Medicel Biobank

Thomas M Attard MD FAAP FACG Consultant Pediatrician Kansas City Childrens Mercy Hospital, MO, Mater Dei Hospital, B’Kara, MaltaAssociate Professor University of Malta

Definition: Biobank / biological resource center (BRC)

• long-term storage of biological samples for research or clinical purposes

• In the broader context, a biobank includes a complete organization with biological samples, linked data, personnel, policies, and procedures for handling specimens and performing other services, such as the management of the database and the planning of scientific studies

Dillner J (ed.), Methods in Biobanking, Methods in Molecular Biology 2011

TISSUE DATA

Population

Patient

Organization – Storage

Retrieval Analysis Biobank research product

Demographic

Personal

Clinical

Central or Regional / National Tissue Banking

• Central tissue repository:

– upfront investment and logistic organization (Ethical Board Review, Transfer of biologic specimens → individual country specific)

– Overall more cost effective: single storage facility, limited number of responsible personnel, uniform SOP in tissue handling and storage

– Faster turnaround for studies, pilot studies more feasible

• National / Institutional Tissue Banking– Model favored by BBMRI (Biobanking and

Biomolecular Resources Research Infrastructure)– Variable institutional/investigator resources →

different timeline / likelihood of setup– More expensive as every center has to replicate

every aspect of tissue handling and storage– Impact on study design, cost, timeline– Risk of fractionation → biobank as consortium of

independent biobanks

Central or Regional / National Tissue Banking

Potential Biobank Study Subject

INDIVIDUAL INVESTIGATOR

DATABASE

CENTRAL BIOBANK –

Linked DATABASE

SAMPLE REPOSITORY

Sampling / Sample

processing

Y

N

Anonymous Outline Clinical

Demographic Form

Clinical Data Entry Form

CODED Identifier

CONSENT PROCEDURE

Committee Approved Research Proposals

• PATIENT RECRUITMENT• CONSENT• CODING• SAMPLE INITIAL

PROCESSING• DATAFORM • IID

• SAMPLE STORAGE• Consent repository• SAMPLE TRANSFER

PROCEDURES

• Central Database• Biobank/Database

Utilization Committee• Support Staff

LOCAL NATIONAL

CENTRAL / REGIONAL

• PATIENT RECRUITMENT• CONSENT• CODING• SAMPLE

INITIAL PROCESSING• DATAFORM

• IID • Consent

repository• SAMPLE

TRANSFER PROCEDURES

• Central Database• SAMPLE STORAGE• Biobank/Database

Utilization Committee• Support Staff

LOCAL NATIONAL

CENTRAL

MEDICEL MULTINATIONAL BIOBANK – Roles and Responsibilities

Individual investigator responsibilities

• Define affiliated staff• Age / cultural appropriate

consent documents• Standardized consent

procedure• Signed consent document

storage• Patient coding• Standardized data entry• Sampling and initial processing

Regional / Principal Investigator Responsibilities

• Define coordinating team• Coded Database

Maintenance• Sample Storage Facilities• BIOBANK UTILIZATION

COMMITTEE• Administrative Support• National Node Data/Sample

Quality Review• Funding

Consent Documents

• Required Components of Informed Consent process include:

– full disclosure of the nature of the research and the participant's involvement

– adequate comprehension on the part of the potential participant

– the participant's voluntary choice to participate.

A common consent can be formulated that includes the minimum required consent parameters

Subjects (donors) have to know• the purpose of the research• the methods used, and the likely risks, immediate and

projected.• the sources of funding• possible conflicts of interest• the intended benefits of the research• any other relevant aspects of the study• their right to withdraw consent.

Informed Consent

Individual Site Responsibilities: Consent

• Consent (adult / parent / guardian) and Assent (minor) forms

• Must address all required components

• A copy of the proposed consent (and translation) needs to be made available to Coordinating site

• Institutional Investigational/Scientific Review Board acceptance documentation to be made available

Coordinating Center Responsibilities: Consent

• Develop and disseminate outline of consent/assent document with minimum content requirements (individual sites may choose more extensive content)

• Review proposed consent/assent forms for adherence to consent principles

• Document informed consent obtained for every subject in biobank

• Periodically review consent procedure and content adequacy

MEDICEL Biobank: Data Protection• Ability to trace back the identity the donor can be an issue where

the samples are not anonymized

• This is important both with respect to patient protection as well as prospective Ethical Review approval

• various methods by which the data can be coded:– Direct identification– Coded - identifiable data is physically separated from the personal data but the procurer

of the sample has access to the code – Encrypted - third party persons transform the code into a number of characters, thus

identificable by third party– Anonymized - connection between the code and the identifiable data is completely lost

MEDICEL Biobank – Tissue Types and Storage

• Choice of Tissue type depends on funding (mainly processing/transport and storage), accessibility to sampling process and overall goals/scope of Biobank

Storage Use Pro ConDry Sample on Filter paper Room Temperature

•DNA analysis•Protein/Amino Acid

•Relatively small storage space•Easily obtained•Can remain viable for

decades

•Sensitive to humidity especially fungal attack•Requires adequate drying

at sampling time•Amount of tissue limited

Whole Blood -20 oC

•DNA analysis•Limited use for

protein/amino acid

•Easily obtained•Can remain viable for

decades•Relatively large

quantity of DNA

•Relatively large storage space•Moderate expense in

adequate sample tubes, freezers, ancillary equipment and energy costs

Medicel Biobank Tissue Sample Responsibilities (Central Model)

Individual investigator responsibilities• Define staff roles and

responsibilities

• Assign unique identifier linked to data entry form

• Sampling SOP in line with common biobank guidelines

• Initial processing

• Sample storage / sample transfer

Regional / Principal Investigator Responsibilities

• Define staff roles and responsibilities

• Sample storage / backup storage (power failure etc.)

• Continuous storage quality control

• Temperature monitoring procedures

MEDICEL Biobank – Data Entry – Clinical Data

• Medicel Prospective Study already has very comprehensive data entry sheet

• Encrypted identifier to link to Tissue samples

• Survey / expert opinion prior to project on further data / data format

Specimen Shipment• Ultimately, International Shipment of Biological

Samples (tissue) is almost inevitable– Initial sample transport for Biobanking– Study related specimen transport – (alternatively biobank-study related procedures involving

tissue to take place at every center)• The cost / complexity of (air) transport varies with

the tissue in question (DNA – post / whole blood - courier)

• Requiring strict adherence to the relevant rules and regulations. Sexton KC (ISBER) Cell Preserv Technol (2008)

(IATA) http://www.iatabooks.com.

Air transport

• Technical Instructions for the Safe Transport of Dangerous Goods by Air

– ICAOhttp://www.icao.int/safety/DangerousGoods/Pages/technical-

instructions.aspx

• Dangerous Goods Regulations– IATA

• Minimum Category B

• Assign to UN 3373 -

Sending dangerous goods bycourier

• Must meet classification, packaging and labelling requirements

• Give full description of goods to courier in advance

• Some couriers will not carry dangerous goods or impose additional requirements

• It is illegal to conceal dangerous goods in any packaging not showing appropriate labels

Packaging

• All use triple layer system• For some must use UN type-approved

packaging• Quantity limits on packages (and some

primarys) for air transport• Procedure and type specified in applicable

Packing Instruction

Standard Procedures Manual – before initial setup to include:

• Common consent component requirements

• SP for tissue sampling – type of sample, method, containers, cold chain, tissue handling, initial storage, safety procedures,

• SP for transfer / long term storage (regional model)

• SP for laboratory investigation (comparable / identical Tgase assay) / uniform histology reporting (Marsh Classification)

Questions for the Group• Central or Regional/Institutional Tissue Repisotory

• Membership of biobank oversight committee

• Who is the target population? – all celiacs / symptomatic / screening (high risk or general population)

• → may be problematic if certain centers have asymptomatic affecteds screening programs, variability in societal/medical community awareness

• Coded data at national/local – encrypted data for studies etc.

Questions for the Group

• ‘open consent’ for future studies? Consent limited to academic +/- industry sponsored / not defined

• More extensive (/less extensive) data collection form?

• Cost / viability analysis ↔ Funding

Standard procedure for blood collection

• (new, sterile 3 ml or larger syringe and 18 – 22 gauge needle to collect 12 mls of blood from each subject being tested)

• IMMEDIATELY TRANSFER the blood to a lavender (purple) top tube (EDTA anti-coagulant), 5 ml size or larger.

• INVERT THE TUBE several times to prevent clotting. (DNA cannot be extracted from clotted blood.)