicenter clinical trials have specifically requested significant international participation.
Q. As a foreign PET/CT center what would we need to do participate in the trial?
A. Steps for international participation in the registry are no different than for US sites. Click on the "Register Your Imaging Center Now" button on the Imaging Site Registry page and complete the enrollment page.
Q. What is the infrastructure required along with the protocol and regulations?
A. Each individual multicenter clinical trial requires the development of a standardized imaging protocol specific to the investigation (eg, drug/biologic) of interest. All sites participating in a trial, both US and international, must comply precisely with the approved protocols.
Q. Are the international protocols different from ones applicable to US centers?
A. All sites participating in a given trial must adhere to the same imaging protocol. However, the detailed site data collection request international participants to specify any local �FDA-like� regulations that they must also comply with in order to participate in a US-sponsored clinical trial (eg, local CMC compliance or scientific review committee). There may be barriers to participation in a given clinical trial based on local country-by-country regulations and the specific needs of the sponsoring drug developer.
Q. How can I join the biomarker manufacturer's registry?
A. If you would like to join the Network's manufacturer's registry, we can add you to the current registry list now. Simply email your desire to register to clinicaltrials@snmmi.org. Include your name, institution/business, street address, plus the phone and email addresses of the best contact person for your facility's registration.
Q. I have been providing radiotracers for investigational studies for many years. We are USP 797 compliant and have extensive experience with RDRC committees, human use committees, pharmacy regulations, and FDA regulations. How can we help?
A. If you are interested in being considered as a potential manufacturer of a biomarker in a future multicenter clinical trial, please register immediately in the Manufacturer's Registry by emailing your contact information to clinicaltrials@snmmi.org. Additional details about participation in the manufacturer's registry will be disseminated later.
Q. I understand the FDA is using a new endpoint specification review process. Will every manufacturing site still have to submit their CMC?
A. Yes, all FLT manufacturers of FLT being administered to subjects under the SNMMI's centralized IND must provide CMC information for FDA review.
Q. Where can I get additional information about submitting my site's CMC to the FDA?
A. You can contact the FDA directly with all questions by emailing newdrugcmc@fda.hhs.gov.
Q. What endpoint specification has the FDA defined for FLT?
A. The FDA is in the process of defining the criteria for a "true positive" and a "true negative" finding for qualitative and quantitative assessment of FLT. A specifically defined endpoint would be implemented for a clinical trial with a statistical analysis, and we have not yet proceeded with a specific clinical trial.
Q. Does the SNMMI have FLT QC release specifications that need to be met and qualified by each site?
A. No, SNMMI has not established FLT QC release specifications. The FDA has agreed to review submitted specifications. No defined specifications have been stated by tje FDA and/or SNMMI at this time (June 2012).
Q. Does the CMC specify a specific precursor for the F-18-FLT manufacturing process under the SNMMI centralized FLT IND?
A. No.
Q. Since manufacturer's must submit CMC specifications, will the FDA base its review on the CMC process or on the final formulation?
A. The FDA addressed formulation by stating it will review the specifications of the final product to be administered to subjects. The FDA requires specification for their review on the final product (formulation) to be administered to subjects. The review process is NOT based solely on the CMC process.
Q. If I participate as a manufacturer in a trial, will SNMMI share my CMC, or will my CMC be available for others to see?
A. No, only the FDA will see your CMC.
Q. If a letter of cross-reference is granted between a Drug Master File and the SNM when using the FLT IND, can the SNM review the details of the DMF?
A. To meet the FDA manufacturing standards under the SNMMI-held FLT IND, an FLT manufacturer must submit to the FDA detailed information related to chemistry, manufacturing and controls (CMC), as well as pharmacology and toxicology information. In place of submitting the detailed information directly, a site can choose to purchase FLT from a commercial manufacturer with an approved Drug Master File (DMF) for FLT on file with the FDA.
When a DMF approach is used, two letters of cross-reference are required. First, the manufacturer must provide the SNMMI with a letter to allow cross-referenced use of their DMF in writing. Second, each imaging site must have a letter of cross-reference from the commercial manufacturer that states the supplier will provide FLT in accordance with the DMF that has been approved. The site must provide that letter to the SNMMI.
Q. Which commercial suppliers have DMF cross-referenced to the SNMMI-held FLT IND?
A. In June 2009, the three largest suppliers of PET radiopharmaceuticals in the US � PETNet Solutions, IBA Molecular, and Cardinal Health, each provided the SNMMI with letters of cross-reference to allow use of their FLT DMFs under the SNMMI-held centralized FLT IND.
Q. Can a site be qualified if it doesn’t complete the database information?
A. No. A fully-qualified site is one that has completed all the site information in the CTN database, successfully passed scanner validation with the CTN phantom and has met the minimum criteria for conducting clinical PET imaging research.
Q. What happens if our scanner does not pass validation? Can we still qualify for trial participation?
A. The CTN Scanner Validation Committee will work with your imaging personnel to try and rectify any problems. However, in some cases, a scanner may never successfully pass validation due to age, problems with the dose calibrator or overall poor image quality. In this case, that scanner would not be qualified for research studies. If a site has more than one PET/CT scanner, one may be validated while the other may not pass. Only one scanner needs to be validated for a site to be qualified, as long as the validated scanner is the one used for research.
Q. If our site becomes fully-qualified, will we automatically be included in a research study?
A. No. The CTN only provides a list of qualified sites to our sponsoring partners. The study sponsor decides which sites to use for their trial based on the study parameters, patient availability, and imaging agent logistics.
Q. Can a site be qualified if site personnel have no experience in PET imaging research?
A. If a site has personnel, such as coordinators and nuclear medicine technologists, who have the time in their schedule and are willing to be trained to follow the protocol and perform other research-related activities, a site could still become fully qualified as long as all the other requirements are met. Although helpful, a site does not have to have experience in PET imaging for clinical research studies.
Q. Once qualified, will a site have to undergo repeat qualification?
A. A site should expect to go through requalification on an annual basis, including scanner revalidation. In some cases, a site may be required to repeat certain tests depending on study-specific criteria or if significant upgrades to equipment and/or personnel occur during the year. In these cases, CTN staff works with the site to complete any necessary procedures to make sure a site remains qualified to participate in multicenter clinical trials.
LAST UPDATED: 7/15/2012