The H5N1 outbreak: unequal vaccine distribution

In 2007, the Indonesian government refused to share samples of H5N1 virus with the WHO unless they were assured access to the vaccines created from the samples. This decision was spurred by historical inequities in vaccine distribution where people in HICs were more likely to be vaccinated than people in LMICs.4 5 In fact, the Indonesian government argued that when LMICs have provided infectious disease data and biosamples to the WHO, pharmaceutical companies in HICs gain access to these samples for free, develop and patent products, and then set unaffordable prices to sell them back to LMICs.18 These LMICs tend to have little bargaining power against technologically advanced wealthier countries,18 19 which can result in uneven vaccine access.

The Ebola epidemic: sample acquisition, sharing and biosafety

More than 50 000 samples collected during the recent 2014−16 Ebola epidemic in West Africa were shipped out of the affected countries to unidentified laboratories around the world, primarily in HICs. This shipment was done without state authorisation or proper participant consent,20–22 amounting to what some deem biopiracy. Biopiracy could occur when researchers from HICs source samples for academic or commercial gain while failing to fairly compensate communities that provided the samples.23 Such acts erode ‘genomic sovereignty’, the ability of LMICs to protect their biogenetic resources.20 After the epidemic, an attempt by the WHO to inventory the remaining samples was thwarted by the refusal of some countries—primarily HICs, but also some LMICs— to cooperate in this regard.21 23 Some of the concerns related to Ebola samples included the high possibility of infectivity, safety concerns over the handling and storage of such highly infectious samples, and that the samples could be used for bioterrorism.3 24 Ultimately, scientists in Sierra Leone, Guinea and Liberia (where the samples were sourced) were unable to access these samples for their research.25

Lessons for COVID-19

These infectious disease outbreaks serve as important examples for biobanking during the COVID-19 pandemic. In fact, similar dynamics are already at play. For example, despite South Africa participating in AstraZeneca COVID-19 vaccine trials, the country has paid double the price per dose compared with European countries.17 26 The stockpiling and resulting global maldistribution of COVID-19 vaccines illustrate the persistence of global inequities (WHO 2021), but is also exacerbating pre-COVID-19 global inequities in healthcare.27 28 These examples also forecast potential ethical issues for COVID-19 biobanking. In terms of sample sharing, early evidence of genetic mutability of SARS-CoV-2 through the appearance of more virulent variant strains was detected by scientists in South Africa.29 Yet given worries about the infectivity of COVID-19 and its samples, similar if not greater challenges related to the exclusion of researchers from LMICs from sample sharing may be on the horizon. While global data and sample sharing are imperative during public health emergencies, these examples highlight the need for greater international research ethics guidance and legislation during and after the COVID-19 pandemic to facilitate the sharing of data and the benefits of research with LMICs. Yet COVID-19 has placed unprecedented burdens on hospitals and critical care facilities throughout the world.30–33 These burdens, coupled with national lockdowns and other social distancing measures, create distinct ethical challenges for biobanking, which we explore below.

Informed consent

Informed consent is an ethical cornerstone of research. While volunteerism is important for research participation in general, obtaining informed consent for COVID-19 biobanking research has numerous logistical challenges, some of which may undermine autonomous decision-making. Non-hospitalised patients are instructed to quarantine, making sample collection virtually impossible, and hospitalised patients may be unconscious, heavily sedated, have impaired cognition or otherwise be too sick to engage with the consent process. Similarly, obtaining proxy consent from a patient’s family may be difficult. In South Africa, as in many countries, hospitalised patients with COVID-19 are not permitted visitors, thus limiting opportunities for obtaining proxy consent.35 In addition, proxy decision-makers may be understandably anxious and not wishing to engage in a research-informed consent process.36 Finally, researchers or others involved in sample collection could be exposed to the virus if proper infection control measures are not in place,37 and the availability and access to appropriate personal protective equipment (PPE) have been limited.38 When PPE is available, its use, including the use of face masks, can preclude optimal face-to-face informed consent discussions.36

Despite logistical difficulties of obtaining informed consent for biobanking, samples are being collected for COVID-19 diagnostic and therapeutic purposes throughout the world. Countries may not have clear regulations that speak to when, if ever, samples collected for these purposes can be repurposed without consent for other research use. For example, in South Africa, health legislation permits collecting samples from hospitalised patients for COVID-19 diagnostic purposes without consent, with provisos, and the Disaster Management Act of 2002 prioritises and makes special allowances for ‘disaster management research.’39 40 Yet both pieces of legislation are silent on whether COVID-19 samples can be used for research without consent. Furthermore, while biobanks likely have clear procedures for when samples may be repurposed without consent, data from a recent international survey of biobankers found that many reported that local Research Ethics Committees (RECs)/Institutional Review Boards (IRBs) were more liberal in their permission to waive consent for biobanking of COVID-19 biospecimens than was their usual practice.34 If samples are to be collected and stored for COVID-19-related research from hospitalised patients under a waiver of consent, patients who are not severely ill can be informed when they are admitted to the hospital and allowed an opportunity to ask questions and possibly opt out, and posters informing patients and loved ones about the biobanking efforts and purpose may be displayed throughout the hospital.

Collecting and storing samples for research from COVID-19-positive patients under a waiver of consent will have public health benefits and must be weighed against respecting individual patient autonomy. Biobankers should develop a plan to deidentify or anonymise collected samples and data prior to sharing to mitigate any possible risks to individuals.36 Waived consent for sample storage during pandemics is arguably justifiable based on necessity provided that future research is COVID-related (or, perhaps, related to other infectious disease outbreaks), in the public interest and approved by an REC/IRB. In addition, existing collections of stored biosamples could be repurposed for research during a pandemic without the need for reconsent provided that studies using such biosamples are appropriately designed and that study benefits are equitably distributed.41 The waiver of reconsent should be consistent with the requirements of country-specific legislative frameworks on consent for research purposes. However, mechanisms must be in place to prevent biopiracy or exploitation of vulnerable participants via material transfer agreements (MTAs), data transfer agreements (DTAs) and authentic collaborative relationships in LMICs. In addition, protections must be in place to prevent the use of samples from countries with looser or fewer regulations on repurposing samples, which may lead to the exploitation of those in LMICs.

Community engagement

CE contributes to procedural justice to ensure fairness in how significant decisions are made in health research.42 Engagement activities are important to conduct when members of marginalised communities are expected to participate in the research or when there are social and economic disparities between those conducting the research and those participating. Either of these situations may be the case for biobanking efforts involving LMICs. Biobanking CE efforts are essential for developing public trust in biobanking42 as it involves communication about the purpose of the biobank, building relationships and collaborations,43 and ensuring communities have a voice in biobanking efforts.44 CE is particularly important if informed consent for biobanking or repurposing of samples will not be sought (eg, an REC/IRB waiver of consent). However, engaging with communities in LMICs during COVID-19 is challenging and traditional CE processes may not be possible. Virtual processes may also prove difficult as community members may not have access to electronic platforms or may not have data for use with mobile phones. This, however, should not be a reason to abandon engagement with community members from LMICs, and legislative bodies or RECs should make the integration of CE a priority.45

Sample and data sharing

Coordinated, global sharing of samples and data during a pandemic is critical to expedite research, and biobanks are key in this endeavour. However, prior research indicates that underutilisation of biobank resources is a common problem for biobanks and a source of ethical concern for biobankers.46 47 Global sharing of samples and data should be a priority, not only during the pandemic but even when the COVID-19 outbreak has waned. There are opportunities to counter traditional challenges in underutilisation of biosamples that inevitably impact the sustainability of biobanks through coordinated and planned efforts for sample and data sharing.48

Individuals involved in biobank governance, such as biobankers, RECs/IRBs and researchers, should be cognisant of the ethical complexities surrounding sample and data sharing. The potential for relaxed research regulations during a pandemic, such as waiving informed consent and decreasing community engagement, increases the imperative for biobanks to strengthen the conditions under which samples and data are accessed and shared. It is not uncommon for samples and data to initially be shared with one group, like academic researchers, only for a third party (such as for-profit companies that fund the research) to gain secondary access.49 One possible ethical approach to increase data sharing between institutions could be through the use of secure online data management systems to facilitate collaboration rather than transfer. Thus, data sharing with third parties could occur without the need to transfer proprietary rights to these entities.49 Proper governance of biobanks must involve clear protocols detailing the process of deidentification or anonymisation of the samples and data prior to sharing during a pandemic. This is particularly important given the potential for stigmatisation. During COVID-19, various groups have been stigmatised during the pandemic, although the particular groups and the extent of the stigmatisation vary from culture to culture.50 51 LMICs face particular risk from the prospect of stigmatisation during a pandemic as the sharing of resources is already ethically fraught, with LMICs often on the losing end. When sharing samples, unambiguous MTAs with clear specifications on how individuals’ and communities’ rights and interests can be protected are imperative. When sharing specimens and data from individuals in LMICs, MTAs should also outline how benefits from any therapeutics or vaccines produced by the research will be shared with the LMICs.

Safe handling of COVID-19 biosamples

At a biobank operational level, COVID-19 biosamples must be handled safely given their potential infectivity.52 Some of the possible adverse consequences related to the processing and storage of COVID-19 biosamples could include accidental spillage of collected samples, risk of exposure, cross-contamination and spread of infection among staff. Thus, reviewing safety measures around the handling of stored coronavirus-related specimens and isolated strains, optimal decontamination processes for the laboratory setting and the availability of PPE for staff is critical24 38 53 Researchers or biobanking staff involved in specimen annotation need to ensure that the integrity of the collected samples is optimally maintained, and there should be ongoing skills development to ensure staff competency in dealing with COVID-19 biosamples so that stored biosamples can be used to advance scientific goals.54

Biobanks should also consider biosecurity measures when dealing with pathogens. ‘Dual use research of concern’ is scientific research that is intended to benefit society but could cause societal harm if misapplied.24 55–57 COVID-19-related research using potentially contagious samples highlights these concerns. The appropriate or beneficial use of research could be to learn more about coronaviruses and treatment regimens, but at the same time such pathogens could also be put to dangerous use such as the creation of bioweapons for bioterrorism.58 59 If samples collected during a pandemic could represent a priority target in bioweapon design, vigilance and proper governance in controlling access to stored samples are essential. Such vigilance, however, should not be used as a reason to restrict scientists and researchers in LMICs from having access to data and samples. Legislation at the country level, as well as international collaboration, is required to ensure proper governance and safe sharing of dangerous pathogens (including the need for proper MTAs in the export of samples).60 61