One objective of the H3Africa consortium was to provide high-quality DNA for future use to maximize the value of these hard-to-obtain specimens with high potential to provide information to the biomedical research community. Therefore, H3Africa required most H3Africa genomic research projects to obtain broad consent to deposit DNA for each study participant. Each of these projects was assigned to an H3Africa biorepository according to its study location (Fig. 1): CLS to projects within Southern Africa, IBRH3AU to projects within East Africa, and I-HAB to projects within West Africa. Researchers could also deposit other biospecimen types voluntarily for storage; however, the consortium does not require such biospecimens to be accessible for research. The biorepositories harmonized practices with research sites by needs assessment, harmonized and standardized documents and processes, trained and provided mentorship to bridge gaps, piloted all processes, and continuously monitored for improvement.

Fig. 1

Research sites and assigned biorepositories

Needs assessment

The biorepositories discussed biospecimen collection and deposit with assigned research sites, visited sites where feasible and reviewed relevant documents and processes to determine needs and devise strategies for support. The biorepository committee (The Committee), composed of NIH technical staff and the biorepositories’ PIs and staff, met bi-weekly during the pilot and early implementation phases and monthly thereafter to establish requirements and processes to accomplish biospecimen deposit and access. Each biorepository also met with the assigned research sites as needed to educate them in biobanking, services, and requirements and to discuss updates, challenges, remediation, and potential needs such as document development and training. Where feasible, H3Africa biorepositories visited research sites to become familiar with relevant processes and to conduct needs assessments. The biorepositories also reviewed relevant documents to ensure compliance and harmony among the various institutions and procedures, and to identify gaps. Document review varied according to need and included MTAs, consent forms, study protocols, standard operating procedures (SOPs), and supply lists. The biorepositories addressed gaps through document development, document revisions, training, and mentorship.

Drafted documents for harmonization and standardization

The Committee harmonized documents to promote accountability, transparency, and consistency. The Committee assembled the Writing Subgroup to draft resource documents and the Data and Biospecimen Access Committee (DBAC) to develop requirements and processes for biospecimen access. The Writing Subgroup developed guidelines, SOPs, forms, minimal datasets, and other reference documents to harmonize and standardize processes. Similarly, the subgroup created a Material Transfer Agreement (MTA) as a resource for institutions that did not have MTAs or had limited experience.

Training and mentorship

The H3Africa research staff involved in processes related to biospecimen deposits were trained in related pre-analytical, analytical, and post-analytical processes to ensure high-quality biospecimen and data. Training opportunities (Fig. 2) were aligned with project needs, as determined from meetings, on-site observations, document reviews, and principal investigator (PI) requests. Training aligned with International Society for Biological and Environmental Repositories (ISBER) best practices, established industry practices, and included theory, class exercises, practical exercises, and competency assessments. Biorepositories also mentored research staff in document development, workflow design, biological transport, laboratory procedures, and areas of improvement identified during training.

Fig. 2

Training and mentorship topics

Piloted ethical and legal procedures and requirementsEthical requirements

H3Africa biorepositories established several mechanisms to ensure biospecimen use was consistent with approved project protocols, policies, procedures, and informed consent. H3Africa biorepositories sensitized their respective institutional review boards (IRB) through trainings, meetings, and/or site visits to promote biobanking awareness and advocate for policies and processes that intercalate biobanking needs and peculiarities: IBRH3AU-Uganda National Council of Science and Technology (UNCST) and Makerere University School of Biomedical Science Research Ethics Committee (SBS REC), I-HAB-National Health Research Ethics Committee (NHREC), and CLS-Human research ethics committee of the University of Witwatersrand. The biorepositories also requested protocols and informed consent to ensure compliance with ethical clearance.

H3Africa biorepositories developed documents and processes to protect the security and integrity of biospecimens and data. As mentioned, the MTA served as a resource that researchers could adapt and adopt to set limitations and expectations in material exchange. Likewise, the H3Africa Data and Biospecimen Access Guidelines provide biospecimen access requirements, processes, and criteria for selection and prioritization to ensure future researchers adhere to the ethical requirements.

Legal requirements

The biorepositories and researchers shared biospecimens and associated data according to universal legal requirements and legal requirements specific to the donor and recipient’s country and institution of origin. In adherence to the International Air and Transport Association (IATA) regulations, the Committee required shippers at research sites and biorepositories to attain and maintain IATA shipping certification and provided additional in-person training and mentorship as needed in IATA, biological packaging, and shipment. Shippers were certified in class 6.2 for biological, infectious substances and class 9 for dry ice as appropriate. The biorepositories investigated import/export requirements and obtained permits as required.

Piloted biospecimen deposit

Although the biorepositories had piloted biospecimen deposits internally to test established procedures, documents, and logistics [11], the biorepositories also piloted processes required for biospecimen deposits with inexperienced researchers as needed. To prepare, the biorepositories developed a pilot protocol and a shipment checklist and reviewed them, the overall process, and the associated documents with the research sites. Biobanks and researchers met all the ethical and legal requirements prior to biospecimen or data exchange.

Research sites

The research sites recruited participants, consented to them, collected biospecimens, processed, and temporarily stored participant biospecimens as part of their ongoing study protocol process. Research sites minimally included DNA as required, but some also included non-DNA biospecimens representative of the biospecimen types they would deposit during implementation. The Biospecimen Deposit Guidelines specified requirements for deposit such as labeling, quality control (QC), and minimum number of aliquots (Fig. 3).

Fig. 3

Biospecimen deposit guidelines—standardization from deposit to distribution

For the pilot, the research sites prepared to deposit biospecimens to their assigned biorepositories. Table 1 summarizes the research sites’ locations, area of research, and biospecimen types deposited. Consult the H3Africa catalog, https://catalog.h3africa.org, for additional information about the research projects, such as study design. The research sites also completed and emailed the sample manifest and accompanying shipping documentation, scheduled biospecimen pick up, and emailed the expected date of shipment/pick up prior to shipment to the biorepository. The sample manifest included all the minimal dataset elements, as well as information relevant to the shipment such as aggregate data on sample types and associated shipping conditions. All biospecimens were shipped in accordance with IATA regulations. The sites shipped serum, plasma, and urine frozen (dry ice or Credo shipper-temperature controlled); whole blood at controlled ambient temperature; and DNA at a combination of controlled ambient, refrigerated, or frozen, in accordance with H3Africa standard operating protocols (SOPs). The sites used reusable quantitative temperature loggers (Sensitech, Beverly, MA, USA) and qualitative disposable 3TM Warmmark time–temperature indicators (Anaheim, TelaTemp, CA, USA) to monitor the shipping environment to determine if the cold chain was compromised (unless indicated otherwise).

Table 1 Research site locations, assigned biorepositories, and biospecimen typesBiorepositories

Once biorepositories received the email alert of the planned biospecimen shipment, the staff prepared for biospecimen deposit. The biorepository reviewed the documents for completeness and accuracy and contacted the researcher if needed for clarification or modification. Upon shipment, the biorepository tracked the shipment daily to monitor the expected date of arrival (DOA) and to detect and rectify potential arising issues such as delays in customs. The biorepository also tracked the Sensitech temperature loggers daily to ensure that the cold chain was not compromised and to intervene should issues arise. Upon receipt of the shipment, the biorepository observed the temperature or indicator of the temperature monitor, subjected the biospecimen to acceptance/rejection criteria, and compared them to the accompanying manifest. Next, the biorepository completed the Shipment Receipt Confirmation and Query Form, documenting any non-conformities, and forwarded it to the researcher to confirm receipt and communicate and resolve non-conformities.

After completing the biospecimen receipt process, the biorepository performed QC for 10% of shipped biospecimen and sub-aliquoted DNA according to the Biospecimen Deposit Guidelines and SOPs and stored the biospecimen. For quality control purposes, the biorepositories determined DNA concentration at an absorbance of 260 nm, determined purity using the 260/280 absorbance ratio, and conducted agarose gel electrophoresis to determine the integrity of the samples [12, 13]. Biorepositories used visual grading for plasma and serum to determine hemolysis and turbidity, and pH and turbidity for urine. Each biorepository used a laboratory information management system (LIMS) to collect and store biospecimen-associated data, importing data from the sample manifest and adding data for sample location, in-house QC, aliquoting, etc. The LIMS included Freezerworks (Dataworks Development, Seattle, WA) for I-HAB and IBRH3AU, and LDMS (Frontier Science Foundation, Amherst, NY) for CLS.

Continuous Quality Improvement (CQI)

The biorepositories and research sites partnered to ensure the gains accomplished through the pilot and remedial actions were maintained through program implementation. Both teams reviewed data for accuracy and completion before and following shipment receipt and communicated discrepancies within 1 week for resolution. The teams also tracked shipments and monitored environmental conditions minimally once per day until delivery. In line with the Biospecimen Deposit Guidelines, the biorepositories performed QC on 10% of the DNA received, if < 90% of those results were beyond A260/280 of 1.7–2.0, or of high molecular weight by gel electrophoresis, the biorepository tested the remaining 90%. For subsequent shipments, 100% QC was conducted until ≥ 90% of the QC results were of acceptable quality. The biorepository also informed the researcher of the discrepancies, shared its in-house results, assisted with root-cause analysis, and supported corrective and preventive actions. The biorepositories continue to meet with the research staff to discuss the challenges and strategies for improvement.