FDA and CMS issue statement on LDTs: Americans Deserve Accurate and Reliable Diagnostic Tests, Wherever They Are Made

This joint statement notes the evolution of Laboratory Developed Tests (LDTs) from the initial rule and approach the FDA had for oversite, and today's environment with the extensive use of LDTs in medical decisions. Last October, the FDA issued a proposed rule change that would go from the historic practice of not enforcing all aspects of the LDT regulations and moving to enforcing the existing regulations.

The CMS portion of the announcement addresses it's role in the Clinical Laboratory Improvement Amendments of 1988 (CLIA) is separate and distinct from the FDA's role in the reviews of the analytical and clinical validity of LDTs.

This Link takes you to the announcement.

ACRO and Trancelerate release infographic on ICH E6(R3) Good Clinical Practice guideline vs R2

If you have or haven't looked at the ICH E6 revision 3 GCP guideline, this may be of interest to see how others perceive the differences from the current guideline.

 From the LinkedIn announcement:

TransCelerate is excited to announce the release of a new co-created resource! We have partnered with the Association of Clinical Research Organizations (ACRO) to release a new infographic that features the key changes to risk management in ICH E6 (R3) between Version 2 and 3.  

#goodclinicalpractice #acceleratinganswers #collaboration 

Learn more and check out the new infographic: https://lnkd.in/gGC-fJtR 

FDA and Health Canada hosting regional public meeting on ICH draft guidelines

 Prior to the next ICH Biannual Assembly meeting the FDA and Health Canada are hosting a virtual public meeting on 22February 2024 from 11:00 AM to 3 PM ET.

A large number of ICH guidelines that are reaching milestones are listed at the announcement website to be presented and discussed:

TOPICS COVERED

• ICH Background
• ICH Guidelines Reaching or Approaching Key Milestones
  • Q2(R2)/Q14 Revision of Q2(R1) Analytical Validation and Analytical Procedure Development
  • Q5(R2) Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin
  • Q9(R1) Quality Risk Management
  • E6(R3) Good Clinical Practice Principles and Annex 1
  • M14, General Principles on Plan, Design, and Analysis of Pharmacoepidemiological Studies that Utilize Real-World Data for Safety Assessment of Medicines
  • E2D(R1) Post-Approval Safety Data Management: Definitions and Standards for Expedited Reporting
  • M12 Drug Interaction Studies
• ICH Cell and Gene Therapy Reflection Paper
• Q&A

The full agenda and registration are available at the website(https://www.fda.gov/drugs/news-events-human-drugs/joint-us-fda-health-canada-ich-public-meeting-02222024?utm_medium=email&utm_source=govdelivery)

Metabolite Bioanalysis in Drug Development: Recommendations from the IQ Consortium Metabolite Bioanalysis Working Group

 

A number of my colleagues participated in developing and writing this article "Metabolite Bioanalysis in Drug Development: Recommendations from the IQ Consortium Metabolite Bioanalysis Working Group" and were led by @Wenkui Li.

Abstract
The intent of this perspective is to share the recommendations of the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ Consortium) Metabolite Bioanalysis Working Group (WG) on the fit-for-purpose metabolite bioanalysis in support of drug development and registration. This report summarizes the considerations for the trigger, timing, and rigor of bioanalysis in the various assessments to address unique challenges due to metabolites, with respect to efficacy and safety, which may arise during drug development from IND enabling studies, and Phase I, Phase II, and Phase III clinical trials to regulatory submission. The recommended approaches ensure that important drug metabolites are identified in a timely manner and properly characterized for efficient drug development.

Link to article

 

FDA Free Webinar: Understanding FDA Inspections and Data (CMC)

This free webinar will be held September 06, 2023 | 1:00 PM - 3:00 PM ET

Registration is available here:

From the announcement:

During this webinar FDA will provide an overview of drug manufacturing inspections. Participants will gain a general understanding of Current Good Manufacturing Practices (CGMPs) and FDA Inspections. FDA subject matter experts will also demonstrate where inspection data is found on FDA’s website and share how to navigate the FDA Inspection Dashboard.

TOPICS COVERED

• • Overview of FDA’s CGMPs and Inspection Practices
  • How to Find FDA Inspectional Findings

Article:Monitoring both extended and tryptic forms of stable isotope-labeled standard peptides provides an internal quality control of proteolytic digestion in targeted mass spectrometry-based assays

The article provides an easy-to-implement approach to determining the extent of tryptic or other enzymatic digestion of a sample prior to the analysis of a surrogate peptide by LC-MS/MS.  Using an extended length (e.g., winged peptide) stable labeled internal standard, they showed that the efficiency of the digestion process could be monitored by analyzing for both the undigested extended length SIL IS and the target SIL IS after digestion.  They looked at a total of 524 assays - 398 using a direct measure of the digest, and 126 using an immunoaffintity extraction).  Of these, measurable amounts of the extended length SIL were found in 54% of the direct and 62% of the immunoaffinity extraction assays. Time course of digestion and using stressors on the digestion aided in characterizing the ability of the undigested/digested SIL to be an indicator of digestion efficiency.

Their work shows that 1) The ratio can be used to optimize the digestion conditions and 2) it is possible to use the measurement of the undigested extended length SIL IS and the SIL IS to assess the extent of enzymatic digestion.  The latter, when performed as part of routine sample analysis, provides a within-sample quality control (QC) check of the digestion. This may lead to the ability to normalize results based on the extent of digestion in each sample. 

Lundeen RA, Kennedy JJ, Murillo OD, Ivey RG, Zhao L, Schoenherr RM,
Hoofnagle AN, Wang P, Whiteaker JR, Paulovich AG, Monitoring both extended and tryptic forms of
stable isotope-labeled standard peptides provides an internal quality control of proteolytic digestion
in targeted mass spectrometry-based assays, Molecular & Cellular Proteomics (2023), doi: https://
doi.org/10.1016/j.mcpro.2023.100621.

 

 

Global health regulators collaborate: International Coalition of Medicines Regulatory Authorities

Founded in 2019, the International Coalition of Medicines Regulatory Authorities (ICMRA) collaborates to review changes to manufacturing or add manufacturing sites to “enable better industry quality management to reliably supply critical medicines for patients in need”.  An article posted by the FDA announces recent progress and future plans (here).

ICMRA has just completed a pilot.  The article notes that the “FDA and EMA regulators completed the first collaborative assessment of a proposed post-approval change for a critical oncology biologic with the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) serving as an observer. The work, in which FDA and EMA reviewed and approved a proposal to add new manufacturing and quality control sites, can help assure the supply of the medicine.”

 

Other activities and future plans make an interesting read, and if successful will simplify and speed future approvals of new therapies and subsequent modifications of their manufacturing to ensure global therapy supply.