Custom Collection Services

What is a Biorepository?

A biorepository is an organization that collects, processes, stores, and distributes tissue samples for clinical research or other scientific investigations. They assist in maintaining and managing specimens such as tissue samples from humans, animals and other living organisms. A biorepository functions to maintain biospecimens, collect relevant information and assure the quality of the samples in their collection. They follow standard operating procedures (SOPs) that reduce anomalies in samples and which also provide guidelines for storage and maintenance. SOPs also ensure that biospecimens collected closely resemble that of their natural state. It helps biorepositories maintain a standardized framework for conducting operations and allows for the seamless implementation of processes.

What is Custom Procurement?

Some biorepositories, like Geneticist Inc., provide custom tissue procurement. This means that they are able to provide custom collection of biofluids, tissue samples, and blood samples in various specialties such as gastroenterology, oncology, rheumatology, neurology, and dermatology. Biorepositories that offer custom collection services have the ability to collect from a vast range of medical procedures such as elective skin biopsies, resections, autopsies, endoscopies, blood draws, and more. Due to the nature of the collection processes and procedures, biorepositories need to have a skilled logistics team and an expert medical courier network. The custom procurement of biospecimens is important especially if:

• Fresh collections are required

• There is a necessity for matched tissue pairs

• Rare indications or specific specimens

• The need for specific procedures during the collection and processing of samples

• Active cases and autopsies are needed

• The study or research is complicated

Examples of Biospecimens

• Biofluids – Examples of biofluids include stool, urine, whole blood, serum, plasma, cerebrospinal fluid, saliva, sputum, and swabbed material. Biofluids can be available frozen or fresh. Depending on client preference, it can be with or without additives.

• Tissue – Some examples of human tissue include fresh tissue, fixed tissue, frozen tissue, formalin-fixed paraffin-embedded (FFPE) blocks, whole tissue samples, stained slides, unstained slides, tissue microarrays, and more. These samples can be annotated with the proper genetic and molecular characterizations, outcomes data, pathology reports, and patient characteristics.

• Cells – Some research may require frozen or fresh cells that are still viable. These cells can be isolated from peripheral blood, cord blood, and bone marrow of normal donors and those with disease. Some examples include myeloid cells, pluripotent stem cells, mononuclear cells, and lymphoid cells.

What to Look For?

There are several factors that help decide which biorepository to go with when custom collection services are needed. Some of the factors that can help decide are:

a)       Procurement format options

Since prospective collection enable clients to decide which elements fit their needs, a custom procurement format can be designed with the help of our experienced team of scientists. Depending on the need of clients, custom procurement of biofluids, fresh tissue, frozen tissue, and more are available. Clients can also set the exclusion and inclusion criteria for specimens and donors.

b)      Partnerships

It is important to look for a biorepository that has a vast network of clinical partners to help ensure the highest quality of required biospecimen collection. It would also increase the access to more human tissue samples in various formats.

c)       Team members

A biorepository with experienced and certified team members would be the best choice as they would be well-trained with the ability to better understand the needs of researchers and to help find better solutions if necessary. With a great team on hand, specimens are more likely to be of the highest quality and fulfill the requirements of clients.

d)      Quality assurance

It is important for the biorepository to perform quality control checks to ensure that specimens are of the highest quality. This means that the staff should understand the appropriate storage or procurement procedures and ensure that the SOPs are adhered to strictly.

e)      Consent and privacy

Biorepositories should follow the procedures and guidelines during the procurement of human tissue samples. Informed consent and privacy of the donors should be of the highest priority to protect their interests.

Why Geneticist?

For custom collection services, the staff at Geneticist can design custom collections of a wide variety of biospecimens. Our staff are certified, experienced, and highly trained. Geneticist is a biorepository that is compliant with the Institutional Review Board (IRB) standards and provides the highest quality of collections. All our biospecimens and material adheres to the official protocols and is approved by the IRB and Independent Ethical Committee (IEC). Geneticist operates in accordance with current Federal Regulations, Health Insurance Privacy and Portability Act (HIPAA) and International Conference on Harmonisation – Good Clinical Practice (ICH-GCP) guidelines. With the proper inventory management process and extensive procurement formats, Geneticist strives to fulfill client requirements and satisfaction.

Specimen Extraction and Collection Process

Introduction to Specimen Extraction

The number of research and clinical studies being conducted to help improve screening procedures, diagnostic tests, therapies, and prognosis is rapidly increasing. This means tissue samples or biospecimens such as fresh frozen tissue and formalin-fixed paraffin-embedded (FFPE) blocks are of great value researchers. Obtaining high-quality samples is the first step towards credible data and testbale results. This is why suppliers of biospecimens should aim to collect, maintain, and disseminate the best biospecimens possible. High-quality samples are those that resemble the biology of the donor before its removal from the host. Once removed, the specimen may change based on the environment. Such things as exposure to different chemicals or environmental factors during the collection or storage procedure are all things that can negatively affect the sample.

Pre-Analytic Variables

Pre-analytic variables are factors that affect the collection, processing, and storage conditions that impact the integrity of the biospecimen before their removal from the host. Examples include, but are not limited to:

a)       Donor Physiology

This includes things such as the health of the donor, consumption of food, beverages or medications before the collection of the specimen, time of day the specimen was collected, and the type of anesthesia used. In female donors, even the time of their menstrual cycle can affect the downstream analysis. This stresses the importance of collecting this information from donors to decrease variability between samples.

b)      Collection Practices

It is important to maintain uniformity during the removal and collection of specimens from donors as different methods can affect the quality of the biospecimens. These specimens should also be preserved very quickly after removal from the donor. Newer preservation methods should be considered as they can allow for better and more accurate preservation of the biospecimen. Some of the factors that should be considered during biospecimen collection include, inter alia:

• The site of collection

• Type of anesthesia used

• Warm ischemia time

• Use of stabilizing agents

• Types of fixatives used

• Exposure time to fixatives

• The temperature for maintaining biospecimens.

All the above factors can affect the stability and degradation of molecules in the samples. Annotation of the biospecimens should include the donor’s information. This data should be recorded and maintained in a database. Handling of biospecimens should also be optimized to reduce molecular changes that may occur due to processing activities.

Analytic Variables

Analytic variables are factors that affect the performance of a testing procedure. To reduce errors, some of the following factors should be considered:

• Always use validated assays whenever possible.

• Train technical staff regarding the standard operating procedure.

• Use uniformed reagents.

• Use the proper type and number of control samples.

• If possible, randomization should be applied.

• Use standardized methods during the documentation and interpretation of results.

Biospecimen Collection and Reference Ranges

The specimens collected has to be appropriate for the clinical study and downstream applications that will be used in the research. Biospecimens should be examined by a qualified histopathologist to ensure quality and accuracy. Reference ranges should be used to ensure that any deviation from the reference range can be accurately detected. This is due to the reason where disease can be defined as a deviation from normal variation. This means the diagnosis of the disease depends on the scope of normal variation. All reagents should be quality controlled, so it is fit to be used in the assay. The standard operating procedures (SOPs) should be reproducible with control biospecimens that have a range of anticipated assay values. Poorly handled biospecimens tend to produce erroneous test results due to molecular changes.

Biospecimen Storage

The following practices should be applied to all types of biospecimens:

• Follow standard protocols when storing biospecimens to maintain quality. Personnel should record the conditions for storage, deviations from SOPs, temperature, equipment failures, and thaw / refreeze episodes. It is essential to validate storage equipment, maintain back up equipment, and identify “hot spots” in the freezer.

• Store specimens in a stabilized state.

• Avoid unnecessary thawing and refreezing.

• Follow protocols if thawing and refreezing are necessary.

• Inventory tracking is desirable as it helps reduce the disruption of the environment during retrieval of samples.

• Consider the length of storage, type of biospecimen, biomolecules of interest, and study goals when selecting storage temperature for samples.

• Use appropriate storage vessels and ensure stability under storage conditions. The proper storage vessel can prevent sample loss and reduce costs of storage and retrieval of biospecimens.

• Choice of labels and printing should include the consideration of long-term storage conditions.

• Protection for personnel such as face shields and gloves should be worn.

• Each specimen should have a unique identifier that is clear, affixed, and able to endure the storage conditions.

• Automated alarms that monitors the storage equipment with the capability to warn personnel when equipment failure occurs should be in place.

• An alternative power source and other backup equipment should activate automatically if there is equipment failure.

• SOPs to routinely test equipment failure, backup equipment, and other emergency situations should be available.

• Specimens should only be available to authorized personnel.

• Ensure appropriate shipping conditions and documentation.

References

Biospecimen collection, processing, storage, retrieval, and dissemination. National Cancer Institute. Accessed 9/18/2018.https://biospecimens.cancer.gov/bestpractices/to/bcpsrd.asp

Tissue Procurement Problems

Introduction

Formalin-fixed paraffin embedded (FFPE) tissue blocks are a valuable resource for many significant research programs as researchers tend to select this type of biospecimen as frozen or fresh tissue blocks may be harder to acquire. There is also the challenge that the number of fresh frozen tissue samples may not be able to fulfill the requirements of the research protocol. The FFPE preservation technique demands a fast and rapid fixation after the process of resection of the target biospecimen in a neutral buffered formalin. Once fixed, the specimen is then embedded in paraffin wax. FFPE is now the commonest tissue preparation method used to archive research biospecimens. Currently, almost all surgeries in this day generate FFPE tissue samples. FFPE tissue blocks are crucial as they offer the potential for the discovery of significant information especially in biomedical research programs and drug discovery. Other research applications that utilize FFPE biospecimens include:

• genetic studies

• biomedical identification or authentication

• visualization of tissue structure

This, therefore, makes FFPE tissue blocks ideal for:

• the study of autoimmune diseases – rheumatoid arthritis, systemic lupus erythematosus

• the study of long-term cancers – colon cancer, lung cancer, breast cancer

Challenges

However, there are several challenges that researchers face when it comes to obtaining FFPE tissue samples. Some of the challenges include:

1)     Oversight of the Pathologist

In some cases, the FFPE samples are not obtained or processed appropriately as the certified pathologist is not on site to supervise and ensure that the proper procedures are followed during the procurement of the specimen. Biorepositories should ensure that they hire enough licensed pathologists to ensure that there is no manpower shortage as it could impact the quality of their tissue specimens.

2)     Difficulty Acquiring Samples

There are certain situations where a research team or company requires access to FFPE tissue samples that are hard to come by. For example, FFPE samples from patients with metastatic melanoma might present a challenge to biorepositories. Research teams should partner with a biorepository that has a vast network for tissue procurement as it can help tremendously in the collection of special samples needed in specific research protocols.

3)     Rapid Turnaround

Studies or research that needs a quick procurement of FFPE tissue blocks may pose a challenge to many biorepositories. These research teams that are looking for a rapid turnaround of samples should ask biorepositories about their accelerated procurement method which may then be able to provide the required biospecimens within the time frame.

4)     Transparency

Research teams looking to procure tissue samples need to keep in mind about transparency as studies rely on well-annotated tissue blocks that go through the proper fixation and preservation technique. Before obtaining samples from the biorepository, be sure to ask regarding their specifics and standard of procedure for the fixation and quality assurance protocols. This can impact the result and credibility of the entire study.

5)     Review of FFPE Biospecimens

Some biorepositories obtain their tissue samples from local sources such as the local hospitals. However, not all providers take the time to ensure that the specimens are of the highest quality. Biorepositories are responsible to ensure that a gross and microscopic examination of the FFPE biospecimens to ensure that the samples obtained are of the highest quality.

6)     Sourcing

With the growing number of organizations and biorepositories, research teams that are looking to source biospecimens should consider companies that follow the best practices and have high standards when it comes to their collection and fixation protocols. Unreliable sources may not be able to provide high-quality FFPE tissue samples. Before procuring the required biospecimens, enquire where the organization obtains their samples and the reliability of it.

7)     Patient Information

The patient information from the samples can be valuable and crucial in a research. The more information you can obtain regarding the patient from their data, it can help with some of the results from the research especially in terms of demographics and risk factors of a disease. Patient information also helps you to find the correct patient cohort as some study designs exclude those below or above a certain age. It is therefore important to procure the biospecimens from a biorepository that can provide the necessary data such as the details or a refractory disease, metastatic diseases, or newly diagnosed disease. A new case of cancer or a relapse can also affect the results of a study greatly.

Conclusion

In conclusion, there are many factors to consider when it comes to selecting a new biorepository or organization to partner with to obtain tissue samples. It is important as these specimens ultimately determine the results and credibility of the study. Choosing a credible company that provides the highest quality FFPE tissue samples is one of the most crucial steps in the early stages of a study. Low-quality biospecimens result in wasted hours of study, effort, and decreases the overall morale of the research team.

References:

Doiron L. Typical problems with FFPE tissue samples – and how to solve them. 2014. Folio Conversant. Accessed 7/11/2018. 

https://www.conversantbio.com/blog/bid/387449/Typical-Problems-with-FFPE-Tissue-Samples-And-How-to-Solve-Them