**1. Introduction**

A biopharmaceutical (biological or biologic), which consists of sugars, proteins, nucleic acids, living cells, or tissues, is a medicinal product manufactured in extracted or semi-synthesized from biological sources like humans, animals, or microorganisms. Different from traditional drugs synthesized from chemical processes, the majority of biopharmaceutical products are derived from biological processes including the extraction from living systems or the production by recombinant DNA technologies (**Table 1**). Transgenic organisms, especially plants, animals, or microorganisms that have been genetically modified, are potentially used to produce biopharmaceuticals.

The recombinant human insulin (trade name "Humulin") was the first biopharmaceutical approved for human therapeutic uses and marketing in 1982. Currently, biopharmaceuticals have been extensively used as therapeutic agents such as vaccines, whole blood (or blood components), immunosera, antigens, hormones, cytokines, enzymes, allergenics, cell therapies, gene therapies, tissues, monoclonal antibodies, and products derived from recombinant DNA, etc. For example, vaccines are used to prevent infectious diseases and some cancers; cell- and gene-based biopharmaceuticals are applied to treat a variety of diseases for which no other drugs or medical devices are available.

The European Medicines Agency (EMA) uses the specific term "advanced therapy medicinal products (ATMPs)" to refer to human medicines that are based on cells, genes, or tissue engineering. Cell therapy products (CTPs) are biomedicines containing cells/tissues that have been manipulated to change their biological characteristics, and these cells/tissues can be used to treat, prevent, or diagnose diseases [1]. Gene therapy products (GTPs) are therapeutic agents to make genetic improvement through the repair, deletion, insertion, or substitution of mutated genes or site-specific modifications for target therapies [2]. Tissue engineering is the application of a combination of cell, engineering, and material methods, and suitable factors

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


**Table 1.** Major sources of biopharmaceuticals.

are added to improve, repair, or replace only part of or whole biological tissues such as bones, cartilages, blood vessels, organs, skins, muscles, etc. It also involves the use of a tissue scaffold for the formation of new viable tissues for medical purposes [3–5].

**2. Application**

**2.1. Therapy**

therapy, prevention, and diagnosis.

**Table 2.** Comparison of a generic drug and a biosimilar.

Identical to reference products Yes

Frequency of quality tests in

Clinical trials requirement for

manufacturing

approval

reduced by using biosimilars.

**2.2. Prevention**

Biopharmaceuticals have multiple clinical applications and various advantages for disease

**Drug property Generic drug Biosimilar**

Characterization Easy Difficult

Production Predictable chemical processes are used

volunteers

Molecular size Small (~150 Da) Large (~150,000 Da)

Structure Simple and well-defined Complex with probable structural

Stability More stable for storage and handling Less stable, very sensitive to its

≤50 ≥250

to manufacture an identical copy

At least, active pharmaceutical ingredients are identical

Small clinical trials in healthy

Adverse immune responses Lower potential Higher potential

Discovery cost Low or even no Relatively high

variations

surroundings

No

Specialized biological processes are used

Introductory Chapter: Biopharmaceuticals http://dx.doi.org/10.5772/intechopen.79194 5

Minor differences in clinically inactive

to manufacture a similar copy

components are acceptable

Large clinical trials in patients

The therapeutic types of biopharmaceuticals mainly include recombinant protein therapy, antibody therapy, cell therapy, and gene therapy. Biopharmaceuticals are able to cure or treat diseases safely and effectively by demonstrating biological activity, and perform specific functions by acting on the disease pathophysiology. Compared with chemical drugs, biopharmaceuticals are more complex in production, have multiple routes of administration and different pharmacokinetics. Their advantages are high selectivity and low nonspecific toxicity; disadvantages include high costs and the induction of antidrug antibodies leading to decreased efficacy or deficiency in biosafety. Treatment can be optimized through the development of dosing schedules and multiple administrative routes. Additionally, the cost can be

A vaccine is the most important biopharmaceutical used for infectious disease prevention. It usually contains a biological agent that resembles a pathogen and is usually made from

A biosimilar, also known as "follow-on biologic," is a biologic medical product that is almost identical to a copy of an original product manufactured by different pharmaceutical companies. It is highly similar to a licensed reference product in spite of minor differences in clinically inactive components. There are no clinically significant differences between the biosimilars and the reference products in terms of the safety, purity, and potency. A generic drug is the same as a brand name drug in dosage, safety, strength, administration, quality, performance, and intended uses. It is required to take a lot of rigorous tests to ensure that the generic drug can substitute for the brand name drug. A generic drug must contain identical active pharmaceutical ingredients (APIs) with the same amount as the brand name product and be proved to be bioequivalent to the brand name drug. The substitutability or therapeutic equivalence of generic drugs has to be evaluated scientifically. If a generic drug is evaluated as therapeutically equivalent as the brand name product, it has equal effects and show no differences compared with the brand name product. Biosimilars, like generic drugs, can be manufactured when the original "innovator" product's patent expires, and are officially approved versions of the original products [6]. However, there are many differences between a generic drug and a biosimilar (**Table 2**). Biosimilars have the same clinical effect as generic drugs but are only similar to the original "innovator" drugs as they are confirmed by validation methods. Biosimilars will not be the same as the reference products, unlike generic drugs in which the APIs are identical to the references [7]. Despite this heterogeneity, all generic drugs and biosimilars have to maintain consistent quality and effective performance throughout their life cycles [8].


**Table 2.** Comparison of a generic drug and a biosimilar.
