 or much less with the other drug. The physician also could originate the switch in an attempt to decrease costs. The essence of a biosimilar is that the drug is highly similar to the originator product without any clinically meaningful differences in the drug's safety profile, purity, and potency. Thus, if the patient experiences a medical problem with either the originator drug or the biosimilar, simply switching from one to the other would not help, as they are essentially just different versions of the same drug (ie the patient would need to switch to a completely different drug). 30

Promoting Patient Access to Innovative Treatments
By introducing new biosimilar products, direct cost savings have been accomplished either by decreased list price compared to the originator or even by provoking reductions in the reference product price and competitor biosimilars; all these matters have opened the door for increased patient access to biologics. 16 This is to say that the introduction of biosimilars triggers a fall in the overall cost of biological therapies. 31 Consequently, this diminished pricing will unleash scarce health resources and preserve the quality of care, which will positively affect healthcare sustainability. As a case in point, published microeconomic data from a Spanish public hospital revealed that treatment expenditures for a patient with Crohn's disease were lowered by almost two-thirds (around 61% reduction) after two years of infliximab-bearing biosimilar acquisition. 2 In light of macroeconomic data, savings of EUR 15 billion were projected between 2015 and 2020 across Europe. 31 This cost-effectiveness has a paramount impact that -with certainty-gives rise to better allocation of healthcare resources and budgetary redistribution and eventually improves patient access to biological treatments. 32 Over and above, these savings and reallocated funds can be invested to acquire new healthcare technologies and services and also, to pave the way to start biological treatment at earlier stages whenever it is needed. 2 The capacity to penetrate the market at a decreased list price is a principle engine for developing a biosimilar product, even if the subsequent biosimilar uptake differs between countries. 33 However, anticipatory rises in originator price that precede the launch of a biosimilar may restrain the cost savings as a whole. 34 Moreover, competitive price reductions offered by manufacturers of the originator product may reduce the return on investment for the biosimilar. 16 As an example, cost savings in the USA attributed to biosimilar filgrastim were lower than what was anticipated. 35 Likewise, and even though FDA/EMA approval of many biosimilar products, revenue from the epoetin alfa originator persists to be high. 16 Finally, it is worth noting that in the USA, unlike in the EU, reduced price competition may be due to the scarcity of biosimilar competitors along with the dominance of biological manufacturers developing biosimilars. 36,37

Benefits Beyond Price
Benefits from biosimilars may broaden beyond direct cost savings, which could be deemed particularly in the case of cancer treatments. In certain instances, an increased uptake can be seen with many combination biological therapies, including combinations of the approved biosimilar with the originator product. In other words, innovation to develop novel treatment strategies that use currently available products to optimize treatment is considered the backbone of therapy for numerous cancer types. 16 Other benefits of biosimilars that transcend price aspects include the inclusive analysis done by manufacturers of biosimilars to reference products. This comprehensive analysis (structural and functional) of reference products in different patches has enhanced the knowledge and understanding of originator biologics properties. 38 Moreover, the introduction of different biosimilar products has mitigated the risk of drug shortages -a serious consideration of healthcare authorities-due to the availability of more than one version in the market. Another important aspect is that manufacturers of originator products may pursue innovation of new molecules or improve existing ones. These ceaseless moves are triggered by the perception of being commercially threatened by the introduction of biosimilars. On the other hand, biosimilars manufacturers will aim to offer privileges such as less immunogenicity, higher stability, or easier delivery modes.

Opportunities of Biosimilars in the Middle East and Africa (MEA) Region
The MEA market shows a notable rise in biologics' value share over recent years, which aligns with the global market trends. From 2015 to 2019, biologics' value share in the MEA region was estimated to reach almost 4.1 billion USD, with a 14.5% annual growth rate. The Kingdom of Saudi Arabia (KSA) is the market leader (with over 1.8 billion USD sales), followed by the United Arab Emirates (UAE), Egypt, and Algeria, with almost 450 million USD each. 39 Moreover, the MEA biosimilars market is forecasted to grow at a Compound Annual Growth Rate (CAGR) of 24.96% from 2021 to 2026. Rises in healthcare expenditures, Gross Domestic Product (GDP), and the demand for costeffective treatments; all resulted in this projected market growth. 40 In Tunisia, the first edition of biosimilars guideline was published in July 2018 by the "Direction de la Pharmacie et du Medicament" (DPM). 41 This guideline referred to world health organization (WHO), EMA, International Council for Harmonisation (ICH), and benchmarked with the Egyptian and Jordanian guidance. This guideline indicates that once the quality comparability to the Reference Medicinal Product (RMP) is proven, preclinical and clinical studies can be pursued. 42 The guideline did not require specific analytic tests; however, it invites the applicant to refer to EMA and ICH guidelines for more details. All pharmaceutical companies are called to renew their applications for EMA every five years. 41 Interchangeability is assessed case by case. However, physicians in public health centers are limited by hospital tenders. 43 The Central Pharmacy of Tunisia, a Ministry of Health (MOH) affiliate, is the unique payer of imported medicines. The monopoly of purchasing enabled the MOH to ensure the stability of prices and to absorb the inflation rate. 44 Moreover, it strengthens the negotiation power and reduces the margin gain of secondary payers and distributors. To implement a long-term cost-saving strategy, the MOH started a health technology assessment program, which reflects the government's incentive to improve the quality of local biosimilars. 41 In Egypt, regulations for the registration of biological products have been implemented since 2009 through the Minister decree 297/2009, adopting guidelines for submission of registration dossier based on full data (quality, preclinical and clinical data). A Guideline for Registration of Biosimilar Products in Egypt was issued in 2014 and has been published and implemented since then. In 2020, the Egyptian Drug Authority (EDA) published its latest guideline for the registration of biosimilar products, including all requirements for the comparability exercise as referred to ICH, WHO, EMA, and the FDA. Registration of a biosimilar product should follow one of two approaches; imported or locally manufactured products. Clear principles for the development of biosimilar products have been stated, such as; the rationale for the choice of the reference product should be provided in the submission, and a comprehensive understanding of all steps in the manufacturing process for the proposed product should be established during product development. A stepwise approach is recommended throughout the biosimilar product development program. Quality aspects include analytical consideration, specifications (release of drug substance/ drug product), references standard, and final formulation. 45 External reference pricing is the policy adopted in Egypt. 46 The Unified Procurement Authority (UPA) in Egypt is the centralized procurement and supply interface that aims to ensure equitable access to medicinal and health technology products through conducting evidence-based technology assessment, strategic value-driven procurement methods, establishing a robust and sustainable supply chain, and enabling efficient utilization of resources.
However, most healthcare systems in the MEA region are price-conscious, and reimbursement decisions are shaped mainly by drug prices and clinical outcomes. The economic turmoil in this region (which is relayed to oil prices) exerts further pressure on healthcare systems, which imposes several worries about their spending capacity compared to developed markets. Countries in this region have varying economies, some can modify their healthcare expenditure, but others are struggling. Other challenges in the region are; the complexity of the manufacturing process, high cost, availability of other generic drugs with lower prices, high prevalence of certain diseases such as diabetes, and increasing cancer-related mortality rates. Lenient government regulations, together with government support and initiatives, should provide major openings in this market. 39,40 Interestingly, the majority of the MEA region countries have a well-defined regulatory landscape for biosimilars (Tables 2 and 3).

Conclusion
Biosimilar products will play a momentous part in the treatment journey of patients with serious ailments. Along with marked decreases in associated expenditures, biosimilars will potentially improve patient access to healthcare, upgrade the quality of care, and enable more patients to reach optimal treatment. The MEA market shows a notable rise in biologics' value share over recent years; however, constraints to increase biosimilars uptake should be addressed. To demonstrate efficacy, safety, and quality in local settings, more stringent biosimilars guidelines, real-world data incentives, and local clinical studies should be established. Also, engaging the local stakeholders in clinical monitoring, raising the awareness among health care practitioners (HCPs) about biosimilars, combining pricing systems to offer a preferential and competitive environment, and fostering agreements and partnerships with recognized biotech industries will help to improve the patients and HCPs' acceptance, offer a preferential and competitive environment, and permit the transfer of the technology and the knowledge. All of these promising strategies can provide major openings in this market and provide better opportunities for the patients.  The Ministry of Health (MOH) in Egypt amounts 35%