SOP’s of a Biorepository

Introduction to Standard Operating Procedures

Biobanks and biorepositories needs to develop and adopt standard operating procedures (SOPs) that describe the policies and processes of the biorepository in detail.
SOPs should be detailed, well structured, and should undergo a strict approval process. SOP’s need to be reviewed periodically to assess the necessity of updates. Once implemented, SOPs should be routinely followed. Copies of SOPs should always also be stored in designated locations accessible to all personnel at any given time. Biorepository and biobank personnel should review SOPs prior to implementation.

Contents of the SOP

The SOP manual can be very dense and detailed, but should at the very least contain the following points:

Informed Consent

All biorepositories need to keep all records and related documents of the informed consent status for every biospecimen. Additionally, the procedures or protocols followed to obtain informed consent must be specified. Along with this the protection of privacy for all participants and data confidentiality should also be described.

Equipment

This section of the SOP should include the monitoring and calibration of all of the equipment. SOPs regarding the maintenance and repair of equipment is also crucial. All biorepositories should have their own procedures that routinely monitor all the equipment that is involved in the preparation and storage of biospecimens. The accurate calibration of equipment is vital to avoid affecting the quality of biospecimens and their data. The operational settings of the equipment should always be recorded along with all of the repairs that have been performed.

Collection Supplies

All biorepositories should have high standards for their reagents and consumable supplies that are used in the collection, processing, and storage of biospecimens. This means that the supplies should be acquired from certified and approved vendors and should meet the material specifications. Personnel should ensure that these supplies are in good condition prior to their utilization.

Identification and Labeling

All biorepositories will need to have their own guidelines and protocols for the labeling and identification of biospecimens. This should be coupled with the linking of biospecimens to their records regarding donor information and informed consent, so that when required it will be readily available.

Collection and Processing Methods

In this section details are extremely important to allow for the accurate replication of collection and processing procedures. This means that detailed descriptions of the supplies and equipment used are necessary. Along with the methods and processes used in the division of biospecimens into respective aliquots. The collection and processing of biospecimens must include records of staff names, dates, and specific times so potential pre-analytical variables are all recorded.

Storage and Retrieval

All procedures for the storage and retrieval of biospecimens from the biobank should be well described. This should include the guidelines for the addition and withdrawal of biospecimens, response to requests, fulfilling requests, and the disposition of biospecimens.

Transport and Distribution

All biorepositories should have designated policies and protocols for the transport and distribution of biospecimens that ensures their integrity, quality, and safety. This means guidelines should include packaging specifications addressing temperature conditions, temperature monitoring, regulations for the transport of hazardous materials, shipment logs, notifications for delivery, delivery confirmation, and agreements that cover transfers.

Quality Control

All biobanks should have their own testing procedures that document the results which are then kept in the records. This should comprise of tests that assess and control the quality of biospecimens, confirmation of histopathology diagnosis, assessment of nucleic acid integrity, biomarker expression, and more.

Informatics

Policies and guidelines for the management of records and procedures that define data collection methods, access to data, reporting, and quality control of data should be available for all biobanks.

Biosafety

It would be best for all biorepositories to have policies and procedures that address biosafety issues such as the reporting of staff injuries, precautions that the staff should have for bloodborne pathogens, the use of personal protective equipment, handling of hazardous material, and the disposal of biohazardous material and medical waste.

Training

All centers should have their own policies and procedures when it comes to the training of their personnel. These training should be documented, corrective actions that are taken, steps taken to resolve discrepancies for inventory or shipment, manage power outages, monitor samples, and the handling of emergencies and natural disasters.

Security

Procedures for security concerning administration and information systems should be available for all biobanks and biorepositories. These SOPs should address the different points of contact and personnel that are involved in backup. Names and contact numbers for the designated personnel should also be available.

Conclusion

It is important for all biorepositories and/or biobanks to have detail-rich standard operating procedures as it helps personnel get organized and offers guidelines in times of emergency. SOPs can also help to provide detailed information about the processes and preservation methods that ensure biospecimens retain their integrity and are of the highest quality.

References:

Quality management: Technical and operational best practices. National Cancer Institute. Accessed 10/18/2018.https://biospecimens.cancer.gov/bestpractices/to/qac.asp#b-3-3

CTM Logistics

Introduction to CTM Logistics

Clinical trial materials (CTM) logistics is an important business that manages the transport and delivery of biospecimens and tissue samples. The business of tissue preservation, meeting demands, and shipping these specimens from places like a biorepository to their destinations does not come without challenges.

Challenges facing CTM Logistics

Besides the conventional logistics and supply-chain challenges, those involved in CTM logistics also face:

1)      Standards

Many countries do not have standard protocols for the entry of trial supplies. Due to the demands of clinical materials worldwide, the challenge of shipping CTMs include the extraordinary constraints of import and export.

2)      Notice

Those involved in CTM logistics have very little to no notice when it comes to knowing when the materials need to be shipped out. The issue of material suppliers being disconnected can also cause delays at trial sites due to a supply chain issue.

3)      Product Standards

There are many trials that need both comparator or placebo drugs along with the trial drug. However, these trials are usually “randomized” throughout the course of the trial. This means that different labels will be needed for different trial protocols or different locations.

4)      Handling and Transport

Since the quality of these materials can be affected during handling and transport, companies involved in CTM logistics need to have the equipment and manpower that are suited to deal with the supplies.

5)      End Users

There is also the issue where some end users (such as researchers and physicians who conduct trials at investigator sites) who are not trained supply chain managers.

6)      Cost

Companies providing CTM logistics services also have a high risk of overrunning their cost due to difficulty addressing all cost drivers, inefficiencies in the system, and potential expenses when corrective actions need to be taken.

7)      Communication

Just like any other field, poor communication and coordination of the supply chain can result in action gaps, duplication of efforts, and delays. Frequent plan revisions are required if there are errors.

8)      Circumstances

Many studies often face the risk of delays and the need to lengthen their timeline in situations where there is the unexpected expiration of products or out of stock situations.

The industry has adapted to some of the challenges and constraints over the years. Although the clinical trials can be affected by issues in the supply chain, the successful completion of these researches has led to the better diagnosis, therapy, and prevention of diseases.

Supply Chain Stages

The following are critical supply chain stages:

• Planning: Those that are responsible forecast and come up with a strategy.

• Sourcing: This is done to acquire the necessary materials such as ancillary supplies, drugs, and lab materials.

• Manufacturing: Once ready, the necessary packaging and labels that are needed are manufactured.

• Storage: The CTMs are stored in the appropriate condition using the proper equipment (if needed).

• Distribution: The CTMs are imported or exported according to local authority regulations.

• Site: The CTMs are stored, samples managed, and data processed.

• Return: The company manages the shipment along with final CTM reconciliation.

• Destruction: The CTMs are recycled or destroyed accordingly.

• Analytics: All accumulated data are processed and analyzed.

Training

Individuals who are interested in positions such as clinical supply chain managers or supervisors and those interested or new to the CTM industry. Employees that go through special training pertaining to CTMs are more efficient in their duties in the company and industry. They learn about:

• The overview of the supply chain from beginning to end

• The appropriate packaging and labeling that suits the needs of a specific study design

• Having a plan of action to prepare the materials

• Implementing their plan and troubleshooting

• The logistics involved for distribution of CTM to trial sites that are located worldwide

• How to outsource vendors for the labeling and packaging purposes

• Interactive Response Technology

• The different roles of their team members and their expectations for the CTM group

• Current Good Manufacturing Practices (cGMP)

• The implementation of cGMP in the packaging process

Services

The company that is in charge of CTM logistics generally provides services for:

• The receiving, storage, and distribution of the materials

• Obtaining the necessary import and export licenses from the authorities

• Acquiring custom clearance for the CTM

• Data management (verification, validation, query, tracking, coding for diseases or medications, result presentation)

• Biostatistics (Statistical analysis, writing, result presentation, and more)

• Importing and exporting CTMs

• Short or long-term storage of specimens

Conclusion

More clinical trials are conducted globally. This creates a significant logistical challenge as the management of CTMs and the supply chain require tactical knowledge and a vast commitment of resources to avoid delays. There are many who would find that it is much more efficient to hire CTM service providers to manage the logistics as there are many challenges in this industry.

References:

1)      Basta N. Clinical trial logistics capabilities are expanding. Pharmaceutical Commerce. Accessed 9/5/2018. http://pharmaceuticalcommerce.com/clinical-operations/clinical-trial-logistics-capabilities-are-expanding/

2)      CTM logistics. Geneticist. Accessed 9/5/2018. https://www.geneticistinc.com/ctm-logistics/

3)      Clinical research services: clinical logistics. Parexel. Accessed 9/5/2018. https://www.parexel.com/files/6714/1155/2827/CLS_Supply_Chain_Poster_Sept14.pdf

4)      Clinical trial materials training course. ISPE. Accessed 9/5/2018. https://ispe.org/training/classroom/clinical-trial-materials

Types of Biorepositories

Introduction

A biorepository is a center that functions to collect, process, store, and distribute tissue samples or specimens to support future research. These tissue samples can be sourced from humans or animals. The biorepository is responsible for maintaining the quality, accessibility, and distribution of these tissue samples.

Operations

• Upon delivery the tissue samples are recorded all information regarding the sample details are keyed into the laboratory information management system.

• Biospecimens are then processed to ensure consistency of the samples. Proper tissue preservation methodology is absolutely crucial to a biorepository.

• These specimens are then stored and held in their appropriate conditions. Sample holding boxes and freezers are sometimes used, however it depends on the storage requirements. For example Formalin-fixed paraffin-embedded tissue blocks can be stored at room temperature.

• Distribution involves retrieving the required samples from the inventory.

Standard Operating Procedures

Standard operating procedures (SOPs) are important for biorepositories as they help in the following:

• Reduce problematic variables within the samples,

• Ensure that biospecimens resemble specimens in their natural state,

• Provide standards on how operations should be conducted.

Types and Uses of Biorepositories

There are many different types of biorepositories that exist. Some help with biomarker validation, and others are integrated with registries. Most biorepositories are focused on collecting biospecimens for specific diseases. Others function to identify genetic clues that can aid in the guidance of therapeutic development. Similair to disease-focused biorepositories there are those  focused on the understanding of practices and habits. Biorepository sponsors can also vary. While some are funded as part of research to aid in the collection of specimens from participants, some are sponsored by organizations or medical centers to collect, process, and store samples from a wide variety of patients. Some biorepositories are organized by patient advocacy organizations to help kick-start research of specific diseases.

Examples

1. The Alzheimer’s Disease Neuroimaging Initiative – is a disease-focused biorepository and biomarker validation program that uses the samples and data collected from Alzheimer’s disease patients and patients with other forms of memory impairment.

2. The Health Outreach Program for the Elderly (HOPE) is a biorepository at Boston University that supports multiple studies. The HOPE registry follows up with their Alzheimer’s patients annually.

3. The United Kingdom Biobank is a biorepository with a broad focus. They aim to improve the diagnosis, treatment, and prevention of various diseases such as cancer, stroke, diabetes, heart disease, eye disorders, depression, dementia, and arthritis. In between 2006 to 2010, they managed to recruit half a million individuals between the ages of 40 to 69. Samples such as blood, saliva, and urine have been donated for analysis. These participants have also provided detailed personal information and consented to future follow up for many years to help researchers discover how various diseases develop.

4. The Autism Research Resource is sponsored by the state of New Jersey to research autism in families where more than one child is affected.

5. The Centers for Disease Control (CDC) Cell and DNA Repository use samples from transformed cell lines available through the Genetic Testing Reference Material Coordination Program. Some of the samples obtained are from diseases such as Cystic Fibrosis, Huntington Disease, Alpha Thalassemia, Fragile X syndrome, and Muenke syndrome.

6. The National Institute of Neurological Disorders and Stroke (NINDS) Human Genetics DNA and Cell Line Repository focuses on the identification of new genes that causes or contributes to conditions such as Parkinson’s disease, Tourettes syndrome, epilepsy, motor neuron disease, and cerebrovascular disease.

7. The National Institute of Aging (NIA) Aging Cell Repository utilizes cellular and molecular research to determine the degenerative mechanisms and causes of aging. They have strict diagnostic criteria with cells collected over a span of thirty years. Scientists are using these cultures to study diseases such as Alzheimer’s disease, Parkinson’s disease, Progeria, and Werner Syndrome.

8. The National Human Genome Research Institute (NHGRI) Sample Repository for Human Genetic Research successfully completed the sequencing of the human genome. They now aim to participate in a variety of studies that focuses on the understanding of the structure and function of the genome and the role it plays in disease and health.

9. The National Eye Institute Age-Related Eye Disease Study (NEI-AREDS) Genetic Repository was founded to identify how macular degeneration and cataracts develop and progress. This is important as these two conditions are two main causes of vision loss among older patients.

Conclusion

Biorepositories are crucial in supporting different areas of research such as those focused on a specific diseases, broadly focused population studies, identification of genetic mutations, and many more. These studies may have a specific length and purpose and are ongoing studies that follow up with their participants for many years.

References:

1)      Biorepository. Wikipedia. Accessed 8/9/2018. https://en.wikipedia.org/wiki/Biorepository

2)      Greenberg B, Christian J, Henry LM, et al. Biorepositories: Addendum to Registries for Evaluating Patient Outcomes: A User’s Guide, Third Edition [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2018 Feb. Types and Uses of Biorepositories and Their Application to Registries. Accessed 8/9/2018. https://www.ncbi.nlm.nih.gov/books/NBK493635/