Standards and regimentations of biosafety and biosecurity in medical biology laboratories in Togo, 2021

Legal instruments are necessary for the regulation of programs such as the biosafety and biosecurity (BSS) system in a country, yet little information is available in this sector in Togo. The study conducted aimed to take an analytical look at the normative and regulatory environment of biosafety and biosecurity in medical biology laboratories in Togo. A documentary review was carried out on the web, in the Official Journal, and on governmental sites between January and June 2021. A total of 76 documents were initially identified and then 14 were included in the synthesis. Of the 14 texts regulating the biosafety and biosecurity sector worldwide, 10 have been ratified or are being used in Togo. In total, 05 laws and 02 decrees are in force in the area of BSS in Togo on June 30, 2021. Our study has also allowed us to highlight several activities to be regulated. The approach adopted has revealed a current deficit in terms of regulations in the area of biohazard management in Togo in a multisectoral framework. It is necessary to strengthen the existing regulatory texts by taking into account the areas required internationally. conveniently grouped into areas of high impact on BSS worldwide. Country-level gaps in terms of BSS regulation were identified.


INTRODUCTION
Faced with major public health regulatory challenges, both biosafety and biosecurity (BSS) call the scientific community's attention to fundamental questions about laboratory practices (Berns, 2014;Gao, 2019;Vogel et al., 2015). Biosafety is the set of containment principles, technologies, and practices implemented to prevent inadvertent exposure to or release of biological agents or toxins (ISO 15190, 2020). Biosecurity is the set of principles, technologies, and practices implemented for the protection, control, and accountability of biological materials and/or equipment, skills, and data related to their handling (ISO 15190, 2020). The expansion of biological hazards and threats is facilitated by noncompliance with approved containment protocols, shortcomings in laboratory storage of infectious pathogens, and the absence of other adequate BSS measures (Berns, 2014;Gao, 2018;Linkous et al., 2021). Laboratories at the forefront of technological advances in the search for human health solutions are useful for more than just responding to health emergencies. They also express concern about the risks of acquired infections to laboratory personnel (Beeckman and Rüdelsheim, 2020). There is also the possibility that dangerous microorganisms or toxins under investigation will escape from the laboratory and cause harm to public health and the environment, as was the case with highly pathogenic H5N1 avian flu and bioterrorism (Gao, 2018;Vogel et al., 2015). The limits of established laboratory measures and the risk of pathogen proliferation thus raise the question of regulation and its effectiveness. Most countries now rely on both the establishment of high-level microbiological safety research centres and the development of a range of laws, regulations, and standards to improve BSS capacity (Beeckman and Rüdelsheim, 2020;Gao, 2018Gao, , 2019Huigang et al., 2021). Despite growing awareness, recent studies show that developing countries are struggling to build or anchor their BSS assurance policies in a global context of expanding diagnostic capacity (Chung et al., 2019;Heckert et al., 2011;Maehira and Spencer, 2019;OMS, 2018). These efforts are therefore insufficient in lowresource countries, as highlighted by the recent International Health Regulations (IHR) joint assessment report in 2018. For example, in Togo, a low-income country, in addition to the country assessments carried out in some laboratories, the IHR assessment noted weaknesses in the monitoring of key aspects of the biosafety and biosecurity system (OMS, 2018). Recommendations were made on compliance with international instruments and the effectiveness of BSS measures (Gao, 2019;OMS, 2018;Wurtz et al., 2014). In view of this situation, it was appropriate to examine the national legal framework for the implementation of BSS in Togo. The objective of this study was to analyze the normative and regulatory environment of Biosafety and Biosecurity in medical biology laboratories in Togo.

Type and period of study
The study was descriptive in nature. Data was collected from Halatoko et al. 131 January to June of 2021.

Inclusion criteria
The study targeted decrees, conventions, standards, laws, policies, and good practice guides. The latest versions of international instruments: standards, conventions, decrees, regulations, frameworks, and laws were consulted and requirements in terms of necessary regulations were identified. At the national level, the relevant legal instruments that have been ratified by Togo until 30 June 2021 were consulted. Similarly, a review of the main BSS management documents in Togo in terms of frameworks, laws, decrees, was carried out. Documents supplementing revised or country-specific regulatory texts and documents dealing exclusively with the animal and environmental sector were excluded.

Data sources
A document review on the Internet was used to explore the different texts. The websites of the National Assembly, the Government and the Ministry in charge of Health were visited. The archives of the Ministry of Health, the central library and the Official Journal of the Togolese Republic were also explored.

Research strategy
The search was done in duplicate and took into account Boolean operators (AND, OR, NOT) and keywords such as: biosecurity, biosafety and biosecurity, biological security, biosafety standards, biosecurity standards were used.

Data analysis
Data were imported into Zotero for further processing. Following the extraction of data, a comparison was made and a flow chart was produced. An analytical approach was used (Gouvernement du Canada, 2020; WHO, 2020a) to highlight the strengths, weaknesses, opportunities, and threats of each legal instrument. We highlighted several activities to be regulated that were conveniently grouped into areas of high impact on BSS worldwide. Country-level gaps in terms of BSS regulation were identified. Figure 1 illustrates the selection process of international BSS normative and regulatory documents. Of 76 documents consulted, 14 were included in the synthesis.

International regulatory texts on biosafety and biosecurity
A total of 14 texts regulate the BSS sector worldwide, 10 of which have been ratified or are in use in Togo. Full text document excluded, with reasons*** (n = 05) Documents included in the qualitative synthesis (n = 14) Documents included in the quantitative synthesis (n = 14)  Table 1, 09 take into account the specificity of medical biology laboratories, including three standards not adopted by Togo. Table 2 shows the areas recommended for national regulation by each standard, regulation, protocol, convention or guide listed. The main areas of national These documents take into account the specificity of medical laboratories at the international level. Other accreditation standards ISO15189: 2012 and ISO/IEC 17025: 2017 relating to quality management devote a chapter to the management of laboratory premises and environment. The former was adopted by Togo in 2015.

Areas of national biosafety and biosecurity regulation recommended by the international instruments listed
Source: Authors biosafety and biosecurity regulation recommended by the international instruments listed have been grouped into 07 and their contents represented in Table 3.

International normative and regulatory instruments on biosafety and biosecurity in medical biology laboratories
From the process of selecting normative and regulatory documents on BSS at the international level, 76 documents were initially listed, and then 14 were included in the summary. Our study showed that of the 14 international instruments listed, 10 had been ratified or were used by Togo, with 09 texts taking into account the specificity of medical biology laboratories. The ISO 15190 (2020) and ISO 35001 (2019) standards, which should help in the proper implementation of the BSS, have not been officially adopted, even though Togo's internal documentation on the  Title of the regulatory area Content National cross-sectoral biosafety and biosecurity framework Biohazard management, compliance with international agreements Biomedical waste management Production, control of transport on territory/cross-border, storage, decontamination, disposal, traceability Management of bioresources (modified living organisms, viruses, bacteria, fungi, prions, toxins...), chemicals and biological weapons Transport of samples/infectious substances, transfer of samples, import, manufacture export, threshold quantities, other controls, use of living modified organisms, toxins, management of genetic resources, biosafety provisions, chemical and pesticide management, consent procedure, handling of samples, shelf life of samples, pathogen and toxin inventory, traceability Information management and security, shelf life of laboratory archives, potential dual use Retention period of laboratory records, specific requirements for competence, impartiality and consistent operation of bio-banks, eligibility and reliability of staff Containment, facilities, personnel protection: requirements for handling human specimens, tissues or residues Bio-containment, standard laboratory layout, environmental impact, general health and safety, provision and use of personal protective equipment, protection of workers' rights, medical surveillance Qualification, registration of in vitro diagnostic devices and reagents for biomedical laboratories Qualification/registration of in vitro diagnostic devices and reagents for biomedical laboratories

Bioethics Bioethics
Source: Authors of laboratory premises and environment.

On an international level
Over the past decade, although there has been little scientific publication on BSS legislation, the normative framework is being updated in the light of technological advances (Huigang et al., 2021;Maljean-Dubois, 2021;Qiu and Hu, 2021 The COVID-19 pandemic demonstrated the importance of reforming health systems to reduce the spread of infectious diseases early (Loh et al., 2020). Thus, every laboratory must have a BSS manual and the WHO manual (WHO, 2020b) details good practice in this area. In the same vein, Canada has developed a new version of the BSS analytical approach strategy tool in 2019 (Gouvernement du Canada, 2020). This evolving toolkit provides practical guidance to help other countries around the world independently establish or strengthen their biomonitoring policies and frameworks.

At the regional level
In Africa, countries such as Togo are adopting more of a preventive approach and there is a similarity in the regulatory efforts of the BSS. The Bamako convention on the ban of the import into Africa and the control of transboundary movements of hazardous wastes has been ratified by several countries (Secrétariat de la Convention sur la diversité biologique, 2000). In Mali, waste management in general has been regulated since 2000 through Law N°00-081 and then Decree N° 01-394 P RM, of September 6, 2001 (République du Mali, 2001). In Benin, in addition to Decree No. 2002-484 making any producer of waste responsible for its disposal and making it a condition for the opening of health centres, Law No. 2021-01 was passed  (République du Sénégal, 2008). The Senegalese approach could be a model for several reasons. It applies to all structures involved in the biomedical waste management chain. In addition to being binding, clauses on the obligation to pre-treat waste within 48 h and the obligation of traceability have greater weight than general waste laws common in several other West African sub-regional countries. In Burkina Faso, legislative and regulatory texts have been adopted in the area of health to ensure hygiene, quality of care in hospitals (Burkina Faso, 2005), and sustainable management of biomedical waste for the safety of users and staff (Burkina Faso, 2008).

Synthesis
The various international instruments for the prevention of global threats (Bakanidze et al., 2010) described in this study have been designed to address the multitude of BSS challenges. However, the provisions for assessment control and resource allocation are bottlenecks in the implementation of this of many underdeveloped countries and even in Europe (Denault and Gardner, 2021). In the US, biodefense has been strengthened since the September 11, 2001 attack thanks threat reduction programs and global health security (Linkous et al., 2021). In China, it is only recently, on 15 April 2021, in the midst of the COVID-19 pandemic, that the first fundamental, comprehensive and systematic law came into effect in the national governance of BSS to minimize biological threats (Huigang et al., 2021). Thus, following this analysis at the international level, it is appropriate to highlight the areas of legislation covered by these instruments before looking at the regulations in force in Togo.

Areas to be covered by country texts under international biosafety and biosecurity instruments
Our study has highlighted several activities that could be regulated in the context of BSS. These activities have been conveniently grouped into seven areas of high impact on BSS worldwide. Although very few studies on this aspect have been conducted in the last decade, our results are consistent with the recommendations on regulation in this area in the Canadian Analytical Approach Guide (Gouvernement du Canada, 2020), the WHO guidelines on regulation (WHO, 2020b), and the BSS regulation study by Beeckman and Rüdelsheim in 2020 (Beeckman and Rüdelsheim, 2020). It is therefore necessary to analyze the inclusion of these key areas of BSS regulation in Togo's legal and regulatory texts.

Togo's instruments relating to biosafety and biosecurity in medical laboratories
In our study, out of 7 instruments relating to the BSS listed, 2 were specific to medical biology laboratories. The decree on the creation of the national network of laboratories for the rapid confirmation of epidemics (République du Togo, 1998) and the one on the adoption of the ISO 15189 standard (République du Togo, 2015) as a quality management standard in Togo are far from being binding and mandatory. A comparison of the content of the texts on BSS in Togo and the seven areas of regulation listed has made it possible to highlight the gaps in terms of inadequacies in the regulation of BSS in Togo.

Multi-sectoral regulatory framework of BSS
From the literature consulted, it appears that the backbone of regulation is a national cross-sectoral BSS framework. This framework will need to be brought in line with international standards and legislated on risk-based Halatoko et al. 137 approaches for all licensing, monitoring and enforcement of BSS requirements (Gouvernement du Canada, 2020; WHO, 2020c). The country BSS framework should, according to Huigang et al. (2021), the country BSS framework should, according to Huigang et al, be a governing mechanism controlling the entire risk management process, which is crucial for global public health governance. Similarly, Qiu and Hu (2021) analyzing BSS legislation in China, noted that cogovernance in BSS control is more than a necessity (Qiu and Hu, 2021). Togo has had a national biosafety framework in place since 2004 that deals primarily with LMO aspects (République du Togo, 2004). Not only are administrative controls on other bioresources not taken into account, this document is no longer operational in a globalization context. Its organizational structure is also no longer in line with current WHO regulations (Gouvernement du Canada, 2020; WHO, 2020a). The 2005 national biosafety framework of Mali, for example, has the same structure as that of Togo.

Biomedical waste management regulations
In terms of biomedical waste management, almost all the instruments analyzed place it in first position (Gouvernement du Canada, 2020; WHO, 2020c). Its regulation should take into account the production of waste, the control of transport on the territory, transboundary transport, storage, decontamination, disposal, and traceability. In relation to the legislation on the control of the waste management chain in Togo, several actions have been taken. Togo has put in place a national plan for the management of health care waste, revised in the 2016-2020 strategic plan (République du Togo, 2016) in addition to the Health Code (République du Togo, 2009). This code includes provisions on waste management in its sub-section 4 similar to that of Burkina Faso (Burkina Faso, 2005). In addition, Law N°2008-005 of May 30, 2008 (République du Togo, 2008) on the environment has the merit of being binding and compulsory; provisions for promoting compliance and an environmental police force have been included. However, the specificities of biomedical laboratories and the traceability aspect are not taken into account.

Regulation of bioresource management and bioweapons
For bioresource management, legislation should include activities involving all pathogens and toxins and bioweapons. Also, to be considered for infectious materials are the rules for transport, transfer, import, manufacture, export as well as the threshold quantities and control of the use of LMOs. In the same area of regulation, there are other equally important aspects to consider. These include the management of genetic resources; provisions on risk prevention; the handling of human samples, tissues or residues; the length of time samples are kept in serum banks; the inventory of pathogens and toxins and their traceability (Gouvernement du Canada, 2020;ISO 15190, 2020;WHO, 2020c). In this very critical area where international bodies leave the choice to states to legislate in their environment, the aspects taken into account in the Public Health Code in force in Togo are not likely to guarantee the necessary controls on the panoply of present and future biological resources.

Information security regulations, retention period of laboratory archives, potential for dual use
The security of information, the retention period of the laboratory's archives, and the potential for dual use must be controlled (Moritz et al., 2020). The conditions of admissibility, reliability, and moral probity of the staff must be taken into account. Specific requirements for the competence, impartiality, and coherent operation of biobanks must also be taken into account. Several suspected or confirmed biological samples are increasingly kept in bio-banks in Togo, especially concerning manipulated viruses such as LASSA, H5N1, and Covid-19. Malicious exploitation of knowledge, skills, and technology remains a concern and needs to be regulated (Berger, 2021;Evans et al., 2020;MacIntyre et al., 2020;Messaoudi et al., 2020). As regards the regulation of information, including dual use in the context of BSS, no regulatory text was identified in Togo during this study.

Bio-containment regulations, installation, personnel protection
In the area of bio-containment, facilities and personnel protection, the regulation should include the required conditions for handling human samples, tissues or residues. Also, to be taken into account are standard laboratory space plans, environmental impact, general health and safety, availability and use of personal protective equipment, protection of employees' rights and medical surveillance (Gouvernement du Canada, 2020; OIT and OMS, 2020; WHO, 2020a). In Togo, the legal framework is characterized by an absence of specific legislation in this area. Nevertheless, according to the Health Code in force, the protection and promotion of the health of the population as well as the provision of care and services are the responsibility of the State (République du Togo, 2009). However, this code does not effectively or explicitly guarantee the protection of laboratory staff. Under the terms of Article 67 of this code, an economic measure is provided for health personnel in the prevention and control of epidemics and in vaccination against certain transmissible diseases. Also, this code specifies that the opening and operation of a medical biology laboratory are subject to prior authorization by the Minister in charge of Health. However, the opening conditions set out in section 2 of the code do not explicitly include the obligations of the BSS. Other aspects of regulation, notably containment, standard installations and laboratory levels, are not covered by this code, SW.

Regulation of the qualification and registration of in vitro diagnostic devices and reagents in biomedical laboratories
It is equally important to put in place legislation governing the qualification and registration of in vitro diagnostic devices and reagents in biomedical laboratories. This registration is done at the Ministry of Health in Togo (République du Togo, 2009) and contributes to biosecurity, thus protecting medical staff from the use of harmful and counterfeit reagents.

Bioethics regulation
Bioethics needs a regulatory framework that helps the community to regulate and comply with BSS standards. It helps promote compliance and more generally fosters a culture of innovation while protecting the health and safety of the population (Messaoudi et al., 2020;Stoeklé et al., 2020;World Medical Association, 2013). In Togo, the legal framework is supported by institutional bodies set up by decree and order.
A Bioethics Committee, -Comité de Bioéthique pour la Recherche en Santé (CBRS)‖ (République du Togo, s. d.), has been created for this purpose. This committee, which has a charter as its rules of procedure, is an autonomous multidisciplinary structure responsible for giving opinions on clinical and biomedical or epidemiological research projects.

Conclusion
In the context of the improvements of the regulations in Togo in terms of biosafety and biosecurity in medical biology laboratories, the study carried out aimed to identify gaps in internationally accepted legislations. This analysis at the country level showed that some actions have been taken into account in the existing texts, but not enough to guarantee a better protection of humans and the environment against biological risks. The existing legal instruments are not all operational or are rather oriented by predilection towards living modified organisms, one element among the multitude of biological agents. This study shows that there is a current deficit in terms of regulations aimed at guaranteeing the protection of laboratory staff, but above all, at potentiating efforts to set up a biosafety and biosecurity system in Togo in a multisectoral framework. This situation thus requires, in the light of the country's national security and safety strategy and in the face of the Covid-19 pandemic, a paradigm shift by proposing a legal framework aimed at ensuring the protection of medical and paramedical staff, the community and the environment.. This will raise the issue of human resources capable of identifying, assessing, mitigating and communicating risks and safety solutions, including dual use of biological materials. It is necessary to strengthen the existing regulatory texts taking into account the areas identified in this study and then to analyze the human environment for the implementation of biosafety and biosecurity in Togo.

Recommendations
In order to improve and strengthen the legislative construction, we propose that concerned bodies should: 1. Develop a national biosafety and biosecurity framework in Togo in a multisectoral context; 2. Develop and adopt the application texts of the various laws and international standards and implement them; 3. Set up an effective mechanism to disseminate the texts; 4. Mobilise more human and financial resources to support the implementation of the legal framework for biosafety and biosecurity in Togo.