Food and Drug Administration’s Position on Commonly Injected Biologic Materials in Orthopaedic Surgery

2021 ◽  
pp. 036354652199090
Author(s):  
William H. Fang ◽  
C. Thomas Vangsness
Keyword(s):  
Bone Marrow ◽  
Amniotic Fluid ◽  
Umbilical Cord ◽  
Drug Administration ◽  
Tissue Regeneration ◽  
Orthopaedic Surgery ◽  
Platelet Rich Plasma ◽  
Food And Drug Administration ◽  
Regulatory Pathways ◽  
Placental Membranes

The use of biologically based therapies is becoming a popular less-invasive therapy for relieving pain and promoting tissue regeneration. The most commonly used biologics are autologous adipose-derived products, bone marrow aspirations, and platelet-rich plasma (PRP). Birth tissue is a common allogenic source of biologics, including umbilical cord, placental membranes, and amniotic fluid. Injected biologics, depending on the indication and how they are processed, formulated, delivered, and promoted, can be subject to different regulatory pathways. The aim of this review is to provide an overview of these products and procedures and educate the musculoskeletal community about the relevant current Food and Drug Administration (FDA) regulations.

scholarly journals To what degree are review outcomes aligned for new active substances (NASs) between the European Medicines Agency and the US Food and Drug Administration? A comparison based on publicly available information for NASs initially approved in the time period 2014 to 2016

BMJ Open ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. e028677 ◽  
Author(s):  
Thomas Christian Kühler ◽  
Magda Bujar ◽  
Neil McAuslane ◽  
Lawrence Liberti
Keyword(s):  
Drug Administration ◽  
Food And Drug Administration ◽  
European Medicines Agency ◽  
Regulatory Pathways ◽  
Time Period ◽  
The Us ◽  
New Chemical Entities ◽  
Assessment Guidelines ◽  
Available Information ◽  
Active Substances

ObjectiveTo compare review outcome alignment between European Medicines Agency (EMA) and US Food and Drug Administration (FDA) for medicines approved by both agencies in the time period 2014–2016.DesignUsing publicly available information from FDA and EMA websites, new active substances (NASs) approved by each agency from 2014 to 2016 were identified and their characteristics assessed. Divergences in regulatory outcomes for simultaneous (within 91 days) submissions to both agencies were identified and then examined for use of facilitated regulatory pathways and orphan designations; submitted versus approved indications; and approval times.ResultsIn 2014–2016, 115 NASs were approved by EMA or FDA or both; 74/115 were new chemical entities and 41 new biological/biotechnology entities; 82/115 were approved by both agencies, 24 only by FDA and nine only by EMA. Simultaneous submission occurred for 52/115; 13/52 received expedited review by both agencies and 18 only by FDA; 8/52 received conditional approval from both agencies, 2/52 only from FDA and 1/52 only from EMA; 17/52 were designated as orphans by both agencies and 10/52 by FDA only; 31/52 indications were approved as submitted and 21 changed by EMA and 29/46 were approved as submitted (six not assessed) and 17/46 changed by FDA. Median FDA review timelines were 319 days compared with 409 days for EMA.ConclusionsThere was general agreement in EMA / FDA conditional approvals. FDA used expedited pathways and orphan designation more often than EMA, suggesting stricter EMA criteria or definitions for these designations or less flexible processes. Despite consistency in submitted indications, there was lack of concordance in approved indications, which should be further investigated. FDA review times are faster because of a wider range of expedited pathways and the two-step EMA process; this may change with recent revisions to EMA accelerated assessment guidelines and the launch of Priority Medicines.

Is cosmetic platelet-rich plasma a drug to be regulated by the Food and Drug Administration?

2011 ◽  
Vol 10 (3) ◽  
pp. 171-173 ◽  
Author(s):  
Christopher J Centeno ◽  
Mitchell Fuerst ◽  
Stephen J Faulkner ◽  
Michael Freeman
Keyword(s):  
Drug Administration ◽  
Platelet Rich Plasma ◽  
Food And Drug Administration

Postmarketing Modifications of Drug Labels for Cancer Drugs Approved by the US Food and Drug Administration Between 2006 and 2016 With and Without Supporting Randomized Controlled Trials

2018 ◽  
Vol 36 (18) ◽  
pp. 1798-1804 ◽  
Author(s):  
Daniel Shepshelovich ◽  
Ariadna Tibau ◽  
Hadar Goldvaser ◽  
Consolación Molto ◽  
Alberto Ocana ◽  
...  
Keyword(s):  
Drug Administration ◽  
Health Care Professionals ◽  
Controlled Trial ◽  
Food And Drug Administration ◽  
Drug Approval ◽  
Cancer Drug ◽  
Drug Label ◽  
Regulatory Pathways ◽  
Randomized Controlled ◽  
Study Characteristics

PurposeModifications in cancer drug indications, dosing, and related toxicities after Food and Drug Administration approval are common. It is unclear whether drug approval without a supporting randomized controlled trial (RCT) influences the probability of such modifications.MethodsWe searched the Drugs@FDA Web site for new drug indications for solid tumors approved between January 2006 and December 2016. Study characteristics, regulatory pathways, and label modifications from approval to October 2017 were collected from drug labels. Label modifications were considered to be major if defined as such in the drug label. Indications approved with and without supporting RCTs were compared using logistic regression. The Benjamini-Hochberg false discovery rate method was used to adjust for multiplicity.ResultsWe identified 59 individual drugs for 109 solid tumor indications. Of these, 17 indications (15.6%) were not supported by an RCT, with no change over time. Indications not supported by RCTs were more likely to require companion diagnostic tests (odds ratio [OR], 3.90; P = .02), to include surrogate end points as primary outcomes (OR, 7.88; P < .001), and to receive breakthrough therapy designation (OR, 7.62; P = .006) or accelerated approval (OR, 17.67; P < .001). Indications not supported by RCTs were associated with significantly higher odds of postapproval modifications in common adverse events (71% v 29%; OR, 5.78; P = .002). A nonsignificantly higher odds of postapproval major modifications in warnings and precautions was also observed (88% v 62%; OR, 4.61; P = .051). Postapproval major modifications in indication and usage, dosing and administration, boxed warnings, and contraindications were comparable in the two groups.ConclusionCancer drug indications not supported initially by RCTs are associated with more postmarketing safety-related label modifications. Health care professionals should be vigilant for unrecognized adverse effects when prescribing drugs approved without a supporting RCT.

Comparison of equine bone marrow-, umbilical cord matrix and amniotic fluid-derived progenitor cells

2010 ◽  
Vol 35 (2) ◽  
pp. 103-121 ◽  
Author(s):  
Arianna Barbara Lovati ◽  
Bruna Corradetti ◽  
Anna Lange Consiglio ◽  
Camilla Recordati ◽  
Elisa Bonacina ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Amniotic Fluid ◽  
Progenitor Cells ◽  
Umbilical Cord ◽  
Umbilical Cord Matrix ◽  
Equine Bone

Disease Burden Affects Outcomes in Pediatric and Young Adult B-Cell Lymphoblastic Leukemia After Commercial Tisagenlecleucel: A Pediatric Real-World Chimeric Antigen Receptor Consortium Report

2021 ◽  
Author(s):  
Liora M. Schultz ◽  
Christina Baggott ◽  
Snehit Prabhu ◽  
Holly L. Pacenta ◽  
Christine L. Phillips ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Drug Administration ◽  
Chimeric Antigen Receptor ◽  
Disease Burden ◽  
Lymphoblastic Leukemia ◽  
Food And Drug Administration ◽  
Antigen Receptor ◽  
Response Analysis ◽  
Intent To Treat

PURPOSE Tisagenlecleucel is a CD19-specific chimeric antigen receptor T-cell therapy, US Food and Drug Administration–approved for children, adolescents, and young adults (CAYA) with relapsed and/or refractory (RR) B-cell acute lymphoblastic leukemia (B-ALL). The US Food and Drug Administration registration for tisagenlecleucel was based on a complete response (CR) rate of 81%, 12-month overall survival (OS) of 76%, and event-free survival (EFS) of 50%. We report clinical outcomes and analyze covariates of outcomes after commercial tisagenlecleucel. METHODS We conducted a retrospective, multi-institutional study of CAYA with RR B-ALL across 15 US institutions, who underwent leukapheresis shipment to Novartis for commercial tisagenlecleucel. A total of 200 patients were included in an intent-to-treat response analysis, and 185 infused patients were analyzed for survival and toxicity. RESULTS Intent-to-treat analysis demonstrates a 79% morphologic CR rate (95% CI, 72 to 84). The infused cohort had an 85% CR (95% CI, 79 to 89) and 12-month OS of 72% and EFS of 50%, with 335 days of median follow-up. Notably, 48% of patients had low-disease burden (< 5% bone marrow lymphoblasts, no CNS3, or other extramedullary disease), or undetectable disease, pretisagenlecleucel. Univariate and multivariate analyses associate high-disease burden (HB, ≥ 5% bone marrow lymphoblasts, CNS3, or non-CNS extramedullary) with inferior outcomes, with a 12-month OS of 58% and EFS of 31% compared with low-disease burden (OS; 85%, EFS; 70%) and undetectable disease (OS; 95%, EFS; 72%; P < .0001 for OS and EFS). Grade ≥ 3 cytokine release syndrome and neurotoxicity rates were 21% and 7% overall and 35% and 9% in patients with HB, respectively. CONCLUSION Commercial tisagenlecleucel in CAYA RR B-ALL demonstrates efficacy and tolerability. This first analysis of commercial tisagenlecleucel stratified by disease burden identifies HB preinfusion to associate with inferior OS and EFS and increased toxicity.

Platelet-rich plasma enhanced umbilical cord mesenchymal stem cells-based bone tissue regeneration

2014 ◽  
Vol 59 (11) ◽  
pp. 1146-1154 ◽  
Author(s):  
Yong Wen ◽  
Weiting Gu ◽  
Jun Cui ◽  
Meijiao Yu ◽  
Yunpeng Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Tissue ◽  
Umbilical Cord ◽  
Tissue Regeneration ◽  
Platelet Rich Plasma ◽  
Bone Tissue Regeneration
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