Critical Analysis and Quality Assessment of Nanomedicines and Nanocarriers in Clinical Trials: Three Years of Activity at the Clinical Trials Office
Abstract
:1. Introduction
2. Materials and Methods
3. Results
3.1. Type of Nanomedicines
3.2. Quality Issues
3.2.1. Stability
3.2.2. Specifications
3.2.3. GMP Compliance
3.2.4. Description of the Manufacturing Process and Process Controls
3.2.5. Batch Analyses
3.2.6. Control of Materials
3.2.7. Quality Documentation Compliance
3.2.8. Process Validation and/or Evaluation
3.2.9. Pharmaceutical Development
3.2.10. Controls of Critical Steps and Intermediates
3.2.11. Reference Standards or Materials
3.2.12. Container Closure System
3.2.13. Impurities
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Appendix A
Code | Description | Nanomedicine-Related Term | Analytical Method Confirming Nanoscale Dimension | Pharmaceutical Form | Study Phase | Therapeutic Area | Active Substance of Chemical Origin | Active Substance of Biological/Biotechnological Origin | Gene Therapy Medicinal Product |
---|---|---|---|---|---|---|---|---|---|
N23 | RNA–peptide | Polymer | Yes | Solution for injection | I | Cancer | No | Yes | No |
complex | therapeutic | ||||||||
N24 | Recombinant type 5 adenovirus vector | Nanocarrier | Yes | Concentrate for solution for infusion ev | III | Cancer | No | No | Yes |
N25 | Pegylated protein | Polymer | No | Solution for injection | I/II | Cancer | No | Yes | No |
therapeutic | |||||||||
N17 | Pegylated peptide | Polymer | No | Solution for infusion | III | Blood and lymphatic | Yes | No | No |
therapeutic | diseases | ||||||||
N26 | Recombinant | Nanocarrier | No | Solution for infusion ev | III | Blood and lymphatic | No | No | Yes |
adeno-associated virus | diseases | ||||||||
vector serotype 5 | |||||||||
N27 | Monoclonal antibody conjugated to a fluorochrome through a linker | Antibody–drug conjugate (ADC) | No | Concentrate for solution for injection | III | Cancer | No | Yes | No |
N28 | Monoclonal antibody conjugated to a cytotoxic agent through a linker | Antibody– | No | Powder for concentrate for solution for infusion | III | Cancer | No | Yes | No |
drug | |||||||||
conjugate | |||||||||
(ADC) | |||||||||
N29 | Recombinant protein attached to an albumin binding moiety | Nanocarrier | No | Solution for injection | III | Hormonal diseases | No | Yes | No |
N30 | Recombinant adenovirus serotype 155 viral vector | Nanocarrier | No | Suspension for injection | I | Respiratory tract diseases | No | Yes | No |
N17 | Pegylated peptide | Polymer | No | Solution for injection | III | Eye diseases | Yes | No | No |
therapeutic | |||||||||
N17 | Pegylated peptide | Polymer | No | Solution for injection | III | Eye diseases | Yes | No | No |
therapeutic | |||||||||
N7 | Pegylated enzyme | Polymer | No | Concentrate for solution for infusion | III | Body processes—genetic phenomena | No | Yes | No |
therapeutic | |||||||||
N31 | Recombinant adeno-associated viral vector | Nanocarrier | Yes | Concentrate for solution for infusion | I/II | Congenital, hereditary, and neonatal diseases and abnormalities | No | No | Yes |
N32 | Liposomal adjuvant | Liposome | Yes | Powder for solution for injection | II | Respiratory tract diseases | No | Yes | No |
N33 | Beads coated with the active ingredient | Nanocarrier | No | Soft capsule | II | Immune system diseases | No | Yes | No |
N34 | Pegylated recombinant protein | Polymer | No | Powder for solution for injection | II | Cancer | No | Yes | No |
therapeutic | |||||||||
N35 | Recombinant adeno virus vector serotype 26 | Nanocarrier | Yes | Solution for injection | III | Virus diseases | No | Yes | No |
N36 | Recombinant adeno-associated virus vector serotype 2 | Nanocarrier | No | Solution for injection | I/II | Blood and lymphatic diseases | No | No | Yes |
N37 | Pegylated peptide | Polymer | No | Solution for injection | II | Hormonal diseases | Yes | No | No |
therapeutic | |||||||||
N38 | Pegylated enzyme | Polymer | No | Concentrate for solution for infusion ev | III | Congenital, hereditary, and neonatal diseases and abnormalities | No | Yes | No |
Therapeutic | |||||||||
N39 | Liposome-based adjuvant | Liposome | Yes | Powder for solution for injection | II | Virus diseases | No | Yes | No |
N28 | Monoclonal antibody conjugated to a cytotoxic agent through a linker | Antibody– | No | Powder for concentrate for solution for infusion | III | Cancer | No | Yes | No |
drug | |||||||||
conjugate | |||||||||
(ADC) | |||||||||
N28 | Monoclonal antibody conjugated to a cytotoxic agent through a linker | Antibody– | No | Powder for concentrate for solution for infusion | III | Cancer | No | Yes | No |
drug | |||||||||
conjugate | |||||||||
(ADC) |
Code | Description | Nanomedicine-Related Term | Analytical Method Confirming Nanoscale Dimension | Pharmaceutical Form | Study Phase | Therapeutic Area | Active Substance of Chemical Origin | Active Substance of Biological/Biotechnological Origin | Gene Therapy Medicinal Product |
---|---|---|---|---|---|---|---|---|---|
N40 | Monoclonal antibody | Antibody–drug conjugate (ADC) | No | Powder for solution for injection | II | Cancer | No | Yes | No |
conjugated to a | |||||||||
cytotoxic agent through | |||||||||
a linker | |||||||||
N41 | Plasmid vector | Nanocarrier | No | Solution for injection | II | Cancer | No | Yes | No |
N42 | Antibody conjugated with a biopolymer | Polymer therapeutic | No | Solution for injection | II | Eye diseases | No | Yes | No |
N43 | Adeno-associated virus serotype 9 vector | Nanocarrier | No | Concentrate for solution for infusion ev | III | Nervous system diseases | No | No | Yes |
N44 | Monoclonal antibody | Antibody–drug conjugate (ADC) | Yes | Concentrate for solution for infusion | III | Cancer | No | Yes | No |
conjugated to a | |||||||||
cytotoxic agent through | |||||||||
a linker | |||||||||
N45 | Monoclonal antibody | Antibody–drug conjugate (ADC) | No | Powder for solution for infusion | I | Cancer | No | Yes | No |
conjugated to a | |||||||||
cytotoxic agent through | |||||||||
a linker | |||||||||
N46 | Monoclonal antibody conjugated to a cytotoxic agent through a linker | Antibody–drug conjugate (ADC) | No | Concentrate for solution for infusion | III | Cancer | No | Yes | No |
N7 | Pegylated enzyme | Polymer | No | Concentrate for solution for infusion | III | Body processes—genetic phenomena | No | Yes | No |
therapeutic | |||||||||
N47 | Pegylated oligonucleotide | Polymer therapeutic | No | Solution for injection | III | Eye diseases | Yes | No | No |
N48 | Adenoviral vector | Nanocarrier | No | Suspension for injection | I | Virus diseases | Yes | Yes | No |
N34 | Pegylated recombinant protein | Polymer therapeutic | No | Powder for solution for injection | III | Cancer | No | Yes | No |
N49 | Trivalent nanobody | Nanobody | No | Solution for infusion ev | II | Cancer | No | Yes | No |
N50 | Pegylated monoclonal antibody | Polymer therapeutic | No | Powder for solution for infusion ev | III | Immune system processes | No | Yes | No |
N51 | Liposomal formulation | Liposome | Yes | Powder for nebulization solution | II | Virus diseases | Yes | No | No |
N52 | Monoclonal antibody conjugated to a cytotoxic agent through a linker | Antibody–drug conjugate (ADC) | No | Powder for solution for infusion ev | II | Cancer | No | Yes | No |
N53 | Liposome suspension | Liposome | No | Inhalation suspension | III | Respiratory tract diseases | Yes | No | No |
N54 | Adenoviral vector | Nanocarrier | Yes | Solution for injection | III | Respiratory tract diseases | No | Yes | No |
N42 | Antibody conjugated with a biopolymer | Polymer therapeutic | No | Solution for injection | III | Eye diseases | No | Yes | No |
N53 | Liposome suspension | Liposome | No | Inhalation suspension | III | Respiratory tract diseases | Yes | No | No |
Classification Label of Quality Issues | Totals Per Classification | |
---|---|---|
CTA Form Compliance | 18 | |
Quality documentation compliance (IMPD, S-IMPD, SmPC, CE mark) | 31 | |
GMP compliance: information about all manufacturers involved (drug substance, drug product) and evidence of GMP (manufacturing licenses/GMP certificates, QP declarations, CEPs provided) | 75 | |
Drug Substance (DS) | ||
General information | Nomenclature | 0 |
Structure | 6 | |
General properties | 6 | |
Biological properties | 1 | |
Manufacture | Description of manufacturing process and process controls | 42 |
Control of materials | 45 | |
Control of critical steps and intermediates | 15 | |
Process validation and/or evaluation | 6 | |
Manufacturing process development | 22 | |
Characterization | Elucidation of structure and other characteristics | 19 |
Impurities | 23 | |
Control of drug substance | Specifications | 44 |
Analytical procedures | 13 | |
Validation of analytical procedures | 9 | |
Batch analyses | 33 | |
Justification of specification(s) | 12 | |
Reference standards or materials | 20 | |
Container closure system | 9 | |
Stability | 57 | |
Drug Product (DP) | ||
Description and composition of the investigational medicinal product | 20 | |
Pharmaceutical development | 26 | |
Manufacture | Batch formula | 2 |
Description of manufacturing process and process controls | 19 | |
Controls of critical steps and intermediates | 10 | |
Process validation and/or evaluation | 22 | |
Control of excipients | 2 | |
Control of drug product | Specifications | 47 |
Analytical procedures | 9 | |
Validation of analytical procedures | 4 | |
Batch analyses | 17 | |
Characterization of impurities | 5 | |
Justification of specification(s) | 11 | |
Reference standards or materials | 5 | |
Container closure system | 16 | |
Stability | 84 | |
Labeling | 8 | |
Adventitious agents’ safety | 9 | |
TOTAL | 822 |
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Year | CTs Submitted | CTs Authorized | CTs in Scope |
---|---|---|---|
2018 | 716 | 666 | 433 |
2019 | 722 | 672 | 449 |
2020 | 815 | 683 | 359 |
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Dri, D.A.; Gaucci, E.; Torrieri, I.; Carafa, M.; Marianecci, C.; Gramaglia, D. Critical Analysis and Quality Assessment of Nanomedicines and Nanocarriers in Clinical Trials: Three Years of Activity at the Clinical Trials Office. Pharmaceutics 2022, 14, 1438. https://doi.org/10.3390/pharmaceutics14071438
Dri DA, Gaucci E, Torrieri I, Carafa M, Marianecci C, Gramaglia D. Critical Analysis and Quality Assessment of Nanomedicines and Nanocarriers in Clinical Trials: Three Years of Activity at the Clinical Trials Office. Pharmaceutics. 2022; 14(7):1438. https://doi.org/10.3390/pharmaceutics14071438
Chicago/Turabian StyleDri, Diego Alejandro, Elisa Gaucci, Ilaria Torrieri, Maria Carafa, Carlotta Marianecci, and Donatella Gramaglia. 2022. "Critical Analysis and Quality Assessment of Nanomedicines and Nanocarriers in Clinical Trials: Three Years of Activity at the Clinical Trials Office" Pharmaceutics 14, no. 7: 1438. https://doi.org/10.3390/pharmaceutics14071438
APA StyleDri, D. A., Gaucci, E., Torrieri, I., Carafa, M., Marianecci, C., & Gramaglia, D. (2022). Critical Analysis and Quality Assessment of Nanomedicines and Nanocarriers in Clinical Trials: Three Years of Activity at the Clinical Trials Office. Pharmaceutics, 14(7), 1438. https://doi.org/10.3390/pharmaceutics14071438