Biobanks process, store and distribute high-quality and clinically annotated biological materials. Implementing a quality management system (QMS) at biobank can improve biological material and associated data (BMaD). High-quality BMaD is fundamental for research and benefits both human and veterinary patients. The quality of biological material is dependent on diverse factors throughout the life cycle of the samples, from collection to final utilization. By adhering to biobanking conformity assessment standards, they are well-positioned to provide the consistent quality control and assurance required for research. Implementing standardized practices also helps decrease irreproducibility in the study. However, without conformity assessment, users cannot assure compliance. First, second, or third-party attestation methods can accomplish conformity assessment.

Biobanks receive accreditation when biobanking processes and personnel competence are assessed to be in conformance with standard requirements. With the publication of the ISO standard 20387:2018, biobanks gained access to third-party accreditation to this standard. The Cornell Veterinary Biobank (CVB) recognized this advantage and its commitment to providing researchers with high-quality BMaD. American Association for Laboratory Accreditation (A2LA) evaluated CVB in April 2019. It became the first biobank in the world to gain accreditation to an ISO biobanking standard within eight months. This article describes how CVB attained compliance with ISO 20387:2018 and provides a perspective on the challenges and opportunities encountered. The prototype developed was done based on animal samples; no human samples were used. 

Materials and Methods

CVB began implementing compliant practices following the publication of ISO 20387:2018. International Society for Biological and Environmental Repositories (ISBER) and National Cancer Institute (NCI) provided a solid foundation for CVB. The first stage of implementation was to establish an intra-university consortium with diverse expertise. A QMS was developed and compiled into a QMS manual. The manual follows ISO standards, with each clause presenting a CVB policy and referencing procedures for each requirement. Procedures relating to needs and detailed documentation of all processes on scope (Table 1) were created. Methods describing the control of documents and records were implemented to provide a foundation to build QMS. It ensured that all documents generated during the creation of the QMS would be uniform within the CVB. CVB personnel prepared for assessment by regularly meeting with the QA manager. 

Results

Creating controlled documents and records

Controlled documents are divided into five types:

1. Standard operating procedures (SOPs)- to provide consistent and uniform instructions.
2. Forms- to record information related to CVB procedures.
3. Charts- for graphical representations or abbreviated summaries of procedures. 
4. Manuals- as detailed instructions for an entire system. 
5. External documents- included equipment manufacturer instruction manuals, external submission forms, external standards, and external references for other controlled documents. 

A corrective action report (CAR) and action item report were created to document nonconforming output and other events that could adversely affect the quality of CVB products or services. As risks were identified using CARs and action items, these controlled documents were updated, and training events took place to ensure relevant personnel was informed and in compliance.

Governance, Management, and Preparation for Assessment

Documents related to CVB management, structure, equipment, and sample data were created. In addition, the CVB presented the list of proposed materials and processes with corresponding sample life cycle charts, floor plans of CVB facilities, and an entire catalog of banked biological materials. The CVB underwent an assessment visit on April 4 and 5, 2019, consisting of a  QMS and technical review. The QMS review aimed to evaluate the evidence of compliance for each clause of the ISO 20387 standard. The technical review aimed to assess the traceability, technical competence, appropriate use of equipment, and accurate description of processes listed on the scope. 

After the reviews, the assessor team provided CVB with a list of four deficiencies that needed to be addressed within 40 days for accreditation. A copy of the report and supporting evidence were submitted to A2LA for review upon satisfactory completion of the corrective action. CVB was granted accreditation to ISO 20387 on April 23, 2019, on acceptance of the submitted evidence. 

Conclusion

CVB met its accreditation objectives and experienced improvements in operational efficiency, participation from BMaD providers, increased researcher interest, and philanthropy. Another benefit was developing a controlled document system that allows for the rapid identification of required documents while maintaining control of content and distribution. Compliance with ISO 20387 provided unforeseen benefits to CVB’s response to the COVID-19 pandemic. 

Accreditation to ISO 20387 can be achieved by all biobanks, including humans, animals, plants, and microorganisms, regardless of size or equipment availability. A review of the ISBER Self-Assessment Tool completed by 62 biobanks between 2015 and 2017 revealed that 43% do not have a QMS in place, suggesting that much progress is needed within the international biobanking community to achieve standardization. As more users/ researchers become educated about the benefits of standardized processes in biobanking, they may request evidence of this compliance. This will encourage biobanks to achieve accreditation to biobanking standards. 

Acknowledgments

https://www.liebertpub.com/doi/full/10.1089/bio.2020.0068

COVID-19 has infected more than 110 million individuals worldwide, with about 2.5 million deaths. It is very crucial to find an intervention that successfully prevents or mitigates morbidity and mortality. Biospecimen research can provide novel insights into the disease, clinical trials, and the development of effective and life-saving treatments. However, any such study raises ethical concerns plus practical challenges for investigators and participants. 

The University of Cambridge introduced a weekly asymptomatic testing program for students as part of its efforts to reduce the spread of COVID-19. Dr Caitriona Cox, NIHR Academic Clinical Fellow at THIS Institute and project lead, said: “The framework and checklist are freely available and will hopefully act as valuable and timely resources for higher education institutions seeking ethically sound ways to keep people safe and support public health efforts.” (1)

In March 2021, ThePrint reported (2) that the use of placebo controls in clinical trials remains controversial, and researchers are increasingly questioning its role in testing Covid-19 vaccines. “We want to critique it (the WHO ad hoc group’s position), we do not agree with such a kind of position. Long back in 1990s, when the HIV epidemic was prevalent in different countries, this issue was settled, there are informational guidelines, and the Helsinki declaration that says that if you have an effective vaccine available, you cannot use placebo-controlled trials,” Dr Amar Jesani, the editor of IJME, told ThePrint.

On 15th March 2021, the Netherlands (3) and Ireland (4) announced the suspension of the AstraZeneca vaccine amid blood clot reports, followed by other countries like Germany, Italy, and France (5). “The decision has been made… to suspend the use of the AstraZeneca vaccine as a precaution, hoping that we can resume it quickly if the judgement of the EMA allows it,” Mr Macron told a press conference, adding that an announcement by the EMA was expected on Tuesday afternoon.

This article casts light on the ethical issues associated with autonomy, benignity, and justice in COVID-19 research. It describes the strategies to manage the practical challenges, emphasizing human research participants’ rights and welfare. The 1978 Belmont Report established the foundation for research oversight with three ethical principles. These principles include: 

Respect for Persons

COVID-19 biospecimen research faces several issues that complicate its ethical oversight, such as 

1. Vulnerable groups are disproportionately affected by COVID-19. These individuals may lack the capacity to give informed consent. The heightened anxiety faced by legally authorized representatives (LARs) can result in delays in obtaining consent.
2. In the current situation, blood samples from patients with COVID-19 are crucial for improving scientific understanding of the virus and its consequences. However, sometimes a participant or their LAR cannot be located. 

The institutional review board (IRB) can use the following strategies to approach the situation:

1. Account for these multiple obstacles in obtaining informed consent from patients or their LARs. In case the LARs cannot be located, the samples must be destroyed or de-identified.
2. Be sensitive to the medical issues while recruiting human participants for COVID-19 biospecimen research.

Beneficence

Violation of participant privacy and breach of confidentiality are significant risks in biospecimen research. Another issue is the exploitation of protected and vulnerable groups. COVID-19 study offers the hope that participants would receive the social benefits of advancements quickly. COVID-19 research proponents anticipate that their work will have a high impact on mitigating the disease.

To protect the participants and the research study:

1. Maintain patient privacy and keep health records private.
2. Treat minority and economically disadvantaged communities equally.
3. Create a population-friendly environment- build trust and understand the public’s perspective. 
4. Make sure that the participants are aware of short-term and long-term benefits.

Justice

Every pandemic evokes new questions about what justice requires, even as the pandemic also potentially worsens existing inequalities. Expediting pandemic-related research and allowing waivers of informed consent for the initial biospecimen collection procedures relies on social arguments about the responsibility to participate in research that likely yields collective benefits. In the COVID-19 situation, the most vulnerable groups have suffered. During such cases, IRBs must:

1. Prioritize research that will deliver the greater public good. 
2. Consider meeting the demands of justice in the initial review of COVID-19 research protocols and subsequent requests for access to biospecimens.
3. Ensure fair access to the therapeutic benefits of research and promote the inclusion of vulnerable groups.
4. Focus on equitable recruitment and inclusion to allocate the research benefits and burdens.
5. Engage susceptible people in the post–COVID-19 era to assess whether the public agrees with a waiver of consent and what types of research they are willing to engage in without giving explicit informed consent. 

Acknowledgments

Read the full article here: https://www.mayoclinicproceedings.org/article/S0025-6196(20)31208-8/fulltext 

References

https://web.archive.org/web/20120426013513/http://ohsr.od.nih.gov/guidelines/belmont.html#gob1  

The requirements for the establishment, obtainment, and use of samples in these two different types of biobanks are very diverse. In disease-oriented biobanks, samples are collected from patients for diagnosis/treatment. Whereas in population-based biobanks, samples are collected from healthy participants. 

Biobanks involve the collection, storage, and distribution of biological samples for research purposes. This activity includes an effective, efficient, and modern research system. The development of technologies and the need to have research results have made it mandatory to start the biobanks implementation phase.

Advances in Technical Storage

The fundamental elements for creating functional biobanks are – quality, quantity, collection, and harmonizing the samples. Biospecimens require high standards of storage and shared protocols. This is to ensure the maintenance of sample quality and biobanks’ sustainability that supports these samples. Consequently, it is vital to integrate the traditional-technical principles with which biobanks were developed. This could make it possible to ensure large numbers of samples and their variability, ensuring high-quality standards and cost containment.

Harmonization and Standardization

Biobanks aim to find collaborative dialogue platforms, application of shared protocols, and standard rules. It includes obtaining samples, collection and storage, treatment data, and exchanging material and information. It also involves the infrastructures’ administrative and financial management. 

Better harmonization can lead to meaningful results, such as:

1. Obtaining an orderly and multicenter collection of data and samples.
2. Creating uniform groups of patients with extensive and well-described case histories.
3. The opportunity of creating studies on large cohorts and sub-cohorts of patients. 

Biobank Network

Basic and translational research has very complex molecular biology procedures. In such cases, it is vital to have suitable samples in large quantities. A single biobank may not guarantee the availability of many samples that comply with adequacy standards. Therefore, several infrastructures must harmonize with each other. The networking of biobanks allows:

1. Multiple collections and storage sites unite into a single platform for sharing and exchanging resources. 
2. This can result in exchanging samples and data, favoring collaboration both at a national and international level. 
3. Networking of biobanks within academic facilities could push non-academic researchers, private research facilities, and pharmaceutical industries to find samples from other sources.
4. Improved research quality standards.

Examples of biobank network

1. EuroBioBank: The EuroBioBank network is the first operating network of biobanks in Europe, providing human DNA, cell, and tissue samples to the scientific community researching rare diseases. It is the only network dedicated to rare disease research in Europe. It is the biobank network of RD-Connect.
2. Swiss Biobanking Platform (SBP): SBP is the research infrastructure of national importance supporting human and non-human biobanks.
3. BBMRI-ERIC: BBMRI brings together all the leading players from the biobanking field – researchers, biobankers, industry, and patients – to boost biomedical research.
4. Tissue Directory and Coordination Centre (TDCC): TDCC has developed the UK’s only register of sample collections covering multiple diseases.
5. Spanish Biobank Network: Adds value to the Spanish biobank group, intending to provide high scientific, technical, and technological support by providing human biological samples and associated data of excellent quality.

Biobanks’ Sustainability

As the global economic situation has deteriorated, funding for most public biobanks has shrunk. The aim should be to make these infrastructures more efficient and sustainable. The basic steps to achieve this are: 

1. To hire expert consultants in finance and business organizations and educate them on the peculiarities of a biobank.
2. Analyze costs and improve the relationship between cost and effectiveness.
3. Maximize the availability and usability of samples limiting the sample waste.
4. Develop a business model that identifies potential users by aligning the supply of samples to stakeholders’ needs.

The Future of Data Protection

Patients and donors must be thoroughly apprised about the risk of disclosing the donor’s identity. The four measures that have been considered crucial by the International Bioethics Committee (IBC) to protect individuals’ rights and management of big data are governance, education, capacity building, and benefit-sharing. These aspects, also concerning data protection, cannot be forgotten in the management of biobanks.

Conclusions 

The future of biobanks is already here. The need for technological headway can aid in the evolution of research. Nevertheless, biobanks’ management must be up to date from both a financial and an ethical and regulatory point of view.

Acknowledgments

https://www.mdpi.com/2673-6284/9/4/23/htm

References

https://youtu.be/rWELVe7Upb0

Automated systems provide valuable knowledge, streamlined process steps, and enhanced quality. Automation also leads to “economies of scale” so that the biobank can manage growth without a significant increase in labor, materials, or equipment. 

There are automated storage solutions for every need and budget. Size-wise they can range from compact instruments fitting next to the laboratory bench to modular units in large rooms. 

Why Automate?

1. Standardization and Quality Assurance:

The way samples are processed and stored plays a critical role in their quality. E.g., temperature fluctuations compromise the sample’s quality. 

Three vital parameters in this respect are:

1. The time between sample collection and its processing (e.g., a few minutes vs. hours)
2. Type of sample processing
3. Storage conditions

2. Scaling up:

Managing a large number of samples using manual freezers significantly increases the risk of errors and poor quality. Automation drastically decreases the probability of errors by standardizing each of the steps in the workflow. 

3. Efficiency:

Automation can eliminate many human handling steps, which are a significant source of errors. E.g., mislabeling, misplacing, losing a sample, etc.

An automated storage system can also be integrated with sample preparation steps, such as DNA extraction, for further streamlining.

Hamilton BiOS and Univ of Maryland (UMM) Biorepository:

Hamilton BiOS is an automated storage system designed to store sensitive biological samples at -80°C. The UMM Biorepository uses BiOS for the automated storage and retrieval of specimens. UMM biorepository extracts and stores serum, plasma, and also DNA from the blood for genomic studies.

BiOS uses cutting-edge technology to improve research efficiency, like:

1. Magnetic bead technology to move DNA from place to place and undergoes six wash steps
2. Retrieves purer DNA sample
3. A dual refrigeration and backup system stores samples at ultra-low temperatures
4. Sample retrieving is done by robots quickly and accurately. More importantly, without exposing the rest of the specimens to room temperature.

OpenSpecimen usage at UMM

UMM Biorepository is using OpenSpecimen since 2017 as their Biobanking LIMS. OpenSpecimen is integrated with Hamilton BiOS using REST APIs. Refer to this blog post for more details.

Automated Freezer Vendors

1. Hamilton BiOS
2. Brooks Automation BioStore II Automated Sample Management & Storage System
3. ALS Freezers: Smartfreezer® Series
4. Celltrio, Inc.: Celltrio RoboStor
5. TTP Labtech Arktic

Acknowledgments:

• https://robotics.hamiltoncompany.com/wbiobanking
• https://www.linkedin.com/feed/update/urn:li:activity:6728981250889027584/
• https://youtu.be/o3ydPmLd5D4

References:

• https://www.grandviewresearch.com/industry-analysis/biobanks-industry#
• https://perkinelmer-appliedgenomics.com/home/applications/biobanking-automation/
• https://www.genengnews.com/magazine/145/automation-improves-biobanking-efficiency/

Written by: Divya Prabhu, Member of Domain Staff, Krishagni

For more details, email contact@krishagni.com

Due to environmental and climatic variations, we are losing some ecologically and industrially relevant microbial community components. Microbiome preservation is crucial for future cultivation and to study the effects of ecological and climatic variations on community functionality and shift with time. Although methods for pure culture preservation are almost optimized, microbiome preservation techniques remain an unsolved challenge for microbiologists due to technical and physiological constraints.

This paper explores the different aspects of research in microbiome biobanking and answers tertiary questions around the field, such as the necessity of the area, as well as possible methodologies of how to implement them. 

The Current European and International Landscape Underpinning Microbiome Research Is Fragmented.

Preservation and Storage:

The challenges of preserving microbiome samples are immense. Removing a single critical microbial component at the functional level due to applying a non-optimized storage approach could irreversibly affect the system’s integrity.

Bell quoted Adams ‘If you try and take a cat apart to see how it works, the first thing you have on your hands is a non-working cat,’ which is a crucial issue to conserve a microbiome sample. 

When considering microbiome preservation, two essential questions need to be answered: 

• What should be preserved, and 
• What is the best way of preserving it?

Capacity is one significant challenge to this approach. The question of how much sample is required to be representative of the microbiome in question becomes critical. 

Cryopreservation has been the ‘gold standard’ for microbial storage since the 1960s. But in the microbiome system of multiple components, if cryopreservation is not applied optimally, it will result in unintended selective pressures on the community. 

Assessing Success and Quality:

A variety of metagenomics to transcriptomics has been used to assess the microbiome concerning both its construction and functionality. These approaches could evaluate the success of preservation and the storage regime, but each has its limitations. Tests should be undertaken before preservation/storage to characterize the microbiome, and one post preservation to ensure the compositional and functional integrity.

Summary Recommendations and the Way Forward:

The question of why and what should be conserved has to be addressed in detail considering scientific, economic, social, and environmental perspectives. A prioritized list is required to focus the efforts and achieve advancements, considering the diversity and complexity of microbiomes across environments.

The most significant technological bottleneck is the development of optimized methodologies for preserving microbiomes and assessing preservations’ success in maintaining the composition and functionality of microbiomes.

The evident complementarity between culture collections and biobanks necessitates an approach to enable both works together to ensure that this critical microbiome research field has adequate support. This will require identifying infrastructural overlaps to gauge what is needed and what is available/missing within the EU and beyond.

How can OpenSpecimen Help?

Managing the data related to microbes, the primary component of the microbiomes, is equally essential. OpenSpecimen helps in managing the data of the complete life cycle of microbes, including preservation and storage. The diagnostic division of Clinical Bacteriology and Mycology of Prof. Adrian Egli in University Hospital Basel, Switzerland, uses OpenSpecimen regularly to manage their longitudinal bacterial strain collections from routine diagnostics. This includes samples for quality measurements or outbreak management. Besides, a series of clinical research trials are also managed by OpenSpecimen, e.g., 

• A study exploring the skin microbiome in patients with Graft Versus Host Diseases (GVHD) including swab and skin-tissue samples collection to study skin conditions
• A study to explore community-acquired pneumonia and associated sepsis, which involves the collection of different types of specimens to study changes during severe community-acquired pneumonia and subsequent development of sepsis.

For more details, refer to the case study of the University Hospital Basel, Switzerland.  

Acknowledgments

This paper is an output from the EU project MicrobiomeSupport. For more details, refer to the original paper here.

References:

• https://en.wikipedia.org/wiki/Microbiome
• https://www.youtube.com/watch?v=VzPD009qTN4&feature=youtu.be
• https://en.wikipedia.org/wiki/Microbiological_culture
• https://www.sciencedirect.com/science/article/pii/S0966842X20301888#bb0015

Written by: Divya Prabhu, member of domain staff at OpenSpecimen. 

For more details email contact@krishagni.com