**5. Biosafety and bioethics issues in handling mammalian cells**

Biosafety is a notion that requires protecting human health and the surroundings of pathogenic and genetically modified mammalian cells or organisms used in the research. Mammalian cell culture is identified as a shelter for infectious etiologic substances, and it should change the compliance with containment measures recommended for the etiologic agent itself. The utility of cell cultures comes under the preview of a range of regulatory provisions that consider the estimation of biological risks. Genetically modified mammalian cell cultures were used in different continents; in that case, a bio-safety assessment should be regulated. The major guidelines issued to mitigate the biological risks for the users and environment are mainly by the World Health Organization; the Centers for Disease Control and Prevention, and the Swiss Expert Committee for Biosafety. Several countries or geographical zones have different directives; for example, in Europe, genetically modified research was brought into the regulatory provision (Directive 2009/41/EC). Mammalian cell culturing activities focusing on developing pharmaceutical drugs are covered by the Regulation (EC) No 726/2004 and its amendment laying down actions for the authorization and direction of medicinal goods for human and animal use. 3D cultures, especially organoid culture systems, are regularly used for disease modeling and studying nanomaterialbased physiological effects. Human Pluripotent stem cell-derived organoids are being

*Nanotechnology Application and Intellectual Property Right Prospects of Mammalian Cell... DOI: http://dx.doi.org/10.5772/intechopen.99146*

generated from various human cell types and need better bio-safety and bioethics assessment. It must be ascertained that rules focusing on extenuating the biological risks for laboratory researchers, public health, and the environment falls under the preview one or several regulatory provisions based on biological risk assessment. Here, we are going to address the bio-safety issues involving mammalian cell cultures.

#### **5.1 Bio-safety assessments of mammalian cell cultures**

Biosafety refers to the way of protecting scientists, the health of other humans, and the environment from the probable side effects of microorganism, pathogenic, and genetically modified organisms and cells from human and mouse backgrounds. Laboratory biosafety uses safety principles and techniques to minimize the health hazard from accidental exposure or unplanned spillage while using infectious agents, toxins and other biological hazards in the laboratory setting. The bio-safety assessments applied to mammalian cells depend on a systematic assessment of the intrinsic attributes of the mammalian cultures like genetically modified cells and contaminated or intentionally infected with pathogens. **Figure 2** shows a summary of the biosafety assessment and management process that is followed while handling cell culture-based experiments. This also considers an exposure analysis, which means that type of exploitation carried out with the cultures should be considered. The risk analysis of cell cultures that carry the pathogens follows the same methods for analyzing pathogens themselves. Primarily, the inclusive depiction of major pathogens is measured by the subsequent guidelines (i) pathogenicity and the infectious dose (ii) mode of transmission, (iii) host range, (iv) the epidemiology, potential reservoir and vectors, and the ability to zoonosis (v) the stability and the resilience of the pathogens in the surroundings.

Moreover, information related to the physicochemical properties of the pathogenic organism is considered, such as (i) susceptibility to disinfectants, (ii) physical

#### **Figure 2.**

*Flow diagram illustrating the summarizing the biosafety assessment and management process while handling cell culture-based experiments. Flow chart is inspired by reference [55].*

inactivation, and (iii) drug susceptibility (e.g., sensitivity and known resistance to antibiotics or antiviral compounds). Lastly, aspects related to the disease caused by the pathogen are also to be taken into consideration. This includes (i) the availability of effective prophylaxis, (ii) the availability of efficient therapy, and (iii) any reported case of laboratory-acquired infections (LAIs). Even though underemphasized, several LAIs of mammalian cell cultures (or having virus suspension) has appeared. Among all, the exposure to vaccinia viruses amplified in mammalian cell cultures causes infections to laboratory researchers. Guidelines have been developed recently to work cautiously with vaccinia viruses and take a count of LAIs relating to this virus [55].

Understanding and having a complete analysis of the intrinsic infections of cell cultures help to perform well and safe mammalian cell culture. To assess biological risks connected with the mammalian cell cultures, three intrinsic properties related to cell cultures should be considered: the species of origin, the cell type or type of tissue (the organ of origin of the cell line), and the status of the culture. Correspondingly, mammalian cells other than human cells render less risk; still, some infectious agents are proficient at crossing one species to another species, leading to zoonosis. Highly reported infections of viruses comprise hantavirus, hemorrhagic fever viruses, bird Influenza virus, and severe acute respiratory syndrome (SARS) associated virus. Primary cell cultures are created from organ tissues. Highly characterized mammalian cells give the lowest risks compared to primary cultures or less characterized cell lines. Mammalian cells originating from different laboratories without having any proof of identity may cause cross-contamination and pathogen spreading problems, and thereby proper risk assessment and cell characterization are warranted [55, 56]. Several techniques are available for the bio-safety assessment, like RT-PCR, flow cytometry, cytogenetic analysis, DNA fingerprinting, and iso-enzyme analysis. Adventitious contagions of mammalian cell cultures are a vital problem for any activity that involves cell culturing. Contamination agents for cell cultures are bacteria, fungi, mycoplasms, parasites, viruses, prions, and even other animal cells. Modulated experimental results suggest that they spoil the cell cultures. Bio-safety point of view modified mammalian cell cultures for laboratory research, production purposes, or diagnosis purposes they may give support for contaminating materials that cause harm to human health.

#### **5.2 Bioethics and mammalian cell culture**

The futuristic technologies in bio-medicine are changing the current concepts and opening up new dimensions. Interestingly as new optimistic channels are opening and expanding, the issues of bioethics are becoming accurate and pertinent. Bioethics is the use of ethical principles in the field of medicine and healthcare. The rational application of ethics in evaluating mammalian cell culture-based experiments is highly warranted, especially during the emerging waves of change in biomedicine. Increased International cross-connection to facilitate open discussion in bioethics and related fields across cross-cultural aspects in bioethics is vital [57]. Several relevant questions arise regarding the private and sensitive use of source data for cells, moral concerns regarding the uses of embryonic and fetal tissue, genetic manipulation, gene therapy, mixing of animal and human cells, tissue banking, legal and intellectual properties associated with *ex vivo* tissue-engineered cell-based products, an extension of human-ness, etc.

Regarding the humane use of animals, the National Institutes of Health has issued policies as mentioned in the Public Health Service Policy on Humane Care and Use of Laboratory Animals. FDA Human Tissue Task Force and the Center for

### *Nanotechnology Application and Intellectual Property Right Prospects of Mammalian Cell... DOI: http://dx.doi.org/10.5772/intechopen.99146*

Biologics Evaluation and Research (CBER) regulates the use of human cells or tissue for implantation, transplantation, infusion, or transfer into a human recipient. The International Society for Stem Cell Research (ISSCR) has also released guidelines for stem cell research and clinical translation. The United States Congress and state legislatures are instrumental in creating laws concerning bioethics. Several professional bioethics organizations, including the American Society for Bioethics and Humanities, American Society for Law, Medicine, and Ethics, Canadian Bioethics Society, provide a platform for discussion over bioethics [57]. Several public institutions supported by academicians and researcher-based initiative for propagating public dialog plays a vital role in educating the masses.
