Has COVID-19 Affected the Handling of Biospecimens?

The collection of biospecimens continue even during the midst of the Coronavirus pandemic. Even though there is a global concern about COVID-19, laboratories, experimentation, and sample collection must continue. Some biorepositories and laboratories will turn to focus on the collection and examination of Covid-related biospecimens, others will continue to forge ahead trying to make a difference in their fields of influence. Research must continue as patients are not exempt from serious diseases and conditions due to the pandemic. Repositories must continue collecting tissue and cell samples and making them available for research purposes. But how does the Covid pandemic affect biospecimen collecting, storage, and distribution?

Handling Biospecimens

In general, guidelines for the safe handling of biospecimens are in place and do not require further recommendations. Precautions are in place for the purpose of infection control when handling all types of biospecimens. The CDC has offered some safe-handling guidelines for laboratories and related facilities. These guidelines include:

·   Laboratories should perform a site-specific and activity-specific risk assessment and continue to follow standard precautions when handling any biospecimen.

·   Environmental Protection Agency-approved disinfectants should be used to control viral pathogens.

·   Biospecimens which are suspected to be positive or confirmed SARS-CoV-2 positive specimens, isolates, or cultures, should be packaged and shipped as a Category B UN 3373 Biological Substance.

General Biospecimen Handling

Biospecimen quality has a direct and significant impact on diagnostic testing, clinical and preclinical research. Specimens of poor quality can lead to inaccurate test results and experimental errors. Because we understand the importance of high-quality specimens, our biorepository handles all specimens with care and precision, so our clients receive the highest quality of specimens. We observe the strictest guidelines including those set forth by the CDC and WHO to maintain sample quality across the board.

Labs must be adamant about ensuring COVID-19 lab safety and following standard biological safety procedures whether handling COVID-19 and other biospecimens. Staff should have PPE (personal protective equipment) available for staff including disposable gloves, eye protection, and lab coats or gowns. Biobanks should have a dedicated area for staff to put on or remove PPE.

The World Health Organization and the Centers for Disease Control and Prevention have both stressed the importance of using standard precautions. These precautions include decontaminating workspaces, treating waste to ensure viral particles are inactive, and eliminating unguarded aerosol production. As the pandemic continues to unfold guidelines will continue to be updated.

WHO and CDC Biosafety Guidance During the Covid-19 Pandemic

The CDC and WHO have issued interim biosafety guidance. Here are some of the current recommendations for the handling of biospecimens if they have known or are suspected to have contacted COVID-19.

·   Continue strict observance of relevant protocols including having all risk assessments and procedures conducted by capable personnel.

·   All lab techs should continue to wear appropriate PPE.

·   Processing should be conducted in a validated biosafety cabinet or a primary containment device.

·   The level of biosafety will depend on the nature of the work. BSL-2 for non-propagative work, and BSL-3 for propagative work.

·   All procedures in the bio lab should be done in such a way as to minimize the generation of aerosols.

·   Proper handling of biolaboratory waste.

·   Biospecimens should be placed in a secondary container if they are being transported.

·   Proper shipping of biospecimens based on their substance category.

All biospecimens should be handled as if they are infectious eliminates switching between protocols. Handling them as though they are infections also minimizes their exposure potential and the types of implications such exposure could have on the community and lab personnel.

There are exceptions when handling nucleic acid extracts, formalin-fixed, and paraffin-embedded (FFPE) tissue. When these processed biospecimens are handled using standard precautions and wearing appropriate PPE, no special considerations are necessary. Based on earlier studies of coronaviruses, the routine histologic fixation and processes should render SARS-CoV-2 inactive.

You can be assured that the products received from our repository are handled according to the ethical standards set forth by the World Health Organization. 100% of collected tissue samples are subjected to our strict quality control and all biospecimens are collected in accordance with our strict Standard Operating Procedure.

Resources:

https://academic.oup.com/ajcp/article/155/1/55/5911469

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543273/

https://www.biobanking.com/safety-for-biobanks-strategies-for-safe-covid-19-specimens-handling/

https://research.ucsf.edu/covid-19-biospecimen-guidelines

Interim Guidelines for Biosafety and COVID-19 | CDC

5 Laws That Apply to Biorepositories

With the increase of biological and pharmaceutical research, biorepositories are surfacing as a huge, important component. Biorepositories store and catalog a variety of biological samples. They must adhere to stringent regulations when handling and using biological specimens, especially when human samples are involved. Here are some of the legal guidelines biorepository staff much be familiar with and adhere to.

HIPAA Compliance

HIPAA or the Health Insurance Portability and Accountability Act is a US law. It is designed to protect patient’s medical records and privacy. Any business that handles any type of patient information much follow HIPAA regulations and practices to protect patient privacy. Biorepositories store samples were taken from human patients. If there is a breach in patient data or if the biorepository is not compliant with the guidelines set forth in HIPAA, they can be subject to criminal or civil penalties.

Informed Consent and Human Tissue Samples

The IRB (Institutional Review Board) oversees studies at research institutions when they involve human subjects. The review board is set up to help protect people from possible negative consequences when they are involved in research studies. In most cases, specimens collected from research participants or patients require the signing of an informed consent form approved by the IRB. Specimens are often stored in biorepositories for future use. These specimens require signed informed consent documents. It is often difficult to know when specimens will be used in research, donors may be able to withdraw their authorization for tissue sample use.

Patient’s Right to Withdraw from Research

When patients consent to the use of their samples for future research, they retain their right to withdraw that consent. As far as sample management and protocol in general, it can vary between institutions. Biorepositories should outline their best practices and how the specimens will be handled in cases where a patient withdraws consent. For instance, biorepositories may choose to destroy the sample, or they may be able to transfer the sample to a different donor-approved research project. Having a transparent operating procedure to follow for cases where donors withdraw consent, helps protect biorepositories from unintentional violations of HIPAA or IRB regulations.

Custody and Ownership of Samples

The laws vary from state to state and between institutions as they pertain to biological repository sample ownership and custody. In most cases, collected samples are owned by the organization that gathered them. Researchers who collect samples usually retain custody of them since they are using them for a particular study or purpose. Other times, they are in the custody of an IRB-approved biospecimen regulatory body. Biorepositories should have clearly stated guidelines for the ownership, custody, and distribution of samples. They should also have a clear plan for cases when a researcher leaves their institution.

Access to Biological Specimens and Data

Biorepositories also need to tightly control access to biological samples and the data associated with them. This helps ensure both the integrity and security of the specimen. Access to samples should be limited to authorized researchers and specific biorepository staff. Logs should be diligently maintained by biorepository staff. These logs should contain detailed audit trails for each sample including access logs.

Biological research is growing rapidly and as with other technologies, the pace is often faster than regulations. Laws that affect biorepositories are still relatively young and it’s likely that they will change as products, research, and technology continue to advance. Staff members at biorepositories should continue to be aware of regulatory developments as they occur in the future.

Biobanking of Fresh Frozen Tissue from Clinical Surgical Specimens

Fresh Frozen Tissue and Clinical Surgical Specimens

Since many pathology departments at hospitals have procedures for the reception and handling of fresh specimens, a biobanking manual based on the already established structure to enable the collection of unfixed tissue samples can be produced. This allows the collection of all types of surgical lesions. The procedures can be used for all specimens such as a tumor, rejected transplanted organs, atherosclerosis, inflammatory bowel disease, etcetera. Most surgical specimens are transported to the pathology department for potential biobanking. One of the most important concerns for all clinical biobanks is diagnostic security. The pathologist involved has the responsibility to report the diagnosis based on the fresh specimen.

One main limiting factor in frozen tissue biobanking is the well-understood hesitance of pathologists to remove abnormal tissue for biobanking purposes as it may jeopardize the appropriate diagnosis and treatment for the patient. A potential solution to this issue is to perform cryosection and histological examination of the specimen once it enters the biobank. Another important concern for biobanks is the possibility of tissue degradation during transport from the surgical theater to a facility. However, most tissues are usually stable for hours since it is transported on ice. It is also important for each research project to define their tissue quality criteria to ensure that the samples meet their standards.

Tissue Sample Collection and Biobanking

These are some of the methods that can be applied through different stages of biospecimen collection:

1) Surgical Theater

• Fresh specimen should only be handled in a designated area. Between each case, the area should be decontaminated by removing material from previous cases. Specimens should only be handled using gloves and instruments. Responsibilities of various staff members should be documented.

• The pathology chart should note the time when the specimen has been removed from the patient.

• Specimens should be placed in a clean surgical cloth, plastic bag, jars, or a test tube. It should also be immersed in a cold saline solution.

• The specimen should be transported at ±0⁰C (partly filled with wet ice). It is important to note that the specimen should not be in direct contact with the cooling agent (water or ice) during transport.

• Inform the technician at the pathology department for reception of the specimen. The communication routine between the theater and pathology department should be safe and clear. Ensure that the specimen is delivered.

2) Pathology Department

• Upon arrival at the pathology department, the time of arrival should be noted on the chart. It should be registered in the clinical laboratory management system and labeled with a case number.

• The pathologist on call should be notified regarding the arrival of the specimen. If a delay is inevitable, the specimen should be placed in the refrigerator.

• Once ready, the specimen is removed and placed on a clean sheet of filter paper. The macroscopic features of the specimen (weight, measurements, description) should be noted in the chart.

• Pieces of the specimen that represents the lesion and normal tissue should be cut out and placed into a cryomold for cryogel coverage. Storage of samples in cryogel prevents the lyophilization of the specimens. It also helps o keep the DNA and RNA intact. The mold is then snap-freeze in dry ice or isopentane. The time of freezing, biobank numbers, pathologist signature, and technician signatures are noted. These tissue blocks are then transferred to a low-temperature freezer.

• It should be noted that the thawing of a sample during the lifespan of a fresh frozen biobank sample is one of the most important risk factors for the degradation of tissue. A cryostat to avoid thawing during delivery can be used to slice sections for protein, DNA, or RNA extraction. The tissue lock can also be cracked on a cutting board that has been cooled on dry ice if a larger portion of the sample is needed.

3) Biobank

• The biobank technician then makes cryosections of the biobank samples.

• An adhesive tape helps support the section during the cutting and transfer process to prevent folds and tears. Once the section is crossed-linked onto a slide, the tape can be peeled off.

• Sections are fixed, stained, mounted, and lastly labeled with a case number. These slides are then delivered to the pathologist who is responsible for reporting the diagnosis. The biobank technician registers the case along with relevant information such as name, identification number, age, gender diagnosis, and more.

• Biobanking protocols concerning biospecimens should be integrated with both local and national established clinical or diagnostic procedures. The protocols should also be authorized by those relevant.

Conclusion

It is critical for research teams involved in molecular diagnostics and translational cancer to have access to quality fresh frozen tissue. This article helps to describe a workflow for the collection of frozen biospecimens after derived from patients after surgery. These routines are used at Uppsala University Hospital since 2001 where the team integrates cryosection and histopathologic examination of the samples in the manual this is to help procure small lesions while avoiding a diagnostic hazard due to the removal of abnormal tissue from the surgical specimen.

References
Botling J, Micke P. Biobanking of fresh frozen tissue from clinical surgical specimens: transport logistics, sample selection, and histologic characterization. Joakim Dillner (ed.). Methods in Biobanking, Methods in Molecular Biology, vol. 675: page 299-306.

Quality Management in International Biobanking

Introduction to International Biobanking

Biobanks and biorepositories fulfill clinical or research purposes through the collection, processing, storage, and distribution of various biospecimens or materials that are often required. With time, it has been recognized that biobanks and biorepositories should follow a complex array of regulatory or ethical considerations. The procedures and policies they follow are usually documented by the best practices that can either be voluntary or by rules and regulations reinforced by Institutional Review Boards (IRBs), governments, and organizations. Issues of concern include participant privacy, informed consent, quality control of biospecimens, and various other matters.

Since biobanking is now a global endeavor, international collaboration and national networks are more important than ever. It is also vital that standards and practices are coordinated and developed. Although biobanking may be a business endeavor to some, it is still important that formal plans are in place to ensure the survival of associated research programs. With increasing development of new technology to aid in diagnoses, treatment, and genetic evaluation of diseases, more patients are now aware of the importance of biobanking in research. As a result, donors who participate in studies are also interested in learning more about their sample and results from the research. The following question is addressed by various experts in their field:

What are the important issues that are related to quality management in the collection, processing, and storage of samples?

T. Peakman:

• Specimens should be collected in the form that is best for scientific research. This means that the specimen should resemble the biological environment as closely as possible. Variables should also be avoided as much as possible.

• Shipping of samples for processing can lead to loss of unstable markers due to the time delay.

• Local processing of samples can be challenging due to the maintenance of consistent intersite processing.

• In many studies, the pre-analytical stage is often the greatest source of variation. This can be managed through a proper quality program that helps to make the collection and processing as standard as possible.

• A quality management process should include documentation of the sample such as dates, temperatures, times, operator, location, and more. Other important factors include the use of standard operating procedures (SOPs), audits, training of staff, review of critical materials, etcetera.

• Barcodes are also important to reduce the risk of misidentification.
  Systems and processes should be established to ensure the stability of samples and analytes used.

P. Watson and L. Matske:

• Quality management is essential in the maintenance and operation of a biobank. Biobanks should be able to track each biospecimen as this helps to manage biospecimen quality and the effective use of the sample in the future.

• Quality systems should involve protocols, SOPs, verification, staff education, and training. A good reference point would be standards set by international organizations.

• Quality management can be time-consuming and costly. It is therefore important for the scale of the quality management program to be dictated by the scope of the biobank and researches it supports.

• Training and education of staff are important to ensure they are up-to-date on current role specific practices to ensure consistent quality control and assurance.

H. Moore:

• The meaning of quality can vary among different individuals. In biobanking, complex procedures regarding the collection, processing, annotation, storage, and transport of biospecimens are required for quality management.

• Some crucial elements involve well-documented SOPs that are easily understood and accepted by staff and personnel. Foundational training and annotation of SOP deviations should also be done.

• A quality management plan should be reasonable in scope with room for expected errors. A good example would be the unavoidable biospecimen degradation in certain circumstances. It is vital to be aware of this possibility with the ability to measure relative degradation.

• A good quality management plan can lead to higher quality biospecimens and reproducible research results.      

              
A. Abayomi:

• Attention to detail is critical especially in regions with extreme temperatures where samples may be required to travel large geographical distances.

• The key to ensuring sample integrity is clear and comprehensible SOPs with frequent training, especially at sample acquisition research sites.

• The minimization of preanalytical variables allows the biospecimen to stabilize and closely resemble the donor’s state. This can be possible with a team that is strategic, good with logistics, and can synchronize operations between biobanking staff and researchers. Communication is an essential factor in this process.

Harmonized operational activity and good training are essential in the development and dispatch of kits to collection sites. This is mandatory until the sample reaches the final storage site.
In some environments, the use of appropriate transportation technology and room temperature storage to stabilize biospecimens after collection or isolation of nucleic acids can be extremely useful.

Conclusion

This article addresses one main critical issue that many biobanks or biorepositories are currently facing. Quality management of the biospecimens is important to ensure the highest quality of samples and reproducible results from research.

Reference

Vaught J, Abayomi A, Peakman T, Watson P, Matzke L, Moore H. Critical issues in international biobanking. Clinical Chemistry. 2014; 60(11): 1368-1374.

The Difference Between Biobanks and Biorepositories

What is a Biorepository

A biorepository is a center that functions to:

• Collect

• Process

• Store

• Distribute

Biospecimens help support present and future research studies and investigations. It is a place where various specimens from many living organisms such as, animals and humans are contained and managed. Many life forms such as arthropods, vertebrates and invertebrates can be analyzed and studied through the preservation and storage of their tissue samples. Besides maintaining the relevant biological specimens, biorepositories also have a role to collect the associated information from these specimens for future use in research. One of the most crucial roles the biorepository plays is to ensure the quality of the collected samples. They also have to manage the accessibility of biospecimens while handling the disposition and distribution of their collection.

Biorepository Operations

As previously mentioned, the four main operations of a biorepository are collection, processing, storage and distribution. For elaboration purposes:

a)       Collection – This is the first step where biospecimens are obtained and recorded in the records. This can be done by scanning the sample’s barcode where the information regarding the sample is then transferred into the biorepository’s laboratory information management system. Examples of the information recorded would include the origin of the sample and the time the sample arrived.

b)      Processing – This phase involves the testing of the biospecimens to minimize variation and preparing them for storage. One example is the processing of DNA samples into a salt buffer to stabilize the DNA for long-term storage.

c)       Storage – After the biospecimens are collected and processed, they are stored accordingly based on the required temperature and environment. Some samples are stored in freezers while some can be stored at room temperature. This is where all biospecimens are held before distribution.

d)      Distribution – This occurs when the biorepository fills an order or request from a research team from the biorepository’s inventory system.

Biorepository Standard Operating Procedures

Standard operating procedures or SOPs are vital in a biorepository. It helps to:

·         Minimize variation between samples and reducing issues through standardized guidelines

·         Ensure that biospecimens closely resemble their natural state

·         Provide a framework of how operations should be conducted in a biorepository

·         Ensure reliable and seamless process during operations

·         Provide guidelines for backup during emergencies

An Overview of Biobanks

A biobank is a type of biorepository that stores biological samples that are usually human for research. Biobanks are an important resource for medical research as it helps support various types of contemporary research. It allows access to data for researchers that represent a large population. Samples and data available in biobanks can also be used by many different researchers for various studies. This is crucial as there are many researchers who have difficulty acquiring samples before biobanks existed.

Although many issues such as privacy, medical ethics, and research ethics have been raised, a consensus has been reached that operating biobanks should consider the policies and governing principles that protect the communities that participate in their programs. The term “biobank” can be defined as “an organized collection of human biological material and associated information stored for one or more research purposes”. While biospecimen collections from other living organisms can also be called biobanks, many prefer to reserve the term only for human biospecimens.

Types of Biobanks

Biobanks can be classified based on their purpose or design. Both the terms “biobanks” and “biorepositories” have been used interchangeably. In the United States, the National Cancer Institute thinks of biorepository as a place or organization where biospecimens are stored. The term “biobank” is also being used in the same context in the United States and European institutions. Biobanks can be classified based on different approaches such as:

• Population-based biobanks

• Hospital or academic based biobanks

• Disease-oriented biobanks

• Non-profit organizations or commercial companies

Biobanks can also vary in nature, contents, participants, and scale. For example, a human biobank can be classified based on the tissue type, their research purpose, or ownership of the biobank. The size of the biobank can be based on the disease group, national, statewide, or regional. Other experts classify biobanks into four different basic types:

• Clinical or control based biospecimens from non-diseased donors and donors with specific diseases.

• Biobanks that follow their participants over a long period of time, also known as longitudinal population-based biobanks.

• Biobanks with twin registries that obtain samples from both dizygotic and monozygotic twins.

• Population isolate biobanks that have a setup using homogenous genetic donors.

Despite the various classifications of biobanks from various experts, the currently accepted classification is from the pan-European Biobanking and Biomolecular Resources Research Infrastructure (BBMRI). They distinguish only two types of biobanks which are:

• Disease-oriented biobanks where it contains clinical data and tissue samples

• Population-based biobanks where the focus is on the study and development of complex and common diseases.

Conclusion

In conclusion, both the terms “biorepository” and “biobank” are often used interchangeably as the distinction is blurry. However, one of the most significant differences is that biobanks often refer to collections of human biological material while biorepositories can refer to collections of all living organisms.

References:

1)      Biorepository. Wikipedia. Accessed 11/8/2018. https://en.wikipedia.org/wiki/Biorepository

2)      Biobank. Wikipedia. Accessed 11/8/2018. https://en.wikipedia.org/wiki/Biobank

3)      Kinkorova J. Biobanks in the era of personalized medicine: objectives, challenges, and innovation. EPMA J. 2016; 7(1):4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4762166/

Biospecimen Collection, Processing, Storage, and Information Management

Introduction To Biospecimen Management

Biospecimens have been collected for various uses such as clinical trials, molecular epidemiology, and other research. It is important for specimen management to occur in a controlled environment. An environment where there are strict policies and guidelines in place that help ensure the quality and integrity of the specimen and data. With proper procedures, biorepositories are able to produce high quality biospecimens that are needed for research. Biospecimens are collected from donors for patient monitoring, care, and research studies. They have helped many medical advances such as those for cancer, heart disease, and AIDs. Due to the increased sensitivity and specificity of analytic techniques over the years, it is crucial that biospecimens are of the highest quality.  

Biospecimen Collection

There are various types of specimens that are required based on different research goals. Some examples include:

• Whole blood and blood fractions (red blood cells, serum, plasma, buffy coat)

• Tissue obtained from transplants, surgery, or autopsy

• Urine

• Buccal cells and saliva

• Bone marrow

• Placental tissue, cord blood, or meconium

• Feces

• Hair

• Semen

• Nail clippings

• Etcetera

Specimens should be collected, processed, and stored according to guidelines that take into account future analyses. The collection procedures will differ for different biospecimens and intended analyses. However, all procedures should be accurately documented.

a)       Blood Collection

Blood sample collection should be performed by a trained phlebotomist to reduce donor discomfort and to avoid compromising the quality of the sample. These standard protocols should be followed.

• Glass or plastic tubes with appropriate additives should be used

• Blood should be drawn in an orderly manner to avoid cross-contamination of additives.

• Serum should be separated from other components as soon as possible to reduce contamination. This is important as serum can be used for the improved analyses of nutrients, lipids, antibodies, and lipoproteins.

• Follow guidelines and recommendations for time elapsed between blood collection or removal from the storage unit and temperature for processing of blood specimens depending on the intended analyses.

• Avoid thaw and refreeze cycles.

• Since RNA and proteins are vulnerable to enzymatic degradation, follow necessary protocols that help ensure their integrity during the collection and processing phase.

b)      Tissue Collection and Fixation

Most tissues are obtained through surgery, biopsy, or autopsy. Generally, it would be best if the procurement of the specimen is performed by a trained pathologist. The time between the collection and stabilization process should be minimal. This means that the best approach is to collect, stabilize, and process the specimens rapidly. Detailed records regarding the timing for excision, fixation, or freezing should be kept. For autopsy specimens, it is vital to know the interval between death, collection, and processing of the specimen as tissues degrade rapidly after death. Tissues can be fixed using formalin, alcohol, and paraffin embedding as it has a relatively low cost when freezing or when storage facilities are unavailable.

c)       Urine Collection

Urine collection can be performed in some study designs and to achieve certain analytical goals. Examples of this include:

• Urine collected upon waking up in the morning

• Random specimens used for drug monitoring or cytology studies

• Timed urine collections

• Etcetera

Urine specimens should be kept refrigerated or kept on ice with or without a preservative.

d)      Saliva or buccal cell collection

Saliva along with buccal cells are a great source of DNA for genetic studies. Samples are easily collected by asking donors for self-collection. Methods include using cytobrushes, swabs, and a mouthwash protocol.

Preservation of Biospecimen Stability

As previously mentioned, it is important to minimize the interval between collection and stabilization. The temperature of biospecimens should be reduced when freezing is the endpoint. Control of processing time is necessary if fixation is the stabilization endpoint. Biobanks should utilize the method that preserves the highest number of analytes.

Biospecimen Processing

Biospecimens should be processed using the methods that preserve the analytes of interest or following the study design. For blood specimens, the processing method used should be based on the laboratory analyses. Tissues can be processed in the pathology suite or operating room once the specimen is resected. Buccal cells can be processed via centrifugation. For DNA extraction, the gold standard method is phenol-chloroform extraction. However, other methods can be used.

Storage of Biospecimen

Based on the intended laboratory analyses and requirements, biospecimens can be stored in various conditions. Examples include mechanical freezers, liquid nitrogen tank, room temperature, among others. Backup and alarm systems are necessary in case of mechanical failure. Staff should be trained for maintenance and repair of equipment. The labels used for biospecimens should be capable of withstanding the storage conditions.

Information Management and Specimen Tracking

Information management involves the collation and analysis of data associated with biospecimens as it helps support research. Since there are vast amounts of data, extensible and flexible informatics systems will be required. Biospecimens are documented and tracked using various forms of data management tools such as notebooks, multi-user software, and various automated information systems.

References

Vaught JB, Henderson MK. Biological sample collection, processing, storage, and information management. IARC Sci. Publ. 2011; 163:23-42. Accessed 10/25/2018. https://publications.iarc.fr/_publications/media/download/1398/68b153f74693289ae66d767a8cbe1ca667df4f1b.pdf

Human Blood Samples in Biobanks

What are Blood Samples?

Blood samples are most commonly obtained from the antecubital fossa where the veins are closest to the surface. The blood sample can be taken by anyone from a doctor to a phlebotomist or a nurse. Most blood sample collections will occur at a clinic, hospital, or at a pathology collection center. A tourniquet is first wrapped around the upper arm to slow down the blood flow while the area where the insertion area for the needle is cleaned with an antiseptic cloth. The needle is inserted, and the blood sample is transferred into containers or tubes. Proper dressing of the wound is then administered to prevent infection and to keep it clean. These tubes are then labeled with a unique identification number along with other important information. These samples are then transported to their respective destinations, such as laboratories or biorepositories.

An Introduction to Biorepositories

Biobanks and biorepositories assist in providing the materials required in clinical trials and research. There is a growing number of biobanks that help to collect data and samples from the population as a response to the increased demand of these services. The services provided by various biobanks also mean that acquiring biological materials can be guaranteed. The existence of biobanks has allowed the accumulation of biological samples from various resources. 

Biospecimens in Biobanks

Some of the examples of human biospecimens available through biorepositories include both normal and diseased states such as:

• Purified DNA

• Hair tissue

• Nail

• Whole blood

• Plasma

• Serum

• Red blood cells

• Platelet concentrates

• Platelet-rich plasma

• Saliva

• Semen

• Breast milk

• Organ tissue

• Etcetera

All specimens should be collected and processed according to the proper guidelines and procedures. 

Functions of Biorepositories

While collecting biospecimens, biorepositories also collect demographic data such as medical history, lifestyle habits, medications, and family history to create an accurate scientific database. These samples are only labeled with a unique code for identification purposes. These specimens are then maintained in the proper environment and equipment to ensure the highest quality. Another crucial point in the management of any biobank is the privacy and rights of the donors. This means biobank managers need to train their staff regarding the policies and standard operating procedures (SOPs) of the biobank.

Whole Blood and Blood Cells 

In human biospecimens, the buffy coat and whole blood are essential for biorepositories. Whole blood refers to a sample that consists of red blood cells, white blood cells, platelets, and plasma. The buffy coat describes the white blood cells and platelets that form the anti-coagulated blood sample. Both these samples are essential as they are the main source for cellular nucleic acids, construction of a DNA biobank, and achieving the maximum quality and quantity of germline DNA. 

Storage for Human Blood Cells

Blood is one of the most common biospecimens collected in human biobanks as it is a source for DNA and RNA. This is why anti-coagulated blood is a prerequisite for plasma-derived cell-free circulating nucleic acid molecules and genomic or mitochondrial DNA and RNA. One of the most commonly used anticoagulants is ethylenediaminetetraacetic acid (EDTA) for various protein assays and DNA based studies. However, citrate is more appropriate for white blood cell cultures. Storage conditions and quality of biospecimens are of vital importance as it determines the yield of extracted DNA and RNA from buffy coat or whole blood samples. 

Since RNA is easily degradable, the World Health Organization – International Agency for Research on Cancer (WHO-IARC) has suggested that it be stored in nitrogen storage below -130⁰C. Samples stored at -140⁰C by liquid nitrogen have been observed to keep the RNA in a functional state and intact for more than 50 months. To maintain the biospecimen’s reliability and preventing the possibility of multiple freeze-thaw cycles, DNA protection and stabilization can be done at room temperature which eliminates the costs for freezer storage and lowering maintenance costs for biobanks. While purified DNA can be stored at -20⁰C for months, both purified DNA and RNA are much more stable at -80⁰C in nuclease-free water or aqueous buffers for long-term storage. 

For plasma, anticoagulants such as lithium-heparin and EDTA can be used. Storage of both serum and plasma at -80⁰C have shown that there is adequate stability in the different biomolecules. The cycle of freezing and thawing should be avoided as it leads to the degradation of nucleic acids and proteins. 

Conclusion

Due to the increasing scientific developments in the past few years, it has increased the need for biological material in clinical trials and research. Biorepositories play a crucial role in supporting the researcher’s access to samples that meet their scientific criteria. It is important for biobanks to play their role in the management of data, collection, processing, and storage of biospecimens.  

References:

Mohamadkhani A, Poustchi H. Repository of Human Blood Derivative Biospecimens in Biobank: Technical Implications. Middle East J Dig Dis 2015;7:61-8.

Newborn Genetic Screening Program

What actually happens to newborn DNA samples once its been tested for genetic disorders?

In the last five decades, most babies born in the United States have unknowingly participated in a test called the Newborn Genetic Screening program. The test has been established to identify treatable genetic disorders in newborn infants. Early identification of these disorders is crucial in addressing symptoms and preventing a lifetime of disability. The test is a simple one: one small prick to the heel to collect a blood sample. With this sample doctors and nurses test for a variety of hereditary and congenital disorders. The controversy surrounding this program doesn't start until after the completion of the testing, whereby the samples are often stored in state-run biobanks.

Your or your child's DNA may have been stored and shared without your consent. Given that this has been going on since the 1960’s it is more likely than not that your samples are out there without your knowledge. Most people don't even know what the Newborn Genetic Screening test is or that they were a part of it. It’s importance and significance in identifying preventable disorders is not under question, but what happens to residual samples should be brought to light. State-run biobanks (or data repositories as the Association of Public Health Laboratories calls them) are established to store these samples and are shared with departments such as law enforcement for analysis and research. 

What is the Newborn Genetic Screening Test?

The Newborn Genetic Screening test began in the 1960’s. Back then it served to simply detect one genetic disorder, phenylketonuria. A condition that causes brain damage but, if caught early enough can be treated. Since then our knowledge of genetic disorders has improved immensely, largely due to the NGS Program. Collection of the blood sample must be completed within 12 to 48 hours after birth and can now detect between 30 and 50 genetic disorders. It is without a doubt an important and lifesaving program, and an estimated 12,500 newborns are diagnosed and saved annually. Participation in the NGS Program is a legal requirement. and therefore, parental consent is not required. However most states allow parents to “opt out” if there are religious or philosophical reasons. However hospitals do not usually inform the parents that the test will be conducted, making it challenging to opt out.

Duration and Location of DNA Storage

Your blood sample storage is different depending on state of birth. The most common practice is for it to be stored in state-run biobanks. Parental consent laws also differ for storage, in some states parental consent is necessary before storage of samples. In California for example, once tested the state retains the rights to store the samples. other states destroy the samples after six to twelve months whilst other store it much longer, ranging from 21 years to indefinitely.

How are These Samples Used?

Even though states might not use the samples, other researchers and government agencies still have access to them. It might be necessary for parents to find out what their or their children residual blood spots are used for. Residual blood spots storage can be used in the following.

a. Research purposes such as:

• Retesting the samples to confirm the screening results

• Developing new screening tests

• Developing new techniques for forensic studies

• Identification of new diseases

• Quality control purposes

• Access for those who are not biorepository lab technicians (such as those people in law enforcement)

b. Law enforcement purposes such as:

• According to a Columbia Broadcasting System (CBS) report, they discovered that a minimum of four court orders and fie search warrants were obtained for identified blood spots. One of these cases involved a request to test the residual blood spot for drugs at birth. There are also cases where coroners use these samples to help in the identification of bodies or parents who request it to prove paternity.

Most famously the issue of storing these samples was brought to light during the trial of the Golden State Killer. The DNA from the crime scene was matched by law enforcement officials with DNA from a California state-run biobank. They used an open-source genetic database, called GEDmatch to identify the killer.

Controversies

As you can imagine the NGS Program presents several opportunities for abuse. These residual blood spots are easily accessed and many issues can be raised, including: 

a)     Consent

Parents of the children are not usually informed or asked for consent to the screening. Given the nature of the information collected during this test many people are concerned with the number of loopholes that exist. In the Genetic Information Nondiscrimination Act of 2008 that exists to prevent genetic discrimination from health insurance companies. Since the screening is paid for through health insurance companies. Many fear that a positive test could very well taint a child's record and that insurance companies could use it against people in the future.

b)      Ethics

There are ethical concerns surrounding residual bloodspots. Some are concerned that residual blood spot research is a way for the government to further control its citizens and have access to not only their records but also their genetic material.

c)       De-identification

While some believe that de-identification of DNA is possible by not storing the identifying information together with the blood samples, many argue that the DNA itself is an individual’s unique code and can always be used to identify individuals.

Conclusion

The laws for residual blood spots vary depending on the state one is born in. Those concerned should read up on the state’s procedures and policies. It is also important to note that policies and laws can change with time. This means individuals concerned with what happens to DNA samples should stay up-to-date with the new policies.

Ethics in Biobanking

Introduction

Biobanking ethics are important and one of the most debated issues in public health and bioethics. Biorepositories carry the potential to advance disease research in unprecedented ways. There are however concerns about donor privacy and not all biorepositories make sure that they follow ethical standards. People’s DNA and tissue sample has been used without respect for their rights. Regardless of peoples differing views and perspectives, one thing can be agreed upon among most experts, that biobanks are revolutionary. Biobanking ethics include issues such as, but not limited to:

• Controversies and key challenges faced in biobanking ethics

• Issues of informed consent

• Withdrawal from participants

• Broad consent

• Ethics of re-contact

• Confidentiality issues

• Ownership, property and commercialization problems

Issues in Brief

1)      Informed Consent

Informed consent is crucial in ensuring that ethical standards are followed in both research and therapy. It ensures that the participant understands “the nature, duration, and purpose of the experiment; the method and means it is to be conducted; all inconveniences and hazards reasonable is to be expected; and the effects upon the individual’s health may be due to the participation in the experiment." (Excerpt from Springer Article) One of the major issues of informed consent in biobanking is that it only applies to the donor and not those who are connected to the donor. Next, since biospecimens can be used in future studies, participants cannot be “informed” at the time their tissue is obtained as the nature of future researches are not yet known.

2)      Broad Consent

There are some experts who believe that broad consent can be a potential solution to the issues of informed consent in biobanking. However, there are some who disagree as it offers minimal protection and minimal guarantees. Broad consent is the permission given by the donor for the biobank, so the biorepository can do what they see fit with the genetic material. While some individuals argue that broad consent is a means of maximizing autonomy, some see it as the opposite where it is an abuse for autonomy. Ethicists worry that broad consent causes donors to relinquish their rights regarding how their genetic material is used in the future.

3)      Confidentiality

One of the main features of genetic information is that it can be used to identify the donor and those related to them. While ethicists argue that identification can be discouraged through various methods of anonymization, there is always the possibility that identification is possible. The risk of identification increases as databases grow.

4)      Property and Profit

There is also the issue that participants or donors do not own their tissue samples. This is based on the traditional understanding that body parts are res nullius which means that they do not belong to anyone once detached. Ethicists have argued that there are valid reasons for following the “no property” rule for biospecimens. Allowing property would restrain studies and research to the point where it would become untenable. Another issue is that commercial companies may look to make very large profits from donated samples.

5)      Feedback to Participants

Another ethical issue is whether or not to tell participants regarding incidental findings from their donated tissue samples. Incidental findings can be defined as “observations of potential clinical significance that have been discovered unexpectedly in a healthy subject unrelated to the purpose and variables of the study.”(Excerpt from Springer Article)

6)      Participation, Representation, Maintenance of Trust

Biorepositories are also worried about the mass withdrawal of participants as it will ultimately result in the loss of set-up costs. The maintaining of trust between the public and biobanks are crucial to prevent participant withdrawal and biobank failure. Currently, there is still no one way that is viewed as the best method of practice in this area.

7)      Re-contact

Re-contact is becoming an increasingly crucial issue as there is very little industry conformity on how re-contact should be managed. There needs to be a balance between what donors are informed and what's included without overburdening them. Biorepositories and research teams should view the ability to re-contact as a limited resource. Currently, there is no standard that biobanks can look to adopt for this issue.

Conclusion

The problems and challenges in biobanking ethics mean that there is a need for alternative models to address the issues. Biobanking presents important and significant ethical challenges. It is important for those involved to be aware of the advancements and developments in the debates surrounding these issues. By raising awareness of these issues, public interest of will increase and as a result biobanking can continue to change the medical research landscape.

References:

Widdows H, Cordell S. The ethics of biobanking: key issues and controversies. Health Care Anal. 2011; 19:207-219.