An overview of the National Biobank of the National Health Laboratory Service: a South African national treasure for biological resources

Section A: Repository planning considerations

The NHLS Biobank which is situated at the National Institute for Occupational Health (NIOH), a division of the NHLS, is a physical repository of national importance to SA and global researchers [31]. It was established in 2012 as a not-for-profit entity purposefully designed to serve as a research infrastructure to support the research community undertaking research to alleviate the growing burden of communicable and non-communicable diseases in SA [31]. The NHLS Biobank is a population-based human biobank with a capacity to store a wide variety of samples. The NHLS Biobank scope of practice is to formally manage, in an organised manner, the collection, processing, storage, retrieval and distribution of human biological materials (HBMs) and their associated data for research purposes both now and in future nationally [31, 32]. The NHLS Biobank infrastructure has the capacity to store 4 million samples; 39% of its storage capacity is currently utilized with a total of 1,558 144 samples (buffy coat n=6,752; cytology microscope slides n=200,000; cytology block samples n=6,709; DNA n=3,466; histology microscope slides n=766,500; histology block samples n=75,750; Microbanks n=189; plasma n=351,017; serum n=146,360; and urine n=1,401) in storage as illustrated in Figure 1.

Figure 1:

Sample types and quantities in storage at the NHLS Biobank.

Sample collection is handled by the clients who determine their specific research interests (needs), donors and donor characteristics that they require. All samples types were collected from participants who were patients presenting with HIV, TB, metabolic diseases (e.g. diabetes) as well as patients requiring cytopathology and histopathology tests at government hospital settings. Table 1 is a representation of the sample profiles and downstream applications for samples currently in storage. Notably, due to the long-term nature of biobank research, the specific research details and associated downstream application(s) is not always possible.

The NHLS Biobank acknowledges the genetic diversity in SA and recognises it as a national treasure [9]. Availability and accessibility of HBMs within legal and ethical boundaries will foster national research initiatives and capacity building. Consequently, sample and data protection and control while safeguarding the interests of research participants.

The successful operation and management of the NHLS Biobank activities is owed to the governance mechanisms that support transparency, accountability and oversight. The NHLS Board, CEO and the NIOH executive are in charge of the NHLS Biobank. The NHLS gets monthly updates of the biobank from the Projects Manager of the NHLS Biobank. The Projects Manager reports to the NIOH Executive and the operation of the biobank are reported on a monthly basis to the Executive Committee (EXCO) of the NHLS, who then report to the NHLS board. The NHLS board reports to the Minister of Health. An annual report is produced to inform public and stakeholders of the biobank operations.

The NHLS Biobank has an elaborate business plan and governance framework that covers the entire biobanking lifecycle, this is documented in quality manuals, policies and standard operating procedures (SOPs) to ensure correct implementation of crucial components of biobanking and these documents are made accessible to stakeholders (Table 2) [32, 33].

Legitimacy of biobanks and subsequently its social license is heavily reliant on the governance structure [34]. The NHLS Biobank upholds governance by adopting the commonly used governance strategies in biobanking. These strategies include communication, compliance, expert advice, external review, internal procedures and partnerships [34].

Section B: Facilities

Section C: Storage and processing equipment

Biobank equipment indicated in Section A are traceable through an Equipment Inventory Log where the equipment is assigned a unique asset number. Elaborate procedures to follow for equipment maintenance, equipment downtown, and unit decontamination is provided in SOPs. A yearly calibration and preventative maintenance/service plan is scheduled and conducted for all equipment by service providers accredited by South African National Accreditation System (SANAS). Storage equipment in the NHLS Biobank is accommodative for a variety of samples requiring short-term and long-term storage. The requirements for service are discussed during the initial engagement with potential clients [23].

Section D: Quality management

ISBER Best Practices for Biorepositories was instrumental in the development of the infrastructure and QMS for the NHLS Biobank. In April 2019, the NHLS Biobank met the QMS requirements for ISO 9001:2015 and was certified after it was assessed for compliance in terms of providing products and services that consistently meet customer requirements and evidence of continual improvements in the QMS. Having met the requirements for ISO 9001:2015 certification, which satisfies the quality assurance (QA) aspect of the QMS, provision for the implementation of ISO 20387, overarching the guiding principle of suitability specific to biobanking is underway for the NHLS Biobank. Accreditation with ISO 20387:2018 together with the quality control (QC) assays implemented for the biobanking processes will confirm the reliability of the biological resources in the NHLS Biobank. This will propel the NHLS Biobank towards integration and harmonization, thereby enabling the sharing of high-quality and well-annotated biological resources that will contribute to modern biomedical research on an international scale [8].

Section E: Method validation and quality control considerations

Methods are adopted or developed and validated to execute the different phases of the NHLS biobanking processes while preserving the quality and relevance of the samples in the long-term [43, 44]. Different parameters of analysis are used for validation in order to effectively detect defective outputs of methods employed to carry out the biobanking processes. QC measures are conducted using certified reference material that establishes tractability of the accurate value and establishes the stated level of confidence. QC protocols employed depend on the sample type and utility of the samples. Section K provides more information specific to the collection and storage phases of the biobank process with relevance to method validation and QC considerations.

Section F: Safety

A safety plan which ensures the safe operation of the biobank for the protection of staff and visitors was developed through a comprehensive risk assessment which involved the overall process of accurate identification, analysis and evaluation of risks inherent to the operational activities and layout of the biobank. Hazards to the health and safety of employees and visitors are identified for the NHLS Biobank and these are categorised as biological, chemical, physical and psycho-social hazards. Examples of the categorised hazards are shown in Table 3.

The highest level of control is implemented where reasonably practicable, to completely eliminate exposure of staff and visitors to the identified hazards in the long-term or to minimize exposure to the hazard and this was achievable by applying the principles of hierarchy of hazard control [45]. The NHLS Biobank adheres to the occupational health and safety management system of the NHLS which is governed by the Occupational Health and Safety Act (OHS Act 85 of 1993) [46], an SA regulation governing the safety and health of employees and persons that might be affected by the work being conducted.

Biobank staff are supplied with adequate personal protective equipment (PPE). For every task or procedure carried out, the required PPE and equipment to ensure safety of the staff is outlined in SOPs as well as in the risk assessment document. Health and safety related training and information is available on the NHLS intranet for all staff. Due to the variety of samples handled in the Biobank, staff are vaccinated against blood borne pathogens such as hepatitis B, and baseline X-ray checks are done for tuberculosis, followed by screening which is self-administered quarterly. Covid-19 control measures for infection prevention in the workplace which includes daily screening of biobank staff for Covid-19 symptoms is also administered.

Section G: Training

The NHLS Biobank staff are comprised of laboratory clerks and medical scientists who report to the manager. Staff are responsible for the daily operations of the Biobank and are assigned responsibilities based on their job description and competencies. Training is an integral part of competence determination. Staff have the necessary qualifications, training, and experience to effectively and safely operate the biobank. Competencies and qualifications of staff are filled in their respective personnel files for record keeping. Knowledge and practice is kept up to date by reviewing staff training needs annually or as changes to the system are effected. Determination of personnel competence is identified through task appropriate academic qualifications and training, and this is structured as part of a broader quality system within the biobank operation [32]. Key performance indicators (KPIs) are set annually and capabilities and needs of staff are detectable during staff appraisals and there are procedures in place that promote staff progression. Personnel complement of the biobank is indicated in Table 4 with the respective KPI aspects. Over and above the provision of storage services, the NHLS Biobank conducts teaching and training of medical students in universities on biobanking, training of other interested parties on starting biobank operations nationally and internationally. Furthermore, the NHLS Biobank provides sample reception services for departments within the NIOH and NHLS Central Laboratory Support Services (CLSS).

Section H: Cost management

The NHLS Biobank is a non-profit generating entity operating on a cost recovery business model. Resources required for optimum functioning of the biobank were forecasted during the design and development planning of the NHLS Biobank which continuously informs annual budgetary allocations and sustainability of the model by Management and key stakeholders. The NHLS Biobank receives its annual budget from national treasury and these funds are administered by the NHLS to its divisions. The annual budget of the NHLS from national treasury dictates the percentage allocated to the NHLS Biobank. The budget ranges between 5 and 10% of the overall budget allocated for operational activities by the NHLS. Over and above the allocated budget, the NHLS biobanking services generate revenue that is reinvested into the model as a cost recovery strategy.

The assessment of sources of costs, which is done for infrastructural and operational needs of the NHLS Biobank, is employed to control costs. Sustainability heavily depends on how well the activities concerned with the biobank are translated into cost information that prompts decision making favourable to sustain the business model in the long-term by maximizing outputs with the least costs, a method called cost minimisation [47].

Biobank daily operations are costly and management has to choose from economic efficiency to technical efficiency. The biobank input costs involve labour, equipment service and calibration, electricity, sample transport cars and fuel, liquid nitrogen, training and education, certification and membership costs.

Factors such as inflation affects the budget of the biobank as this directly result in increased cost recovery charges. Cost is managed by monthly stock count and checking the utilisation of inputs. The amount of labour needed in the biobank is constantly scrutinised against the method used to collect and store samples and the associated data. Energy efficient processing and storage equipment are employed to keep operating costs to a minimum.

Section I: Repository management information system

The NHLS Biobank is equipped with an electronic inventory system for the management and accounting of biological samples and their data. The physical storage of samples and their associated data is configured and traceable on the password protected system, to ensure biomaterials and data privacy and protection [32, 48]. The biobank LIMS not only enables tracking of sample usage, movement within the repository, retrieval and dissemination to clients, and sample return from clients, it also permits search and query abilities for all data stored. Critical to the synergy between the physical and electronic storage of samples is the sample unique identifier and the accurate labelling of samples and capturing of data. Samples in the NHLS Biobank are assigned unique identification numbers and labelled as such using the barcode system readable to humans and computers. The usage of a barcode scanner for data input is employed to prevent transcription errors. Unique identification numbers are employed to de-identity personal information traceable to the donor.

The extent to which staff can access and use the system is task dependent and user restrictions are configured by the manager for the purpose of data protection and upholding confidentiality for those that have donated the samples. Activities of staff on the system is traceable to an individual and this is ensured by staff having personal login credentials used when they access the system. An audit trail and periodic repository inventory is conducted which can either be regular or random to ensure the effectiveness of the system as intended for biobanking processes. The system is programmed to log off users after a specified time of inactivity while logged on to the system. Data in the system is frequently backed-up to protect against data loss. The back-end of the system is maintained by the Information Technology Department.

Section J: Packaging and shipping

Within the context of a biobank, retention of sample integrity and stability as much as possible is crucial. This ensures quality of the stored samples, consequently reliability of the data generated from processing of samples. Provision for procedures applicable to road and air transporting of samples is necessary. The Biobank takes into account considerations for infectious and diagnostic substances, classified by International Air Transport Association (IATA) as dangerous goods [49]. Key factors considered in ensuring adequate sample preservation include; (1) efficient logistics system, (2) availability of constant power (back-up power in cases of power failure), (3) constant availability of frozen ice packs or dry ice [30, 50, 51]. The Biobank is compliant with IATA guidelines as demonstrated by personnel that have been trained and certified accordingly. This ensures control and mitigation of potential risk factors that may influence sample quality including; (1) limited space for biobank sample transport when delivery is combined with other laboratory sample deliveries and (2) turn Around Times (TATs) for sample shipping. Availability of at least one vehicle dedicated to biobank sample shipping is highly recommended. The biobank utilizes its own transport system with access to vehicle service records as a means of assessing transport efficiency to avoid breakdowns which might compromise sample quality and integrity. Sample cold chain during shipping is maintained using ice packs or dry ice. Digital thermometers are used for monitoring of transit temperatures according to manufacturer’s instructions translated into SOPs. Digital thermometers are typically used with software that enables retrieval of transit temperature recordings (pre- and post-delivery readings). Transit temperature readings are assessed for any temperature deviations and all records kept.

Section K: Specimen collection, processing, receiving, and retrieval

The process of biobanking, which includes sample and data collection, processing, receiving and retrieval is documented in SOPs. There are quality checks for each of the processes listed above to ensure that the process and the end product is fit for purpose. These checks include competency of staff involved, effectiveness of equipment and method employed, sample integrity and viability through transit temperature monitoring and recording, as well as 100% error checks for transcription errors for sample registration. For instance, during collection, in-transit temperature of samples is monitored to ensure that cold chain is maintained while samples are in-transit to and from the NHLS Biobank, especially for temperature sensitive samples. This is achieved by using calibrated electronic temperature logging devices against a reference standard from a SANAS accredited facility. The temperature of samples during transit to the biobank is documented together with other pre-analytical variables inherent to the collection, processing and storage phases of the biobank lifecycle. Knowledge of pre-analytical variables inherent to the biobanking processes is fundamental for downstream applications and accurate interpretation of research results derived from the samples [23, 43, 44].

Conditions of the Biobank storage equipment are assessed through inter-laboratory storage of QC samples and subsequent testing of these samples to determine reproducibility of results run in parallel to those stored at another laboratory over a period of time using baseline results as reference (Figure 2A–E). The findings of the QC checks are documented and corrective actions are effected where there are discrepancies. These processes are conducted by trained and competent staff and each process has a workflow authorised by the manager. As indicated in Section L below, there are qualifying criteria to be met before initiating collections and the exchange of samples between involved parties ensues. Liquid samples are stored in aliquots to avoid multiple freeze-thaw cycles of the entire quantity of a given sample at a given time, and these are stored in different storage units. Multiple samples from individual patients are frequently collected for redundancy.

Figure 2:

Process flowchart for optimising storage conditions for biospecimens at the NHLS Biobank.

The unique identifier for samples ensures efficient traceability for retrieval purposes from the inventory system. As with the collection stage, the retrieval of samples is also documented and factors such as time, temperature, person involved in the retrieval process and the reason(s) for retrieval are documented and subjected to QC. These processes must also be traceability on the inventory system. Internal or external factors that pose as a risk to the efficient operation of the biobank activities is documented on a risk register and mitigations strategies to lower the risk or eliminate it are effected.

Section L: Legal and ethical issues for biospecimens

There are no biobank specific regulations and legislation in SA, therefore, a number of national regulatory instruments and legislation as well as international guidelines and declarations govern the NHLS Biobank processes and research [38, 39, 52]. MTAs are signed by all parties prior any transfer of material (specimens and associated data). In the MTA, rights and responsibilities of both the Biobank (provider of service) and the transferring institution (receiver of service or custodian) are clearly stipulated and defined [52], [53], [54]. The MTA also protects the rights of people from whom the materials have been collected in line with principles of ethics as well as the law and regulations [52], [53], [54]. Some of the elements of the MTA that ensure sound ethical conduct and adherence to the law include a requirement for HREC review prior material transfer by the custodian to the Biobank, custodianship and benefit sharing as well as a responsibility for privacy and confidentiality by the Biobank [52], [53], [54]. This ensures respect for participant autonomy while public (community) engagement activities ensure beneficence for SA communities by distributing the relevant biobank and biobank research information which in turn strengthens participant autonomy, i.e. providing full information necessary for the consent process. The transfer of materials back to the custodian is only released upon permission by the custodian to prevent inappropriate sharing and use.

Section M: Specimen access, utilization, and disposition

Clients of the NHLS Biobank are custodians of the samples and their associated data currently in storage, third party access to these collections is protected as per ethical and legal requirements [32]. Samples can be collected and distributed to NHLS researchers, private researchers and industry on the conditions of joint collaboration projects using samples that have been collected using broad consent [55]. Requests to biospecimen, data and resources access for research from the NHLS is facilitated by AARQA and the process workflow is illustrated in Figure 3 [55]. All applications are registered and submitted on the Academic Affairs and Research Management System (AARMS) of the NHLS and the applications are processed by the Academic Affairs Research (AAR) Office which forms part of AARQA [55]. Access criteria is facilitated as a function of scientific value and ethical soundness of the proposed project(s). Under no circumstances are the specimens and associated data used by Biobank personnel or third parties unless otherwise agreed upon and in collaboration with the custodians. To date, 20% of the total number of samples that were in storage (plasma, serum, urine, histology slides and block samples) have been retrieved for research and pathology referral purposes by custodians.

Figure 3:

Flowchart for the application process for access to biospecimens, data and resources of the NHLS for research purposes.

Disposal of specimens at the Biobank is regulated by the National Waste Act No. 59 of 2008 [56], as well as Occupational Health and Safety (OHS) rules. All of the specimens to be disposed of are considered biohazardous and the appropriate procedure for discarding biohazardous biomaterial is followed. Physical disposal of specimens is preceded by destruction on LIMS.

The flowchart is adopted from the flowchart for the application and submission process outlined by AAR to access biospecimens and/or data from the NHLS for research purposes [55].