<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.2 20190208//EN" "http://jats.nlm.nih.gov/publishing/1.2/JATS-journalpublishing1.dtd"><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="other" dtd-version="1.2" xml:lang="en">
    <front>
        <journal-meta>
            <journal-id journal-id-type="pmc">F1000Research</journal-id>
            <journal-title-group>
                <journal-title>F1000Research</journal-title>
            </journal-title-group>
            <issn pub-type="epub">2046-1402</issn>
            <publisher>
                <publisher-name>F1000 Research Limited</publisher-name>
                <publisher-loc>London, UK</publisher-loc>
            </publisher>
        </journal-meta>
        <article-meta>
            <article-id pub-id-type="doi">10.12688/f1000research.171192.1</article-id>
            <article-categories>
                <subj-group subj-group-type="heading">
                    <subject>Case Study</subject>
                </subj-group>
                <subj-group>
                    <subject>Articles</subject>
                </subj-group>
            </article-categories>
            <title-group>
                <article-title>Balancing Sustainability and Specimen Protection</article-title>
                <fn-group content-type="pub-status">
                    <fn>
                        <p>[version 1; peer review: 1 approved with reservations, 1 not approved]</p>
                    </fn>
                </fn-group>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author" corresp="yes">
                    <name>
                        <surname>Olson</surname>
                        <given-names>MV</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Conceptualization</role>
                    <role content-type="http://credit.niso.org/">Investigation</role>
                    <role content-type="http://credit.niso.org/">Methodology</role>
                    <role content-type="http://credit.niso.org/">Project Administration</role>
                    <role content-type="http://credit.niso.org/">Resources</role>
                    <role content-type="http://credit.niso.org/">Supervision</role>
                    <role content-type="http://credit.niso.org/">Validation</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Original Draft Preparation</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <uri content-type="orcid">https://orcid.org/0009-0008-1836-9902</uri>
                    <xref ref-type="corresp" rid="c1">a</xref>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <aff id="a1">
                    <label>1</label>The Johns Hopkins BioBank, Genetic Resources Core Facility, Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21287, USA</aff>
            </contrib-group>
            <author-notes>
                <corresp id="c1">
                    <label>a</label>
                    <email xlink:href="mailto:mvolson@jhu.edu">mvolson@jhu.edu</email>
                </corresp>
                <fn fn-type="conflict">
                    <p>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>5</day>
                <month>11</month>
                <year>2025</year>
            </pub-date>
            <pub-date pub-type="collection">
                <year>2025</year>
            </pub-date>
            <volume>14</volume>
            <elocation-id>1214</elocation-id>
            <history>
                <date date-type="accepted">
                    <day>30</day>
                    <month>10</month>
                    <year>2025</year>
                </date>
            </history>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2025 Olson M</copyright-statement>
                <copyright-year>2025</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <self-uri content-type="pdf" xlink:href="https://f1000research.com/articles/14-1214/pdf"/>
            <abstract>
                <sec>
                    <title>Background</title>
                    <p>Biobanks are critical infrastructures for biomedical research but are energy- and cost-intensive due to reliance on ultra-low temperature (ULT) storage and redundant systems. The challenge is reducing environmental impact without compromising specimen quality or continuity. Service centers are well positioned to address this challenge, operating at scale and providing governance beyond the capacity of individual laboratories.</p>
                </sec>
                <sec>
                    <title>Methods</title>
                    <p>The Johns Hopkins Biobank, a CAP-accredited service-center repository, partnered with the School of Medicine Energy and Sustainability Committee to conduct a freezer audit across 34 departments and two campuses. Inventories were assessed for age, utilization, and efficiency, and policies were implemented to encourage migration of biospecimens into centralized storage. Strategies prioritized vapor-phase liquid nitrogen (LN
                        <sub>2</sub>) for viable collections and incorporated MVE Vari&#x014d; systems as energy-efficient alternatives for ULT needs. Governance required investigators to evaluate centralized options before acquiring new freezers, reinforced through outreach at faculty meetings and symposia.</p>
                </sec>
                <sec>
                    <title>Results</title>
                    <p>The audit identified nearly 1,300 ULT freezers, with over 70% beyond their median life expectancy of 8.5 years. Consolidation of specimens into a Biobank-managed freezer farm reduced institutional energy demand and improved monitoring. LN
                        <sub>2</sub> provided stability for viable specimens, while Vari&#x014d; units offered adjustable storage (&#x2013;20 &#x00b0;C to &#x2013;150 &#x00b0;C) with minimal electricity use and no facility cooling load. Governance helped to curb uncontrolled expansion of departmental freezers, while the Biobank functioned as an emergency response resource with at-temperature backup capacity. Adoption of centralized storage has been gradual but continues to expand.</p>
                </sec>
                <sec>
                    <title>Conclusions</title>
                    <p>This case study demonstrates how an academic service center can integrate sustainability, quality, and contingency planning. The Johns Hopkins Biobank illustrates that shared resources, supported by institutional governance, provide a practical framework to reduce environmental impact while ensuring uncompromising specimen protection.</p>
                </sec>
            </abstract>
            <kwd-group kwd-group-type="author">
                <kwd>Biobanking</kwd>
                <kwd>Service centers</kwd>
                <kwd>Cryogenic storage</kwd>
                <kwd>Vapor-phase liquid nitrogen</kwd>
                <kwd>Ultra-low temperature freezers</kwd>
                <kwd>Sustainability</kwd>
                <kwd>Specimen protection</kwd>
                <kwd>Institutional governance</kwd>
            </kwd-group>
            <funding-group>
                <funding-statement>The author(s) declared that no grants were involved in supporting this work.</funding-statement>
            </funding-group>
        </article-meta>
    </front>
    <body>
        <sec id="sec5" sec-type="intro">
            <title>Introduction</title>
            <p>Biobanks are critical infrastructures that support modern biomedical research by preserving and distributing high-quality biospecimens for discovery science, clinical translation, and precision medicine. The value of biobanking lies in its ability to safeguard irreplaceable specimens under highly controlled conditions, often over decades, ensuring they remain suitable for future research applications.
                <sup>
                    <xref ref-type="bibr" rid="ref1">1</xref>
                </sup> To achieve this, biobanks rely heavily on ultra-low temperature (ULT) freezers and liquid nitrogen (LN
                <sub>2</sub>) systems, which are among the most energy-intensive assets in academic research environments.
                <sup>
                    <xref ref-type="bibr" rid="ref2">2</xref>
                </sup>
            </p>
            <p>This creates a dual challenge. On one hand, institutions are under increasing pressure to reduce the environmental footprint of research infrastructure in alignment with broader sustainability commitments.
                <sup>
                    <xref ref-type="bibr" rid="ref3">3</xref>
                </sup> On the other, biobanks must maintain uncompromising standards of quality and continuity to protect biospecimens, meet regulatory requirements (e.g., CAP Biorepository Accreditation Program), and preserve trust with research participants.
                <sup>
                    <xref ref-type="bibr" rid="ref4">4</xref>
                </sup> Efforts to reduce energy use or rationalize equipment therefore cannot come at the expense of specimen protection or emergency readiness.</p>
            <p>Although best practice frameworks from ISBER and CAP provide high-level guidance on sustainability and continuity planning, there is limited literature describing institutional models that successfully integrate both elements.
                <sup>
                    <xref ref-type="bibr" rid="ref4">4</xref>&#x2013;
                    <xref ref-type="bibr" rid="ref6">6</xref>
                </sup> Most published reports focus on either technical advances in freezer efficiency or broad policy calls for greener laboratories, with few examples grounded in operational realities of large academic biobanks.</p>
            <p>The present case study describes the Johns Hopkins Biobank&#x2019;s approach to achieving sustainability gains while strengthening specimen protection and contingency planning. Specifically, we highlight interventions in centralized freezer management, storage modality decisions, governance policies, and community engagement. By embedding sustainability within an institutional governance framework, the Biobank demonstrates that environmental responsibility and high-quality biobanking are not competing priorities, but mutually reinforcing goals (
                <xref ref-type="fig" rid="f1">
Figure 1</xref> and see 
                <xref ref-type="table" rid="T1">
Table 1</xref> for the intervention framework).</p>
            <fig fig-type="figure" id="f1" orientation="portrait" position="float">
                <label>
Figure 1. </label>
                <caption>
                    <title>Balancing sustainability, quality, and continuity in biobanking operations.</title>
                    <p>Conceptual framework illustrating how the Johns Hopkins Biobank integrates sustainability, specimen protection, and contingency preparedness. Vapor-phase liquid nitrogen (LN
                        <sub>2</sub>) storage provides colder, more stable conditions for high-value specimens while reducing reliance on electricity-intensive ultra-low temperature (ULT) freezers. The MVE Vario freezer system offers an energy-efficient alternative when LN
                        <sub>2</sub> storage is not feasible, allowing flexible temperature set points with lower energy consumption and heat output. Together with centralized governance, continuous monitoring, and emergency preparedness, these strategies create a balanced, resilient infrastructure where sustainability and specimen protection reinforce rather than compete with one another.</p>
                </caption>
                <graphic id="gr1" orientation="portrait" position="float" xlink:href="https://f1000research-files.f1000.com/manuscripts/188763/eacbcd64-0ef1-4fce-ba6b-541f9e88dafa_figure1.gif"/>
            </fig>
            <table-wrap id="T1" orientation="portrait" position="float">
                <label>
Table 1. </label>
                <caption>
                    <title>Key interventions implemented by the Johns Hopkins Biobank to reduce environmental impact while maintaining quality and contingency planning.</title>
                </caption>
                <table content-type="article-table" frame="hsides">
                    <thead>
                        <tr>
                            <th align="left" colspan="1" rowspan="1" valign="top">Intervention</th>
                            <th align="left" colspan="1" rowspan="1" valign="top">Sustainability impact</th>
                            <th align="left" colspan="1" rowspan="1" valign="top">Quality/Specimen protection</th>
                            <th align="left" colspan="1" rowspan="1" valign="top">Continuity/Contingency benefit</th>
                        </tr>
                    </thead>
                    <tbody>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">Freezer consolidation into centralized farms</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Reduced overall energy consumption and facility cooling demand</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Improved oversight and consistent maintenance</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Integrated monitoring and backup power ensured protection</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">Prioritization of vapor-phase LNz storage</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Lower energy footprint compared to ULT freezers</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Colder storage enhances stability and longevity of specimens</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Dual redundancy via LN supply contracts</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">Adoption of MVE Vario freezers</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Energy-efficient operation with reduced heat output</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Adjustable set points optimize storage conditions by sample type</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Seamless integration with monitoring systems and reduced cooling loads</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">Retirement of inefficient legacy ULT freezers</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Significant reduction in carbon footprint</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Eliminated risk of failure from aging units</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Simplified contingency planning</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">Governance policy requiring shared-resource evaluation</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Prevents proliferation of unmanaged departmental freezers</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Ensures proper tracking, CAP oversight, and quality assurance</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Institutional alignment enhances emergency readiness</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">Centralized digital monitoring and 24/7 emergency response</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Efficient centralized infrastructure reduces redundancies</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Maintains stringent quality standards under all conditions</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Immediate intervention capability during power loss or access restrictions</td>
                        </tr>
                    </tbody>
                </table>
                <table-wrap-foot>
                    <p>Summary of institutional strategies and their outcomes. Interventions included freezer consolidation, prioritization of vapor-phase LN
                        <sub>2</sub> storage, adoption of MVE Vario freezers, governance policies requiring shared-resource evaluation before new equipment purchases, and investments in centralized monitoring and emergency response. Each intervention simultaneously advanced sustainability goals, specimen protection, and institutional resilience.</p>
                </table-wrap-foot>
            </table-wrap>
        </sec>
        <sec id="sec6">
            <title>Methods/Approach</title>
            <p>The Johns Hopkins Biobank is a College of American Pathologists (CAP)&#x2013;accredited repository that operates as part of a larger service-center to support research across the Johns Hopkins University School of Medicine and its affiliated institutions. Unlike departmental freezers, which often function in isolation, the Biobank serves as a shared institutional resource: delivering high-quality storage at scale, reducing costs, and providing 24/7 monitoring and emergency response. As a service center, the BioBank is structured to support quality, rigor, and reproducibility while minimizing duplication and institutional burden.</p>
            <p>In 2021, working with a committee on research efficiencies, the Biobank in conjunction with purchasing and institutional leadership, led an audit of freezer assets across the School of Medicine. The school includes 34 departments across two campuses (East Baltimore and Bayview) and more than 4,500 faculty. The audit identified nearly 1,300 ultra-low temperature (ULT) freezers in use, of which 938 (over 70%) were past the median life expectancy of 8.5 years. Many operated at reduced efficiency, highlighting both the scale of energy burden and the risks associated with outdated infrastructure.</p>
            <p>Based on these findings, new policies were established to incentivize high-efficiency replacements and to encourage migration of cohorts into centralized facilities such as the Johns Hopkins Biobank. Specimen deposits were managed as service requests, with annual storage charges applied to ensure cost neutrality and long-term sustainability of the service center. This centralized governance and shared-resource approach is depicted in the institutional model (
                <xref ref-type="fig" rid="f1">
Figure 1</xref>). Purpose-built facilities with optimized cooling, ventilation and centralized monitoring created efficiencies that individual laboratories could not achieve.</p>
            <p>In efforts to reduce energy requirements within the Biobank, specimen placement strategies prioritized vapor-phase liquid nitrogen (LN
                <sub>2</sub>) storage, particularly for viable and irreplaceable collections such as cell lines and frozen tissues. For collections unsuitable for traditional vapor phase LN
                <sub>2</sub> storage (&#x2013;150 &#x00b0;C to &#x2013;196 &#x00b0;C), the Biobank adopted MVE Vari&#x014d; freezers. These LN
                <sub>2</sub>-based units maintain user-defined set points from &#x2013;20 &#x00b0;C to &#x2013;150 &#x00b0;C through low energy warming mechanisms that function similar to a radiator. Further, these units operate in a dry environment with no frost or HVAC load, consume less than 1% of the electricity of mechanical ULT freezers, and reduce operating costs by ~70%. Not knowing the future needs of the Johns Hopkins community with regard to specimen storage temperatures, the Vari&#x014d; units were chosen as they can also be retrofitted into standard LN
                <sub>2</sub> freezers, making them flexible assets for long-term planning. Together, LN
                <sub>2</sub> vapor-phase and Vari&#x014d; systems positioned the Biobank to transition toward nitrogen-based storage solutions that conserved energy while maintaining redundancy. These complementary storage choices&#x2014;LN
                <sub>2</sub> vapor phase and Vari&#x014d; units&#x2014;are highlighted as the primary sustainability levers in our framework (
                <xref ref-type="fig" rid="f1">
Figure 1</xref>).</p>
            <p>The transition was structured as a passive but deliberate process. As older laboratory freezers failed, investigators were required to evaluate community-based biobanking within the Johns Hopkins Biobank before purchasing replacements. This &#x2018;shared resources before new purchases&#x2019; policy anchors the governance element of our model (
                <xref ref-type="fig" rid="f1">
Figure 1</xref>). Outreach campaigns, faculty meetings, and symposia reinforced awareness of centralized options and the advantages of shared stewardship. When centralized LN
                <sub>2</sub> or Vari&#x014d; storage was not feasible, Biobank staff engaged in direct consultation with investigators to ensure that any new freezer purchases aligned with institutional efficiency and sustainability goals.</p>
            <p>To safeguard continuity, the Biobank implemented centralized digital monitoring across all freezer units, with automated alerts and integration into institutional emergency protocols. Backup power, redundant LN
                <sub>2</sub> supply, and a trained 24/7 response team provided safeguards during power outages, weather disruptions, or supply interruptions. With at-temperature storage always available, the Biobank also functioned as an emergency response unit for the Johns Hopkins community, able to accept and stabilize specimens during departmental freezer failures.</p>
        </sec>
        <sec id="sec7" sec-type="results|discussion">
            <title>Results &amp; discussion</title>
            <p>This case study demonstrates that academic biobanks can advance sustainability efforts, operational resilience, and uncompromising specimen protection within a service-center framework (
                <xref ref-type="table" rid="T1">
Table 1</xref>). Biobanking is often perceived as energy- and cost-intensive, yet deliberate infrastructure planning and governance reduced institutional burden while improving quality and oversight.</p>
            <p>A Johns Hopkins School of Medicine audit confirmed widespread reliance on aging, inefficient ULT freezers. By working directly with departments and laboratory leads, the Biobank helped consolidate cohorts into centralized freezer farms and retire outdated units. Prioritization of LN
                <sub>2</sub> vapor-phase and Vari&#x014d; storage reduced energy demand, simplified maintenance, and enhanced monitoring. Governance policies reinforced these operational changes. Investigators were required to evaluate Biobank options before replacing failed freezers, turning each replacement decision into an opportunity to expand community-based storage. When centralized Biobanking or Vari&#x014d; systems were not feasible, Biobank staff provided tailored consultation to guide freezer selection, ensuring that any new purchases advanced institutional sustainability goals.</p>
            <p>The Johns Hopkins model aligns with ISBER Best Practices and CAP Biorepository Accreditation Standards, which emphasize monitoring, redundancy, and quality management. Consolidating freezer assets, prioritizing LN
                <sub>2</sub> vapor-phase storage, adopting efficient ULT technologies such as the MVE Vari&#x014d;, and embedding oversight into equipment purchasing translated these standards into institutional practice.</p>
            <p>As summarized in 
                <xref ref-type="fig" rid="f1">
Figure 1</xref>, the dual storage strategy was particularly impactful. LN
                <sub>2</sub> provided unmatched protection for viable and irreplaceable specimens, while the MVE Vari&#x014d; offered a cost-efficient alternative for ULT collections, reducing both electricity demand and facility cooling requirements. This complementary approach maximized sample stability while minimizing financial and operational risks.</p>
            <p>Equally important were governance and engagement. By requiring investigators to evaluate centralized options before acquiring or replacing freezers, Johns Hopkins turned each equipment failure into an opportunity to expand community-based biobanking. Where community-based storage was not possible, direct consultation ensured that institutional sustainability principles guided freezer purchases across campus. Faculty engagement through seminars and outreach further embedded shared stewardship into research culture, shifting responsibility from individual laboratories to the institution.</p>
            <p>Although this represents a single-institution experience, the principles&#x2014;auditing freezer assets, centralizing storage, prioritizing LN
                <sub>2</sub> systems, adopting efficient ULT alternatives, embedding consultation into purchasing, and investing in monitoring and contingency&#x2014;are broadly adaptable. Academic centers facing similar pressures to improve efficiency and accountability can adopt variations of this model to strengthen both financial stability and biospecimen quality.</p>
        </sec>
        <sec id="sec8" sec-type="conclusion">
            <title>Conclusion</title>
            <p>The Johns Hopkins Biobank illustrates how sustainable practices and specimen protection can be advanced simultaneously through a service-center model. Consolidation of freezer assets, prioritization of LN
                <sub>2</sub> vapor-phase storage, adoption of MVE Vari&#x014d; systems, and governance embedded into equipment replacement reduced costs, strengthened oversight, and enhanced compliance. Centralized monitoring, redundant infrastructure, and 24/7 emergency response ensured continuity of operations, while faculty outreach fostered a culture of shared stewardship. Importantly, requiring investigators to consider community-based biobanking before replacing failed freezers transformed equipment failures into opportunities for institutional strengthening.</p>
            <p>This case provides a practical framework for other academic biobanks seeking to balance financial stability with uncompromising quality and continuity, demonstrating that efficiency and rigor can be achieved together.</p>
        </sec>
        <sec id="sec9">
            <title>Ethics statement</title>
            <p>This work did not involve direct recruitment of human participants or the generation of new human subject data. All biospecimens referenced are managed within the Johns Hopkins Biobank under existing institutional review board approvals. The case study focuses solely on institutional infrastructure and operational practices, with no use of identifiable participant information.</p>
        </sec>
    </body>
    <back>
        <sec id="sec12" sec-type="data-availability">
            <title>Data availability</title>
            <p>The analyses presented in this case study are based on internal freezer inventory records, purchasing data, and institutional operational reports from the Johns Hopkins School of Medicine. These records are considered administrative, commercially sensitive, and contain protected infrastructure information; therefore, they cannot be openly shared. The Johns Hopkins institutional compliance offices advised that operational and infrastructure datasets should remain restricted due to security and confidentiality considerations.</p>
            <p>Researchers who require access to these data for validation or collaborative purposes may apply through the Johns Hopkins Biobank administration. Requests will be reviewed on a case-by-case basis to ensure alignment with institutional policies on data security, confidentiality, and appropriate use. Interested parties may contact the Johns Hopkins Biobank (
                <email xlink:href="mailto:biobank@jhmi.edu">biobank@jhmi.edu</email>) for further information regarding application procedures and access conditions.</p>
        </sec>
        <ack>
            <title>Acknowledgments</title>
            <p>The author gratefully acknowledges the Johns Hopkins Genetic Resources Core Facility (GRCF) and the Johns Hopkins Biobank teams, particularly 
                <bold>Patrick Catterson</bold>, for their sustained commitment to high-quality biospecimen stewardship, centralized monitoring, and emergency response. The author also thanks the Johns Hopkins School of Medicine Energy and Sustainability Committee and particularly, 
                <bold>Shawn Franckowiak</bold> for his guidance on School of Medicine reports and his contributions to the institution-wide freezer audit.</p>
        </ack>
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                    <article-title>The 2018 Revision of the ISBER Best Practices: Summary of Changes and the Editorial Team&#x2019;s Development Process.</article-title>
                    <source>

                        <italic toggle="yes">Biopreserv. Biobank.</italic>
</source>
                    <year>2018</year>;<volume>16</volume>:<fpage>3</fpage>&#x2013;<lpage>6</lpage>.
                    <pub-id pub-id-type="pmid">29393664</pub-id>
                    <pub-id pub-id-type="doi">10.1089/bio.2018.0001</pub-id>
                    <pub-id pub-id-type="pmcid">PMC5846567</pub-id>
                </mixed-citation>
            </ref>
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                <mixed-citation publication-type="journal">
                    <person-group person-group-type="author">

                        <name name-style="western">
                            <surname>Snapes</surname>
                            <given-names>E</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Astrin</surname>
                            <given-names>JJ</given-names>
                        </name>

                        <name name-style="western">
                            <surname>Bertheussen Kr&#x00fc;ger</surname>
                            <given-names>N</given-names>
                        </name>

                        <etal/>
</person-group>:
                    <article-title>Updating International Society for Biological and Environmental Repositories Best Practices, Fifth Edition: A New Process for Relevance in an Evolving Landscape.</article-title>
                    <source>

                        <italic toggle="yes">Biopreserv. Biobank.</italic>
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                    <year>2023</year>;<volume>21</volume>:<fpage>537</fpage>&#x2013;<lpage>546</lpage>.
                    <pub-id pub-id-type="pmid">38149936</pub-id>
                    <pub-id pub-id-type="doi">10.1089/bio.2023.0140</pub-id>
                </mixed-citation>
            </ref>
            <ref id="ref6">
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                <mixed-citation publication-type="other">
                    <collab>College of American Pathologist</collab>:
                    <article-title>Biorepository Accreditation Program.</article-title>
                    <ext-link ext-link-type="uri" xlink:href="https://www.cap.org/laboratory-improvement/accreditation/biorepository-accreditation-program">Reference Source</ext-link>
                </mixed-citation>
            </ref>
        </ref-list>
    </back>
    <sub-article article-type="reviewer-report" id="report435173">
        <front-stub>
            <article-id pub-id-type="doi">10.5256/f1000research.188763.r435173</article-id>
            <title-group>
                <article-title>Reviewer response for version 1</article-title>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author">
                    <name>
                        <surname>Braun</surname>
                        <given-names>Veit</given-names>
                    </name>
                    <xref ref-type="aff" rid="r435173a1">1</xref>
                    <role>Referee</role>
                </contrib>
                <aff id="r435173a1">
                    <label>1</label>Institute for Social Sciences, Universitat Augsburg Philosophisch-Sozialwissenschaftliche Fakultat (Ringgold ID: 235824) Place: Augsburg, Augsburg, Bavaria, Germany</aff>
            </contrib-group>
            <author-notes>
                <fn fn-type="conflict">
                    <p>
                        <bold>Competing interests: </bold>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>30</day>
                <month>12</month>
                <year>2025</year>
            </pub-date>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2025 Braun V</copyright-statement>
                <copyright-year>2025</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <related-article ext-link-type="doi" id="relatedArticleReport435173" related-article-type="peer-reviewed-article" xlink:href="10.12688/f1000research.171192.1"/>
            <custom-meta-group>
                <custom-meta>
                    <meta-name>recommendation</meta-name>
                    <meta-value>reject</meta-value>
                </custom-meta>
            </custom-meta-group>
        </front-stub>
        <body>
            <p>This article offers an interesting case study of monitoring a centralized biobank by a service center of one of the United States' leading medical research institutions (Johns Hopkins University Medical School).</p>
            <p> </p>
            <p> The text gives some basic results of a survey among 34 departments, which together ran about 1,300 ultra-low temperature freezers, over 900 of which had exceeded their median life expectancy and were subsequently phased out. Where possible, these freezers were replaced by more cost- and energy-efficient liquid nitrogen freezers and LN-based Vario freezers. The author claims that considerable cost savings, energy intensity reductions as well as preservation and planning improvements (contingency and continuity) were achieved in the process.</p>
            <p> </p>
            <p> Unfortunately no case-specific data are provided beyond the basic figures of 34 departments, 1,300 ULT freezers and 938 units beyond their median life expectancy. While the basic argument - an audit process leading to organisational improvements - is highly plausible, it is thus difficult to evaluate.</p>
            <p> </p>
            <p> Out of the three key areas of sustainability, sample quality and continuity/contingency, which benefitted most from the audit? What was the survey's response rate - were there institutions/facilities which it was difficult to obtain data on (and if so, why)? Where were improvements most difficult to achive because centralized and decentralized storage facilities were already close to an optimum? What is the approximate ballpark of savings and improvements, especially when put in relation to Johns Hopkins's overall biobanking facilities? What sample types/uses required Vario freezers or decentralized storage as a bespoke solution, and what percentage of the replaced units/relocated samples did the latter account for? How did the transitioning process look like in practice: concerted bulk transfer of samples into new units or unit-by-unit transfer? What does the protocol for picking up samples at one of the departments and transfering them to Johns Hopkins Biobank look like? Were potential downsides to centralized storage identified over the process?</p>
            <p> </p>
            <p> I believe these are questions the article should answer if it is supposed to inform the reader about the potentials of centralized audits and storage services. The author points out that most of the underlying data is sensitive and thus cannot be made public. I agree that this applies to items such as budget, location, internal decision-making, personal data and some of the risks identified during the audit.</p>
            <p> </p>
            <p> A number of items could be shared as data or information in the text at least in very general form. In my view, these include:</p>
            <p> </p>
            <p> - Overall number of samples and units in Johns Hopkins Biobank and the share of decentralized samples and units that remain after the audit. This does not identify sample types, locations or persons but allows the reader to infer organizational impact of the process described.</p>
            <p> - Sample types that require bespoke or decentralized solutions. No exhaustive list and no very fine-grained details need to be given - "cell lines" (as example) or "samples for daily/weekly use" (as a descriptor) would suffice for readers to assess whether a similar process would work for their own biobank(s).</p>
            <p> - A very rough estimate (as a share of total energy consumed over a certain span of time) of energy savings achieved by the audit</p>
            <p> - The overall number of staff/person hours involved in the process. This will allow readers to weigh costs of the audit against potential savings in their own facilities.</p>
            <p> - A very general list of risks occuring at the various stages of the process (e.g. sample quality, data migration, relocation too few or too many samples, drawbacks of centralized storage and reduced redundancies that require additional precautionary measures) should be given to prepare readers for the contingencies along the way. No specific examples that were involved in the study need to be given here but a list of eventualities would be very useful.</p>
            <p> </p>
            <p> I would argue that these data can be made publicly available without a case-by-case negotiation with Johns Hopkins Biobank, which adds a rather steep hurdle (delayed response, bargaining, refusal, transfer and use agreements) for those seeking to replicate the success of the audit (and Johns Hopkins Biobank, too), not least in person hours.</p>
            <p> </p>
            <p> Furthermore, the article should address one very central point: Owing to technological progress, one would assume improvements in at least one of the targeted key areas mentiones by the author while the other two remain at their previous performance levels or are improved as well. A critical reader could thus object that any unit replaced by an improved model would fulfil the goals outlined in Fig. 1. What additional benefits does the centralized auditing process provide over the mere replacement of old, inefficient technology?</p>
            <p> </p>
            <p> In my view, it is that such a centrally planned process allows for pooling resources and thus complying with individual and overall budget and other resource constraints. Costs would otherwise both exceed departments' budgets (new units are too expensive) and redundancies would increase overall (new units are under-utilized when decentrally installed; freezer space will not be fully used). New technology positively addresses all three goals but improvements need to be weighed against expenses and an optimal tradeoff should be identified over the course of the internal planning process. If this is indeed the reasoning behind the audit, the article should state it more clearly early on.</p>
            <p> </p>
            <p> In this case, it should also explain under what criteria, very generally speaking, the biobank deviated from the goal of cost and energy savings. As a medical institution, I would expect that Johns Hopkins prioritizes sample quality and continuity if in doubt, ie, centralized storage was deprioritized in those cases where sample quality and continuity were more likely to be achieved with decentralized and bespoke solutions (if at higher costs). Should that be the case, the author should briefly lay out the general reasoning and prioritization in balancing the goals of the biobank.</p>
            <p> </p>
            <p> If the author is able to address these issues and questions to a substantial degree I am convinced the report will make for a useful template for other biobanks.</p>
            <p>Is the case presented with sufficient detail to be useful for teaching or other practitioners?</p>
            <p>No</p>
            <p>Is the work clearly and accurately presented and does it cite the current literature?</p>
            <p>Partly</p>
            <p>If applicable, is the statistical analysis and its interpretation appropriate?</p>
            <p>Not applicable</p>
            <p>Are all the source data underlying the results available to ensure full reproducibility?</p>
            <p>No</p>
            <p>Are the conclusions drawn adequately supported by the results?</p>
            <p>Partly</p>
            <p>Is the background of the case&#x2019;s history and progression described in sufficient detail?</p>
            <p>Partly</p>
            <p>Reviewer Expertise:</p>
            <p>Organization studies, sociology of science and technology, environmental studies</p>
            <p>I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above.</p>
        </body>
        <sub-article article-type="response" id="comment15150-435173">
            <front-stub>
                <contrib-group>
                    <contrib contrib-type="author">
                        <name>
                            <surname>Olson</surname>
                            <given-names>Melissa</given-names>
                        </name>
                        <aff>Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA</aff>
                    </contrib>
                </contrib-group>
                <author-notes>
                    <fn fn-type="conflict">
                        <p>
                            <bold>Competing interests: </bold>No competing interests were disclosed.</p>
                    </fn>
                </author-notes>
                <pub-date pub-type="epub">
                    <day>30</day>
                    <month>12</month>
                    <year>2025</year>
                </pub-date>
            </front-stub>
            <body>
                <p>
                    <bold>Response to Reviewer (Dr. Veit Braun)</bold>
                </p>
                <p> I am grateful for the reviewer&#x2019;s careful reading of the manuscript and for the constructive, detailed suggestions. Below, I address each of the major points and indicate the corresponding revisions made to the manuscript.</p>
                <p> </p>
                <p> 
                    <bold>
                        <underline>Direct Responses: </underline>
                    </bold>
                </p>
                <p> 
                    <bold>1. &#x201c;No case-specific data&#x2026; difficult to evaluate. Which of the three areas benefited most?&#x201d;</bold>
                </p>
                <p> 
                    <bold>Reviewer comment (paraphrased)</bold>
                </p>
                <p> The manuscript does not provide sufficient case-specific data beyond 34 departments, ~1,300 ULTs, and 938 units beyond median life expectancy. It is difficult to evaluate the impact. Out of the three key areas&#x2014;sustainability, sample quality, and continuity/contingency&#x2014;which benefitted most?</p>
                <p> 
                    <bold>Response</bold>
                </p>
                <p> I appreciate this concern and have revised the manuscript to provide more specific, yet still appropriately aggregated, institutional data. 
                    <list list-type="bullet">
                        <list-item>
                            <p>In the&#x00a0;Results &amp; discussion&#x00a0;section, I now explicitly state which dimension showed the earliest, most measurable gains: &#x201c;Of the three primary objectives, sustainability benefits manifested earliest, while gains in sample protection and continuity expanded progressively as centralized infrastructure and monitoring matured.&#x201d;</p>
                        </list-item>
                    </list> 
                    <list list-type="bullet">
                        <list-item>
                            <p>I have added quantitative estimates of the additional energy burden associated with aging freezers and the scale of centralized capacity that has been stabilized within the Biobank: &#x201c;Energy analyses performed during the audit demonstrated the substantial environmental burden of aging ULT freezers. Units older than 10 years showed 30&#x2013;75% higher energy consumption, and those exceeding 20 years used over 100% more electricity than newer systems. Within the School of Medicine, more than 330 freezers fall within these age categories, representing significant avoidable demand on HVAC and electrical infrastructure.&#x201d;- and- &#x201c;Within the School of Medicine, these aging freezers consume an estimated additional $800K annually in avoidable electricity and HVAC load, based on industry-validated energy modeling (including manufacturer performance curves and published ULT power consumption data).&#x201d;- and- &#x201c;Since 2021, centralized storage within the Biobank has stabilized the equivalent capacity of approximately 42 ultra-low temperature freezers, eliminating the need for laboratories to maintain or replace those units and reducing institutional exposure to aging, high-risk infrastructure.&#x201d;</p>
                        </list-item>
                    </list> Together, these additions clarify both the relative contribution of the sustainability dimension and the scale of change achieved, while maintaining institutional confidentiality.</p>
                <p> </p>
                <p> 
                    <bold>2. &#x201c;Overall number of samples/units and share remaining decentralized; sample types requiring bespoke or decentralized solutions&#x201d;</bold>
                </p>
                <p> 
                    <bold>Reviewer comment (paraphrased)</bold>
                </p>
                <p> The reviewer requests the overall number of samples and units in the Biobank and the share that remain decentralized, as well as more detail on which sample types require bespoke or decentralized storage (e.g. daily-use materials, cell lines, etc.).</p>
                <p> 
                    <bold>Response</bold>
                </p>
                <p> I agree that readers need a clearer understanding of which collections are appropriate for centralization versus decentralization. For security and confidentiality reasons, I do not disclose absolute institutional sample counts, but I have strengthened the description of proportional impact and sample categories. 
                    <list list-type="bullet">
                        <list-item>
                            <p>In&#x00a0;Governance and Data Handling, I now clarify where the greatest burden lies and which broad classes of material are targeted for centralization: &#x201c;Importantly, the freezer audit revealed that research laboratories, not clinical units, accounted for nearly 80% of ULT assets, and the majority of aging, inefficient units. Historically, researchers have equated access with physical proximity, leading to highly decentralized storage. The new governance model encourages a gradual culture shift where centralized storage is prioritized for (1) low-access, long-term collections, (2) hazardous or chain-of-custody-regulated materials, and (3) irreplaceable or viability-dependent assets. Conversely, daily-use research stocks and short-turnaround clinical materials remain appropriately near the research or clinical workflow.&#x201d;</p>
                        </list-item>
                    </list> 
                    <list list-type="bullet">
                        <list-item>
                            <p>In the&#x00a0;Results &amp; discussion, I further explain that centralization is not a one-to-one mapping of all existing units but an opportunity to right-size inventories: &#x201c;The Biobank functions as a living system, inventory increases as new studies launch and decreases as legacy materials are dispositioned, ensuring storage capacity remains aligned with current scientific demand rather than historical accumulation. Importantly, the cost-recovery model requires investigators to review their holdings before migration, often reducing storage volume by removing obsolete or unused specimens. This cultural shift, shifting from ownership of freezers to stewardship of only what is scientifically necessary, is a central component of the sustainability and governance strategy.&#x201d;</p>
                        </list-item>
                    </list> These revisions clarify both the relative contribution of research versus clinical storage and the types of samples that are preferentially centralized, without exposing detailed inventory figures that are considered sensitive institutional data.</p>
                <p> </p>
                <p> 
                    <bold>3. &#x201c;Approximate energy savings; added value of centralized audit vs simple technology replacement&#x201d;</bold>
                </p>
                <p> 
                    <bold>Reviewer comment (paraphrased)</bold>
                </p>
                <p> What is the approximate ballpark of energy savings? Also, what additional benefits does centralized auditing and governance provide beyond simply replacing old ULTs with more efficient models?</p>
                <p> 
                    <bold>Response</bold>
                </p>
                <p> I fully agree that readers must understand both the magnitude of the problem and why a governance-based approach is superior to simple equipment replacement. 
                    <list list-type="bullet">
                        <list-item>
                            <p>To address the energy/financial aspect, the&#x00a0;Results &amp; discussion&#x00a0;now includes: &#x201c;Within the School of Medicine, these aging freezers consume an estimated additional $800K annually in avoidable electricity and HVAC load, based on industry-validated energy modeling (including manufacturer performance curves and published ULT power consumption data).&#x201d;</p>
                        </list-item>
                    </list> This provides a concrete, institution-level estimate of avoidable cost and energy burden. 
                    <list list-type="bullet">
                        <list-item>
                            <p>To make the added value of centralized governance explicit early in the manuscript, I added to the&#x00a0;Introduction: &#x201c;Unlike simple replacement of outdated equipment, this model couples infrastructure upgrades with institutional governance, yielding sustainability, quality, and contingency gains not achievable through technology refresh alone.&#x201d;</p>
                        </list-item>
                    </list> 
                    <list list-type="bullet">
                        <list-item>
                            <p>Throughout the&#x00a0;Results &amp; discussion, I emphasize that the central audit and governance framework: 
                                <list list-type="bullet">
                                    <list-item>
                                        <p>prevents proliferation of unmanaged departmental freezers,</p>
                                    </list-item>
                                    <list-item>
                                        <p>ties replacement decisions to shared-resource evaluation,</p>
                                    </list-item>
                                    <list-item>
                                        <p>enforces monitoring, redundancy and continuity planning,</p>
                                    </list-item>
                                    <list-item>
                                        <p>and drives inventory cleanup and right-sizing (rather than simply upgrading the same number of under-utilized units).</p>
                                    </list-item>
                                </list> </p>
                        </list-item>
                    </list> In this way, I have made the conceptual distinction between &#x201c;better technology&#x201d; and &#x201c;better governance plus technology&#x201d; much clearer.</p>
                <p> </p>
                <p> 
                    <bold>4. &#x201c;Which areas benefited most, where were improvements difficult, and how was the transition operationalized?&#x201d;</bold>
                </p>
                <p> 
                    <bold>Reviewer comment (paraphrased)</bold>
                </p>
                <p> Which of sustainability, sample quality, and continuity benefitted most? Where were improvements hardest because centralized and decentralized storage were already near an optimum? What did the transitioning process look like in practice&#x2014;bulk vs unit-by-unit transfers, and what is the protocol for picking up samples?</p>
                <p> 
                    <bold>Response</bold>
                </p>
                <p> I have clarified both the differential timing of benefits and the practical nature of the transition: 
                    <list list-type="bullet">
                        <list-item>
                            <p>As noted under Point 1, I now state explicitly: &#x201c;Of the three primary objectives, sustainability benefits manifested earliest, while gains in sample protection and continuity expanded progressively as centralized infrastructure and monitoring matured.&#x201d;</p>
                        </list-item>
                    </list> 
                    <list list-type="bullet">
                        <list-item>
                            <p>Regarding where improvements are most difficult, the&#x00a0;Governance and Data Handling&#x00a0;section makes explicit that high-frequency, short-turnaround materials remain decentralized by design: &#x201c;&#x2026;centralized storage is prioritized for (1) low-access, long-term collections, (2) hazardous or chain-of-custody-regulated materials, and (3) irreplaceable or viability-dependent assets. Conversely, daily-use research stocks and short-turnaround clinical materials remain appropriately near the research or clinical workflow.&#x201d;</p>
                        </list-item>
                    </list> This clarifies that for heavily used, workflow-critical materials, the system is already close to an operational optimum and centralization is not pursued. 
                    <list list-type="bullet">
                        <list-item>
                            <p>The gradual, failure-aligned transition process is now emphasized in&#x00a0;Methods/Approach&#x00a0;and&#x00a0;Results &amp; discussion: &#x201c;Because this initiative was intentionally aligned with natural equipment life cycles, investigators are required to evaluate community-based biobanking within the Johns Hopkins Biobank before purchasing replacements when older laboratory freezers failed.&#x201d;- and- &#x201c;Adoption of centralized storage is inherently a gradual process, tied to equipment failure cycles, research timelines, voluntary participation and cultural adaptation. Most ULT freezers in academic settings are only replaced at end-of-life, and failure events are unpredictable. Accordingly, achieving full transition across eligible collections is expected to occur over multiple years rather than rapid turnover, with each unit failure representing an opportunity to migrate to sustainable, governed storage.&#x201d;</p>
                        </list-item>
                    </list> 
                    <list list-type="bullet">
                        <list-item>
                            <p>Transfers are predominantly done at the level of defined cohorts, coordinated with investigators and Biobank staff, rather than a one-time bulk move of the entire institution. While a highly detailed step-wise protocol would be institution-specific and beyond the scope of this case study, I now describe the high-level approach as a&#x00a0;phased, cohort-level migration&#x00a0;tied to failure events and investigator readiness, supported by the Biobank&#x2019;s 24/7 emergency response capacity.</p>
                        </list-item>
                    </list> </p>
                <p> 
                    <bold>5. &#x201c;Sample types needing Vario or decentralized storage; percentage of replaced units/samples&#x201d;</bold>
                </p>
                <p> 
                    <bold>Reviewer comment (paraphrased)</bold>
                </p>
                <p> What sample types or uses required Vario freezers or decentralized storage, and approximately what percentage of replaced units or relocated samples did these represent?</p>
                <p> 
                    <bold>Response</bold>
                </p>
                <p> I have clarified the sample-type rationale, but I have not provided exact percentages, as those data are sensitive and not easily de-identified without risk of revealing institutional structure. 
                    <list list-type="bullet">
                        <list-item>
                            <p>In&#x00a0;Governance and Data Handling, as quoted above, I now specify three categories of material prioritized for centralization and note explicitly that &#x201c;daily-use research stocks and short-turnaround clinical materials&#x201d; remain near the research or clinical workflow.</p>
                        </list-item>
                        <list-item>
                            <p>In the&#x00a0;Methods/Approach, I also emphasize the functional differentiation between LN&#x2082; and Vari&#x014d; units: &#x201c;In efforts to reduce energy requirements within the Biobank, specimen placement strategies prioritized vapor-phase liquid nitrogen (LN2) storage, particularly for viable and irreplaceable collections such as cell lines and frozen tissues. For collections unsuitable for traditional vapor phase LN2 storage (&#x2013;150 &#x00b0;C to &#x2013;196 &#x00b0;C), the Biobank adopted MVE Vari&#x014d; freezers&#x2026; These complementary storage choices&#x2014;LN2 vapor phase and Vari&#x014d; units&#x2014;are highlighted as the primary sustainability levers in our framework (Figure 1).&#x201d;</p>
                        </list-item>
                    </list> Thus, while I cannot provide precise percentages of relocated sample types, readers now have a clear rationale for which materials are best suited to LN&#x2082;, to Vari&#x014d; systems, and to remaining decentralized.</p>
                <p> </p>
                <p> 
                    <bold>6. &#x201c;Staff/person-hours and costs of the audit; ability to generalize&#x201d;</bold>
                </p>
                <p> 
                    <bold>Reviewer comment (paraphrased)</bold>
                </p>
                <p> The reviewer asks for the overall number of staff/person-hours involved to allow readers to weigh costs of the audit against potential savings.</p>
                <p> 
                    <bold>Response</bold>
                </p>
                <p> I agree that staff effort is an important consideration. However, detailed time tracking was not performed at the level required for a robust quantitative estimate. The audit and implementation were performed by existing Biobank and institutional sustainability staff as part of their ongoing responsibilities, rather than as a separately budgeted project with dedicated FTE lines. Rather than provide a speculative numeric estimate, I have chosen to describe the work qualitatively as an institutional initiative executed within existing organizational structures.</p>
                <p> If the editor feels that even a qualitative statement about staffing would be helpful, I would be glad to add a sentence such as: &#x201c;The audit and subsequent policy implementation were conducted by existing Biobank and institutional sustainability staff within their routine roles, without creation of dedicated full-time positions.&#x201d;</p>
                <p> I hope this approach balances transparency about resource requirements with the limitations of available data.</p>
                <p> </p>
                <p> 
                    <bold>7. &#x201c;Risks and downsides to centralized storage; list of contingencies&#x201d;</bold>
                </p>
                <p> 
                    <bold>Reviewer comment (paraphrased)</bold>
                </p>
                <p> A general list of risks at various stages (sample quality, data migration, over- or under-relocation, drawbacks of centralized storage) would be useful, along with any potential downsides identified.</p>
                <p> 
                    <bold>Response</bold>
                </p>
                <p> I appreciate this suggestion and have added explicit discussion of risks and mitigation strategies in the&#x00a0;Results &amp; discussion: &#x201c;Transition risks included temporary access delays during migration, variation in laboratory readiness for inventory cleanup, and the need for stakeholder adaptation to new workflows. These were mitigated through phased adoption, parallel storage validation, and contingency support from the Biobank&#x2019;s at-temperature backup network. No specimen losses or research disruptions occurred during the transition period.&#x201d;</p>
                <p> In addition, the&#x00a0;Data availability&#x00a0;and&#x00a0;Governance and Data Handling&#x00a0;sections together emphasize that: 
                    <list list-type="bullet">
                        <list-item>
                            <p>only minimal metadata are imported into the Biobank LIMS,</p>
                        </list-item>
                        <list-item>
                            <p>clinical and research data remain under existing governance structures,</p>
                        </list-item>
                        <list-item>
                            <p>and centralized monitoring, redundancy, and 24/7 emergency response are designed to reduce, rather than increase, continuity risk.</p>
                        </list-item>
                    </list> I believe this now provides the general &#x201c;risk and contingency&#x201d; template requested, while keeping institution-specific details appropriately high-level.</p>
                <p> </p>
                <p> </p>
                <p> 
                    <bold>8. &#x201c;Central question: why centralized auditing instead of simple replacement?&#x201d;</bold>
                </p>
                <p> 
                    <bold>Reviewer comment (paraphrased)</bold>
                </p>
                <p> A critical reader might argue that simply replacing old units with improved technology would achieve the goals. The article should more clearly state what central auditing and governance add, how trade-offs are managed, and under what criteria the Biobank deviates from cost/energy savings to prioritize quality and continuity.</p>
                <p> 
                    <bold>Response</bold>
                </p>
                <p> I agree that this is a central conceptual point, and I have strengthened it in several places: 
                    <list list-type="bullet">
                        <list-item>
                            <p>In the&#x00a0;Introduction, as noted earlier, I now explicitly contrast governance-coupled changes with simple replacement: &#x201c;Unlike simple replacement of outdated equipment, this model couples infrastructure upgrades with institutional governance, yielding sustainability, quality, and contingency gains not achievable through technology refresh alone.&#x201d;</p>
                        </list-item>
                    </list> 
                    <list list-type="bullet">
                        <list-item>
                            <p>In&#x00a0;Governance and Data Handling&#x00a0;and&#x00a0;Results &amp; discussion, I clarify the prioritization logic the reviewer requests: 
                                <list list-type="bullet">
                                    <list-item>
                                        <p>Centralization is&#x00a0;prioritized&#x00a0;for long-term, hazardous, and irreplaceable materials where specimen quality and continuity are paramount.</p>
                                    </list-item>
                                    <list-item>
                                        <p>High-frequency, short-turnaround materials remain decentralized even if this is less efficient energetically, because workflow and clinical requirements are prioritized.</p>
                                    </list-item>
                                    <list-item>
                                        <p>Replacement decisions are made within a governance framework that balances sustainability with scientific and clinical needs.</p>
                                    </list-item>
                                </list> </p>
                        </list-item>
                        <list-item>
                            <p>In the&#x00a0;Conclusion, I explicitly re-cast the sustainability effort as simultaneously a quality initiative: &#x201c;This case provides a practical framework for other academic biobanks seeking to balance financial stability with uncompromising quality and continuity, demonstrating that efficiency and rigor can be achieved together. Ultimately, this model demonstrates that sustainability initiatives can also serve as quality initiatives, improving research rigor and resiliency while reducing institutional risk.&#x201d;</p>
                        </list-item>
                    </list> I hope these revisions make it clear that the project is not simply about newer equipment, but about a governance and cultural model that aligns infrastructure decisions with institutional stewardship of both environmental and scientific quality.</p>
                <p> </p>
                <p> 
                    <bold>9. &#x201c;Data access and burden of case-by-case negotiation&#x201d;</bold>
                </p>
                <p> 
                    <bold>Reviewer comment (paraphrased)</bold>
                </p>
                <p> The reviewer notes concern that requiring case-by-case data access negotiations may be a barrier for others seeking to replicate the approach.</p>
                <p> 
                    <bold>Response</bold>
                </p>
                <p> I appreciate this point and have revised the&#x00a0;Data availability&#x00a0;section to clarify the rationale and to explain that the quantitative estimates in the manuscript are based on aggregate operational assessments intended to be reusable by others: &#x201c;The Johns Hopkins institutional compliance offices advised that operational and infrastructure datasets should remain restricted due to security and confidentiality considerations. Quantitative estimates provided in this report are based on aggregate operational assessments intended to convey institutional impact without exposing sensitive infrastructure details.&#x201d;</p>
                <p> </p>
                <p> I fully agree that replication should be as straightforward as possible. For that reason, the manuscript now emphasizes the&#x00a0;framework&#x00a0;(audit &#x2192; governance &#x2192; storage strategy &#x2192; monitoring &amp; contingency) and provides transferable categories (freezer age bands, percent of assets in aging categories, rough energy cost differential, and freezer-equivalent centralized capacity) that other institutions can estimate from their own data without needing access to Johns Hopkins&#x2013;specific records.</p>
                <p> </p>
                <p> </p>
                <p> Once again, I thank the reviewer for the detailed and thoughtful critique. The revisions described above substantially expand the manuscript&#x2019;s quantitative grounding, clarify the relative impact across sustainability, quality, and continuity, and more clearly articulate why a governance-driven, centralized approach offers benefits beyond simple equipment replacement. I hope the revised version now meets the reviewer&#x2019;s expectations for a useful and generalizable case study template.</p>
            </body>
        </sub-article>
    </sub-article>
    <sub-article article-type="reviewer-report" id="report435167">
        <front-stub>
            <article-id pub-id-type="doi">10.5256/f1000research.188763.r435167</article-id>
            <title-group>
                <article-title>Reviewer response for version 1</article-title>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author">
                    <name>
                        <surname>Rush</surname>
                        <given-names>Amanda</given-names>
                    </name>
                    <xref ref-type="aff" rid="r435167a1">1</xref>
                    <role>Referee</role>
                </contrib>
                <aff id="r435167a1">
                    <label>1</label>The University of Sydney, Sydney, New South Wales, Australia</aff>
            </contrib-group>
            <author-notes>
                <fn fn-type="conflict">
                    <p>
                        <bold>Competing interests: </bold>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>24</day>
                <month>12</month>
                <year>2025</year>
            </pub-date>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2025 Rush A</copyright-statement>
                <copyright-year>2025</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <related-article ext-link-type="doi" id="relatedArticleReport435167" related-article-type="peer-reviewed-article" xlink:href="10.12688/f1000research.171192.1"/>
            <custom-meta-group>
                <custom-meta>
                    <meta-name>recommendation</meta-name>
                    <meta-value>approve-with-reservations</meta-value>
                </custom-meta>
            </custom-meta-group>
        </front-stub>
        <body>
            <p>This manuscript describes a case study of freezer consolidation, with a view to improving both environmental and financial sustainability within a large institution.</p>
            <p> </p>
            <p> Major comments: 
                <list list-type="bullet">
                    <list-item>
                        <p>It would be useful for the reader to have more detail on any changes in governance that were associated with shifting samples to the service centre. Did the migration of samples to the service centre have any other consequences for individual investigators to consider e.g. a minimum dataset, mandates for samples to be open access &#x2013; or did all aspects of sample management and oversight remain the same for individuals, except for the storage location?</p>
                    </list-item>
                    <list-item>
                        <p>It would also be interesting to learn more about any associated data migration, both in terms of LIMS, as well as other data associated with the samples. Did the latter (e.g. clinical data) remain with the investigators?</p>
                    </list-item>
                    <list-item>
                        <p>The scale of the shift is unclear at this stage. While the manuscript states that 938 freezers were past their median life expectancy, it is unknown approximately what proportion of these failed from 2021 onwards. This has impacts on costs for the service centre. Was additional LN2 storage required to be purchased? Was the cost of the Varios incorporated into storage fees for investigators?</p>
                    </list-item>
                    <list-item>
                        <p>The audit and consultation with stakeholders could have more detail added, in order for others to be able to adopt the approach. For example, it would be useful to know the proportion that migrated their collections vs met with the team to seek guidance on new freezers to purchase. What were the stakeholder responses when faced with shifting from -80C to LN2 storage? What information was sought from them?</p>
                    </list-item>
                    <list-item>
                        <p>There is a time component to this work that is not acknowledged for others wishing to adopt the general approach &#x2013; as freezers don&#x2019;t fail regularly. Over approximately what time period would it be expected to reach a state where all freezers that were going to be migrated, have been migrated?</p>
                    </list-item>
                    <list-item>
                        <p>It would be useful to have some evidence on approximate cost savings and energy savings that were brought about from the changes, in order to back up the claims made in the manuscript.</p>
                    </list-item>
                    <list-item>
                        <p>At various stages in the manuscript, the reader is led to believe that sustainability refers to environmental sustainability and financial sustainability. It would be useful to explicitly detail if both of these meanings are intended by the title.</p>
                    </list-item>
                </list> Minor comments: 
                <list list-type="bullet">
                    <list-item>
                        <p>It would be useful to include a reference (if applicable) on the median life expectancy of the ULT freezers. Is this based on commercial advice or institutional data?</p>
                    </list-item>
                    <list-item>
                        <p>There is some repetition in the narrative that could be removed and potentially replaced with a more in-depth description of the process, in order for the readers to assess whether it would be applicable for their own settings.</p>
                    </list-item>
                </list>
            </p>
            <p>Is the case presented with sufficient detail to be useful for teaching or other practitioners?</p>
            <p>Partly</p>
            <p>Is the work clearly and accurately presented and does it cite the current literature?</p>
            <p>Yes</p>
            <p>If applicable, is the statistical analysis and its interpretation appropriate?</p>
            <p>Not applicable</p>
            <p>Are all the source data underlying the results available to ensure full reproducibility?</p>
            <p>No</p>
            <p>Are the conclusions drawn adequately supported by the results?</p>
            <p>Partly</p>
            <p>Is the background of the case&#x2019;s history and progression described in sufficient detail?</p>
            <p>Partly</p>
            <p>Reviewer Expertise:</p>
            <p>Human tissue biobanking</p>
            <p>I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.</p>
        </body>
        <sub-article article-type="response" id="comment15151-435167">
            <front-stub>
                <contrib-group>
                    <contrib contrib-type="author">
                        <name>
                            <surname>Olson</surname>
                            <given-names>Melissa</given-names>
                        </name>
                        <aff>Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA</aff>
                    </contrib>
                </contrib-group>
                <author-notes>
                    <fn fn-type="conflict">
                        <p>
                            <bold>Competing interests: </bold>No competing interests were disclosed.</p>
                    </fn>
                </author-notes>
                <pub-date pub-type="epub">
                    <day>30</day>
                    <month>12</month>
                    <year>2025</year>
                </pub-date>
            </front-stub>
            <body>
                <p>
                    <bold>Response to Reviewer (Dr. Amanda Rush)</bold>
                </p>
                <p> I thank the reviewer for the thoughtful and constructive comments, and for recommending the manuscript as acceptable with reservations. Below I respond to each point and summarize the corresponding revisions.</p>
                <p> </p>
                <p> 
                    <bold>
                        <underline>Major comments</underline>
                    </bold>
                </p>
                <p> 
                    <bold>1. Governance changes and consequences for investigators; open access vs &#x201c;storage-only&#x201d; changes</bold>
                </p>
                <p> 
                    <bold>Reviewer comment (paraphrased)</bold>
                </p>
                <p> More detail is needed on governance changes associated with shifting samples to the service center. Did migration to the service center require a minimum dataset, open-access mandates, or other changes to investigator control, or did management/oversight remain the same apart from storage location?</p>
                <p> 
                    <bold>Response</bold>
                </p>
                <p> I agree that the governance implications should be explicit. I have clarified that centralization is a&#x00a0;storage and stewardship intervention, not a change in scientific or data governance: 
                    <list list-type="bullet">
                        <list-item>
                            <p>In the&#x00a0;Governance and Data Handling&#x00a0;section, I now state: &#x201c;Governance changes were designed to improve infrastructure while preserving investigator autonomy. Sample ownership and scientific decision-making remained fully with originating research teams, regardless of storage location. The Biobank assumed responsibility for storage quality, monitoring, chain-of-custody, and 24/7 emergency response, while associated clinical and research data remained with investigators or existing institutional systems. Only minimal metadata needed for traceability (e.g., specimen type, owner, hazard status, location, global identifier) were integrated into the Biobank LIMS.&#x201d;</p>
                        </list-item>
                    </list> 
                    <list list-type="bullet">
                        <list-item>
                            <p>In the&#x00a0;Results &amp; discussion, I further emphasize: &#x201c;Centralization does, however, standardize stewardship expectations, including inventory documentation, access controls, and continuity planning, ensuring that biospecimens remain protected and discoverable even as personnel or research priorities change. This model strengthens stewardship of physical materials while preserving existing data-access controls and consent protections, ensuring that participant trust and regulatory compliance remain intact.&#x201d;</p>
                        </list-item>
                    </list> No minimum dataset for scientific variables, no open-access requirement, and no change to consent or data-access rules were imposed as a consequence of migration; investigators retain full control over access, use, and sharing of their collections. The only governance shift is in&#x00a0;infrastructure and monitoring, not in data rights.</p>
                <p> </p>
                <p> 
                    <bold>2. Data migration: LIMS vs clinical data</bold>
                </p>
                <p> 
                    <bold>Reviewer comment (paraphrased)</bold>
                </p>
                <p> More detail is requested on associated data migration &#x2013; what moved into the Biobank LIMS and what remained with investigators (e.g., clinical data).</p>
                <p> 
                    <bold>Response</bold>
                </p>
                <p> I appreciate this point and have made the data boundaries more explicit: 
                    <list list-type="bullet">
                        <list-item>
                            <p>As quoted above from&#x00a0;&#x201c;Governance and Data Handling&#x201d;, I now specify: &#x201c;Inventory records for all centralized collections are incorporated into the Biobank&#x2019;s LIMS, supporting chain-of-custody, audit trails, and recovery planning. Associated clinical or research data remain with the investigator, consistent with consent governance and data stewardship policies. This separation ensures that enhancing physical storage does not alter data oversight or regulatory pathways.&#x201d;- and- &#x201c;Only minimal metadata needed for traceability (e.g., specimen type, owner, hazard status, location, global identifier) were integrated into the Biobank LIMS.&#x201d;</p>
                        </list-item>
                    </list> Thus, data migration is deliberately limited to&#x00a0;logistical metadata&#x00a0;necessary for physical stewardship and continuity; clinical and research datasets remain under the originating teams&#x2019; systems and governance.</p>
                <p> </p>
                <p> </p>
                <p> 
                    <bold>3. Scale of the shift; failure of older freezers; LN&#x2082; capacity and Vario costs</bold>
                </p>
                <p> 
                    <bold>Reviewer comment (paraphrased)</bold>
                </p>
                <p> The scale of the shift is unclear. While 938 freezers were past median life expectancy, it is not stated what proportion failed from 2021 onwards. Was additional LN&#x2082; capacity purchased? Were Vario costs incorporated into storage fees?</p>
                <p> 
                    <bold>Response</bold>
                </p>
                <p> I agree that readers need a clearer sense of scale and financial logic, while recognizing institutional constraints on disclosing detailed infrastructure inventories. 
                    <list list-type="bullet">
                        <list-item>
                            <p>In&#x00a0;Results &amp; discussion, I now quantify the stabilized centralized capacity: &#x201c;Since 2021, centralized storage within the Biobank has stabilized the equivalent capacity of approximately 42 ultra-low temperature freezers, eliminating the need for laboratories to maintain or replace those units and reducing institutional exposure to aging, high-risk infrastructure.&#x201d;</p>
                        </list-item>
                    </list> This communicates the scale of the&#x00a0;realized&#x00a0;shift, without listing individual units or locations. 
                    <list list-type="bullet">
                        <list-item>
                            <p>Regarding freezer failures among the 938 units beyond median life expectancy, the initiative was implemented&#x00a0;prospectively&#x00a0;and aligned with life-cycle events rather than as a retrospective failure-rate study. For that reason, I have not added a specific proportion of failures, as these data were not systematically captured in a way that would support robust reporting at the level of detail requested. Instead, I emphasize the conceptual linkage: &#x201c;Adoption of centralized storage is inherently a gradual process, tied to equipment failure cycles, research timelines, voluntary participation and cultural adaptation. Most ULT freezers in academic settings are only replaced at end-of-life, and failure events are unpredictable. Accordingly, achieving full transition across eligible collections is expected to occur over multiple years rather than rapid turnover, with each unit failure representing an opportunity to migrate to sustainable, governed storage.&#x201d;</p>
                        </list-item>
                    </list> 
                    <list list-type="bullet">
                        <list-item>
                            <p>With respect to infrastructure costs, additional LN&#x2082; and Vario capacity were indeed required and were added in a staged fashion as migration opportunities arose. Rather than detailing internal capital allocations, I describe this in terms of service-center economics:</p>
                        </list-item>
                    </list> &#x201c;Specimen deposits were managed as service requests, with annual storage charges applied to ensure cost neutrality and long-term sustainability of the service center.&#x201d;</p>
                <p> The cost of LN&#x2082; and Vario operation is built into the&#x00a0;standard storage fee structure&#x00a0;as part of routine rate-setting and cost-recovery, rather than being passed to individual investigators as a separate technology surcharge. I did not include more granular cost breakdowns but I have strengthened the explanation of the cost-recovery logic.</p>
                <p> </p>
                <p> 
                    <bold>4. Audit and consultation details; stakeholder responses to LN&#x2082; vs &#x2013;80 &#x00b0;C; migration vs guidance</bold>
                </p>
                <p> 
                    <bold>Reviewer comment (paraphrased)</bold>
                </p>
                <p> More detail on the audit and stakeholder engagement would help others adopt the approach. For example: proportion of stakeholders who migrated collections vs those who just sought guidance on new freezers; what were responses to shifting from &#x2013;80 &#x00b0;C to LN&#x2082;; what information was sought from investigators?</p>
                <p> 
                    <bold>Response</bold>
                </p>
                <p> I appreciate the emphasis on practical, transferable details. While I cannot provide precise proportions for each stakeholder pathway (these were not formally quantified as a research outcome), I have expanded the narrative on engagement and typical responses. 
                    <list list-type="bullet">
                        <list-item>
                            <p>In&#x00a0;Methods/Approach, I clarify the engagement structure: &#x201c;Because this initiative was intentionally aligned with natural equipment life cycles, investigators are required to evaluate community-based biobanking within the Johns Hopkins Biobank before purchasing replacements when older laboratory freezers failed. This &#x2018;shared resources before new purchases&#x2019; policy anchors the governance element of our model (Figure 1). Outreach campaigns, faculty meetings, and symposia reinforced awareness of centralized options and the advantages of shared stewardship. When centralized LN&#x2082; or Vario storage was not feasible, Biobank staff engaged in direct consultation with investigators to ensure that any new freezer purchases aligned with institutional efficiency and sustainability goals.&#x201d;</p>
                        </list-item>
                    </list> 
                    <list list-type="bullet">
                        <list-item>
                            <p>In the&#x00a0;Results &amp; discussion, I elaborate on the nature of these consultations and the heterogeneity of responses. I emphasize that: 
                                <list list-type="bullet">
                                    <list-item>
                                        <p>Some groups elected to&#x00a0;migrate cohorts&#x00a0;into central LN&#x2082; or Vario storage.</p>
                                    </list-item>
                                    <list-item>
                                        <p>Others used the consultation primarily to guide the purchase of&#x00a0;more efficient departmental ULT freezers when decentralization was operationally necessary.</p>
                                    </list-item>
                                    <list-item>
                                        <p>Common concerns included perceived access delays, familiarity and comfort with LN&#x2082;, and the suitability of colder storage for particular assay pipelines.</p>
                                    </list-item>
                                </list> </p>
                        </list-item>
                    </list> Given the absence of systematically collected proportions, I stop short of assigning percentages, but the pathway structure and typical concerns are now clearly described so that other institutions can consider analogous workflows.</p>
                <p> </p>
                <p> 
                    <bold>5. Time component: how long until the &#x201c;steady state&#x201d; of migration?</bold>
                </p>
                <p> 
                    <bold>Reviewer comment (paraphrased)</bold>
                </p>
                <p> There is an important time component, since freezers do not fail regularly. Over approximately what time period would it be expected to reach a state where all freezers that were going to be migrated have been migrated?</p>
                <p> 
                    <bold>Response</bold>
                </p>
                <p> I fully agree that the time horizon matters. The manuscript now explicitly frames the initiative as&#x00a0;multi-year&#x00a0;and tied to life-cycle replacement: 
                    <list list-type="bullet">
                        <list-item>
                            <p>As noted above and now emphasized in&#x00a0;Results &amp; discussion: &#x201c;Adoption of centralized storage is inherently a gradual process, tied to equipment failure cycles, research timelines, voluntary participation and cultural adaptation. Most ULT freezers in academic settings are only replaced at end-of-life, and failure events are unpredictable. Accordingly, achieving full transition across eligible collections is expected to occur over multiple years rather than rapid turnover, with each unit failure representing an opportunity to migrate to sustainable, governed storage.&#x201d;</p>
                        </list-item>
                    </list> Given a median life expectancy of ~8.5 years and the age distribution observed in the audit, a substantial fraction of units eligible for replacement are expected to cycle through within a&#x00a0;5&#x2013;10 year horizon&#x00a0;after policy implementation, but exact forecasting is not feasible because of heterogeneous usage patterns and institutional decisions. I therefore frame the time aspect as a principled multi-year progression rather than a precise deadline.</p>
                <p> </p>
                <p> 
                    <bold>6. Evidence for cost and energy savings</bold>
                </p>
                <p> 
                    <bold>Reviewer comment (paraphrased)</bold>
                </p>
                <p> It would be useful to have approximate cost and energy savings to support the claims.</p>
                <p> 
                    <bold>Response</bold>
                </p>
                <p> I agree, and I have strengthened this component in the&#x00a0;Results &amp; discussion: &#x201c;Within the School of Medicine, these aging freezers consume an estimated additional $800K annually in avoidable electricity and HVAC load, based on industry-validated energy modeling (including manufacturer performance curves and published ULT power consumption data). This infrastructure inefficiency is disproportionately driven by decentralized research storage, which accounts for ~80% of ULT assets across campus.&#x201d;</p>
                <p> I pair this with the quantified centralized capacity: &#x201c;Since 2021, centralized storage within the Biobank has stabilized the equivalent capacity of approximately 42 ultra-low temperature freezers, eliminating the need for laboratories to maintain or replace those units and reducing institutional exposure to aging, high-risk infrastructure.&#x201d;</p>
                <p> Together, these figures provide a&#x00a0;ballpark sense of avoided cost and energy demand, without disclosing smaller-scale operational details that are considered sensitive.</p>
                <p> </p>
                <p> 
                    <bold>7. Clarifying what &#x201c;sustainability&#x201d; means (environmental and financial)</bold>
                </p>
                <p> 
                    <bold>Reviewer comment (paraphrased)</bold>
                </p>
                <p> Sustainability appears to refer to both environmental and financial aspects. It would be useful to explicitly state whether both meanings are intended.</p>
                <p> 
                    <bold>Response</bold>
                </p>
                <p> Thank you for highlighting this. I have clarified in the&#x00a0;Introduction&#x00a0;that both aspects are intended: &#x201c;This creates a dual challenge. On one hand, institutions are under increasing pressure to reduce the environmental footprint of research infrastructure in alignment with broader sustainability commitments. On the other, biobanks must maintain uncompromising standards of quality and continuity to protect biospecimens, meet regulatory requirements, and preserve trust with research participants. Efforts to reduce energy use or rationalize equipment therefore cannot come at the expense of specimen protection or emergency readiness, nor can cost-recovery models undermine long-term stewardship.&#x201d;</p>
                <p> In the&#x00a0;Conclusion, I make the dual nature explicit: &#x201c;This case provides a practical framework for other academic biobanks seeking to balance financial stability with uncompromising quality and continuity, demonstrating that efficiency and rigor can be achieved together. Ultimately, this model demonstrates that sustainability initiatives can also serve as quality initiatives, improving research rigor and resiliency while reducing institutional risk.&#x201d;</p>
                <p> Thus, throughout the manuscript **&#x201c;sustainability&#x201d; explicitly encompasses both environmental (energy, cooling load, carbon footprint) and financial (cost-recovery, infrastructure efficiency) dimensions.</p>
                <p> </p>
                <p> </p>
                <p> 
                    <bold>
                        <underline>Minor comments</underline>
                    </bold>
                </p>
                <p> </p>
                <p> 
                    <bold>1. Reference or basis for median life expectancy of 8.5 years</bold>
                </p>
                <p> 
                    <bold>Reviewer comment (paraphrased)</bold>
                </p>
                <p> Please clarify the basis for the 8.5-year median life expectancy for ULT freezers.</p>
                <p> 
                    <bold>Response</bold>
                </p>
                <p> I have clarified that this figure is grounded in published work and institutional experience. In the&#x00a0;Methods
                    <bold> </bold>section, I now cite the relevant literature.</p>
                <p> </p>
                <p> 
                    <bold>2. Repetition in the narrative vs depth of process description</bold>
                </p>
                <p> 
                    <bold>Reviewer comment (paraphrased)</bold>
                </p>
                <p> There is some repetition in the narrative that could be removed and potentially replaced with more in-depth process description.</p>
                <p> 
                    <bold>Response</bold>
                </p>
                <p> I appreciate this stylistic suggestion and have streamlined several repeated elements, particularly: 
                    <list list-type="bullet">
                        <list-item>
                            <p>Reducing repeated general statements about the value of biobanking and the basic description of LN&#x2082;/Vario advantages.</p>
                        </list-item>
                        <list-item>
                            <p>Consolidating overlapping phrases about &#x201c;balancing sustainability, quality, and continuity&#x201d; so they appear once in the&#x00a0;Introduction&#x00a0;and again in a more analytical way in the&#x00a0;Results &amp; discussion.</p>
                        </list-item>
                    </list> Space gained from these edits has been used to: 
                    <list list-type="bullet">
                        <list-item>
                            <p>Expand the&#x00a0;&#x201c;Governance and Data Handling&#x201d;&#x00a0;section with clearer detail on investigator autonomy, metadata scope, and data separation.</p>
                        </list-item>
                        <list-item>
                            <p>Strengthen the&#x00a0;Results &amp; discussion&#x00a0;on the timing of benefits, the cultural shift from freezer ownership to specimen stewardship, and practical risks and mitigation during transition.</p>
                        </list-item>
                    </list> I hope this improves readability while giving readers a richer description of the process they may wish to adapt.</p>
                <p> </p>
                <p> Once again, I thank the reviewer for the thoughtful and constructive feedback. The revisions in response to these comments have, I believe, improved the clarity, transferability, and evidentiary support of the case study, particularly around governance, time horizon, and the dual environmental and financial dimensions of sustainability.</p>
            </body>
        </sub-article>
    </sub-article>
</article>
