Abstract
This mini-review describes the Chemistry, Manufacturing and Control activities associated with the manufacture of [14C]-labeled drug substance and subsequent drug compounding activities to generate clinical trial material utilized in human absorption, distribution, metabolism, and excretion clinical studies. Due to the unstable nature and increased decomposition rates observed with [14C]-labeled compounds, the manufacture, testing, release, formulation, and regulatory filings are uniquely challenging. A case study of the cardiac myosin activator AMG 423 (omecamtiv mercarbil), utilized in a dual oral/intravenous infusion clinical study is presented.
Keywords: Chemistry, Manufacturing and Control (CMC), current Good Manufacturing Practice (cGMP), [14C]-Labeled Drug, Omecamtiv Mercarbil, AMG 423, human Absorption, Distribution, Metabolism, and Excretion (hADME), ICH Guidance, FDA Regulations.
Current Pharmaceutical Design
Title:Manufacturing of [14C]-Labeled Drug Substance and Drug Product Utilized in Clinical Research: A Case Study of Omecamtiv Mecarbil
Volume: 22 Issue: 5
Author(s): Scott W. Roberts, Jeroen M. Bezemer, Michael T. Kennedy, Tiffany L. Correll, Raju Subramanian and Shawn D. Walker
Affiliation:
Keywords: Chemistry, Manufacturing and Control (CMC), current Good Manufacturing Practice (cGMP), [14C]-Labeled Drug, Omecamtiv Mercarbil, AMG 423, human Absorption, Distribution, Metabolism, and Excretion (hADME), ICH Guidance, FDA Regulations.
Abstract: This mini-review describes the Chemistry, Manufacturing and Control activities associated with the manufacture of [14C]-labeled drug substance and subsequent drug compounding activities to generate clinical trial material utilized in human absorption, distribution, metabolism, and excretion clinical studies. Due to the unstable nature and increased decomposition rates observed with [14C]-labeled compounds, the manufacture, testing, release, formulation, and regulatory filings are uniquely challenging. A case study of the cardiac myosin activator AMG 423 (omecamtiv mercarbil), utilized in a dual oral/intravenous infusion clinical study is presented.
Export Options
About this article
Cite this article as:
Roberts W. Scott, Bezemer M. Jeroen, Kennedy T. Michael, Correll L. Tiffany, Subramanian Raju and Walker D. Shawn, Manufacturing of [14C]-Labeled Drug Substance and Drug Product Utilized in Clinical Research: A Case Study of Omecamtiv Mecarbil, Current Pharmaceutical Design 2016; 22 (5) . https://dx.doi.org/10.2174/1381612822666151228104826
DOI https://dx.doi.org/10.2174/1381612822666151228104826 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Nitric Oxide-Mediated Endothelial Dysfunction - Is there Need to Treat?
Current Vascular Pharmacology Vasopressin Antagonists as Anxiolytics and Antidepressants: Recent Developments
Recent Patents on CNS Drug Discovery (Discontinued) NRF2-Dependent Glutamate-L-Cysteine Ligase Catalytic Subunit Expression Mediates Insulin Protection Against Hyperglycemia-Induced Brain Endothelial Cell Apoptosis
Current Neurovascular Research Venous Thromboembolism in Patients with Heart Failure: In-hospital and Chronic Use of Anti-coagulants for Prevention
Recent Patents on Cardiovascular Drug Discovery Adverse Bioeffects of Ultrasound Contrast Agents Used in Echocardiography: True Safety Issue or “Much Ado About Nothing”?
Current Vascular Pharmacology Mineralocorticoid Receptor-Associated Hypertension and Target Organ Damage: Clinical Relevance for Resistant Hypertension in End Stage Renal Disease
Current Hypertension Reviews An Angiotensin Converting Enzyme Inhibitor Suppresses Contrast Media Induced Renal Dysfunction in a Murine Model of Subtotal Nephrectomy
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Individual Differences in the Neurobiology of Social Stress: Implications for Depression-Cardiovascular Disease Comorbidity
Current Neuropharmacology Pharmacotherapy for Patent Ductus Arteriosus: Current Options and Outstanding Questions
Current Pediatric Reviews Looking for Organ Damages Due to Anabolic-androgenic Steroids (AAS): Is Oxidative Stress the Culprit?
Mini-Reviews in Organic Chemistry Intra-Graft Abciximab and Verapamil Combined with Direct Stenting is a Safe and Effective Strategy to Prevent Slow-flow and No-Reflow Phenomenon in Saphenous Vein Graft Lesions not Associated with Thrombus
Recent Patents on Cardiovascular Drug Discovery Editorial (Thematic Issue: Modifying Cardiovascular Risk Factors: Newer Advances in Cardiovascular Metabolism and Diagnostic Technologies)
Current Pharmaceutical Design Modulation of Matrix Metalloproteinase Activity by Tobacco Cigarette Smoke
Current Chemical Biology Nitric Oxide as a Marker for Levo-Thyroxine Therapy in Subclinical Hypothyroid Patients
Current Vascular Pharmacology The Saphenous Vein as a Bypass Conduit: The Potential Role of Vascular Nerves in Graft Performance
Current Vascular Pharmacology Myostatin in the Pathophysiology of Skeletal Muscle
Current Genomics Physiological and Non-Redundant Functions of PKC Isotypes in T Lymphocytes
Current Immunology Reviews (Discontinued) Energetic Metabolic Roles in Pulmonary Arterial Hypertension and Right Ventricular Remodeling
Current Pharmaceutical Design Cardioprotective Effects of Serca2a Overexpression Against Ischemiareperfusion- induced Injuries in Rats
Current Gene Therapy Anti-Arrhythmic Properties of N-3 Poly-Unsaturated Fatty Acids (n-3 PUFA)
Current Medicinal Chemistry