Stupendous elevation in the healthcare costs has followed with the inception of the current unconventional options of treatment available for cancer patients. There is a dire need of innovative financing approaches to lessen the financial load on healthcare system. Biosimilars are biological drugs consisting of an active ingredient from a reference biological drug that has a great potential of relieving financial load. Strict requirements from regulatory point of view are required as biosimilars are exceedingly similar to but not identical to the reference product. This provides with a certainty that no consequential differences from clinical point of view as compared to the respective biologics exists with regards to efficacy, safety and purity. Safety and effectiveness of biosimilars have been disclosed since more than 10 years of affirmations. However, there is a need to educate the healthcare professionals to abolish potential misconceptions and coalesce biosimilars into regular clinical practice. The present review focuses on providing an overview of regulatory aspects and requirements for biosimilars, the main challenges in the selection and development of biosimilars and the economic impact and financial savings observed in recent studies carried out in different parts of the world. In addition, we have discussed the different successful comparative studies which have been done in different parts of the world to depict the biosimilarity for monoclonal antibodies such as bevacizumab, trastuzumab and rituximab.
Kaida-YipFDeshpandeKSaranT, et al.
Biosimilars: review of current applications, obstacles, and their future in medicine. Wjcc2018;
6: 161–166.
2.
LymanGH.Emerging opportunities and challenges of biosimilars in oncology practice.
Alexandria, VA:
American Society of Clinical Oncology, 2017.
3.
JanjigianYY, et al.
Talking to patients about biosimilars. Future Oncol2018;
14: 2403–2414.
4.
KonstantinidouSPapaspiliouAKokkotouE.Current and future roles of biosimilars in oncology practice. Oncol Lett2020;
19: 45–51.
5.
TanCJKeYChanA.Proceedings of the biosimilars workshop at the international symposium on oncology pharmacy practice 2019. J Oncol Pharm Pract2020;
26: 33–39.
6.
ChopraRLopesG.Improving access to cancer treatments: the role of biosimilars. J Glob Oncol2017;
3: 596–610.
7.
PatelKBArantesLHJrTangWY, et al.
The role of biosimilars in value-based oncology care. Cmar2018;
10: 4591–4602.
8.
Unni N. Biosimilars in oncology 2020; 1–19 (accessed 23 March 2021).
9.
FoodUAdministrationD.Scientific considerations in demonstrating biosimilarity to a reference product: guidance for industry.
Silver Springs, MD:
US Department of Health and Human Services, 2015.
Standardization WECoB. Guidelines on evaluation of similar biotherapeutic products (SBPs). WHO Technical Report Series 2009; 1–38 (accessed 23 March 2021).
WalshGJefferisR.Post-translational modifications in the context of therapeutic proteins. Nat Biotechnol2006;
24 : 1241–1252.
15.
ManziAE and Ultee ME. Biosimilars drug substance development and manufacturing: effective CMC strategy. In: Gutka HJ, Yang H, Kakar S (eds.) Biosimilars. Berlin: Springer, 2018, pp.173–186.
16.
UseCfMPfH.Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: non-clinical and clinical issues.
London:
European Medicines Agency, 2006.
FoodUAdministrationD.Biosimilar product information.
Rockville, MD:
US Food and Drug Administration, 2018.
21.
VandekerckhoveKSeidlAGutkaH, et al.
Rational selection, criticality assessment, and tiering of quality attributes and test methods for analytical similarity evaluation of biosimilars. Aaps J2018;
20: 1–9.
22.
KirchhoffCF, et al.
Biosimilars: key regulatory considerations and similarity assessment tools. Biotechnol Bioeng2017;
114: 2696–2705.
23.
O’CallaghanJBarrySPBerminghamM, et al.
Regulation of biosimilar medicines and current perspectives on interchangeability and policy. Eur J Clin Pharmacol2019;
75: 1–11.
24.
FarhatF, et al.
The concept of biosimilars: from characterization to evolution – a narrative review. Oncologist2018;
23: 346.
25.
CuellarSMcBrideAMedinaP.Pharmacist perspectives and considerations for implementation of therapeutic oncology biosimilars in practice. Am J Health-System Pharm2019;
76: 1725–1738.
26.
ForemanE, et al.
A survey of global biosimilar implementation practice conducted by the International Society of Oncology Pharmacy Practitioners. J Oncol Pharm Pract2020;
26: 22–32.
27.
AzevedoVDörnerTStrohalR, et al.
Biosimilars: considerations for clinical practice. Considerations Med2017;
1: 13–18.
28.
CampenCJ.Integrating biosimilars into oncology practice: implications for the advanced practitioner. J Adv Pract Oncol2017;
8: 688.
29.
TaberneroJVyasMGiulianiR, et al.
Biosimilars: a position paper of the European Society for Medical Oncology, with particular reference to oncology prescribers. ESMO Open2016;
1: e000142.
30.
AlvarezDFWolbinkGCronenbergerC, et al.
Interchangeability of biosimilars: what level of clinical evidence is needed to support the interchangeability designation in the United States?BioDrugs2020;
34: 723–710.
31.
ChanA, et al.
Assessing biosimilar education needs among oncology pharmacy practitioners worldwide: an ISOPP membership survey. J Oncol Pharm Pract2020;
26: 11–21.
32.
RugoHS, et al.
A clinician’s guide to biosimilars in oncology. Cancer Treat Rev2016;
46: 73–79.
33.
Nava-ParadaPShelbayaANabhanC.Rituximab biosimilars in hematologic malignancies: the need for a real-world approach. Future Oncol2020;
16: 2017–2027.
34.
AzizK.Biosimilars: the process & quality system approach to clinical applications. Asploro J Biomed Clin Case Rep2020;
2020: 33.
35.
HalimiVDaciAAncevska NetkovskaK, et al.
Clinical and regulatory concerns of biosimilars: a review of literature. Ijerph2020;
17: 5800.
36.
ShakeelSIffatWAhmedH.Biosimilar products’ application in advanced drug therapy; a qualitative insight. J Med Diagn Meth2016;
05: 2.
37.
IsakovLJinBJacobsIA.Statistical primer on biosimilar clinical development. Am J Ther2016;
23: e1903.
38.
StebbingJ, et al.
Understanding the role of comparative clinical studies in the development of oncology biosimilars. J Clin Oncol2020;
38: 1070.
39.
RastogiSShuklaSSharmaAK, et al.
Towards a comprehensive safety understanding of granulocyte-colony stimulating factor biosimilars in treating chemotherapy associated febrile neutropenia: trends from decades of data. Toxicol Appl Pharmacol2020;
395: 114976.
40.
HuangH-Y, et al.
Availability of anticancer biosimilars in 40 countries. Lancet Oncol2020;
21: 197–201.
41.
ShakeelSHassaliMARehmanH, et al.
Knowledge, attitude, and practice towards biosimilars and interchangeable products: a prescriptive insight by the pharmacists. Ijgm2020;
13: 1075–1082.
42.
HuangH-YLiuC-CYuY, et al.
Pharmacoeconomic evaluation of cancer biosimilars worldwide: a systematic review. Front Pharmacol2020;
11: 1749.
43.
AbrahamI, et al.
Cost savings from anemia management with biosimilar epoetin alfa and increased access to targeted antineoplastic treatment: a simulation for the EU G5 countries. Future Oncol2014;
10: 1599–1609.
44.
SimoensS.How do biosimilars sustain value, affordability, and access to oncology care?
Abingdon:
Taylor & Francis, 2020.
45.
LammersP, et al.
Barriers to the use of trastuzumab for HER2+ breast cancer and the potential impact of biosimilars: a physician survey in the United States and emerging markets. Pharmaceuticals2014;
7: 943–953.
46.
CornesP.The economic pressures for biosimilar drug use in cancer medicine. Targ Oncol2012;
7: 57–67.
47.
Al-KinaniKKIbrahimMJAl-ZubaidiRF, et al.
Iraqi regulatory authority current system and experience with biosimilars. Regul Toxicol Pharmacol2020;
117: 104768.
48.
JangMSimoensSKwonT.Budget impact analysis of the introduction of rituximab and trastuzumab intravenous biosimilars to EU-5 markets. BioDrugs2021;
35: 89–13.
49.
JönssonB, et al.
The cost and burden of cancer in the European Union 1995–2014. Eur J Cancer2016;
66: 162–170.
50.
Luengo-FernandezR, et al.
Economic burden of cancer across the European Union: a population-based cost analysis. Lancet Oncol2013;
14 : 1165–1174.
51.
MegerlinF, et al.
Biosimilars and the European experience: implications for the United States. Health Affairs2013;
32: 1803–1810.
52.
GiulianiJBonettiA.The economic impact of biosimilars in oncology and hematology: the case of trastuzumab and rituximab. Anticancer Res2019;
39: 3971–3973.
53.
HübelKKronFLuxMP.Biosimilars in oncology: effects on economy and therapeutic innovations. Eur J Cancer2020;
139: 10–19.
54.
MullalleyM, et al. Cost savings of biosimilars in oncology: a single institution experience.
Alexandria, VA:
American Society of Clinical Oncology, 2020.
55.
KhanMAAseeriMAAlshamraniMA, et al.
Emerging role of biosimilars in oncology-hematology in Saudi Arabia: a practical perspective. Glob J Qual Saf Healthc2020;
3: 22–29.
56.
YangYWuBHuangL, et al.
Biosimilar candidate IBI305 plus paclitaxel/carboplatin for the treatment of non-squamous non-small cell lung cancer. Transl Lung Cancer Res2019;
8: 989–999.
57.
FilonO, et al. Efficacy and safety of BCD-021, bevacizumab biosimilar candidate, compared to Avastin: results of international multicenter randomized double blind phase III study in patients with advanced non-squamous NSCLC.
Alexandria, VA:
American Society of Clinical Oncology, 2015.
58.
OrlovSV, et al. Pharmacokinetics and safety of BCD-021, bevacizumab biosimilar candidate, compared to Avastin in patients.
Alexandria, VA:
American Society of Clinical Oncology, 2014.
59.
Taïeb J, et al. Clinical and regulatory considerations for the use of bevacizumab biosimilars in metastatic colorectal cancer. Clinical Colorectal Cancer 2020; 20 : 42–51.
60.
ReinmuthN, et al.
PF-06439535 (a bevacizumab biosimilar) compared with reference bevacizumab (avastin®), both plus paclitaxel and carboplatin, as first-line treatment for advanced non-squamous non-small-cell lung cancer: a randomized, double-blind study. BioDrugs2019;
33: 555–570.
61.
KnightB, et al.
A phase I pharmacokinetics study comparing PF-06439535 (a potential biosimilar) with bevacizumab in healthy male volunteers. Cancer Chemother Pharmacol2016;
77: 839–846.
62.
LiCSSweeneyKCronenbergerC.Population pharmacokinetic modeling of PF-06439535 (a bevacizumab biosimilar) and reference bevacizumab (avastin®) in patients with advanced non-squamous non-small cell lung cancer. Cancer Chemother Pharmacol2020;
85: 487–499.
63.
ThatcherNGoldschmidtJHThomasM, et al.
Efficacy and safety of the biosimilar ABP 215 compared with bevacizumab in patients with advanced nonsquamous non–small cell lung cancer (MAPLE): a randomized, double-blind, phase III study. Clin Cancer Res2019;
25: 2088–2095.
64.
WuX, et al.
A global phase I clinical study comparing the safety and pharmacokinetics of proposed biosimilar BAT1706 and bevacizumab (avastin®) in healthy male subjects. BioDrugs2019;
33: 335–342.
65.
ChoS-H, et al.
A randomized, double-blind trial comparing the pharmacokinetics of CT-P16, a candidate bevacizumab biosimilar, with its reference product in healthy adult males. BioDrugs2019;
33: 173–181.
66.
SocinskiMA, et al. A bioequivalence study of proposed bevacizumab biosimilar, MYL-1402O (A) vs EU-Avastin (B) and US-Avastin (C).,
Alexandria, VA:
American Society of Clinical Oncology, 2017.
67.
SteninaMB, et al. Pharmacokinetics and safety of BCD-022, trastuzumab biosimilar candidate, compared to Herceptin in patients.
Alexandria, VA:
American Society of Clinical Oncology, 2014.
68.
KolbergH-CColleoniMDemetriouGS, et al.
Cardiac safety of the trastuzumab biosimilar ABP 980 in women with HER2-positive early breast cancer in the randomized, double-Blind, Active-Controlled LILAC study. Drug Saf2020;
43: 233–242.
69.
YinD, et al.
A randomized phase 1 pharmacokinetic trial comparing the potential biosimilar PF‐05280014 with trastuzumab in healthy volunteers (REFLECTIONS B 327‐01). Br J Clin Pharmacol2014;
78: 1281–1290.
70.
LammersPE, et al.
Neoadjuvant PF-05280014 (a potential trastuzumab biosimilar) versus trastuzumab for operable HER2+ breast cancer. Br J Cancer2018;
119: 266–273.
71.
PegramMD, et al.
PF-05280014 (a trastuzumab biosimilar) plus paclitaxel compared with reference trastuzumab plus paclitaxel for HER2-positive metastatic breast cancer: a randomised, double-blind study. Br J Cancer2019;
120: 172–182.
72.
PivotX, et al.
Phase III, randomized, double-blind study comparing the efficacy, safety, and immunogenicity of SB3 (trastuzumab biosimilar) and reference trastuzumab in patients treated with neoadjuvant therapy for human epidermal growth factor receptor 2-positive early breast cancer. J Clin Oncol2018;
36: 968–974.
73.
PivotX, et al.
A phase III study comparing SB3 (a proposed trastuzumab biosimilar) and trastuzumab reference product in HER2-positive early breast cancer treated with neoadjuvant-adjuvant treatment: final safety, immunogenicity and survival results. Eur J Cancer2018;
93: 19–27.
74.
PivotX, et al.
Three-year follow-up from a phase 3 study of SB3 (a trastuzumab biosimilar) versus reference trastuzumab in the neoadjuvant setting for human epidermal growth factor receptor 2–positive breast cancer. Eur J Cancer2019;
120: 1–9.
75.
StebbingJBaranauYBaryashV, et al.
CT-P6 compared with reference trastuzumab for HER2-positive breast cancer: a randomised, double-blind, active-controlled, phase 3 equivalence trial. Lancet Oncol2017;
18: 917–928.
76.
EstevaF, et al.
Efficacy and safety of CT-P6 versus reference trastuzumab in HER2-positive early breast cancer: updated results of a randomised phase 3 trial. Cancer Chemother Pharmacol2019;
84: 839–847.
77.
RugoHS, et al.
Effect of a proposed trastuzumab biosimilar compared with trastuzumab on overall response rate in patients with ERBB2 (HER2)–positive metastatic breast cancer: a randomized clinical trial. Jama2017;
317: 37–47.
78.
HanesV, et al.
A randomized, single-blind, single-dose study evaluating the pharmacokinetic equivalence of proposed biosimilar ABP 980 and trastuzumab in healthy male subjects. Cancer Chemother Pharmacol2017;
79: 881–888.
79.
WallerCF, et al.
A pharmacokinetics phase 1 bioequivalence study of the trastuzumab biosimilar MYL‐1401O vs. EU‐trastuzumab and US‐trastuzumab. Br J Clin Pharmacol2018;
84: 2336–2343.
80.
CuellarS.Integrating trastuzumab biosimilars and HER2-directed therapies into HER2-positive breast cancer management. Am J Manage Care2020;
26: S32–S40.
81.
CandelariaMGonzálezDEDelamainMT, et al.; on behalf of the RTXM83 Study.
Rituximab biosimilar RTXM83 versus reference rituximab in combination with CHOP as first-line treatment for diffuse large B-cell lymphoma: a randomized, double-blind study. Leuk Lymphoma2019;
60: 3375–3385.
82.
ViswabandyaA, et al.
Randomized, double-blind, pharmacokinetic equivalence trial comparing DRL-rituximab with MabThera in patients with diffuse large B-Cell lymphoma. J Glob Oncol2019;
5: 1–13.
83.
OguraM, et al.
Efficacy, pharmacokinetics, and safety of the biosimilar CT-P10 in comparison with rituximab in patients with previously untreated low-tumour-burden follicular lymphoma: a randomised, double-blind, parallel-group, phase 3 trial. Lancet Haematol2018;
5: e543–e553.
84.
BuskeC, et al.
An introduction to biosimilar cancer therapeutics: definitions, rationale for development and regulatory requirements. Future Oncol2017;
13: 5–16.
