First-Generation Guidelines for NCI-Supported Biorepositories, 25184-25203 [06-3997]

Agencies

• DEPARTMENT OF HEALTH AND HUMAN SERVICES
• National Institutes of Health

[Federal Register Volume 71, Number 82 (Friday, April 28, 2006)]
[Notices]
[Pages 25184-25203]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 06-3997]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


First-Generation Guidelines for NCI-Supported Biorepositories

AGENCY: National Institutes of Health (NIH), National Cancer Institute 
(NCI).

ACTION: Notice.

-----------------------------------------------------------------------

SUMMARY: The NCI is establishing common guidelines for the collection 
of biospecimens and their accompanying data by NCI-sponsored 
biorepositories. These guidelines are intended to standardize and 
enhance the quality of research material and data used in cancer 
research.

DATES: Effective Date: May 30, 2006.

ADDRESSES: These guidelines are open for public comment for a period of 
30 days. After the comment period has closed, any comments received 
will be considered in a timely manner by the NCI Office of 
Biorepositories and Biospecimen Research and appropriate changes will 
be made and the final guidelines will be published and voluntarily in 
effect. After the effective date of publication of the final 
guidelines, written comments will continue to be accepted for the first 
year of implementation and can be sent to: First-Generation Guidelines, 
Office of Biorepositories and Biospecimen Research, Office of the 
Deputy Director for Advanced Technologies and Strategic Partnerships, 
National Cancer Institute, National Institutes of Health, 31 Center 
Drive, Room 10A03, Bethesda, MD 20892. Comments submitted via e-mail 
should use biospecimens@mail.nih.gov and enter ``First-Generation 
Guidelines Comment'' in the subject line. During the first year of 
implementation, the NCI will review any additional comments and 
experience with the guidelines to evaluate a possible need for future 
guidelines modification.

FOR FURTHER INFORMATION CONTACT: Implementation assistance and 
inquiries should be directed to senior staff of the relevant NCI 
Extramural and Intramural Program offices.

SUPPLEMENTARY INFORMATION: 

I. Introduction

    The guidelines assembled in this document are intended as a first 
step toward unifying policies and procedures for NCI-supported 
biorepositories. This process was initiated by the NCI through a 
multiyear process that began in 2002, including a 2004 report compiled 
for the National Cancer Advisory Board that showed substantial 
heterogeneity in biorepository management practices across the 
Institute (NCAB 2004). This study showed that NCI-supported 
biorepositories are not optimized in terms of operational, legal, and 
ethical policies and procedures, nor are they coordinated to provide a 
unique resource value. Specifically, it showed that:
     The NCI invests more than $50 million annually in 
biorepository programs, not including biorepositories supported through 
individual investigator grants, such as R01s.
     The 125 programs included in the study collected, 
maintained, and/or stored approximately 4 million human biospecimens in 
FY 2003.
     These programs support basic, epidemiologic, 
translational, and clinical research.
     Most programs collect frozen biospecimens and support 
genomic and proteomic research.
     Across the broad range of programs, there are no common 
standard operating procedures (SOPs) or Quality Assurance/Quality 
Control (QA/QC) measures.
     The programs lack a common database.
     There is no consistent, defined mechanism to access NCI-
supported biospecimen resources.

II. Background

    In 2005 the NCI took several actions to respond to these findings, 
including establishment of the Biorepository Coordinating Committee 
(BCC) in early 2005. The BCC is advisory to the NCI's Office of 
Biorepositories and Biospecimen Research (OBBR). The primary purpose of 
the BCC is to work with the OBBR to coordinate the NCI's 
biorepositories in a manner that optimizes the quality and 
accessibility of biospecimens for the broad cancer research community. 
Toward this goal, the OBBR and the BCC organized two workshops during 
the summer of 2005 to inform the development of specific 
recommendations on policy and operational issues. These workshops, 
which were based on the development of a series of white papers that 
consolidated documents and the overall knowledge base in biospecimens, 
brought together diverse representatives from the cancer research 
community as well as ethics, policy, and legal experts to discuss and 
propose approaches that could help unify, integrate, and improve the 
transparency of NCI-supported biorepository activities. The report and 
recommendations that resulted from the workshops are summarized in the 
document Harmonizing Processes and Policies for NCI-Supported 
Biorepositories, which was presented to the National Cancer Advisory 
Board in September, 2005. The report can be found at https://
biospecimens.cancer.gov/biorepositories/bcc_summary.asp.
    NCI defines a biorepository as a place, room, or container where 
human biospecimens are stored. Biorepositories may vary considerably, 
ranging from formal organizations to informal collections of materials 
in an individual researcher's freezer.
    Currently biorepositories serve as critical resources to the 
research community in the performance of postgenomics cancer research. 
It is becoming increasingly important that all biorepositories strive 
to achieve the best possible biospecimen quality, which would 
necessarily call for the adoption of consistent documentation, 
collection, processing, storage, and retrieval guidelines such as those 
outlined in this document. The workshops' recommended approaches were 
reported to the NCAB in September 2005. Proposed approaches, as well as 
additional meetings and work over the

[[Page 25185]]

past 3 years, form the basis of the first-generation NCI biorepository 
guidelines. These guidelines will be distributed to managers of all 
NCI-supported intramural and extramural biorepositories, who will be 
initially asked to conform to them on a voluntary basis. It is 
important to note that developing a workable set of guidelines is an 
evolving process that, with the emergence of new technologies and 
clinical practices, will require periodic revision. Therefore, these 
guidelines will be revised iteratively, with input from researchers, 
biorepository managers, advocates, policymakers, and related 
stakeholders.

III. Guidelines

Overview

1. Technical and Operational Guidelines

A. Biospecimen Collection, Processing, Storage, Retrieval, and 
Dissemination
    1. Collect and process biospecimens under conditions appropriate 
for each biospecimen type and for the intended analyses, using 
collection protocols that are based on authoritative best practices or 
solid research data, when available. Ensure that proper informed 
consent protocols are followed.
    2. Base all protocols on SOPs that are established using 
authoritative best practices or solid research data, when available.
    3. Maintain a thorough and consistent level of biospecimen 
annotation while maintaining donor patient privacy pursuant to informed 
consent provisions.
    4. Use a computerized inventory system that tracks the specific 
position of every stored aliquot. Each storage container should be 
labeled with a unique identifier. All other relevant information should 
be tied to this unique identifier. Inventory systems should contain 
security provisions sufficient to safeguard privacy and other informed 
consent provisions.
    5. Develop a comprehensive quality management system (QMS). 
Standardized protocols should be applied consistently to ensure 
biospecimen quality and to avoid introducing variables into research 
studies. Document all collection and processing steps in the 
computerized inventory tracking system.
    6. Ensure that all laboratory personnel are well qualified, trained 
to adhere to biorepository SOPs, and monitored for high-quality 
performance.
    7. Ensure that a pathologist directs the collecting and processing 
of surgical and autopsy biospecimens to ensure that clinically 
important issues related to the biospecimens are adequately and 
accurately addressed and that patient care is not compromised.
    8. Store biospecimens in a stabilized state. In selecting the 
biospecimen storage temperature, consider the biospecimen type, the 
anticipated length of storage, the biomolecules of interest, and 
whether goals include preserving viable cells. Use stabilizing agents 
as appropriate. Storage vessels should be durable under planned storage 
conditions. Follow consistent freezing and thawing protocols to ensure 
consistent quality for assays.
    9. Establish rules for biospecimen disposal before storing the 
biospecimens in the biorepository and monitor compliance with the 
rules. Consider the anticipated storage interval when selecting storage 
conditions.
    10. For tissue biospecimens, minimize the time for collection and 
processing as much as possible (unless inadequate processing time is 
known to interfere with the analysis method); reduce biospecimen 
temperature as soon as possible after collection. Optimal processing 
times may vary for other types of biospecimens depending on the 
analysis method for which they are used.
    11. Establish inventory tracking systems and storage organizational 
methods to minimize disruption of the stable environment during sample 
retrieval.
    12. Regularly review the performance of all long-term storage 
systems and equipment using standardized protocols.
    13. Choose biospecimen containers with analytical goals in mind. 
This may require, for example, screening of containers for trace metals 
that may interfere with laboratory analyses.
    14. Adhere to biosafety, packaging, and shipping regulations. Use a 
tracking system for biospecimen shipments. The biorepository should 
notify a recipient before shipping to confirm that the recipient can 
accept the package and properly store the biospecimen.
    15. Retrieve biospecimens from storage according to SOPs that 
safeguard biospecimen quality.
    16. When it is necessary to control biospecimen temperature during 
shipping, consider the shipping time, distance, climate, season, and 
method of transportation and modify distribution schedules accordingly, 
if possible. Ensure proper temperature during shipment, taking into 
account the type of biospecimen and its intended use. Tracking devices 
may be useful to ensure proper temperature throughout the shipment 
duration.
    17. Prior to shipment, execute appropriate Material Transfer 
Agreements (MTAs) addressing donor privacy, as appropriate, 
intellectual property (IP), data sharing, and other similar 
requirements.
    18. Consult International Society for Biological and Environmental 
Repositories (ISBER) best practices (ISBER 2005) for guidance on 
international transport regulations (governed by the International Air 
Transport Association) and information on classifying biospecimens for 
shipment. Train personnel in the shipment of biospecimens and update 
their training every 2 years. Maintain training records for all 
employees involved in shipping.
B. Collecting and Managing Clinical Data
    1. Strive to collect and store all relevant clinical or 
epidemiologic data associated with a biospecimen, including, as study 
requirements dictate, longitudinal data. Follow applicable informed 
consent requirements and institute appropriate security/data-access 
control measures to address privacy issues. The NCI will work with 
biorepositories to establish a minimal ``universal'' clinical data set.
    2. Use an informatics system that tracks all aspects of biospecimen 
collection, processing, and distribution to prevent biospecimen 
identification discrepancies and to support annotation.
    3. Comply with applicable privacy and human subjects protection 
regulations governing the acquisition of biospecimens and associated 
clinical data. Link biospecimens to clinical data in compliance, as 
applicable, with the Health Insurance Portability and Accountability 
Act of 1996 (HIPAA) and U.S. Department of Health and Human Services 
(HHS) and U.S. Food and Drug Administration (FDA) human subjects 
protection regulations.
C. Quality Assurance/Quality Control (QA/QC)
    1. Adhere to a written QMS. The QMS should describe the 
biorepository's QA/QC programs and approaches for ensuring that program 
requirements are met.
    2. Require that staff be trained in QA/QC and maintain training 
records.
    3. The SOPs should be printed in a manual that is readily available 
to all laboratory personnel and dated according to the most recent 
revision. The SOPs should state policies and define and describe 
procedures in detail. Develop procedures for

[[Page 25186]]

periodically reviewing and revising SOPs as necessary.
    4. Establish security systems, including equipment monitoring and 
alarm systems that are monitored both locally and remotely, with plans 
to respond at any time. Emergency power systems should be ready to 
operate all critical equipment during power outages.
    5. Use a data management system that includes a computerized 
inventory tracking system with appropriate security/access-control 
safeguards.
    6. Develop a facility disaster plan based on a local area risk 
assessment. The plan should include appropriate measures to protect 
personnel and equipment during a disaster.
    7. Maintain and repair all equipment according to SOPs. Establish 
preventive maintenance schedules.
D. Biosafety
    1. Assume that all human biospecimens are potentially infective and 
biohazardous. Use universal precautions practices in biorepositories 
similar to those used in other laboratories and clinical settings. 
Handle biospecimens according to, at a minimum, Biosafety Level 2 (BSL-
2) as outlined in the CDC/NIH booklet Biosafety in Microbiological and 
Biomedical Laboratories.
    2. Immunize employees (e.g., for hepatitis) when appropriate 
vaccines are available.
    3. Develop a safety program and associated training procedures by 
identifying governmental and accrediting agency requirements regarding 
biohazards and likely sources of current information concerning 
laboratory biosafety. Among the agencies that oversee laboratory 
biosafety programs are the Occupational Safety and Health 
Administration (OSHA), the CDC, and the Clinical and Laboratory 
Standards Institute (CLSI).
    4. Identify and address risks and other general issues of 
biosafety. Identify frequent biorepository activities and analyze 
safety issues involved with each activity. Take appropriate actions to 
ameliorate hazards.
    5. Document all incidents where personnel are exposed. Response and 
treatment protocols should be prepared to be available in the event of 
potential exposure and infection.
    6. Establish indemnification agreements with users of biospecimens 
except where prohibited by law.
    7. Follow U.S. regulations concerning chemical safety, which 
protect employees from exposure to biohazardous levels of chemicals. 
Biorepositories should also develop a chemical hygiene plan in 
compliance with the OSHA's laboratory standards.
    8. Properly ground freezers and other electrical equipment.
    9. Establish fire emergency plans and practice them regularly.
    10. Take precautions to prevent repetitive strain and back injuries 
and other accidents and injuries typical of the laboratory/
biorepository environment.
    11. For any laboratory or biorepository that processes radioactive 
materials, ensure that proper training of personnel and acquisition of 
necessary equipment to obtain licenses from the Nuclear Regulatory 
Commission (NRC) and/or local agencies are carried out.
E. Biorepository Informatics: Data Management and Inventory Control and 
Tracking
    1. Assign a unique identifier (such as a number or barcode) to each 
biospecimen at the time of collection. Identify specific clinical and 
epidemiological data by the same number and/or barcode. Use the number 
or code to track a biospecimen from collection through processing, 
storage, and distribution.
    2. Update the biorepository database each time a biospecimen is 
moved within or out of the biorepository.
    3. Use informatics systems that support the linking of biospecimens 
with associated research data and, when available, the limits, if any, 
on the use of the sample. When applicable, track the levels of consent 
that each patient has given for the use of their biospecimens and 
whether that consent has been withdrawn.
    4. To protect the health information of patients, adhere to privacy 
laws with respect to informatics systems.
    5. The NCI Center for Bioinformatics (NCICB) has developed 
additional bioinformatics guidelines and tools that address the issues 
of functionality of informatics systems, integration with existing 
systems, and interoperability among individual systems at 
biorepositories. The NCICB has developed the Cancer Biomedical 
Informatics Grid, or caBIG \TM\. caBIG (see https://cabig.nci.nih.gov/) 
(NCI 2005) is a voluntary network or grid connecting individuals and 
institutions to enable the sharing of data and tools. caBIG silver-
level compatibility is recommended for NCI-supported biorepositories 
(see https://cabig.nci.nih.gov/guidelines_documentation).

2. Ethical, Legal, and Policy Guidelines

A. Informed Consent
    1. Use a process of informed consent for each biospecimen 
collection event. The NCI will provide all of its biorepositories with 
a sample consent template, which should be reviewed and adapted by the 
relevant IRB. Biorepositories should adapt the template to their needs. 
The consent form should address the use of biospecimens or data by 
private entities, the possible future development of commercial 
products through research, and the release of individual research 
results to participants.
    2. Allow research participants to specify the types of research for 
which their biospecimens may be used, including use in additional 
future projects.
    3. Document clear policies for biospecimen and data access.
    4. Develop policies to handle biospecimens and data for which 
consent has been withdrawn.
    5. Monitor the need for obtaining informed consent when the 
biorepository houses identifiable biospecimens and data from children, 
that were obtained with parental or guardian permission, when a child 
reaches the legal age to consent for a research study.
    6. Consider FDA regulations concerning research on existing 
biospecimen collections, for any study that could involve FDA oversight 
in the future. These regulations do not exempt in vitro studies from 
the requirement for documented, institutional review board (IRB)-
approved consent from the sources, even in cases where biospecimens 
have been deidentified.
    7. Establish and document transparent policies governing the 
retention of records and biospecimens. For clinical biospecimens, State 
laws may also govern how long records must be retained. For research 
specimens, the ideal is permanent storage if resources and storage 
space are sufficient. However it should be noted that biospecimens 
degrade over time and/or may no longer be useful due to changes in 
science and technology.
    For additional information about IRBs and the requirement for the 
HHS Office for Human Research Protections (OHRP)-approved assurance of 
compliance, see the OHRP Web site at https://www.hhs.gov/ohrp/. Specific 
OHRP guidance concerning tissues and biorepositories is included among 
the documents referenced at https://www.hhs.gov/ohrp/policy/
index.html#tissue.

[[Page 25187]]

B. Access to Biospecimens and Data
    1. Establish clear guidelines for sample distribution (and clinical 
data sharing) consistent with ethical principles, prevailing laws, and, 
if applicable, consent form language. The guidelines should be flexible 
so that biorepositories may respond to changing scientific needs.
    2. Ensure that investigators have timely, equitable, and 
appropriate access to human biospecimens and associated clinical data 
stored at NCI-supported biorepositories without undue administrative 
burden. Access should be guided by policies and procedures such as the 
following:
     Scientific validity of the research proposal.
     Investigator's agreement covering confidentiality, use, 
disposition, and security of biospecimens and associated data.
     Investigator's written agreement in a Material Transfer 
Agreement to comply with the NIH Research Tool Guidelines. (https://
ott.od.nih.gov/policy/rt_guide_final.html).
     Investigator and institutional research qualifications.
     Ethical oversight where required by Federal regulations or 
local institutional requirements.
     Adequate funding for the biorepository.
    In addition to the above, the following points should also be 
considered while assessing access privileges:
    a. Biospecimens and associated clinical data should be 
appropriately matched with the specific scientific investigations for 
which they are intended.
    b. The local decision-making body should take local principles into 
account. Ethical considerations should come first among principles that 
guide the decisionmaking process.
    c. Biorepositories should establish an appeals process for 
addressing disputes over allocation decisions.
    3. Apply guidelines to all new collections and, whenever possible, 
to existing collections.
    4. If applicable and where monetary charges are necessary, charge 
only to recover costs as appropriate to retrieve and disseminate 
specimens.
    5. If a biorepository must close due to lack of funding or 
otherwise cannot maintain or use the biospecimens, the availability of 
biospecimens should be announced for transfer to the research community 
(e.g., via a Web site). Transfer should be consistent with the informed 
consent and allowable use of biospecimens.
    6. Within the biorepository, use a system of data access with 
defined levels of access privileges. Restrict access to research 
subjects' identities and medical, genetic, social, and personal 
histories to necessary biorepository staff members who need such access 
as part of their duty or to persons permitted access by law. Monitor 
personnel compliance with access restrictions.
    7. Store human biospecimens only for research purposes according to 
approved protocols, not to serve individual research participants' 
needs or wishes.
C. Privacy Protection
    1. Institute the level of security appropriate to the type of 
biorepository and to protect study participant privacy for the 
biospecimens stored in the biorepository.
    2. In applications for support, include documentation of policies, 
mechanisms for auditing the effectiveness and enforcement of policies, 
required training, and security measures pertaining to employee access 
to data or biospecimens.
    3. Institute the level of security appropriate to the type of 
biorepository.
D. Custodianship
    1. In the application for proposal for biorepository funding, 
propose plans for formal and continuing responsibility for 
custodianship (not ownership) of collected biospecimens and associated 
data as part of the biorepository protocol.
    2. In the application for proposal for biorepository funding, also 
address plans for the handling and disposition of biospecimens and 
associated data at one or more of the following points: (a) End of the 
active support of the grant, (b) accomplishment of the specific 
research objectives of the study, (c) depletion of biospecimens, and/or 
(d) achievement of critical data endpoints.
    3. Require disclosure of financial or professional conflicts of 
interests of biorepository personnel, consistent with institutional 
procedures and policies.
    4. Use clear and specific informed consent language to ensure that 
those who contribute biospecimens and/or data for research purposes are 
fully informed that the research done with these biospecimens may help 
develop products, tests, or discoveries that may have commercial value 
(also see A.1. above).
E. Intellectual Property
    1. For the transfer of materials in academic-industrial 
collaborations, use the NIH Simple Letter Agreement (SLA), the Uniform 
Biological Material Transfer Agreement (UBMTA), or other MTA with terms 
consistent with the NIH Research Tools Policy and NIH data sharing 
policies, e.g., the Final NIH Statement on Sharing Research Data. These 
agreements should be modified where necessary to cover human subjects 
research. A sample NIH SLA modified to address the transfer of human 
biospecimens is attached as Appendix 2.
    The following Internet sites are relevant to this issue:
     https://ott.od.nih.gov/policy/research_tool.html.
     https://www.autm.net/aboutTT/aboutTT_umbta.cfm.
     https://grants1.nih.gov/grants/policy/data_sharing/
index.htm.
    2. Recognize that biorepository staff members as custodians of 
biospecimens are not a priori considered inventors under patent law for 
inventions made using materials distributed by the biorepository. In 
general, the staff should be informed that one whose sole contribution 
to an invention consists of the routine collection, handling, storage, 
and disbursement of biospecimens might not rise to the level of 
``inventor'' of an invention. Inventorship is determined by patent law 
and must be considered on a case-by-case basis by trained legal 
personnel.
    3. Recognize that biorepositories have no inherent rights to future 
IP, including reach-through rights in inventions made by investigators 
using samples obtained from the biorepository.
    4. Ensure through MTAs that research data developed using 
biospecimens are made available to the research community. (See sample 
in Appendix 2.)

Guidelines Details

1. Technical and Operational Guidelines

A. Biospecimen Collection, Processing, Storage, Retrieval, and 
Dissemination
    Although the specific mission of a biorepository will result in the 
use of different collection and processing procedures, common 
principles should apply to all biospecimen types. The guidelines below 
are based on current, published information and will be revised 
periodically as new information is generated from ongoing research 
projects.
Determining Which Biospecimens To Collect
    1. Collection priorities should be based on the defined purpose of 
each NCI-supported biorepository in supporting specific types of 
research. Biorepositories should track researchers' requests to guide 
the collection and

[[Page 25188]]

storage process and to attempt to anticipate which biospecimen types 
(e.g., matched blood, serum, plasma, buffy coat, saliva, urine) will 
make the biorepository most useful for future research. Researchers 
should involve biorepository scientists as early as possible during 
study planning to develop a strong approach for biospecimen collection.
    2. NCI-sponsored biorepositories should strive to collect materials 
from diverse populations representative of the United States. However, 
this goal may depend on the specific purpose, such as the disease 
focus, of the NCI studies supported by the biorepository.
Biospecimen Collection and Processing
    Biospecimen collection occurs in many contexts, including surgical 
procedures, organ donation and transplantation, autopsies, 
venipuncture, and evacuation; for population-based studies, collection 
may occur in field locations such as hospitals or study participants' 
homes.
    1. The NCI will provide guidance in the future on guidelines for 
biospecimen collection while allowing for flexibility when new 
methodologies are warranted. SOPs will enhance the comparability of 
research results and help make biospecimens interchangeable. This 
guidance will include:
     Collection protocols for various biospecimen types based 
on solid research data.
     A high level of biospecimen annotation, consistent across 
NCI-sponsored biorepositories, recording key data, such as time to 
banking, time of ischemia, time of biospecimen excision, character of 
chemical preservation, time of fixation, etc. For paraffin-embedded 
biospecimens, it may prove important for the interpretation of analytic 
data derived from these biospecimens to have documentation of the 
specific protocol through which a biospecimen was processed before it 
was placed in paraffin. Appropriate and complete documentation 
surrounding biospecimen collection, processing, and storage are 
essential and relevant to the quality of research data to be obtained.
     Uniform, nonredundant sample nomenclature across NCI-
sponsored biorepositories.
     State-of-the-art sample tracking procedures and supporting 
informatics.
     A QMS to ensure adherence to standards.
    2. Biorepositories should record data relevant to research goals. 
As appropriate for the study, for all types of biospecimens, the amount 
of time elapsed during collection and processing should be recorded and 
tracked in the biorepository informatics system. Biorepositories should 
also record data on the collection and processing procedures used.\1\
---------------------------------------------------------------------------

    \1\ NCI will support research to determine the effects of 
various biospecimen processing methods on analyte preservation. 
Biorepositories should continually attempt to improve collection and 
processing methods to maximize the quality of materials for 
molecular analysis. NCI-supported biorepositories should document 
the effects of different processing methods and develop guidelines 
for biospecimen processing based on the goal of preserving various 
analytes.
---------------------------------------------------------------------------

     For tissue biospecimens, the time for collection should be 
minimized as much as possible; biospecimen temperature should be 
reduced as soon as possible after collection. Biospecimen processing 
time should be minimized if freezing is the stabilization endpoint. If 
fixation is the stabilization endpoint, control of processing time 
between maximum and minimum durations may be required.
     Rapid processing may not be as critical for other types of 
biospecimens, such as blood, and optimal processing times may vary 
depending on the analysis method for which a biospecimen is used. 
Examples of data to record for blood biospecimens include collection 
time relative to treatment or other interventions, time of day at 
collection, whether the patient was fasting, and whether he or she was 
sitting or standing during collection.
    3. NCI-supported biorepositories should seek to use the processing 
method that preserves the greatest number of analytes, unless the aim 
of a particular study specifically requires alternative processing. To 
select processing methods (such as freezing, fixation, and the use of 
stabilizing additives), a biorepository should define its goals and the 
research priorities of the studies it supports. Procedures should 
maximize the potential for biospecimen distribution and research use. 
When possible, individual biospecimens should be divided into aliquots 
or fractions and/or preserved by multiple processing methods. 
Biorepositories that validate biospecimen quality for specific research 
applications should use as little of the biospecimen as possible.
Biorepository Personnel
    Personnel involved in biorepository management and use, including 
researchers, technicians, nurses, surgeons, pathologists, 
anesthesiologists, and assistants, should be aware of the purpose and 
goals of the biorepository. To ensure the collection of high-quality 
biospecimens for research, collection, and processing, personnel should 
be well qualified and trained to adhere to applicable SOPs. A 
pathologist should be involved for expertise in collecting and 
processing surgical and autopsy biospecimens. It is important that a 
pathologist determine what tissue is necessary for pathologic diagnosis 
and what is excess and can be given to the biorepository for research 
purposes. This is crucial in ensuring that patient care is not 
compromised.
Biospecimen Storage
    The following general guidelines section applies to all types of 
biospecimens, such as wet tissue, frozen tissue, paraffin-embedded 
tissue, glass slides, blood, serum, and urine. Individual types of 
biospecimens should be handled according to SOPs specific to each 
biospecimen type and to the biomolecules to be analyzed in that 
biospecimen type (e.g., RNA, DNA, protein, lipid, etc.).
    1. Standardized protocols should be applied consistently in 
preparing and storing biospecimens to ensure their quality and to avoid 
introducing variables into research studies. Biorepositories should 
record storage conditions and especially deviations from SOPs, 
including information about temperature, thaw/refreeze episodes, and 
equipment failures. Each piece of storage equipment should have a log 
containing the manufacturer's manual, records of equipment operation, 
and descriptions of maintenance, repairs, and calibration. Storage 
conditions should be recorded automatically, and the performance of all 
long-term storage systems and equipment should be reviewed annually 
using standardized protocols (Mager et al. 2004). Calibrated devices 
should be used to validate automated temperature measurements.
    2. Biospecimens should be stored in a stabilized state. For blood 
biospecimens, all components should be stored where possible. This is 
particularly important for large, population-based studies, for which 
it is difficult to predict how biospecimens will be analyzed in the 
future.
    A biorepository should avoid unnecessary thawing and refreezing of 
frozen biospecimens or frozen samples of biomolecules extracted from 
the biospecimens. When thawing/refreezing is necessary, a biorepository 
should follow consistent and validated protocols to ensure continued 
stability of the analytes of interest. Methods, such as inventory 
tracking, should be established to minimize disruption of the stable 
environment during sample retrieval.
    In selecting biospecimen storage temperature, consider the 
biospecimen type, the anticipated length of storage,

[[Page 25189]]

the biomolecules of interest, and whether goals include preserving 
viable cells. Paraffin blocks should be stored at temperatures below 80 
[deg]F (27 [deg]C) in an area with pest and humidity control. In the 
case of liquids, such as blood and urine, consider separating 
biospecimen components before storage to preserve each constituent 
under its optimal condition. However, whole-blood (rather than 
fractional) cryopreservation is recommended as an efficient and cost-
effective option for processing viable cells in large-scale studies 
(Hayes et al. 2002). When in doubt as to possible future uses, store 
tissues in the vapor phase of liquid nitrogen freezers to ensure long-
term viability. Lower storage temperatures and the use of a 
cryoprotectant (such as DMSO) are recommended to maintain viable cells 
for long periods of time (ISBER 2005). Planned analyses should consider 
the difference in temperature between the bottom and top of a liquid 
nitrogen freezer; the temperature at the top of a liquid nitrogen 
should be consistently below -140 [deg]C.
    Avoid self-defrosting freezers that cause damaging effects to 
biospecimens, even those in capped tubes, by enhancing desiccation 
(Holland et al. 2003).
    3. Biorepositories should establish rules for disposing of 
biospecimens before storing them. Consider the anticipated storage 
interval when selecting storage conditions. If possible with available 
resources, store control biospecimens under each condition used in the 
biorepository and assess these control biospecimens at regular 
intervals to assess the effects of storage time on desired qualities 
such as viability, preservation of morphology, and biochemical 
integrity.
    4. Storage vessels should be stable under planned storage 
conditions. Vial size and number should be suitable for typical 
aliquots, anticipated investigator uses, and number of investigators. 
Volume and type of containers should prevent sample loss and minimize 
the costs of collection and storage. Screw-cap cryovials should be used 
for long-term, low-temperature storage; glass vials or vials with popup 
tops are unsuitable for long-term storage (Caporaso & Vaught 2002). 
Wrap snap-frozen biospecimens in aluminum foil or place them in 
commercial storage containers to minimize desiccation (Grizzle 2004). 
Choose labeling and printing systems that will be stable under the 
long-term storage conditions appropriate for the biospecimen. Face 
shields and appropriate gloves should be worn for worker protection.
    Biospecimen containers should be chosen with analytical goals in 
mind. For example, when samples will be tested for the presence of 
xenobiotic chemicals, containers should be free of xenobiotic 
contamination. Certified RNase-free containers should be used for all 
steps in handling RNA samples.
    5. Each storage container should have a unique identifier for the 
biospecimen aliquot that is firmly affixed to the container, clearly 
and legibly marked, and able to endure storage conditions. All other 
relevant information should be tied to this unique identifier, bearing 
in mind study participant confidentiality, security, and informed 
consent provisions. Inventory systems should relate the presence of 
each aliquot to its specific position in a specific freezer, 
refrigerator, or shelf.
    6. Automated security systems should continuously monitor the 
function of storage equipment. Backup equipment, such as an alternative 
power source, should be automatically activated when necessary. 
Emergency procedures should be in place if freezers fail or exceed a 
preset temperature. SOPs should be in place for alerting personnel and 
for moving biospecimens to alternative storage locations. Biorepository 
SOPs should include procedures for responding to severe weather and 
floods as well as specific power and equipment failures. Personnel 
should be trained in safety related to biospecimen handling, use of 
equipment, and SOPs for responding to emergency situations. For 
particularly valuable biospecimens, an empty, functioning freezer 
should be available in case of single-freezer failure. Also consider 
storing replicate biospecimens in at least two different locations to 
safeguard against storage or handling failures (NBN Blueprint 2003; 
Landi and Caporaso 1997; Caporaso and Vaught 2002; Eiseman et al. 
2003).
Shipping Biospecimens
    1. Retrieval. Biospecimens should be retrieved from storage 
according to biorepository SOPs that safeguard biospecimen quality. 
Before retrieval, systems should be in place to verify that the request 
has received approval from the appropriate committee(s). SOPs should 
include a checklist to confirm completion of the retrieval process. 
Document deviations during retrieval, such as inventory 
inconsistencies, damaged containers, thawing or refreezing, etc.
    2. Shipping conditions. When seeking to regulate biospecimen 
temperature during shipping, consider the shipping time, distance, 
climate, season, method of transportation, and regulations as well as 
the type of biospecimens and their intended use (Landi and Caporaso 
1997). The number of biospecimens per package also affects whether 
temperature can be maintained for all biospecimens in the shipment. 
Send a prior test shipment, of frozen water samples for example, before 
shipping extremely valuable samples, to check the adequacy of coolants 
and any potential obstacles to a successful shipment. In addition, 
conditions throughout a critical shipment can be monitored by enclosing 
a device that records temperature during transport. Placing samples in 
sealed bags with a desiccant can be used to control humidity.
    To maintain proper temperature during shipping, use appropriate 
insulation, gel packs, dry ice, or liquid nitrogen (dry shipper). To 
maintain refrigerated temperatures (2[deg]C to 8[deg]C), use gel packs 
conditioned at -15[deg]C or phase change material rated for 
refrigerated transport. To maintain frozen temperatures, use gel packs 
conditioned at or below -20[deg]C. For frozen temperatures at -
70[deg]C, use dry ice pellets or sheets. Note that dry ice is 
considered a hazardous substance for shipping purposes. For maintaining 
temperatures at or below -150[deg]C, use a liquid nitrogen dry shipper 
(ISBER 2005). Use insulated packaging to protect biospecimens from 
extremely hot or cold ambient conditions. Whenever intending to 
maintain samples below ambient temperature, include enough refrigerant 
to allow for a 24-hour delay in transport (ISBER 2005). Temperature-
sensitive material should be handled by a courier with resources to 
replenish the refrigerant in case of a shipping delay (ISBER 2005).
    Paraffin blocks and slides should be shipped at room temperature in 
an insulated package via overnight carrier. The use of insulated 
packages is important to minimize the effect of temperature 
fluctuations and to protect the blocks from temperatures higher than 
80[deg]F (27[deg]C). Flat biospecimens, such as dried blood samples on 
absorbent pads or cards, should be enclosed in watertight plastic bags 
and shipped in a sturdy outer package or commercial envelope. Samples 
on glass or plastic slides should be cushioned and shipped inside a 
sturdy (not flexible) outer package. Triple packaging should be used 
for liquid samples.
    3. Documentation. The biorepository should notify a recipient 
before shipping to confirm that the recipient can accept the package 
and properly store the biospecimens. Packages should be bar-coded and 
tracked by the biorepository and the recipient. A

[[Page 25190]]

biorepository shipping log, either written or computerized, should 
track shipments from and to the biorepository and include the following 
information: shipment/invoice number; recipient (or source); date 
shipped (or received); courier name and package tracking number; sample 
description; number of samples shipped (or received); condition on 
arrival; study name and number, if available; key investigator's name; 
and signature of biospecimen recipient (ISBER 2005).
    Standardized paperwork should accompany shipments. Biorepository 
personnel should send a shipping manifest, a list of sample 
identification numbers, and descriptions of samples electronically to 
the biospecimen recipient and include a hard copy of the manifest in 
the shipment itself. Identifying data should be available for the use 
of shipping or customs agents as well. Some shipping agents require an 
itemized list of contents between the secondary and outer packaging of 
diagnostic biospecimens.
    Biorepository personnel should verify biospecimen labels and 
pathology reports against the packing list for consistency and 
correctness.
    A feedback questionnaire should be enclosed in each shipment for 
QA/QC purposes, requesting feedback about the quality of samples 
received (Eiseman et al. 2003).
    4. Regulatory considerations. Consult ISBER Best Practices (ISBER 
2005) for information concerning international transport regulations 
and classifying biospecimens for shipment. Failure to conform to 
international air transport regulations will result in delay or refusal 
of shipment and probable biospecimen deterioration. Regulations must be 
followed precisely, since improperly packaged or labeled goods will be 
refused for transport by airlines or delayed at customs (Holland et al. 
2003). For international shipments, biorepository personnel should 
prepare safety declarations for foreign customs (Landi and Caporaso 
1997).
    For packaged biospecimens, International Air Transport Association 
(IATA 2004) regulations require three packaging components: (1) A 
primary inner receptacle, (2) secondary packaging, and (3) rigid outer 
packaging. The primary receptacles should be packed in the secondary 
packaging so that, under normal conditions of transport, they cannot 
break, be punctured, or leak their contents into the secondary 
packaging. Secondary packaging should be secured in outer packaging 
with cushioning material. Secondary containers for diagnostic 
biospecimens should be certified by the manufacturer prior to use. 
Outer packaging is regulated as to material, size, and ability to 
withstand a 1.2-meter drop test as outlined in IATA Section 6.6.1. 
Leakage of the contents should not affect the cushioning material or 
outer packaging (IATA 2004). Some shipping agents designate the same 
three layers of packaging and absorbent material between outer and 
secondary packaging. Specifics of the primary containers for diagnostic 
biospecimens, liquid biospecimens, and solid biospecimens are described 
on the shipping agents' Web sites. Styrofoam[supreg] chests containing 
dry ice may be used to ship samples that should be maintained at low 
temperatures (Landi and Caporaso 1997). However, the shipping agent may 
exclude Styrofoam[supreg] as an acceptable outer packaging. To confirm 
that shipping conditions meet sample needs, shipping personnel should 
review test reports from packaging that has been tested to meet 
regulation requirements. Packaging should be used in the same 
configuration under which it was tested (ISBER 2005).
    Consult OSHA regulations to determine whether a substance requires 
a biohazard label. Ship Category A infectious substances in accordance 
with IATA Packing Instruction (PI) 602 (IATA 2004). Ship Category B 
infectious substances (also designated as diagnostic specimen, clinical 
specimen, or biological specimen, category B) in compliance with IATA 
PI 650.
    Ship dry, noninfectious biospecimens (e.g., dried blood, tissue, 
saliva, or hair) with special packaging as specified by the shipping 
agent. Wet-fixed biospecimens shipped in formalin/formaldehyde should 
include ``ICAO/IATA'' under additional handling information (Grizzle 
2004).
    5. Training. Training of personnel for shipment of biospecimens is 
strongly recommended (ISBER 2005). Training should be updated at least 
every 2 years. Dangerous goods training may be required for some 
biorepository personnel. A record of training should be maintained of 
all employees involved in the shipping process. Training and 
certification are available through various shipping vendors (ISBER 
2005). On completion of training, the training organization issues a 
certificate of completion.
B. Collecting and Managing Clinical Data
    Extensive annotation of tissue biospecimens is crucial to the 
overall usefulness of the biorepository as a resource for scientific 
research (Eiseman et al. 2003). Biorepositories store biospecimens 
collected using multiple methodologies and procedures, including tissue 
collection, blood draws, and buccal cell and urine collections. 
Researchers rely on banked biospecimens for a wide variety of purposes, 
including target discovery and validation, prevention research, 
research on early detection, genetic studies, and epidemiologic 
analyses. The data recorded by biorepositories depend on the types of 
biospecimens they collect and the studies they support. It is 
critically important for excellence in research that NCI-supported 
biorepositories use SOPs for biospecimen collection, processing, and 
storage. While harmonization of these procedures is the ultimate goal, 
the NCI is engaged in research to identify the best set of protocols 
and methods to produce high-quality biospecimens. Regardless, 
biospecimens must maintain donor privacy in all collection of clinical 
data.
Determining Data Sets
    1. The NCI will define the minimal clinical data to be collected 
for all biospecimens, as appropriate for the research protocol at NCI-
supported biorepositories. This universal set will change over time. 
Biorepositories should adopt the harmonized nomenclature being 
developed by the NCI for clinical data and establish algorithms to 
translate raw data into standard nomenclature.
    2. NCI-supported biorepositories should establish additional data 
categories for specific types of research.
Collecting Clinical Data
    1. NCI-funded biorepositories should strive to collect and store 
all relevant clinical data associated with a biospecimen. This will 
maximize the use of biospecimens for current and future short-term and 
longitudinal studies. Biorepositories should encourage participating 
investigators to annotate biospecimens to the fullest extent possible 
consistent with biorepository goals and/or study design. Data 
collection activities should conform to FDA requirements if and where 
applicable, so that the data can be cited and/or used in 
Investigational New Drug and Investigational Device Exemption 
applications.
    2. The NCI will develop a tiered system of clinical data 
annotation, which will define the potential of any given biospecimen in 
supporting high-quality research and will guide decisions on the 
appropriate use of biospecimens by the scientific community.

[[Page 25191]]

    3. NCI-supported biorepositories should employ a uniform, 
nonredundant vocabulary (caBIG common data elements [CDEs]) for 
clinical data across sponsored biorepositories.
    4. NCI-supported biorepositories should track researchers' requests 
for specific clinical data to guide refinements of data collection 
guidelines.
    5. NCI-supported biorepositories should employ a method for 
validating the clinical data collected. These data should be validated 
to ensure accuracy in downstream scientific research.
    6. NCI-supported biorepositories should comply with applicable 
privacy and human subjects protection regulations governing the 
acquisition of biospecimens and associated clinical data. Biospecimens 
should be linked to clinical data in compliance, as applicable, with 
the HIPAA regulations and with HHS and FDA human subjects protection 
regulations.
Longitudinal Clinical Data \2\
---------------------------------------------------------------------------

    \2\ The NCI plans to partner with its cancer centers, advocacy 
groups, and relevant stakeholders to collect longitudinal data 
related to particular studies.
---------------------------------------------------------------------------

    1. As the study requirements dictate, NCI-supported biorepositories 
should collect and store longitudinal data following applicable 
informed consent requirements.
    2. Depending on the study design, information linked to samples 
should include demographic data, lifestyle factors, environmental and 
occupational exposures, cancer history, structured pathology data, any 
additional diagnostic studies, information on initial staging 
procedure, treatment data, and any other information relevant to 
tracking a patient's future status for clinical outcomes. NCI-supported 
biorepositories should facilitate followup with patients.
    3. NCI-supported biorepositories should maintain identifying and 
contact information as detailed in the study protocol and as permitted 
under law and by patient consent to enable biospecimen use for 
longitudinal studies.
    4. NCI-supported biorepositories should establish, as necessary, 
new policies and protocols to facilitate the submission of outcome 
data, ensure uniformity and patient privacy, and track treatment and 
outcomes.
    5. To collect high-quality longitudinal information, NCI-supported 
biorepositories should require dedicated and trained personnel to 
curate the validation process and QA/QC.
Informatics To Support the Tracking of Data \3\
---------------------------------------------------------------------------

    \3\ The NCI intends to assist biorepositories in choosing 
informatics approaches that meet the necessary data tracking and 
management requirements set forth by the institute.
---------------------------------------------------------------------------

    1. A biorepository informatics system should track all aspects of 
biospecimen collection, processing, and distribution to prevent the 
confusion of samples and to support annotation.
    2. A biorepository should comply with applicable privacy laws, 
human subjects regulations, and local institutional requirements 
governing the acquisition of biospecimens and associated clinical data 
(see the section on Ethical, Legal, and Policy Guidelines for more 
discussion of clinical data and the protection of patient privacy).
C. Quality Assurance/Quality Control (QA/QC)
    NCI-supported biorepositories should develop a formalized QA/QC 
policy to minimize errors that could adversely affect scientific 
results. QA/QC policies should be customized for the intended and 
potential uses of biospecimens in a given biorepository.
QMS
    Each biorepository should either establish a written QMS or adhere 
to one published by the organization with which the biorepository is 
associated. The QMS should describe the biorepository's QA/QC programs 
and describe approaches for ensuring that program requirements are met 
(ISBER 2005). The QMS should describe procedures for conducting audits 
in the following areas:
    1. Equipment maintenance and repair.
    2. Training records and adherence of staff to required training 
schedules.
    3. Data management.
    4. Recordkeeping.
    5. Adherence to SOPs.
SOPs Manual
    Each biorepository should develop written policies and procedures 
in an SOPs manual. The SOPs should state policies and define and 
describe all procedures in detail.
    1. Contents. The SOPs manual should specifically include at least 
the following information:
     Biospecimen-handling policies and procedures, including 
supplies, methods, and equipment used.
     Laboratory procedures for tests performed in-house and any 
biospecimen aliquoting or other processing.
     Policies and procedures for shipping and receiving 
biospecimens, including the MTAs to be used.
     Policies for managing records.
     QA/QC policies and procedures for supplies, equipment, 
instruments, reagents, labels, and processes employed in sample 
retrieval and processing.
     Safety programs.
     Emergency safety policies and procedures, including the 
reporting of staff injuries and exposure to potential blood-borne 
pathogens.
     Policies and procedures for the investigation, 
documentation, and reporting of accidents, errors, complaints, and 
adverse outcomes.
     Policies and procedures and schedules for equipment 
inspection, maintenance, repair, and calibration.
     Procedures for disposal of medical waste and other 
biohazardous waste.
     Policies and procedures regarding the training of 
technical and QA/QC staff members.
    2. Implementation. The biorepository director and/or the individual 
responsible for the QA/QC program should review and approve all SOPs 
and associated process validation studies prior to implementation. Upon 
implementation, all SOPs must be followed as written.
    3. Modifications. Each biorepository should have a document control 
program and policies for governing, modifying, or revising SOPs. Each 
modification should be approved by the biorepository director or other 
appropriate individual(s). Implementation dates should be recorded for 
all procedures. All SOPs should be reviewed every 2 years and have the 
current date of renewal on the posted copy.
    4. Staff access and review. Current copies of the SOPs manual 
should be stored in designated locations and available to the staff at 
all times. The staff should review new and revised policies and 
procedures prior to implementation. Documentation of staff review and 
any associated training should be recorded.
D. Biosafety
    Laboratories and biorepositories that handle biospecimens expose 
their employees to risks involving infectious agents and chemicals, as 
well as the general dangers of a laboratory. A predictable, yet small, 
percentage of biospecimens will pose a risk to the biorepository 
workers who process them. All biospecimens should be treated as 
biohazards (Grizzle and Fredenburgh 2001). In addition to taking 
biosafety precautions, biorepositories should adhere to key principles 
of general laboratory safety.

[[Page 25192]]

Biohazard Precautions
    Laboratories and biorepositories must assume that all human 
biospecimens are potentially infective and biohazardous, regardless of 
whether they are frozen, dried, fixed, processed in paraffin, or 
otherwise processed. Human biospecimens are defined as blood, other 
bodily fluids, solid tissues, tissue products, and cell lines. The 
greatest risks are posed by exposure to the human immunodeficiency 
virus (HIV), the hepatitis viruses, and the prion that causes 
Creutzfeldt-Jakob disease, but there are additional significant 
exposures as outlined by Grizzle and Fredenburgh (2001).
    29 CFR 1910.1030 requires that vaccination be offered to all 
personnel who may be potentially exposed to human blood, body fluids 
and tissues, or other potentially infectious materials. Biorepository 
work practices must be based on universal precautions practices similar 
to those used in laboratories and clinical settings. Two basic 
important safety precautions should be followed in laboratories and 
biorepositories that handle biospecimens: Wash hands frequently, and 
always wear face protection and gloves when handling biospecimens or 
working within or around freezers. Additional good general laboratory 
work practices are outlined in Table 4 of Grizzle and Fredenburgh 
(2001).
    A biorepository must establish clear policies regarding the 
inclusion or exclusion of high-risk biospecimens. Human biospecimens 
should be handled according to, at a minimum, BSL-2 as outlined in the 
CDC/NIH booklet Biosafety in Microbiological and Biomedical 
Laboratories (CDC and NIH 1999). Under BSL-2, when biospecimen 
containers are opened for processing, they should be handled in a BSL-2 
biological safety cabinet (hood). All biorepositories that handle human 
biospecimens should operate under the OSHA's blood-borne pathogens 
standard and should develop an exposure control plan (29 CFR 
1910.1030). Additional precautions apply, as outlined in the CDC 
booklet.
    Some activities may require higher containment, and in other cases, 
less stringent practices may be acceptable. Therefore, it is best to 
ensure that biorepository staff members are trained to perform risk 
assessments and determine appropriate biosafety levels.
Guidelines
    1. Identify governmental and accrediting agency requirements 
regarding biohazards and likely sources of current information 
concerning laboratory biosafety for use in developing an overall 
program in safety and associated training programs. Among the agencies 
that oversee laboratory biosafety programs are the OSHA and the CLSI. 
The CDC oversees programs that handle Select Agents.
    2. Identify risks and other general issues of biosafety. Identify 
frequent biorepository activities and analyze safety issues involved 
with each activity, and implement suitable controls.
    3. Improve biosafety by developing written working guidelines that 
are based on Federal and State requirements, experience, and published 
information. These guidelines should be reviewed and updated regularly 
and modified in response to problems or if they prove ineffective.
    4. Develop and implement a training program. Each employee should 
receive training in relevant areas of safety before beginning work, and 
the training should be updated annually.
    5. Record and arrange for treatment for all incidents where 
personnel are exposed to biohazards or are potentially infected.
General Laboratory Safety
    In addition to biosafety, biorepositories need to follow strict 
general safety regulations and procedures. Recommendations regarding 
general laboratory safety follow. Additional details and references 
regarding biorepository safety can be found in the ISBER Best 
Practices, Section J, and Appendix A (ISBER 2005).
    1. Chemical safety. Follow U.S. regulations concerning chemical 
safety, which protect employees from exposure to hazardous levels of 
chemicals in biorepositories, including, for example, formaldehyde used 
to fix tissues. Biorepositories should also comply with OSHA 
regulations governing occupational exposure to hazardous chemicals in 
laboratories (29 CFR 1910.1450).
    2. Electrical safety. Freezers and other biorepository equipment 
must be properly grounded.
    3. Fire safety. Emergency plans must be in place and practiced on a 
regular basis. Purchase noncombustible freezers and refrigerators.
    4. Physical safety. Repetitive strain and back injuries are typical 
occupational biohazards in the biorepository. Take proper precautions 
to prevent these and other accidents and injuries typical of the 
laboratory/biorepository environment.
    5. Radiological safety. Any laboratory or biorepository that 
processes radioactive materials requires proper training and equipment 
to obtain licenses from the NRC and/or local agencies.
E. Biorepository Informatics: Data Management and Inventory Control and 
Tracking
    Driven by advances in genomics and proteomics, informatics systems 
have become increasingly critical to the research enterprise. 
Informatics systems that support NCI-sponsored biorepositories must be 
robust and reliable and able to meet changing needs while remaining 
interoperable.
    An informatics system should support all aspects of biorepository 
operations, including (but not limited to) patient enrollment and 
consent; biospecimen collection, processing, storage, and 
dissemination; QA/QC; collection of patient data; data security; 
validation documentation; and management reporting functions. The 
system should also manage clinical annotations to the biospecimens and, 
where possible, support those patient followup needs permitted by 
ethical considerations and appropriate regulations. Biorepository 
systems should also be interoperable with those that house endpoint 
assay data (e.g., proteomics, genomics) to ensure that integration of 
data from multiple sources will be possible. The NCICB has developed 
caBIG (see https://cabig.nci.nih.gov/), a voluntary network or grid 
connecting individuals and institutions to enable the sharing of data 
and tools. The informatics systems selected or developed for new 
biorepositories should be caBIG-compatible at the ``silver'' level (see 
https://cabig.nci.nih.gov/guidelines_documentation) with the goal of 
interoperability with other systems. Where systems for existing 
biorepositories are being replaced or upgraded, they should also be 
compatible at the silver level. For existing software, migration paths 
to silver level compatibility should be identified, with the 
expectation that this will become a requirement in later versions of 
these guidelines.
General Informatics Guidelines
    1. Each biospecimen should be assigned a unique identifier (number 
and/or barcode) at the time of collection.
    2. Specific clinical and epidemiological data should be identified 
by the same number and/or barcode.
    3. The same number or code should be used to track a biospecimen 
from

[[Page 25193]]

collection through processing, storage, and distribution.
    4. The biorepository database should be updated each time the 
biospecimen is moved within or out of the biorepository.
Functionality of Biorepository Informatics Systems
    1. Biorepository informatics management systems should be based on 
use cases and other domain level modeling techniques (e.g., data or 
object models) that capture the needs for managing biorepositories. 
SOPs for the activities carried out in a biorepository should largely 
drive the design of informatics systems.
    2. At the biorepository