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Askari, S.; Ghofrani, A.; Taherdoost, H. Biosimilar Agents. Encyclopedia. Available online: https://encyclopedia.pub/entry/52629 (accessed on 01 July 2024).
Askari S, Ghofrani A, Taherdoost H. Biosimilar Agents. Encyclopedia. Available at: https://encyclopedia.pub/entry/52629. Accessed July 01, 2024.
Askari, Shadi, Alireza Ghofrani, Hamed Taherdoost. "Biosimilar Agents" Encyclopedia, https://encyclopedia.pub/entry/52629 (accessed July 01, 2024).
Askari, S., Ghofrani, A., & Taherdoost, H. (2023, December 12). Biosimilar Agents. In Encyclopedia. https://encyclopedia.pub/entry/52629
Askari, Shadi, et al. "Biosimilar Agents." Encyclopedia. Web. 12 December, 2023.
Biosimilar Agents
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This entry is adapted from the peer-reviewed paper 10.3390/biomedinformatics3040070

A biosimilar is a biological product highly similar to and interchangeable with an already approved reference product. Innovations in computer-aided discovery for biosimilar agents involve several key approaches. Structural bioinformatics and molecular docking techniques, including homology modeling and molecular dynamics simulations, aid in understanding the structure-function relationships. In silico screening and virtual high-throughput screening, powered by database mining and predictive modeling, expedite the identification of potential biosimilar candidates. Machine learning and artificial intelligence contribute by analyzing large datasets to predict success probabilities and integrating diverse data sources. Immunogenicity prediction tools assess potential immune responses, while network pharmacology and quantitative systems pharmacology provide a holistic understanding of biosimilar effects. Optimization algorithms play a role in formulating biosimilars for desired properties. This dynamic field continues to evolve, with regular updates reflecting the latest advancements in computational tools for biosimilar discovery.

drug biosimilars pharmaceuticals biologics small molecule

1. Introduction

A drug is a non-natural substance used to treat, diagnose, or prevent disease that influences biological processes [1]. Drugs can be made synthetically or from natural sources. An ideal drug would have a well-defined mechanism of action; be chemically and metabolically stable; be amenable to chemical synthesis; be water-soluble at therapeutic concentrations to prevent precipitation in the bloodstream; be lipid-soluble to facilitate transport across cell membranes; and be a novel molecule [2].
Biopharmaceuticals, particularly therapeutic antibodies, are a class of drugs that are becoming increasingly significant in addition to small molecules, and computational techniques for enhancing the stability, selectivity, and affinity of these protein-based treatments have also made significant strides [3]. Biologics are more expensive than conventional therapy options [4], and these drugs may become less effective with continued usage [5]. Drug survival is the likelihood that patients will continue taking a certain drug. In contrast, therapy cessation can happen for various reasons, the most prevalent of which is treatment ineffectiveness [6].
Various items separated from natural sources or produced using living systems are biological drugs. Drugs made chemically are generally 100–1000 times smaller than biologics, and their molecular structures are more difficult to define [7]. Recombinant DNA technology is used to create several proteins that are used in biologics. Developing a biologic is a multi-step procedure that is technically difficult, confidential, and unique to the producer [8]. As a result, a biosimilar developer needs to independently build a new production process that can supply a drug that is strikingly comparable to the original through reverse engineering manufacturing [9].
The development of biosimilars has emerged to lower medical expenses and expand patient treatment alternatives [10]. A biosimilar drug is typically described as a biological substance similar to the reference drug. It has no clinically significant deviations in potency, purity, or safety, even though numerous regulatory definitions exist for this term [11]. Biosimilar drugs have a variety of clinical uses, including the treatment of cancer, rheumatic and intestinal illnesses, neutropenia, and psoriasis [12][13][14]. A fiercely competitive business has developed to create biosimilar drugs due to these treatments’ clinical and financial triumphs [15][16][17].
Drug discovery, preclinical development, and clinical trials are the three key drug research and development phases. A hit molecule is the first step in the drug discovery process. A chemical that causes the required activity in a screening assay is called a hit [18]. Introducing a new medicine to the market takes a lot of money, time, and labor. Drug research and discovery takes 10 to 15 years, costing between USD 800 million [19] and USD 1.8 billion [20]. Because preclinical and clinical data need to be used to support the effectiveness and safety of biosimilars, their development and production are more difficult and expensive than those of synthetic generic drugs. However, it is critical to emphasize that these processes are less expensive than those necessary to create biological drugs [13].
Despite the promising developments in genomics, proteomics, and systems biology, significant scientific and regulatory barriers still prevent the development of effective biologically active agents. As a result, only about 13% of drugs complete the clinical trials stage [21][22]. The time- and money-consuming drug discovery process aims to create new drug candidates [23]. Using computational methods throughout the pre-clinical stage of drug discovery has been one method of accomplishing this [24]. To increase efficiency and widen the feasible window, scientists can design energy harvesting systems and materials thanks to such efforts [25][26].
Computer-aided drug design (CADD) uses computational methods to find, create, and analyze drugs and active compounds with similar biological properties [27][28]. Accordingly, CADD has revolutionized the history of drug discovery, particularly its substantial benefits [29]. These benefits include offering insights into target-drug interactions, utilizing the 3D structure, causing a cost-effective reduction in high-throughput screening failures, inspiring novel drug design concepts, and aiding researchers in predicting targeted proteins and candidate hits [30][31][32].

2. Comparison of Biosimilars and Small Molecule Pharmaceuticals

The USA Food and Drug Administration (FDA) defines a biosimilar as a biological product that, in terms of safety, purity, and potency, is comparable to and lacks any clinically significant changes from an existing FDA-approved reference product [33]. The amino acid sequences of biosimilars and reference products are the same, but they differ in protein aggregation, isoform patterns, glycosylation sites, and 3D structure. To demonstrate their similarity, pharmacodynamic and pharmacokinetic investigations are needed [34].
The development of biosimilar agents according to the requirements of the European Medicines Agency (EMA), the US FDA, or the World Health Organization (WHO) has numerous advantages for patients and society [35]. Because biosimilars can be purchased for up to 30% less than their reference drugs, they allow patients to access cheaper treatments while saving healthcare systems much money [36]. Additionally, biosimilars promote business rivalry, which helps to drive down costs [37].
Despite their many advantages, biosimilars also come with several disadvantages, such as the potential for immunogenicity, the idea of interchangeability, the low level of awareness, the lack of acceptance among patients and healthcare professionals regarding their incorporation in clinical practice, the need for clinical trial testing prior to their approval, a strict regulatory framework limiting the anticipated savings, and certification requirements [38]. Immunogenicity is affected by several variables, including the composition of the biosimilar, the patient’s features, the method of administration, the dosing regimen, and the formulation [39]. In order to show the safety and effectiveness of biosimilars and boost physicians’ confidence in their usage, it is crucial to choose the proper end goals in clinical trials [38].
Comparing the development of biosimilars to that of small-molecule pharmaceuticals involves different difficulties. First of all, the processes involved in developing and approving biosimilars need to be better understood by doctors and patients [40]. The notion of similarity is complicated by the complex nature of biologics, which comprise several molecular variations with comparable amino acid sequences. Although this variability is controlled throughout production and evaluated through testing, misunderstandings exist because the phrase “biosimilar” may imply differences [41]. Conceptually, it cannot be easy to understand how a biosimilar can produce identical clinical results despite structural differences.
Despite being called “abbreviated,” the US regulatory process for biosimilars does not compromise the strictness of the approval requirements. This route enables quicker and more cost-effective development using prior FDA findings [42]. The approval of biosimilars is based on the “totality of evidence,” in which a foundation is laid by analytical analysis and confirmed by clinical efficacy and safety investigations [43]. Biosimilars streamline their clinical information package compared to original biologics, necessitating separate Phase III studies for each indication [42][43]. The total data package, however, keeps the same level of rigor [42][43].
Another area for improvement is indication extrapolation, which depends on functional and structural similarity data many stakeholders are unfamiliar with [42]. A recognized scientific idea, extrapolation is applied in different regulatory situations [44]. The disparities between “interchangeability” and “similarity” in the legislation’s phrasing further complicate matters [45]. The interchangeability standards have different meanings even while the law stipulates that biosimilars need to have “no clinically meaningful differences”. Clarity in communication is essential since interchangeability needs to be proven through separate clinical switching investigations [46].
The difficulties in developing biosimilars compared to small molecule pharmaceuticals highlight the necessity of thorough instruction, exact communication, and a nuanced comprehension of the complex regulatory environment. Because of the complicated nature of biosimilar creation, CADD needs to be used to simplify the process and increase its effectiveness. Table 1 provides a comparison between biosimilars and small-molecule pharmaceuticals.
Table 1. Comparison of biosimilars and small molecule pharmaceuticals.
Aspect Biosimilars Small Molecule Pharmaceuticals
Development Process Complex, requires demonstration of similarity in safety, purity, and potency Relatively simpler, focus on chemical synthesis
Regulatory Approval Based on “totality of evidence” approach, relies on prior FDA findings Strict approval requirements, separate Phase III studies for each indication
Cost Typically 30% cheaper than reference drugs Cost varies based on manufacturing and development
Advantages More affordable, potential for business rivalry Well-established development process, easily understood by doctors and patients
Disadvantages Potential for immunogenicity, lack of awareness and acceptance Limited structural understanding, potential for side effects
Challenges Indication extrapolation, interchangeability confusion Potential for misunderstanding due to the complex nature
Communication Clear communication essential for interchangeability and clinical switching investigations Straightforward communication due to a well-understood development process
Use of CADD Necessary to simplify the complex development process Less necessary due to the simpler development process

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Subjects: Pharmacology & Pharmacy
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Shadi Askari
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Alireza Ghofrani
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Hamed Taherdoost
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Update Date: 13 Dec 2023
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