Specimen sharing for epidemic preparedness: Building a virtual biorepository system from local governance to global partnerships

We present a framework for a federated, virtual biorepository system (VBS) with locally collected and managed specimens, as a ‘global public good’ model based on principles of equitable access and benefit sharing. The VBS is intended to facilitate timely access to biological specimens and associated data for outbreak-prone infectious diseases to accelerate the development and evaluation of diagnostics, assess vaccine efficacy, and to support surveillance and research needs. The VBS is aimed to be aligned with the WHO BioHub and other specimen sharing efforts as a force multiplier to meet the needs of strengthening global tools for countering epidemics. The purpose of our initial research is to lay the basis of the collaboration, management and principles of equitable sharing focused on low- and middle-income country partners. Here we report on surveys and interviews undertaken with biorepository-interested parties to better understand needs and barriers for specimen access and share examples from the ZIKAlliance partnership on the governance and operations of locally organized biorepositories.

Thank you for your review.We corrected the punctuaCon and typing errors pointed out (line 402 and 442-443 and spacing error for line 475 of the original manuscript).For lines 442-443 revised and divided into shorter sentences instead of dashes.The correcCons are now found in line 375, line 431-432 in the revised manuscript.

Reviewer 2:
The authors propose a Virtual Biorepository System (VBS) as a poten9al solu9on to global specimen sharing and epidemic/pandemic responsiveness.I appreciate the goals and sen9ment and their call for increased support of biorepositories par9cularly in LMICs, but overall, I found the perspec9ve narrow and did not see how the VBS framework differs from exis9ng tools and protocols.For example, lines (L) 327-332 exactly describe the formal cataloging process, public databasing, and specimen loan procedures of natural history museums, but with no reference to that community or their published SOPs/best prac9ces.I encourage the authors to expand the perspec9ve to the wealth of literature emana9ng from non-human biorepositories, see: Bakker et al. 2019, Galbreath et al. 2019, Phillips et al. 2019, Brooks et al. 2020, Colella et al. 2020, NASEM 2021, Theirs et al. 2021, Thompson et al. 2021, Adler Miserendino et al. 2022, Hoberg et al. 2022, among others. Last, it's unclear how (or if) VBS will plug into exis9ng biorepository database infrastructure (e.g., Arctos, Specify, Symbiota), established data standards (e.g., DarwinCore), recent efforts to inventory global 9ssue resources (e.g.GGBN), or if VBS intends to reinvent the wheel?
It is not the intent of our manuscript to explore universal biorepository soluCons, we have edited language in the manuscript to clearly say that ours is about access to specimens for outbreak-prone infecCous disease and ours is meant to fill in gaps and synergize with other infecCous disease specimen collecCons.
Thank you for your review and references, we appreciated the point of view about the need for more inclusiveness and collaboraCon between biodiversity/natural history and biomedical biorepositories that have both developed standards and soluCons which could be mutually beneficial.We included the reference by ColeVa et.al that you recommended (line 51) to acknowledge that similar soluCons have been considered by biodiversity/natural history biorepository collecCons.
The authors reviewed a large body of work of peer reviewed publicaCons and iniCaCves related to biomedical biorepositories and more specifically biorepositories for infecCous disease and global public health research, cited throughout the manuscript.Our review of biorespositories in the IntroducCon secCon is meant to give a background understanding of the extensive work and improvement of biorespository sciences.

Response to issues iden,fied as major:
The manuscript almost exclusively addresses commercial uses of biological materials and I wish the authors were more candid about that focus in the abstract/intro, possibly even in the 9tle.Otherwise, how will non-commercial research be accommodated?For example, framing biological materials within 'a federated system [based] on a demand-and supply model' (L476) may make sense for commercial establishments, but it posi9ons biological samples as a commodity that is then bartered and traded by governments.Such a model uninten9onally excludes non-commercial researchers and organiza9ons (e.g., universi9es), par9cularly those from LMICs, from par9cipa9on due to 'buy in' requirements.How will this model be any different?

Focus and scope:
It is not the intent of our manuscript to explore universal biorepository soluCons, we have revised the manuscript to point this out more clearly in lines 46-51 and in lines 407-414 We responded to the comment about inconsistency between reference to biorepositories by further clarifying our focus on biorepositories for specimens from infecCous diseases lines 441-445.

Commercial uses:
There is absolutely no implied intent in the manuscript to prioriCze commercial uses.
For development and validaCon of diagnosCcs and vaccines, collaboraCon between academic researchers, government and not-for profit organizaCons and commercial enCCes are required; finding out what, if any issues IVD developers have for access to high quality specimens and reference materials, as lack of access may result in tests that does not work for the intended uses.We invited commercial enCCes because the research and public health sectors, do not o\en seek IVD developers for input thus there are areas of mistrust and misunderstanding.We believe this interacCon is important to align the needs of both specimen users and providers openly.
A funcConing collaboraCve example is provided in the case of Lyme disease serodiagnosis (reference 24).
Revised the statement "on demand and supply model" to clarify that instead of the most common current paradigm of large, centralized collecCons that are costly to maintain, the federated system proposed for the VBS will make locally held specimens available for sharing when needed.We included a reference to ColeVa to show that such models have been considered for biodiversity biorepositories.
The desired outcome of the VBS is to build capacity in LMICs for biorepositories and laboratories needed for research and diagnosCcs adhering to InternaConal ethical standards and local ethical oversight of human specimens to be incorporated into the VBS governance, would eliminate the concern about misuse (bartering) of specimens.Please see also below in context of the Zika Alliance governance models.

Focus on serology:
As menConed above, the intent is to solve a specific problem, and complement other iniCaCves.There are other iniCaCves focused on pathogens menConed in the manuscript, such as the EVAg and WHOs BioHub.It is not our intent to limit to serology, but it was both an idenCfied unmet need for evaluaCon of diagnosCcs and vaccines and a pracCcal first approach to operaConalizing and tesCng the concept.

Zika Alliance governance
The design of the VBS is a departure from centralized biorepositories more typical of "biomedical" human specimen biorepositories, with centralized maintenance of specimens, oversight, and decision processes.We interviewed the exisCng ZikAlliance biorepository members with intent only to understand their governance and funcCon.We asked how their system worked and could consider the use of their model In the proposed VBS disseminated model the stewardship (or ownership) of specimens remains local in compliance with insCtuConal and naConal requirements.The governance models included in the supporCng material are meant to illustrate the local ownership regarding ethical oversight and decision process for sharing; the detailed examples in Supplements illustrate commonaliCes and differences between the three insCtuCons and countries menConed in the body of the manuscript.

Survey methods
The survey was disseminated by email and posCng on the The Global Health Network website.We don't have the informaCon or a way to answer the selecCon of "other".When "other" was selected, an opportunity for text descripCon was provided.

Issues iden,fied as Minor
Revised throughout by final grammar and spelling check in WORD SubsCtuted: "specimen associated data" for "annotated" Line 23: What kind of barriers.Revised.Barriers were idenCfied in the quesConnaire and interview results.

L32: Add Philips et al. 2019 as an example of best prac9ces, par9cularly for cryogenic 9ssue collec9ons. American Society of Mammalogist's Systema9c Collec9on Commidee is another accredi9ng ins9tu9on.
Ours is focused on human specimens, therefore it is appropriate to use ISO as an accepted comprehensive accreditaCon system for biomedical repositories and laboratories; the College of American Pathologists would be another for human specimens, based on ISBER best pracCces cited in Reference 11.L34-36: Has this been quan9fied?There are also very large natural history biorepositories (100s of thousands to millions of samples/specimens) developed for other purposes that are also available for disease research.Changed to many, instead of most; supported by references cited added Mendy et.al.as a more recent reference, this is in line 73 in the revised manuscript L62-63: All biological materials are subject to the Nagoya Protocol, not just those that contribute Â'to the development of products'.Inserted "including" but not exclusive…line 64 in the revised version of the manuscript L101: "for the "global good" has been used by commercial enterprise ra9onalize resource exploita9on of LMICs and is why the Nagoya Protocol exists.Please rephrase.Thank you for poinCng this out.We have chosen to rephrase this as a "global public good" using the InternaConal Monetary Fund definiCon to be more precise.The new phrase indicates here that the benefits ought to affect all ciCzens of the world that encompasses many aspects of our lives, including health.Changes are made then in the Ctle page, Abstract (line 2), IntroducCon (line 104), in the Conclusion (line 465) in the revised manuscript.No, all users are included.There are no "clients" here only those who are specimen users and contributors , that was our mistake and thank you for point that out, we have removed "clients" and instead used "specimen users" to include all parCes.We chose to engage with commercial enCCes only because of the nature of the VBS, which is a de-centralized approach where each local site maintains stewardship of the specimens then have and can choose selected specimens to share.O\en the view of an IVD-commercial, for profit/non-profit; academic; governmental enCCes are not sought together.We included the commercial enCCes to learn of how they approached acquiring specimens and what the challenges have been.In the end, the goal is to shorten the Cme to validaCng assays, evaluate vaccines/therapeuCcs and conduct research.During COVID-19, the partnership of all enCCes was evident.

Figure 1 does not add the main message of the manuscript -all values are reported in text.
Added as a visual summary, for emphasis; text added addiConal informaCon

SI Figure 1A-C text need to be enlarged. What do the colors mean?
The colors are to denote the different enCCes involved.The authors wish to keep them as it is for their guidance reference.

All there tables seem unnecessary Included as a summary, for clarity and emphasis
On line 48 on the Manuscript, LIMC Acronyms was used for the first 9me without wri9ng it in full.

Has been corrected
Reviewer 3: The manuscript is a qualita9ve research ar9cle developed from the analysis of products of interviews, workshops, and survey/ques9onnaires on proposed Virtual Biorepository System (VBS) framework for specimen sharing for outbreaks preparedness.Generally, the sample size ie number of individuals, ins9tu9ons, organiza9ons and countries' opinion sampled were low to support effec9vely the authors' objec9ve of establishing the VBS framework for specimen sharing.The objec9ve is noble and seriously needed to strengthen the global fight against future outbreaks, as such this work can serve as founda9on for further research on VBS, which the researchers would recruit, collect and analyze larger and more complex data from more individuals, ins9tu9ons, organiza9ons and countries to develop the VBS framework.The following were some other review comments for the authors aden9on: We thank the reviewer for supporCng our goal and concur that manuscript is an iniCal qualitaCve study, to invesCgate interest and acceptance of the concept of the proposed virtual biorepository system, to be followed by further studies to refine and operaConalize the proposed approach.
In line 48 of the manuscript.LIMC acronym was used for the first 9me without wri9ng it in full.Addressed, corrected at Line 48 and corrected throughout the manuscript using "FIND" funcCon.
On line 68-70, a categorical statement was made without any reference being cited.A reference was added by Mendy et.al, in the revised manuscript to be found on Line 73 On line 92, ASTHM acronyms was also used for the first 9me without wri9ng it out full: Was corrected at Line 94 in the revised manuscript On line 149, the methodology of the study lem out ques9ons around opinion of respondents on VBS as it affects their countries' na9onal biosecurity.The intent was to ask about "specific hurdles" they interviewees may have encountered in sourcing specimens, we did not target quesCon regarding whether sharing specimens would affect their naConal biosecurity, this is found in Line 150 in the revised manuscript.We will address naConal biosecurity issues in our follow up when we can define more clearly the role biosecurity may play in sharing specimens.
On line 152 -153, Categories of diagnos9cs industry companies were used in the paper without ci9ng any reference.Please see Reference 22. Now found in Line 141 in the revised manuscript.
On line 154, the geographical coverage of the en99es interviewed was not clear.Was their coverage global or restricted.This could skew findings/opinion and render it not representa9ve enough.Added a sentence regarding geographic locaCon and reach of companies interviewed.This can be found in Line 145 in the revised manuscript.
Understandably companies agreed to parCcipate if not idenCfied by name: of the companies menConed two have internaConal reach and internaConal subsidiaries and one of these is included in the 10 largest diagnosCcs companies; one of the small companies provides quality evaluaCon tools; and the other three companies either provide specialized test plakorms or have a limited numbers of products.Included are US, Europe and Canada based in vitro diagnosCc providers.
On line 178, Don't you think this number of respondents ( 47) is too low to power the deduc9ons from the survey, especially as they also have wide characteris9c base.We agree, it is an iniCal qualitaCve study, and we wished to have had more respondents.We launched at the Cme when COVID-19 Public Health Emergency of InternaConal Concern was invoked, we communicated right away to ask parCcipants to reply and reminded them 4 Cmes (Please see the LimitaCons secCon).The purpose was to gather informaCon: assess interest and acceptance of the VBS concept, complemenCng the informaCon obtained in workshops menConed and to inform next steps.
Throughout this paper, the authors chose to use a mix of the word Specimen and Sample in the manuscript Â-will it not be beder to s9ck to one nomenclature, unless each word carries different meaning where it was used which may be difficult to proof in this paper.Corrected: specimens is used throughout

On line 265, Market size -Can you insert reference for the classifica9on of the in vitro diagnos9cs into the different market sizes used in this manuscript
Reference 22 is widely used and cited but it only lists the largest IVD companies, we moved the word "market" to avoid confusion, simply to say they were of differing sizes in line 247 in the revised manuscript.
On line 301, correct the "European coun9es" in the manuscript to "European countries".Was Corrected, it is found in line 279 in the revised manuscript On line 320, Consor9um was cancelled -Was it not currently in place or Is it a sugges9on for future implementa9on.Corrected-deleted consorCum.
On line 332, The following statement is missing some words, as such it's not reading well -"the PI the forwards it for to the next level to the regulator".Corrected; We changed this to "Approved requests were forwarded to the regulatory agency,…."This can be found in Line 309 in the revised manuscript.