PHARMACEUTICAL & CLINICAL CHALLENGES OF BIOLOGICAL MEDICINES: ONGOING HURDLES FROM DRUG DEVELOPMENT TO THERAPEUTIC APPLICATIONS
Keywords:
Biopharmaceuticals, Structural complexity, Formulation Development, Regulatory Compliance, Quality by Design (QbD), Immunogenicity, BioethicsAbstract
Objective: To analyze current challenges the pharmaceutical industry and clinical institutes face regarding biopharmaceuticals from drug development and therapeutic applications.
Methods: The critical evaluation of biomedicines' challenges was carried out by analyzing the updated information extracted from various databases like Embase, publicly available documents from the different ministries of health, recent research & review articles, and analytical survey documents. The extensive literature search was carried out by applying a set of keywords focusing on the subject matter. Further, a specific terminology-based literature search was carried out to include information beyond generically available. These literatures are then further screened following exclusion criteria like duplicity, non-English papers etc. and the rest are considered for exclusive review.
Results: The systematic review enlightened the hurdles throughout the lifecycle management of biopharmaceuticals namely the structural complexity of biomedicines impacting drug discovery, formulation development, complex manufacturing processes involving living systems (e.g. mammalian cell lines, microbial agents, plants, fungus etc.), temperature & humidity sensitive supply chain management, stringent regulatory requirements, monitoring immunogenicity after drug administration, invasive drug delivery approaches. Animal and clinical testing of the biologics are also very challenging. Novel biopharmaceuticals including cell-based medicines, recombinant products, gene therapy likewise often face ethical as well as higher cost issues.
Conclusion: Proper configuration of regulatory guidelines, innovative bioinformatics & software-based drug discovery tools, implementation of quality by design approaches to identify critical process parameters at the drug developmental phase, the suitable training to healthcare professionals on usage, safety, immunogenicity, handling & storage of biopharmaceuticals would bestow clinical benefits to the intended patients. Continual research is going on to market new biopharmaceuticals in a cost-effective manner for difficult-to-treat terminal diseases preferably via peroral administration.
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References
Misra M. Biosimilars: Current perspectives and future implications. Indian J. Pharmacol. 2012;44(1):12–14. doi: 10.4103/0253-7613.91859.
Leader B, Baca QJ, Golan DE. Protein therapeutics: a summary and pharmacological classification. Nature Reviews Drug Discovery. 2008;7(1):21–39. doi:10.1038/nrd2399.
Leavy O. Therapeutic antibodies: past, present and future. Nature Reviews Immunology. 2010; 10(5):297–297. doi:10.1038/nri2763.
Walsh G, Walsh E. Biopharmaceutical benchmarks 2022. Nature Biotechnology. 2022: 40(12):1722–1760. doi:10.1038/s41587-022-01582-x.
Kesik‐Brodacka M. Progress in biopharmaceutical development. Biotechnology and Applied Biochemistry. 2018; 65(3):306–322. doi:10.1002/bab.1617.
Vlasak J, Bussat MC, Wang S, Wagner-Rousset E, Schaefer M, Klinguer-Hamour C, Kirchmeier M, Corvaïa N, Ionescu R, Beck A. Identification, and characterization of asparagine deamidation in the light chain CDR1 of a humanized IgG1 antibody. Analytical Biochemistry. 2009; 392(2):145–154. doi:10.1016/j.ab.2009.05.043.
Khawli LA, Goswami S, Hutchinson R, Kwong ZW, Yang J, Wang X, Yao Z, Sreedhara A, Cano T, Tesar DB, Nijem I, Allison DE, Wong PY, Kao YH, Quan C, Joshi A, Harris RJ, Motchnik P. Charge variants in IgG1. Mabs. 2010; 2(6):613–624. doi:10.4161/mabs.2.6.13333.
Beck A. Biosimilar, biobetter and next generation therapeutic antibodies. Mabs. 2011; 3(2):107–110. doi:10.4161/mabs.3.2.14785.
Weise M. From bioequivalence to biosimilars: How much do regulators dare? Zeitschrift Für Evidenz, Fortbildung Und Qualität Im Gesundheitswesen. 2019;140;58–62. doi: 10.1016/j.zefq.2018.12.001.
Sharma A, Kumar N, Kuppermann BD, Bandello F, Loewenstein A. Biologics, biosimilars, and biobetters: different terms or different drugs? Eye. 2019; 33(7):1032–1034. doi:10.1038/s41433-019-0391-5.
Weise M, Bielsky MC, de Smet K, Ehmann F, Ekman N, Narayanan G, Heim HK, Heinonen E, Ho K, Thorpe R, Vleminckx C, Wadhwa M, & Schneider CK. Biosimilars—why terminology matters. Nature Biotechnology. 2011;29(8):690–693. doi:10.1038/nbt.1936.
Strohl WR. Fusion Proteins for Half-Life Extension of Biologics as a Strategy to Make Biobetters. BioDrugs. 2015; 9(4):215–239.doi:10.1007/s40259-015-0133-6.
Kim H, Alten R, Cummings F, Danese S, D’Haens G, Emery P, Ghosh S, Gilletta de Saint Joseph C, Lee J, Lindsay JO, Nikiphorou E, Parker B, Schreiber S, Simoens S, Westhovens R, Jeong JH, Peyrin-Biroulet L. Innovative approaches to biologic development on the trail of CT-P13: biosimilars, value-added medicines, and biobetters. Mabs. 2021;13(1): e1868078.doi:10.1080/19420862.2020.1868078.
LoRusso PM, Weiss D, Guardino E, Girish S, Sliwkowski MX. Trastuzumab Emtansine: A Unique Antibody-Drug Conjugate in Development for Human Epidermal Growth Factor Receptor 2–Positive Cancer. Clinical Cancer Research. 2011;17(20):6437–6447. doi:10.1158/1078-0432.CCR-11-0762.
Verma, S., Miles, D., Gianni, L., Krop, I. E., Welslau, M., Baselga, J., Pegram, M., Oh, D.-Y., Diéras, V., Guardino, E., Fang, L., Lu, M. W., Olsen, S., & Blackwell, K., Trastuzumab Emtansine for HER2-Positive Advanced Breast Cancer. New England Journal of Medicine, 367(19), (2012) 1783–1791. https://doi.org/10.1056/NEJMoa1209124.
IQVIA Consulting Services, Case Studies for Value Added Medicines Unlocking the potential of patient-centric continuous innovation.2019. https://www.medicinesforeurope.com/wp-content/uploads/2019/04/IQVIA-MFE_Case-Studies-for-VAMs_Final-Word-Document_vUpdate2019-v3.0.pdf/(accessed on 04 May 2024).
Athauda D, Maclagan K, Skene SS, Bajwa-Joseph M, Letchford D, Chowdhury K, Hibbert S, Budnik N, Zampedri L, Dickson J, Li Y, Aviles-Olmos I, Warner TT, Limousin P, Lees AJ, Greig NH, Tebbs S, Foltynie T. Exenatide once weekly versus placebo in Parkinson’s disease: a randomised, double-blind, placebo-controlled trial. The Lancet. 2017; 390(10103):1664–1675. doi:10.1016/S0140-6736(17)31585-4.
Vijiaratnam N, Girges C, Auld G, Chau M, Maclagan K, King A, Skene S, Chowdhury K., Hibbert S, Morris H, Limousin P, Athauda D, Carroll CB, Hu MT, Silverdale M, Duncan GW, et.al. Exenatide once weekly over 2 years as a potential disease-modifying treatment for Parkinson’s disease: protocol for a multicentre, randomised, double blind, parallel group, placebo controlled, phase 3 trial: The ‘Exenatide-PD3’ study. BMJ Open. 2021;11(5): e047993. doi:10.1136/bmjopen-2020-047993.
Zhao L, Ren T, Wang DD. Clinical pharmacology considerations in biologics development. Acta Pharmacologica Sinica. 2012;33(11):1339–1347. doi:10.1038/aps.2012.51.
Mellstedt H. Clinical considerations for biosimilar antibodies. European Journal of Cancer Supplements. 2013;11(3):1–11. doi:10.1016/S1359-6349(13)70001-6.
Chan JCN, Chan ATC. Biologics and biosimilars: what, why and how? ESMO Open. 2017;2(1): e000180. doi:10.1136/esmoopen-2017-000180.
Morrow T, Felcone LH. Defining the difference: What Makes Biologics Unique. Biotechnology Healthcare. 2004;1(4):24–29. PMID: 23393437
Ciucci G, Colliva A, Vuerich R, Pompilio G, Zacchigna S. Biologics and cardiac disease: challenges and opportunities. Trends in Pharmacological Sciences. 2022; 43(11):894–905. doi: 10.1016/j.tips.2022.06.001.
Ovacik M, Lin K. Tutorial on Monoclonal Antibody Pharmacokinetics and Its Considerations in Early Development. Clinical and Translational Science. 2018; 11(6):540–552. doi:10.1111/cts.12567.
Wang W, Wang E, Balthasar J. Monoclonal Antibody Pharmacokinetics and Pharmacodynamics. Clinical Pharmacology & Therapeutics. 2008;84(5):548–558. doi:10.1038/clpt.2008.170.
Dong JQ, Salinger DH, Endres CJ, Gibbs JP, Hsu CP, Stouch BJ, Hurh E, Gibbs MA. Quantitative Prediction of Human Pharmacokinetics for Monoclonal Antibodies. Clinical Pharmacokinetics. 2011;50(2):131–142. doi:10.2165/11537430-000000000-00000.
Wang YMC, Jawa V, Ma M. Immunogenicity and PK/PD evaluation in biotherapeutic drug development: scientific considerations for bioanalytical methods and data analysis. Bioanalysis. 2014;6(1):79–87. doi:10.4155/bio.13.302.
Medi MB, Chintala R, B Akhilesh. Excipient selection in biologics and vaccines formulation development. European Pharmaceutical Review. 2014; 19:16-20. https://www.europeanpharmaceuticalreview.com/article/24136/excipient-selection-biologics-vaccines-formulation-development/ (accessed on 04 May 2024).
Courtney KN. Key CMC Considerations for Biologic Development. American Pharmaceutical Review. 2021 Dec. https://www.americanpharmaceuticalreview.com/Featured-Articles/581696-Key-CMC-Considerations-for-Biologic-Development/ (accessed on 04 May 2024).
Weinbuch D, Hawe A, Jiskoot W, Friess W. Introduction into Formulation Development of Biologics. In: Warne N, Mahler HC. (eds) Challenges in Protein Product Development. AAPS Advances in the Pharmaceutical Sciences Series. Springer, Cham; 2018; vol 38. p.3-22 doi:10.1007/978-3-319-90603-4_1.
Muralidhara BK, Wong M. Critical considerations in the formulation development of parenteral biologic drugs. Drug Discovery Today. 2020;25(3):574–581. doi: 10.1016/j.drudis.2019.12.011.
Bajracharya R, Song JG, Back SY, Han HK. Recent Advancements in Non-Invasive Formulations for Protein Drug Delivery. Computational and Structural Biotechnology Journal. Sep 2019; 17:1290-1308. doi: 10.1016/j.csbj.2019.09.004.
Ionova Y, Wilson L. Biologic excipients: Importance of clinical awareness of inactive ingredients. PLOS ONE. 2020;15(6): e0235076. doi: 10.1371/journal.pone.0235076.
Kerwin BA. Polysorbates 20 and 80 Used in the Formulation of Protein Biotherapeutics: Structure and Degradation Pathways. Journal of Pharmaceutical Sciences. 2008;97(8):2924–2935. doi:10.1002/jps.21190.
Challener CA. Excipients for High-Concentration Biologics. BioPharm International. 2022;35(3):17-37. https://www.biopharminternational.com/view/excipients-for-high-concentration-biologics (accessed on 04 May 2024).
Bhambhani A, Kissmann JM, Joshi SB, Volkin DB, Kashi RS, Russell MC. Formulation Design and High-Throughput Excipient Selection Based on Structural Integrity and Conformational Stability of Dilute and Highly Concentrated IgG1 Monoclonal Antibody Solutions. Journal of Pharmaceutical Sciences. 2012; 101(3):1120–1135. doi:10.1002/jps.23008.
Irvine DJ, Su X, Kwong B. 2013. Routes of Delivery for Biological Drug Products. In: Pharmaceutical Sciences Encyclopedia, Wiley. 2013: pp. 1–48. doi:10.1002/9780470571224.pse521.
Kruse GB, Amonkar MM, Smith G, Skonieczny DC, Stavrakas S. Analysis of Costs Associated With Administration of Intravenous Single-Drug Therapies in Metastatic Breast Cancer in a U.S. Population. Journal of Managed Care Pharmacy. 2008;14(9):844–857. doi:10.18553/jmcp.2008.14.9.844.
Vescia S, Baumgärtner AK, Jacobs VR, Kiechle-Bahat M, Rody A, Loibl S, Harbeck N. Management of venous port systems in oncology: a review of current evidence. Annals of Oncology. 2008;19(1):9–15. doi:10.1093/annonc/mdm272.
Tetteh EK, Morris S. Evaluating the administration costs of biologic drugs: development of a cost algorithm. Health Econ Rev. Dec 2014;4(1):26. doi:10.1186/s13561-014-0026-2.
van Horssen R, ten Hagen TLM, Eggermont AMM. TNF-α in Cancer Treatment: Molecular Insights, Antitumor Effects, and Clinical Utility. The Oncologist. 2006;11(4):397–408. doi:10.1634/theoncologist.11-4-397.
Grünhagen DJ, de Wilt JH, ten Hagen TL, Eggermont AM. Technology Insight: utility of TNF-α-based isolated limb perfusion to avoid amputation of irresectable tumors of the extremities. Nature Clinical Practice Oncology. 2006;3(2):94–103. doi:10.1038/ncponc0426.
Thurber GM, Schmidt MM, Wittrup KD. Antibody tumor penetration: Transport opposed by systemic and antigen-mediated clearance. Advanced Drug Delivery Reviews. 2008; 60(12):1421–1434. doi: 10.1016/j.addr.2008.04.012.
Chapman AP, Antoniw P, Spitali M, West S, Stephens S, King DJ. Therapeutic antibody fragments with prolonged in vivo half-lives. Nature Biotechnology. 1999;17(8):780–783. doi:10.1038/11717.
Kontermann RE. Strategies to Extend Plasma Half-Lives of Recombinant Antibodies. BioDrugs. 2009;23(2):93–109. doi:10.2165/00063030-200923020-00003.
Herrington-Symes AP, Farys M, Khalili H, Brocchini S. Antibody fragments: Prolonging circulation half-life special issue-antibody research. Advances in Bioscience and Biotechnology.2013; 04(05): 689–698. doi.10.4236/abb.2013.45090.
Badkar Av, Gandhi RB, Davis SP, LaBarre MJ. Subcutaneous Delivery of High-Dose/Volume Biologics: Current Status and Prospect for Future Advancements. Drug Design, Development and Therapy. 2021;15: 159–170. doi:10.2147/DDDT.S287323.
Palm T, Sahin Eren, Gandhi R, Khossravi M. The importance of the concentration-temperature-viscosity relationship for the development of biologics. BioProcess International. 2015. https://bioprocessintl.com/manufacturing/monoclonal-antibodies/importance-concentration-temperature-viscosity-relationship-development-biologics/,2015 (accessed on 04 May 2024).
Garidel P, Kuhn AB, Schäfer Lv, Karow-Zwick AR, Blech M. High-concentration protein formulations: How high is high? European Journal of Pharmaceutics and Biopharmaceutics. 2017; 119:353–360. doi: 10.1016/j.ejpb.2017.06.029.
Frost GI. Recombinant human hyaluronidase (rHuPH20): an enabling platform for subcutaneous drug and fluid administration. Expert Opinion on Drug Delivery. 2007;4(4): 427–440. doi:10.1517/17425247.4.4.427.
Wasserman RL. Recombinant human hyaluronidase-facilitated subcutaneous immunoglobulin infusion in primary immunodeficiency diseases. Immunotherapy. 2017; 9(12):1035–1050. doi:10.2217/imt-2017-0092.
Lugaresi A. Addressing the need for increased adherence to multiple sclerosis therapy: can delivery technology enhance patient motivation? Expert Opinion on Drug Delivery. 2009; 6(9):995–1002. doi:10.1517/17425240903134769.
Genovese MC, Covarrubias A, Leon G, Mysler E, Keiserman M, Valente R, Nash P, Simon‐Campos JA, Porawska W, Box J, Legerton C, Nasonov E, Durez P, Aranda R, Pappu R, Delaet I., Teng J, Alten R. Subcutaneous abatacept versus intravenous abatacept: A phase IIIb noninferiority study in patients with an inadequate response to methotrexate. Arthritis & Rheumatism. 2011; 63(10):2854–2864. doi:10.1002/art.30463.
Kaiser C, Knight A, Nordström D, Pettersson T, Fransson J, Florin-Robertsson E, Pilström B. Injection-site reactions upon Kineret (anakinra) administration: experiences and explanations. Rheumatology International. 2012;32(2):295–299. doi:10.1007/s00296-011-2096-3.
Lugaresi A. Addressing the need for increased adherence to multiple sclerosis therapy: can delivery technology enhance patient motivation? Expert Opinion on Drug Delivery. 2009; 6(9):995–1002. doi:10.1517/17425240903134769.
Verdun di CE, Russell S, Snow T. Understanding and meeting injection device needs in multiple sclerosis: a survey of patient attitudes and practices. Patient Preference and Adherence. Mar 2011; 5:173–180. doi:10.2147/PPA.S14903.
Kuzman D, Bunc M, Ravnik M, Reiter F, Žagar L, Bončina M. Long-term stability predictions of therapeutic monoclonal antibodies in solution using Arrhenius-based kinetics. Scientific Reports. 2021;11(1): 20534. doi:10.1038/s41598-021-99875-9.
Bhatnagar BS, Bogner RH, Pikal MJ. Protein Stability During Freezing: Separation of Stresses and Mechanisms of Protein Stabilization. Pharmaceutical Development and Technology. 2007;12(5):505–523. doi:10.1080/10837450701481157.
Shire SJ. Formulation and manufacturability of biologics. Current Opinion in Biotechnology. 2009;20(6):708–714. doi: 10.1016/j.copbio.2009.10.006.
Thomas CR, Geer D. Effects of shear on proteins in solution. Biotechnology Letters. 2011; 33(3):443–456. doi:10.1007/s10529-010-0469-4.
Mazzeo A, Carpenter P. Stability Studies for Biologics, in: K. Huynh-Ba (Ed.), Handbook of Stability Testing in Pharmaceutical Development -Regulations, Methodologies, and Best Practices. New York: Springer Science+Business Media; 2009. p. 353–369. doi:10.1007/978-0-387-85627-8_17.
Murphy RM. Peptide Aggregation in Neurodegenerative Disease. Annual Review of Biomedical Engineering, 4(1), (2002) 155–174. doi: 10.1146/annurev.bioeng.4.092801.094202.
Jahn TR, Makin OS, Morris KL, Marshall KE, Tian P, Sikorski P, Serpell LC. The Common Architecture of Cross-β Amyloid. Journal of Molecular Biology. 2010;395(4):717–727. doi: 10.1016/j.jmb.2009.09.039.
Riek R, Eisenberg DS. The activities of amyloids from a structural perspective. Nature. 2016;539(7628):227–235. doi:10.1038/nature20416.
Bowerman CJ, Nilsson BL. Review self‐assembly of amphipathic β‐sheet peptides: Insights and applications. Peptide Science. 2012;98(3):169–184. doi:10.1002/bip.22058.
Trainor K, Broom A, Meiering EM. Exploring the relationships between protein sequence, structure and solubility. Current Opinion in Structural Biology. 2017; 42:136–146. doi: 10.1016/j.sbi.2017.01.004.
Zapadka KL, Becher FJ, Gomes dos Santos AL, Jackson SE. Factors affecting the physical stability (aggregation) of peptide therapeutics. Interface Focus. 2017;7(6):20170030. doi:10.1098/rsfs.2017.0030.
Onoue S, Ohshima K, Debari K, Koh K, Shioda S, Iwasa S, Kashimoto K, Yajima T. Mishandling of the Therapeutic Peptide Glucagon Generates Cytotoxic Amyloidogenic Fibrils. Pharmaceutical Research. 2004;21(7):1274–1283. doi:10.1023/B: PHAM.0000033016.36825.2c.
Wurth C, Guimard NK, Hecht MH. Mutations that Reduce Aggregation of the Alzheimer’s Aβ42 Peptide: an Unbiased Search for the Sequence Determinants of Aβ Amyloidogenesis. Journal of Molecular Biology. 2002;319(5):1279–1290. doi:10.1016/S0022-2836(02)00399-6.
Frokjaer S, Otzen DE. Protein drug stability: a formulation challenge. Nature Reviews Drug Discovery. 2005;4(4):298–306. doi:10.1038/nrd1695.
Krielgaard L, Jones LS, Randolph TW, Frokjaer S, Flink JM, Manning MC, Carpenter J F. Effect of tween 20 on freeze-thawing- and agitation-induced aggregation of recombinant human factor XIII. Journal of Pharmaceutical Sciences. 1998;87(12):1597–1603. doi:10.1021/js980126i.
Wang M, Li Y, Srinivasan P, Hu Z, Wang R, Saragih A, Repka MA, Murthy SN. Interactions Between Biological Products and Product Packaging and Potential Approaches to Overcome Them. AAPS PharmSciTech. 2018;19(8):3681–3686. doi:10.1208/s12249-018-1184-z.
Seidl A, Hainzl O, Richter M, Fischer R, Böhm S, Deutel B, Hartinger M, Windisch J, Casadevall N, London GM, Macdougall I. Tungsten-Induced Denaturation and Aggregation of Epoetin Alfa During Primary Packaging as a Cause of Immunogenicity. Pharmaceutical Research. 2012;29(6):1454–1467. doi:10.1007/s11095-011-0621-4.
Harrison B, Rios M. Big Shot: Developments in Prefilled Syringes. 2007; 31:50-60. https://www.pharmtech.com/view/big-shot-developments-prefilled-syringes, 2007 (accessed on 04 May 2024)
Jones LS, Kaufmann A, Middaugh CR. Silicone Oil Induced Aggregation of Proteins. Journal of Pharmaceutical Sciences. Apr 2005;94(4): 918–927. doi:10.1002/jps.20321.
Crommelin DJ, Hawe A, Jiskoot W. Formulation of Biologics Including Biopharmaceutical Considerations. In: Crommelin, D., Sindelar, R., Meibohm, B. (eds) Pharmaceutical Biotechnology. Cham: Springer Nature Switzerland AG; 2019. p 83–103. doi:10.1007/978-3-030-00710-2_5.
Lam XM, Yang JY, Cleland JL. Antioxidants for Prevention of Methionine Oxidation in Recombinant Monoclonal Antibody HER2. Journal of Pharmaceutical Sciences. 1997;86(11):1250–1255. doi:10.1021/js970143s.
Nguyen TH. ChemInform Abstract: Oxidation Degradation of Protein Pharmaceuticals. ChemInform. 1995;26(4). doi:10.1002/chin.199504314.
Janecki DJ, Reilly JP. Denaturation of metalloproteins with EDTA to facilitate enzymatic digestion and mass fingerprinting. Rapid Communications in Mass Spectrometry. 2005; 19(10):1268–1272. doi:10.1002/rcm.1924.
Zhou S, Schöneich C, Singh SK. Biologics Formulation Factors Affecting Metal Leachables from Stainless Steel. AAPS PharmSciTech. 2011;12(1):411–421. doi:10.1208/s12249-011-9592-3.
Yokota H, Saito H, Masuoka K, Kaniwa H, Shibanuma T. Reversed phase HPLC of Met58 oxidized rhIL-11: oxidation enhanced by plastic tubes. Journal of Pharmaceutical and Biomedical Analysis. 2002;24(2): 317–324. doi:10.1016/S0731-7085(00)00419-2.
Castner J, Benites P, Bresnick M. Leachables and Extractables, In: Jameel F, Hershenson S. (Eds.), Formulation and Process Development Strategies For Manufacturing Biopharmaceuticals. New Jersey: John Wiley & Sons; 2010. p 857-880. doi:10.1002/9780470595886.ch34.
Gronemeyer P, Ditz R, Strube J. Trends in Upstream and Downstream Process Development for Antibody Manufacturing. Bioengineering. 2014;1(4):188–212. doi:10.3390/bioengineering1040188.
Tripathi NK, Shrivastava A. Recent Developments in Bioprocessing of Recombinant Proteins: Expression Hosts and Process Development. Frontiers in Bioengineering and Biotechnology, Dec 2019;7:420. doi:10.3389/fbioe.2019.00420.
Roch P, Mandenius CF. On-line monitoring of downstream bioprocesses. Current Opinion in Chemical Engineering. 2016; 14:112–120. doi: 10.1016/j.coche.2016.09.007.
Azevedo AM, Rosa PAJ, Ferreira IF, Aires-Barros MR. Chromatography-free recovery of biopharmaceuticals through aqueous two-phase processing. Trends in Biotechnology. 2009;27(4):240–247. doi: 10.1016/j.tibtech.2009.01.004.
Rathore AS, Kapoor G. Application of process analytical technology for downstream purification of biotherapeutics. Journal of Chemical Technology & Biotechnology. 2015; 90(2): 228–236. doi:10.1002/jctb.4447.
Sarkis M, Bernardi A., Shah N, Papathanasiou MM. Emerging Challenges and Opportunities in Pharmaceutical Manufacturing and Distribution. Processes. 2021;9(3):457. doi:10.3390/pr9030457.
Szkodny AC, Lee KH. Biopharmaceutical Manufacturing: Historical Perspectives and Future Directions. Annual Review of Chemical and Biomolecular Engineering. 2022;13(1): 141–165. doi:10.1146/annurev-chembioeng-092220-125832.
ter Horst JP, Turimella SL, Metsers F, Zwiers A. Implementation of Quality by Design (QbD) Principles in Regulatory Dossiers of Medicinal Products in the European Union (EU) Between 2014 and 2019. Therapeutic Innovation & Regulatory Science. 2021;55(3):583–590. doi:10.1007/s43441-020-00254-9.
Rathore AS. QbD/PAT for bioprocessing: moving from theory to implementation. Current Opinion in Chemical Engineering. 2014; 6:1–8. doi: 10.1016/j.coche.2014.05.006.
Eon‐Duval A, Broly H, Gleixner R. Quality attributes of recombinant therapeutic proteins: An assessment of impact on safety and efficacy as part of a quality by design development approach. Biotechnology Progress. 2012; 28(3):608–622. doi:10.1002/btpr.1548.
Rathore AS. Quality: Design space for biotech products, Biopharm Int. 2007;20 (4):40–45. https://www.biopharminternational.com/view/quality-design-space-biotech-products (accessed on 05 May 2024).
Rathore AS, Singh SK, Kumar J, Kapoor G. Implementation of QbD for Manufacturing of Biologics—Has It Met the Expectations? in: Jagschies G, Lindskog E, Łącki K, Galliher P. (Eds), Biopharmaceutical Processing - Development, Design and Implementation of Manufacturing Processes., Elsevier; 2018. p. 1051-1073. doi:10.1016/B978-0-08-100623-8.00048-7.
Kozlowski S, Swann P. Considerations for Biotechnology Product by Design. In: Rathore AS, Mhatre R. (Eds), Quality by Design for Biopharmaceuticals: Principles and Case Studies, John Wiley & Sons, Inc. 2009. p 9-30. doi: 10.1002/9780470466315.ch2.
Kelley B. Quality by Design risk assessments supporting approved antibody products. Mabs. 2016;8(8):1435–1436. doi:10.1080/19420862.2016.1232218.
Kokil S, Singh S. Current Perspective on Opportunities and Adoption Challenges of QbD Implementation in Pharmaceutical Product Development. Inventi Rapid: Pharmaceutical Process Development. 2016;(2):1-8.
Milmo S. Quality by Design Bridging the Gap between Concept and Implementation. Biopharm International. 2014; 29(4): 40–45. https://www.biopharminternational.com/view/quality-design-bridging-gap-between-concept-and-implementation-0. (accessed on 06 May 2024).
Sykes C. Time- and Temperature-Controlled Transport: Supply Chain Challenges and Solutions. P & T: A Peer-Reviewed Journal for Formulary Management. 2018;43(3):154–170.
Papathanasiou MM, Stamatis C, Lakelin M, Farid S, Titchener-Hooker N, Shah N. Autologous CAR T-cell therapies supply chain: challenges and opportunities? Cancer Gene Therapy. 2020; 27(10–11):799–809. doi:10.1038/s41417-019-0157-z.
Ned P, Lopez E. Top challenges facing drug supply chains. Biopharmdrive. 2018. https://www.biopharmadive.com/news/top-challenges-facing-drug-supply-chains/521876/ (accessed on 04 May 2024).
Jaffer G. Pharma’s Almanac. Keys to Successful Storage, Management and Transport of Biological Materials. 2020. https://www.pharmasalmanac.com/articles/keys-to-successful-storage-management-and-transport-of-biological-materials. (accessed on 04 May 2024).
Tetz A. The evolution of smart temperature-controlled packaging. Packaging Europe. 2017. https://packagingeurope.com/the-evolution-of-smart-temperature-controlled-packaging/2958.article. (accessed on 04 May 2024).
Ibrahim T, Araujo CAS. Biopharmaceutical supply chain challenges in developing countries: an exploratory analysis. Supply Chain Forum: An International Journal.2021; 22(4): 294–309. doi.10.1080/16258312.2021.1936152.
Zobel A, Heelan B. Regulatory, clinical and logistics challenges of Advanced Therapy Medicinal Products (ATMPs) in clinical research. European Pharmaceutical Review. 2017. https://www.europeanpharmaceuticalreview.com/article/81122/regulatory-clinical-and-logistics-challenges-of-advanced-therapy-medicinal-products-atmps-in-clinical-research/, (accessed on 04 May 2024).
Penugonda VLDSS, Cherukuri VP, Vaka NS, Juturi RKR. Development of Biosimilars: An Overview of The Regulatory Framework In India, USA, EU; Major Challenges And Related Case Studies. International Journal of Pharmaceutical Sciences and Research. 2021;12(12): 6341–6352. doi:10.13040/IJPSR.0975-8232.12(12).6341-52.
Chisholm O, Critchley H. Future directions in regulatory affairs. Frontiers in Medicine. 2023;9. doi:10.3389/fmed.2022.1082384.
Druedahl LC, Almarsdóttir AB, Kälvemark Sporrong S, De Bruin ML, Hoogland H, Minssen T, van de Weert M, Kesselheim AS, Sarpatwari A. A qualitative study of biosimilar manufacturer and regulator perceptions on intellectual property and abbreviated approval pathways. Nature Biotechnology. 2020;38(11):1253–1256. doi:10.1038/s41587-020-0717-7.
Lokesh C, Sonia K, Kamaraj R. Regulatory Requirements for Biological product approval process in India. Research Journal of Pharmacy and Technology. 2020;13(2):1050-1054. doi:10.5958/0974-360X.2020.00193.6.
Senior M. Fresh from the biotech pipeline: fewer approvals, but biologics gain share. Nature Biotechnology. 2023;41(2):174–182. doi:10.1038/s41587-022-01630-6.
Sekhon BS, Saluja V. Biosimilars: An overview. Biosimilars. 2011;(1):1–11. doi:10.2147/BS.S16120.
Vugmeyster Y. Pharmacokinetics, and toxicology of therapeutic proteins: Advances and challenges. World Journal of Biological Chemistry. 2012;3(4):73-92. doi:10.4331/wjbc.v3.i4.73.
Wang J, Iyer S, Fielder PJ, Davis JD, Deng R. Projecting human pharmacokinetics of monoclonal antibodies from nonclinical data: comparative evaluation of prediction approaches in early drug development. Biopharmaceutics & Drug Disposition. 2016;37(2):51–65. doi:10.1002/bdd.1952.
Acri KML, Lybecker n. Biologics and Biosimilars: A Primer. Fraser Institute. 2020. https://www.fraserinstitute.org/sites/default/files/biologics-and-biosimilars-a-primer.pdf. (accessed on 04 May 2024).
Schneider CK, Kalinke U. Toward biosimilar monoclonal antibodies. Nature Biotechnology. 2008;26(9):985–990. doi:10.1038/nbt0908-985.
Negrusz-Kawecka M. The role of TNF-alpha in the etiopathogenesis of heart failure. Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego, Jan 2002;12(67):69–72.
Friganović A, Mędrzycka-Dąbrowska W, Krupa S, Oomen B, Decock N, Stievano A. Nurses’ Knowledge and Attitudes towards Biosimilar Medicines as Part of Evidence-Based Nursing Practice—International Pilot Study within the Project Biosimilars Nurses Guide Version 2.0. International Journal of Environmental Research and Public Health. 2022;19(16): 10311. doi:10.3390/ijerph191610311.
Cohen H, Beydoun D, Chien D, Lessor T, McCabe D, Muenzberg M, Popovian R, Uy J. Awareness, Knowledge, and Perceptions of Biosimilars Among Specialty Physicians. Advances in Therapy. 2016;33(12):2160–2172. doi:10.1007/s12325-016-0431-5.
Leonard E, Wascovich M, Oskouei S, Gurz P, Carpenter D. Factors Affecting Health Care Provider Knowledge and Acceptance of Biosimilar Medicines: A Systematic Review. Journal of Managed Care & Specialty Pharmacy.2019;25(1):102–112. doi:10.18553/jmcp.2019.25.1.102.
Dylst P, Vulto A, Simoens S. Barriers to the Uptake of Biosimilars and Possible Solutions: A Belgian Case Study. PharmacoEconomics, 2014;32(7):681–691. doi:10.1007/s40273-014-0163-9.
Pasina L, Casadei G, Nobili A. A survey among hospital specialists and pharmacists about biosimilars. European Journal of Internal Medicine. 2016;35: e31–e33. doi:10.1016/j.ejim.2016.07.010.
O’Callaghan J, Bermingham M, Leonard M, Hallinan F, Morris JM, Moore U, Griffin BT. Assessing awareness and attitudes of healthcare professionals on the use of biosimilar medicines: A survey of physicians and pharmacists in Ireland. Regulatory Toxicology and Pharmacology. 2017; 88:252–261. doi:10.1016/j.yrtph.2017.06.013.
Adé A, Bourdon O, Bussières JF. A survey of pharmacists’ knowledge and views of biosimilars in Quebec and France. Annales Pharmaceutiques Françaises, 2017;75(4):267–275. doi:10.1016/j.pharma.2017.01.003.
Gahlot P, Dhankhar R, Yadav P, Vigarniya MM. Challenges of Biomedical Waste Management, Annals of Biology. 2019;35 (2):191-200.
Mitragotri S, Burke PA, Langer R. Overcoming the challenges in administering biopharmaceuticals: formulation and delivery strategies. Nature Reviews Drug Discovery. 2014;13(9):655–672. doi:10.1038/nrd4363.
Baumann A. Preclinical development of therapeutic biologics. Expert Opinion on Drug Discovery. 2008;3(3):289–297. doi:10.1517/17460441.3.3.289.
Baumann A. Nonclinical development of biopharmaceuticals. Drug Discovery Today. Dec 2009;14(23–24):1112–1122. doi.10.1016/j.drudis.2009.09.013.
Giezen TJ, Mantel-Teeuwisse AK, Meyboom RHB, Straus SMJM, Leufkens HGM, Egberts TCG. Mapping the Safety Profile of Biologicals. Drug Safety. 2010;33(10):865–878. doi:10.2165/11538330-000000000-00000.
Ryan AM. Frontiers in Nonclinical Drug Development. Veterinary Pathology. 2015; 52(2):419–426. doi:10.1177/0300985814547282.
DeSilva B, Smith W, Weiner R, Kelley M, Smolec J, Lee B, Khan M, Tacey R, Hill H, Celniker A. Recommendations for the Bioanalytical Method Validation of Ligand-Binding Assays to Support Pharmacokinetic Assessments of Macromolecules. Pharmaceutical Research, 2003;20(11):1885–1900. doi:10.1023/B:PHAM.0000003390.51761.3d.
Bareham B, Georgakopoulos N, Matas-Céspedes A, Curran M, Saeb-Parsy K. Modeling human tumor-immune environments in vivo for the preclinical assessment of immunotherapies. Cancer Immunology, Immunotherapy. 2021;(70):2737–2750. doi:10.1007/s00262-021-02897-5.
Chakraborty R, Darido C, Liu F, Maselko M, Ranganathan S. Head and Neck Cancer Immunotherapy: Molecular Biological Aspects of Preclinical and Clinical Research. Cancers. 2023;15(3):852. doi:10.3390/cancers15030852.
Ravi M, Paramesh V, Kaviya SR, Anuradha E, Solomon FDP. 3D Cell Culture Systems: Advantages and Applications. Journal of Cellular Physiology. 2015;230(1):16–26. doi:10.1002/jcp.24683.
Belfiore L, Aghaei B, Law AMK, Dobrowolski JC, Raftery LJ, Tjandra AD, Yee C, Piloni A, Volkerling A, Ferris CJ, Engel M. Generation and analysis of 3D cell culture models for drug discovery. European Journal of Pharmaceutical Sciences. 2021;(163) 105876. doi:10.1016/j.ejps.2021.105876.
Moysidou CM, Barberio C, Owens RM. Advances in Engineering Human Tissue Models. Frontiers in Bioengineering and Biotechnology. Jan 2021;8: 620962. doi:10.3389/fbioe.2020.620962.
Freires IA, Morelo DFC, Soares LFF, Costa IS, de Araújo LP, Breseghello I, Abdalla HB, Lazarini JG, Rosalen PL, Pigossi SC, Franchin M. Progress and promise of alternative animal and non-animal methods in biomedical research. Archives of Toxicology. 2023;97(9): 2329–2342. doi:10.1007/s00204-023-03532-1.
Tuveson D, Clevers H. Cancer modeling meets human organoid technology. Science. 2019;364(6444):952–955. doi:10.1126/science.aaw6985.
Belair DG, Visconti RJ, Hong M, Marella M, Peters MF, Scott CW, Kolaja KL. Human ileal organoid model recapitulates clinical incidence of diarrhea associated with small molecule drugs. Toxicology in Vitro. Oct 2020;(68):104928. doi:10.1016/j.tiv.2020.104928.
Hidalgo M, Amant F, Biankin Av, Budinská E, Byrne AT, Caldas C, Clarke RB, de Jong S, Jonkers J, Mælandsmo GM, Roman-Roman S, Seoane J, Trusolino L, Villanueva A. Patient-Derived Xenograft Models: An Emerging Platform for Translational Cancer Research. Cancer Discovery. 2014;4(9):998–1013. Doi.10.1158/2159-8290.CD-14-0001.
Hanna J, Hossain GS, Kocerha J. The Potential for microRNA Therapeutics and Clinical Research. Frontiers in Genetics. 2019;10(478). doi:10.3389/fgene.2019.00478.
Catenacci DVT. Next‐generation clinical trials: Novel strategies to address the challenge of tumor molecular heterogeneity. Molecular Oncology. 2015;9(5):967–996. doi:org/10.1016/j.molonc.2014.09.011.
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