**2. Application**

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

**Source item Extracted from living systems Produced by recombinant DNA**

Biopharmaceuticals produced by recombinant DNA technologies are usually

one of the following three types:

frame.

**1.**Substances that are almost identical to the body's own key signaling proteins. **2.**Monoclonal antibodies that are similar to the antibodies produced by the human immune system against microbes. **3.**Receptor constructs (fusion proteins) that are usually based on a naturally occurring receptor linked to the immunoglobulin

Blood factors, tissue plasminogen activators, hormones, hematopoietic growth factors, interferons, interleukin-based products, vaccines, monoclonal antibodies, tumor necrosis factors, therapeutic enzymes

extracted from animals or humans particularly. **2.**Some biopharmaceuticals were extracted from animals, but they are currently produced by biotechnologies. For example, the therapeutic insulin previously extracted from porcine pancreatic islets is now produced by recombinant DNA technologies in the yeast (*Saccharomyces* 

Characteristic **1.**Some conventional biopharmaceuticals are

4 Biopharmaceuticals

*cerevisiae*) or *E. coli.*

Example Whole blood and blood components, organs and

human reproductive cells

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

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 through-

for the formation of new viable tissues for medical purposes [3–5].

tissue transplants, stem cells, antibodies for passive immunization, fecal microbiota, human breast milk,

out their life cycles [8].

Biopharmaceuticals have multiple clinical applications and various advantages for disease therapy, prevention, and diagnosis.

#### **2.1. Therapy**

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 reduced by using biosimilars.

#### **2.2. Prevention**

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 inactivated microbes, live attenuated microbes, toxoids (toxins), and or part of surface antigens (subunits). Through vaccination, the burst of many infectious diseases has enormously been decreased such as measles, tetanus, and polio; some are even eradicated such as smallpox. However, the burden of noninfectious diseases such as cancers, cardiovascular diseases, metabolic diseases, and neurodegenerative diseases is significantly increasing. Currently, some vaccines are successfully applied to prevent cancers; for example, the human papilloma virus (HPV) vaccine has been approved for the prevention of cervical cancers.

their limitations and result in the development of painless, safe, effective, and economic products. The major challenges are the toxicity of nanoparticles and the immune responses induced by nanoparticles, though some biodegradable and biocompatible nanoparticles have

Introductory Chapter: Biopharmaceuticals http://dx.doi.org/10.5772/intechopen.79194 7

Biotechnologies using recombinant DNA technologies, genetic engineering, and tissue culture encompass a wide range of procedures to modify living organisms for human uses. New vaccines employing biotechnologies improve the product quality and expand the clinical applications [13]. For example, traditional vaccines are only used to prevent infectious diseases, but vaccines based on biotechnologies are being developed to prevent many noninfectious diseases such as cancers, type I diabetes mellitus (T1DM), Alzheimer disease, drug addiction, etc. [13]. In addition, therapeutic vaccines are potentially developing for both infectious and noninfectious diseases using the biotechnologies such as reverse vaccinology, recombinant subunit vaccination, recombinant protein vaccination, DNA vaccination, and RNA vaccination. The major challenge is complex vaccination schedules. The vaccines based on biotechnologies are usually only parts of microorganisms (DNA, RNA, or protein); therefore, it is required to have multiple doses to induce additional "booster" shots for full immunity [13].

Although many CTPs have been approved for marketing in many countries and extensively used for disease treatment [1], current gene therapies predominantly exist in basic research laboratories and their clinical applications are still on trials. Despite of this, some GTPs have been approved by the EMA such as Glybera (alipogene tiparvovec) in 2012, and by the United States Food and Drug Administration (US FDA) such as Kymriah (tisagenlecleucel) and Yescarta (axicabtagene ciloleucel) in 2017, respectively. Recently, gene therapies have become possible through the advances of genetic engineering technology that enabled the manipulation of genome and the development of delivery tools such as lipoids [2, 14], viruses [2, 14], nanoparticles [2, 14], bacteria [15], gene guns [16], electroporation [17], or nanostraws [18]. Therapeutic components must be transported to targeted cells to exert a therapeutic effect. Therefore, the delivery tool is essential for drug delivery to target cells and it is very crucial to select a suitable delivery tool with specificity, efficiency, safety, and economics. However, it is

**1.** Specificity: Some delivery tools are not very specific and may deliver nucleic acids to nontarget cells. It is important to reduce the risk of nonspecific delivery, but the evaluation of

**2.** Efficiency: Not all delivery tools are efficient enough; some of them are low in efficiency and multiple rounds of transfections are needed. Additionally, it is hard to improve and

**3.** Biosafety: Some delivery tools are toxic, biohazardous, or even destructive to normal cells or recipient hosts. Some delivery tools such as lipoids, viruses, bacteria, and nanoparticles may induce vector-associated immune responses in hosts, and to overcome immune barriers is essential [14]. Consequently, it is required to verify their safety in preliminary tests.

challenging for the option of delivery tools due to the following issues.

evaluate their efficiency especially in animals and clinics.

their benefits and risks is complex.

been developed [12].

*3.1.2. Gene therapy*

#### **2.3. Diagnosis**

In addition to clinic significance in therapy and prevention, some biopharmaceuticals can be used to diagnose diseases; for example, monoclonal antibodies have been successfully applied in the diagnosis of some cancers and infectious diseases, and more are being developed [9–11]. Once monoclonal antibodies specified for a given substance are produced, they can be used to detect the presence of this substance. They are also very useful in immunohistochemistry that detects antigens in fixed tissue sections and immunofluorescence tests that detect the substance in frozen tissue sections or in live cells.
