Key Issue: Standards for Radioactive Articles in USP-NF
Original Posting: 24–Nov–2010; Last Update: 31–Jul–2015
- Scientific Liaison: Ravi Ravichandran (USP823@usp.org)
- Media: Theresa Laranang-Mutlu (firstname.lastname@example.org or 301-816-8167)
July 31, 2015:
The scope of this Key Issues page is being expanded from PET drugs to cover all radioactive articles in USP.
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The Second Supplement to USP 37-NF 32, which was published on June 1, 2014, included the omission of eight monographs for non-FDA approved PET drugs. Since the USP typically does not maintain monographs for non-FDA approved products, these changes bring USP’s approach to PET drug monographs in line with other USP monographs. It is important to note that these changes only affect monographs for non-FDA approved PET drugs. USP will continue to maintain monographs for FDA-approved PET drugs.
The changes were approved by the USP Small Molecules–4 Expert Committee, which is responsible for PET drugs. The Committee followed the recommendations of the Society of Nuclear Medicine and Molecular Imaging (SNMMI) Committee on Pharmacopeia (see: Journal of Nuclear Medicine, 2013, vol. 54, no. 3, pp 472-475). The article can be accessed here.
The omission of monographs for non-FDA approved PET drugs becomes official on December 1, 2014. This is the final step in a series of USP activities related to PET drug monographs. The timeline for these activities appears below:
1. SNMMI recommendations to omit monographs for non-FDA approved PET drugs published in March 2013.
2. Omission of monographs for non-FDA approved PET drugs proposed in Pharmacopeial Forum 39(4) [Jul-Aug 2013]. Public comments on this proposal were received until September 30, 2013. There were no comments opposed to the proposed omissions.
3. USP Monographs-Small Molecules 4 Expert Committee voted to approve the omission of monographs for non-FDA approved PET drugs from USP-NF.
4. The omission of monographs for non-FDA approved PET drugs becomes official on December 1, 2014.
An article recently published by the Committee on Pharmacopeia associated with the Society of Nuclear Medicine and Molecular Imaging (SNMMI) describes the impact of potential changes to the role of USP monographs for PET drugs after the sunset of the 1997 FDA Modernization Act requirements for PET drugs. In addition, the article contains recommendations for USP monographs for PET drugs that are currently not approved by the FDA. The article appears in the March issue (JNM, vol. 54, no 3, pp 472-475), and can be accessed here.
The U.S. Pharmacopeial Convention (USP) is announcing the adoption of the revision of General Chapter <823> Radiopharmaceuticals for Positron Emission Tomography (PET)–Compounding in USP 35–NF 30, became official on May 1, 2012. The USP 35–NF 30 commentary, which is a summary of all the comments along with their disposition, can be found on the USP web site (commentary for <823> starts on page 8 of USP 35–NF Commentary.
USP has submitted a Citizen Petition to FDA to update the compendial reference to USP 35-NF 30 in the federal regulations on current good manufacturing practice (cGMP) for PET drugs (21 CFR § 212.5(b)).
The U.S. Pharmacopeial Convention (USP) is announcing the adoption of the revision of General Chapter <823> Radiopharmaceuticals for Positron Emission Tomography (PET)-Compounding in USP 35–NF 30, which will be published in November 2011 and official on May 1, 2012. Once the official date is reached, the title of <823> will change to "Positron Emission Tomography Drugs for Compounding, Investigational, and Research Uses". The proposal was published in Pharmacopeial Forum (PF) 37(1)[Jan–Feb 2011] for the public review and comment period, which ended on March 31, 2011. USP received several comments from industry as well as the FDA. The Drugs for Positron Emission Tomography–Compounding Expert Panel reviewed all comments and recommended subsequent changes to the text to the General Chapters–Physical Analysis Expert Committee (GCPA) and the revision was approved by GCPA. The USP 35–NF 30 commentary, which is a summary of all the comments along with their disposition, will be posted on the USP web site in November 2011, coinciding with the publication. USP has initiated the process to petition FDA to update the compendial reference to USP 35–NF 30 in its regulation. Until the reference is amended, investigational and research PET drug manufacturers will still need to comply with General Chapter <823> of USP 32–NF 27 (2009) or the Code of Federal Regulations Title 21 Part 212 to meet CGMP requirements.
On February 21, 2011 at 1:00pm EST/10:00am PST, USP hosted a live webinar where 75 participants from companies, universities and hospitals across the country shared their questions and concerns. This live event was recorded and is posted below along with the presentation slides and a document listing all the questions from the session with answers.
The U.S. Pharmacopeial Convention (USP) is seeking input on a proposed revision of General Chapter <823> Radiopharmaceuticals for Positron Emission Tomography (PET)—Compounding in the U.S. Pharmacopeia–National Formulary (USP–NF). Input is being sought from practitioners involved in PET drug production and compounding in the fields of nuclear medicine, radiology, and diagnostic imaging and related areas.
Originally published in 1998, General Chapter <823> describes requirements for the production and compounding of PET drugs, typically as injectable solutions in a multi-dose vial. Production is defined as the process of synthesis or formulation of a PET drug for investigational or research uses. Compounding is defined as the process of synthesis or formulation of a PET drug for use in pharmacy and medicine. Since the chapter's publication in 1998, technological, marketplace, and regulatory changes related to PET drugs have necessitated the chapter's revision.
In 2009, the U.S. Food and Drug Administration (FDA) published final regulations (the Final Rule) and an accompanying guidance document for PET Current Good Manufacturing Practices (CGMP). Once the FDA's Final Rule becomes effective on December 12, 2011, General Chapter <823> (as published in USP 32–NF 27) will officially constitute the minimum CGMP requirements for investigational and research PET drugs used in human subjects under an Investigational New Drug application or under the approval of a Radioactive Drug Research Committee. All other PET drugs will be subject to FDA's new CGMP requirements. It is important to note that the FDA Final Rule references General Chapter <823> in USP 32–NF 27. Once the current revision process for General Chapter <823> is completed and the chapter is published, USP will petition FDA to update the reference in its regulation. Until that is accomplished, investigational and research PET drug manufacturers will have to comply with the 1998 version of General Chapter <823> or the Code of Federal Regulations Title 21 Part 212 to meet CGMP requirements.
All comments to the revisions to Chapter <823> may be submitted to Dr. Ravi Ravichandran at USP823@usp.org by March 31, 2011.