CTBS Flashcards
When was the AATB founded?
The American Association of Tissue Banks (AATB) was founded in 1976 as a voluntary, scientific, and educational not-for-profit organization to promote the exchange of information, methods, and procedures that would increase donation and provide safe, transplantable tissues of uniform high quality in quantities sufficient to meet national needs.
What does AATB stand for?
American Association of Tissue Banks
When were the first AATB guidelines published?
A book of “Proceedings” from the first annual meeting was published in 1978 that offered a detailed overview of current tissue banking practices and described the ethics of donation and transplantation.
When was the first edition of AATB’s Standards for Tissue Banking published?
1984
When was the voluntary accreditation program for tissue banks first launched?
1986
GMPs
good manufacturing practices
What is the strictest device classification?
Class III medical device manufacturer
What is the Uniform Anatomical Gift Act?
The Uniform Anatomical Gift Act (UAGA or the Act) was passed in the US in 1968 and has since been revised in 1987 and in 2006. The Act sets a regulatory framework for the donation of organs, tissues, and other human body parts in the US. The UAGA helps regulate body donations to science, medicine, and education.
What is the mission of the AATB?
A mission of the AATB is to establish and promulgate standards to provide tissue banks with performance requirements intended to prevent disease transmission and support quality measures that assist clinical performance of transplanted tissue. Furthermore, the AATB fosters education and research, and promotes quality and safety in cell and tissue banking and transplantation.
These Standards establish performance requirements for informed consent or authorization, donor eligibility assessment through donor screening and testing, as well as for the recovery, processing, storage, packaging, labeling, and distribution of transplantable human tissue
(A) autologous tissue
(BT) birth tissue
(C) cardiac tissue
(CT) cellular tissue
(DM) dura mater
(LD) living donors
(MS) musculoskeletal tissue
(OA) osteoarticular graft
(R) reproductive tissue
(S) skin
(SB) living donor surgical bone for allogeneic use
(V) vascular tissue
What 3 things are required to request a variance to the standards?
1) A request for variance or modification including the particular standard number(s) that applies to the request;
2) Justification of the alternative procedure(s), policy or process that assure(s) equivalency to the intent of Standards;
3) Supporting information such as worksheets, records, data, or other information (e.g., validation of the protocol to be used in the proposed variance, including the scientific data and quality assurance steps).
ACCIDENT
Any occurrence, not associated with a deviation from standard operating procedures (SOPs), standards, or applicable laws and regulations, during donor screening or testing, or tissue recovery, collection or acquisition, processing, quarantining, labeling, storage, distribution, or dispensing that may affect the performance, biocompatibility, or freedom from transmissible pathogens of the tissue or the ability to trace tissue to the donor.
ACQUISITION (BT)
The point after delivery at which tissue is under the control of the tissue bank.
ADEQUATE INFORMATION
Information sufficient for the donor, the authorizing person or the living donor to make a voluntary decision regarding the gift of tissues for transplantation, therapy, research and/or education. The parameters of what constitutes adequate information must include ‘‘Core Elements’’ contained in D2.400 or D3.400, and such additional information as the donor, authorizing person, or living donor requests or which the donation coordinator reasonably believes the donor, authorizing person or living donor should know. When the donor is authorizing the gift of tissue, publicly available information concerning the scope and use of the gift shall be deemed adequate information.
ADVERSE OUTCOME
An undesirable effect or untoward complication in a recipient consequent to or reasonably related to tissue transplantation.
ALLOGENEIC
Used as an adjective to modify donation, tissue, donor or recipient when transplantation is intended for a genetically different person.
ALLOGRAFT
Tissue intended for transplantation into a genetically different person.
ANNUAL
A frequency of activity defined by each tissue bank as 12 months including reasonable tolerance limits (up to 3 months). Justification for the tolerance limits shall be documented by the tissue bank with consideration for the risk associated with the specific activity scheduled.
ANONYMOUS DONOR (R)
A reproductive donor of tissue whose identity is unknown to the recipient (R)
AORTOILIAC GRAFT (C)
The distal segment of the abdominal aorta including the bifurcation and proximal segments of both the left and right common iliac arteries.
ARTERIAL GRAFT (V)
A segment of peripheral artery that is recovered, processed and preserved.
ARTIFICIAL INSEMINATION (R)
The placement of semen within the reproductive tract of a recipient (R)
ASEPTIC PROCESSING
The processing of tissue using aseptic techniques where tissue, containers and/or devices are handled in a controlled environment in which the air supply, materials, equipment and personnel are regulated to prevent microbial contamination of tissue.
ASEPTIC RECOVERY
The recovery of tissue using methods that restrict or minimize contamination with microorganisms from the donor, environment, recovery personnel, and/or equipment.
ASSISTED REPRODUCTIVE TECHNOLOGY PROCEDURE (R)
A medical procedure intended to result in conception, including, but not limited to, therapeutic insemination, in-vitro fertilization (including intracytoplasmic sperm injection), and gamete intrafallopian transfer.
ASYSTOLE
The reference time for cardiac death. A documented pronounced time of death is used as asystole when life-saving procedures have been attempted and there were signs of, or documentation of, recent life (e.g., witnessed event, agonal respirations, pulseless electrical activity). If a death was not witnessed, asystole must be determined by the last time known alive. Asystole will be ‘cross clamp time’ if the tissue donor was also a solid organ donor.
AUDIT
A documented review of procedures, records, personnel functions, equipment, materials, facilities, and/or suppliers to evaluate adherence to the written SOPM, standards, applicable laws and regulations.
AUDIT TRAIL
A process that captures details such as additions, deletions, or alterations of information in an electronic record without obliterating the original record. An audit trail facilitates the reconstruction of the course of such details relating to the electronic record. (FDA Guidance for Industry, Computerized Systems Used in Clinical Investigations, May 2007)
AUTHORIZATION
Permission given after adequate information concerning the donation, recovery and use of tissues is conveyed.
AUTHORIZING PERSON
Upon the death of the donor, the person, other than the donor, authorized by law to make an anatomical gift.
AUTOGRAFT (A)
Tissue intended for implantation, transplantation or infusion into the living donor from whom it was recovered.
AUTOLOGOUS
Used as an adjective to modify donation, tissue, donor or recipient when donation is intended only from him/herself and transplantation is intended only to him/herself.
BATCH
A specific quantity of tissue produced according to a single processing protocol during the same processing cycle.
BIOBURDEN
The number of contaminating organisms found on a given amount of material.
BIRTH TISSUE (BT)
gestational tissue donated at the time of delivery of a living newborn. This includes placenta, Wharton’s jelly, amniotic fluid, chorionic membrane, amniotic membrane, placental/chorionic disc, umbilical veins, and umbilical cord tissue.
BLOOD COMPONENT
Any part of a single-donor unit of blood separated by physical or mechanical means.
CARDIAC TISSUE (C)
Tissue type that includes, but is not limited to, valved conduits, non-valved conduits, aortoiliac grafts, and patch grafts.
CELLULAR TISSUE (CT)
viable cells that are autologous or allogeneic, committed or uncommitted, and non-expanded.
CERTIFIED COPY
Relating to a death certificate, an original, authenticated form produced by a governing authority.
CLAIM
Any written or oral communication alleging the quality, durability, reliability, infectious disease risk, or performance of tissue.
CLIENT DEPOSITOR (R)
A person who consents to collection and/or storage of reproductive tissues for artificial insemination or assisted reproductive technology procedures for themself(ves) or a sexually intimate partner; not considered a reproductive tissue donor.
COLD ISCHEMIC TIME (C)
The time interval from subjecting cardiac tissue to cold rinse (or transport) solution at recovery to the beginning of disinfection.
COLD ISCHEMIC TIME (V)
The time interval from subjecting vascular tissue to transport solution and wet ice temperatures at recovery to the beginning of disinfection.
COLLECTION (R)
The acquisition of reproductive tissue from a donor or client depositor by surgical or non-surgical procedures.
COLLOID
A protein or polysaccharide solution that can be used to increase or maintain osmotic (oncotic) pressure in the intravascular compartment such as albumin, dextran, hetastarch, or certain blood components, such as plasma and platelets.
COMPLAINT
Any written or oral communication concerning dissatisfaction with the identity, quality, packaging, durability, reliability, safety, effectiveness, or performance of tissue.
COMPETENCY
The ability of an employee to acceptably perform tasks for which he/she has been trained.
COMPETENCY ASSESSMENT
The evaluation of the ability of an employee to acceptably perform tasks for which he/she has been trained.
CONSIGNEE
Any tissue bank, tissue distribution intermediary, tissue dispensing service, or end-user (whether individual, agency, institution, or organization) that receives finished tissue.
CONTAINER
An enclosure for one finished unit of transplantable tissue.
CONTRACT SERVICES
Those functions pertaining to the recovery, screening, testing, processing, storage, and/or distribution of human tissue that another establishment agrees to perform.
CONTROLLED AREAS
Restricted work areas of low microbial and particulate content in which non-sterile materials are prepared.
CORRECTION
Related to conformity, remedial action to eliminate a detected nonconformity.
CORRECTIVE ACTION
Action to eliminate the cause and prevent recurrence of a nonconformity or other undesirable situation; may be performed in conjunction with preventive action(s).
CRITICAL
Classification of a supply, reagent, material, instrument or equipment that can affect the quality and/or safety of tissue.
CRITICAL AREAS
Restricted work areas where cells, tissue, containers and/or closures are exposed to the environment.
CROSS-CONTAMINATION
The transfer of infectious agents from one tissue to another from either the same donor or a different donor.
CRYOPRESERVED
Frozen with the addition of, or in a solution containing, a cryoprotectant agent such as glycerol or dimethylsulfoxide.
CRYOPROTECTANT
An additive that serves to minimize osmotic imbalances that occur with the progression of freezing fronts through a substance, and is intended to limit the amount of cell damage caused by cell shrinkage and intracellular ice formation.
CRYSTALLOID
A balanced salt and/or glucose solution used for electrolyte replacement or to increase intravascular volume, such as saline solution, Ringer’s lactate solution, or 5 percent dextrose in water, or total parenteral nutrition (TPN).
DECONTAMINATION
Cleaning the environment, facilities, and/or surfaces (sanitation), or instruments, supplies, and equipment (sanitization), with intent to remove or reduce pathogenic microbes.
DEHYDRATION
The removal of water from tissue. For example, dehydration methods may include chemical (alcohol), critical/supercritical drying, simple air drying, or drying in a dehydrator.
DESICCATION
The removal of water from tissue. For example, desiccation methods may include chemical (alcohol), critical/supercritical drying, simple air drying, or drying in a desiccator.
DEVIATION
An event that is a departure from a procedure or normal practice.
DIRECTED DONOR (R)
A reproductive tissue donor who is known to the recipient (R) but is not the recipient’s (R) sexually intimate partner.
DISINFECTANT
An agent (e.g., heat or a chemical) capable of reducing the number of viable microorganisms. A disinfectant might not kill spores. Use of antimicrobials in tissue processing is included here.
DISINFECTION
A process that reduces the number of viable microorganisms on tissue, but may not destroy all microbial forms, such as spores and viruses. Use of antimicrobials in tissue processing is included here.
DISINFECTION TIME (C, V)
The time interval between subjecting tissue to disinfection solution and transferring tissue to rinsing solutions in preparation for preservation.
DISPENSING SERVICE
A facility responsible for the receipt, maintenance and delivery to the ultimate user (e.g., transplanting surgeon, surgical center or research facility) of tissue for transplantation or research.
DISPOSITION
The final destination of tissue, e.g., use for transplantation, therapy research, education, or discard; also, the final destination of critical supplies, reagents, materials or equipment that can affect the quality and/or safety of tissue, e.g., release for use or discard.
DISTRIBUTION
A process that includes receipt of a request for tissue, selection of appropriate finished tissue, preparation for transport, any required inspections, and subsequent shipment and delivery of tissue to another tissue bank, tissue distribution intermediary, tissue dispensing service, or end-user.
DOCUMENT OF AUTHORIZATION
Legal record of the gift of tissue, permitting and defining the scope of the postmortem recovery and use of tissues for transplantation, therapy, research and/or education signed or otherwise recorded by the authorizing person, pursuant to law.
DOCUMENT OF GIFT
The donor’s legal record of the gift of tissue permitting and defining the scope of the postmortem recovery and use of tissues for transplantation, therapy, research and/or education. It must be signed or otherwise recorded by the donor or person authorized under law to make a gift during the donor’s lifetime.
DOCUMENT OF GIFT/AUTHORIZATION
Term used when the standard refers to both a document of gift and a document of authorization as defined above.
DONATED HUMAN TISSUE
For the purposes of labeling, this is tissue provided for storage or transplantation, either allogeneic or autologous.
DONATION COORDINATOR
A responsible person who seeks authorization from an authorizing person, or who makes notification concerning donation, recovery, and use of the gift, or in the case of a living donor a responsible person who seeks informed consent from a living donor, a birth mother, or a client depositor. For authorization purposes, this person may also be referred to as a ‘‘designated requestor.’’
DONOR
A living or deceased individual whose body is the source of the tissue.
DONOR ELIGIBILITY ASSESSMENT
The evaluation of all available information about a potential donor to determine whether the donor meets qualifications specified in the SOPM and Standards. See relevant medical records.
DONOR RISK ASSESSMENT INTERVIEW (DRAI)
A documented dialogue in person or by telephone with an individual or individuals who would be knowledgeable of the donor’s relevant medical history and social behavior. For example this may be: the donor, if living; the next of kin; the nearest available relative; a member of the donor’s household; other individual with an affinity relationship (e.g., caretaker, friend, significant life partner); and/or the primary treating physician. Alternatively, a living donor may complete a written questionnaire. The relevant social history is elicited by questions regarding certain activities or behaviors that are considered to place such an individual at increased risk for a relevant communicable disease agent or disease (RCDAD).
DONOR REFERRAL SOURCES
Entities such as hospitals, medical examiners, coroners and individual allied health care professionals who identify potential tissue donors and refer them, or their next of kin, to tissue banks.
DONOR REGISTRY
A database established in accordance with law, consisting of legally valid documents of gift.
DOSIMETRIC RELEASE
Tissue release based on dosimetry instead of sterility testing.
DURA MATER (DM)
A type of soft tissue that includes the pachymeninx (thick, membranous) tissue covering the brain.
DYNAMIC
Operational condition during aseptic processing where the controlled environment is functioning in the specified manner, with the specified number of personnel present and working in the manner agreed upon [ISO 14644-1].
ELECTRONIC SYSTEMS
Computerized systems that create source documents (electronic records).
ELECTRONIC QUALITY MANAGEMENT SYSTEMS
Software used in the automation or monitoring of an organization’s quality system that may apply, but is not restricted, to the following: product design and development; supply and/or component acceptance; testing; manufacturing; labeling; packaging; distribution; handling of a complaint, CAPA, error, nonconformity; or any other aspect of the Quality Management Systems.
EMBRYO (R)
Pre-implantation, reproductive tissue resulting from the combination of oocyte and sperm.
EMBRYO BANK
A facility that performs cryopreservation or storage of embryos intended for use in creating pregnancy.
EMBRYO CLIENT DEPOSITOR (R)
A woman and/or man who provides gametes or contracts with a gamete donor(s) responsible for creation of an embryo(s) intended for transfer (R).
EMBRYO DONOR (R)
Embryo client depositor(s) who choose(s) to donate his/her (their) embryos. Ownership of the embryos is transferred to a new client depositor(s) who was (were) not gamete providers
END-USER
A health care practitioner who performs transplantation procedures.
ENVIRONMENTAL CONTROL
Activities performed to control the environment for the purpose of minimizing the potential for contamination or cross-contamination of tissue.
ENVIRONMENTAL MONITORING
Activities performed to systematically observe and record data to characterize the environment to identify conditions under which the potential may exist for contamination or cross-contamination of tissue.
EQUIPMENT QUALIFICATION STUDIES
Protocols designed to adequately evaluate, prior to use, whether pieces of equipment will perform to expectations, and normally function within the required tolerance limits.
ERROR
A deviation from the SOPM, Standards, or applicable laws or regulations.
ESTABLISH
Define, document and implement.
FIELD CORRECTION
For distributed tissue, the repair, modification, adjustment, relabeling, destruction, or inspection (including patient monitoring) without its physical removal to some other location. Reference 21 CFR Part 7, 7.3(h).
FIELD NOTIFICATION
The provision of additional information pertaining to the safety, quality, identification, function and/or use of distributed tissue.
FINISHED TISSUE
Tissue that has been fully processed, enclosed in its final container, labeled, and released to distribution inventory.
GAMETE (R)
Mature human germ cell, whether an oocyte or sperm
IMAGE(s)
A representation of the external form of an object, place or person in a photographic, digital, or videographic format.
INFORMED CONSENT
Permission given by a living donor (LD) or client depositor who is presented with a description of the scope, use and any risks or benefits to her or him of the proposed donation, and who has been given the opportunity to ask questions and receive accurate answers. An LD who gives her or his informed consent to donation shall sign a record of the informed consent.
IN-PROCESS CONTROLS
Any tests, samples, evaluations, monitoring, or measurements performed during processing or preservation that are designed to ensure conformance to specifications in the SOPM.
IN-PROCESS MATERIAL
Any material that is used in the processing of tissue, including, but not limited to, incoming tissue, water, alcohol, acid, containers, and closures.
LABEL
Any written, printed, or graphic material used to identify tissue, cultures, blood specimens or other donor specimens.
LABELING MATERIAL
Any printed or written material, including labels, advertising, and/or accompanying information (e.g., package insert, brochures, and pamphlets), related to the tissue.
LIVING DONOR (LD)
A person who consents to the recovery or collection of his or her tissue, where recovery or collection is to take place while she or he is alive. For all living donors, (LD) standards apply, then tissue-specific standards apply. A living donor is a type of donor and, unless otherwise specified, standards that apply to donors in general apply to living donors.
LOT
Tissue produced from one donor at one time using one set of instruments and supplies. Also refers to a quantity of reagents, supplies, or containers that is processed or manufactured at one time and identified by a unique identification number.
LYOPHILIZED
Tissue dehydrated for storage by conversion of the water content of frozen tissue to a gaseous state under vacuum that extracts moisture.
MANAGEMENT WITH EXECUTIVE RESPONSIBILITY
Those senior employees of a tissue bank who have the authority to establish or make changes to the tissue bank’s quality policy and quality system.
MARKET WITHDRAWAL
A field correction or removal of distributed tissue that involves a minor violation that would not be subject to legal action by the FDA or that involves no violation (e.g., normal stock rotation practices). Reference 21 CFR Part 7, 7.3(j).
MAY
Used to indicate an acceptable method that is recognized but not essential.
MICROORGANISM
A microscopic organism including bacteria and fungi; viruses, while sometimes included in this classification, are not included here.
MUSCULOSKELETAL TISSUE (MS)
Tissue type that includes, but is not limited to, bone and cartilage, and soft tissue such as tendon, ligament, nerve, fascia, pericardium, peritoneal membrane, adipose, and dura mater.
MUST
Used to indicate a mandatory requirement. The same as SHALL.
NONCONFORMITY
A finding that identifies non-fulfillment of an accreditation requirement, a standard, policy, process, procedure, or specification.
NON-TERMINAL IRRADIATION
Ionizing radiation used to reduce microbes prior to processing.
NON-VALVED CONDUIT (C)
A length of cardiac outflow tract (aortic or pulmonic) from which the valve structure has been removed or intentionally rendered completely non-functional.
NOTIFICATION (OF GIFT)
Provision and documentation of notice concerning an anatomical gift that was made by the donor during the donor’s lifetime
OOCYTE DONOR (R)
A person who donates oocytes for use in assisted reproductive technology procedures. An oocyte donor can be further categorized as a directed donor or an anonymous donor but is not a client depositor.
OSTEOARTICULAR GRAFT
A weight bearing allograft with intact articular surfaces, consisting of a joint with associated soft tissue and bone.
PACKAGE
A labeled box, carton, receptacle, or wrapper containing tissue and may contain one or more containers and accompanying labeling materials.
PACKAGE INSERT
The written material accompanying an allograft or autograft bearing further information about the tissue, directions for use, and any applicable warnings.
PACKAGING SYSTEM
The combination of primary package, secondary package, and additional protective packaging, as deemed necessary.
PATCH GRAFT (C)
A segment of cardiac allograft conduit to be used in cardiovascular repair, replacement, construction, or reconstruction.
PERFUSION SOLUTION (V)
A room temperature, sterile isotonic solution such as tissue culture media or PlasmaLyte® utilized to gently perfuse veins at recovery. This solution may also contain an antithrombotic agent (i.e., sodium heparin).
PERFUSION TIME (V)
The time interval from asystole to subjecting the vascular tissue to perfusion solution.
PHYSICAL ASSESSMENT
A recent ante-mortem or postmortem documented evaluation of a deceased donor’s body that can identify evidence of: high-risk behavior and signs of HIV infection or hepatitis infection; other viral or bacterial infections; or, trauma to the potential recovery sites.
PHYSICAL EXAMINATION
A recent documented evaluation of a living donor’s body to determine whether there is evidence of high risk behavior and that determines overall general health of the donor. After a donor risk assessment interview is completed and if any history is suspect, the physical examination should also encompass a directed examination (of a body part or region).
PLASMA DILUTION
A decrease in the concentration of the donor’s plasma proteins and circulating antigens or antibodies resulting from the transfusion of blood or blood components and/or infusion of fluids, e.g., colloid(s) and/or crystalloid(s).
POLICIES AND PROCEDURES MANUAL
See Standard Operating Procedures Manual (SOPM).
POOLING
The physical contact or mixing of tissue from two or more donors in a single receptacle.
PRE-STERILIZATION/PRE-DISINFECTION CULTURE
A culture of tissue obtained prior to exposure to antibiotics, disinfecting chemicals, or sterilizing agents.
PRESERVATION
The use of chemical agents, alterations in environmental conditions or other means during processing to prevent or retard biological or physical deterioration of tissue.
PREVENTIVE ACTION
Action to eliminate the cause of a potential nonconformity or other undesirable situation; may be performed in conjunction with corrective action(s).
PRIMARY PACKAGE
Layer of packaging in direct contact with tissue.
PROCEDURE
A series of steps, which when followed, is designed to result in a specific outcome.
PROCESS CONTROLS
A system of checks and balances incorporated into standard operating procedures involving critical operations to prevent errors.
PROCESS VALIDATION
Establishing by objective evidence that a process consistently produces a results meeting predetermined specifications.
PROCESSING
Any activity performed on tissue other than donor screening, donor testing, tissue recovery, collection, or acquisition functions, storage, distribution or dispensing. It includes but is not limited to disinfecting, sterilizing, packaging, labeling, and testing tissue.
PROFICIENCY TESTING
The evaluation of an individual laboratory’s performance against pre-established criteria by means of inter-laboratory comparisons. (Adapted from ISO/IEC 17043:2010 Conformity assessment - General requirements for proficiency testing)
QUALIFICATION
The process of establishing confidence that equipment, materials, reagents, and ancillary systems are capable of consistently performing within established limits and tolerances. Process performance qualification is intended to establish confidence that the process is effective and reproducible.
QUALITY
Conformance to pre-established specifications, attributes, requirements, regulations, and/or standards.
QUALITY AGREEMENT
an agreement that establishes the quality specifications or standards that must be met for defined activities and delineates responsibilities of each entity involved. It may be a separate document or included as part of a written agreement/contract.
QUALITY ASSURANCE (QA) PROGRAM
The policies and environment required to meet standards of quality and safety, and to provide confidence that the processes and tissue consistently conform to quality requirements.
QUALITY CONTROL (QC)
Specific tests defined by the QA program to be performed to monitor recovery, processing, preservation and storage, tissue quality, and test accuracy. These may include but are not limited to, performance evaluations, inspection, testing, and controls used to determine the accuracy and reliability of the tissue bank’s equipment and operational procedures, as well as the monitoring of supplies, reagents, equipment, and facilities.
QUALITY POLICY
The overall intentions and direction of an organization with respect to quality, as established by management with executive responsibility.
QUALITY SYSTEM
The organizational structure, responsibilities, procedures, processes, and resources for implementing quality management.
QUARANTINE
The identification of tissue, reagents, supplies, materials and equipment as not suitable for use, or that has not yet been characterized as being suitable for use.
RECALL
A field correction or removal of distributed tissue initiated to reduce a risk to health posed by the tissue or to remedy a violation of regulatory requirements that may present a risk to health.
RECIPIENT
A person into whom tissue is transplanted.
RECIPIENT (R)
A woman undergoing an assisted reproductive technology procedure. A recipient (R) can be an intended parent, a gestational carrier, or a gestational surrogate
RECORD
Information that is inscribed on a tangible medium or that is stored in an electronic or other medium and is retrievable in perceivable form.
RECOVERY
Obtaining tissue other than reproductive tissue from a donor that is intended for use in human transplantation, therapy, research or education
RECOVERY SITE
The immediate area or room where a tissue recovery takes place (e.g., dedicated tissue recovery site, healthcare facility operating room, autopsy suite).
RELEVANT MEDICAL RECORDS
A collection of documents including a current donor risk assessment interview, a physical assessment/physical examination, laboratory test results (in addition to results of testing for required relevant communicable disease agents), relevant donor records, existing coroner and autopsy reports, a certified copy or verified copy of the death certificate (when applicable), as well as information obtained from any source or records which may pertain to donor eligibility regarding high risk behaviors, and clinical signs and symptoms for any relevant communicable disease agent or disease (RCDAD), and/or treatments related to medical conditions suggestive of such risk.
REMOVAL
The physical removal of distributed tissue from its point of use to some other location for repair, modification, adjustment, relabeling, destruction, or inspection. Reference 21 CFR Part 806, 806.2(i).
REPRODUCTIVE TISSUE (R)
Any tissue from the reproductive tract intended for use in assisted reproductive technology procedures. This includes, but is not limited to: oocytes, ovarian tissue, embryos, semen, spermatozoa, spermatids, testicular tissue, and epididymal tissue.
REPRODUCTIVE TISSUE BANK (R)
A tissue bank that collects, processes, stores, and/or distributes human reproductive tissue for use in assisted reproductive technology procedures.
RESOLUTION
Adjustment, clarification, and/or correction of practices and/or procedures that results in compliance with the SOPM and/or standards.
RESPONSIBLE PERSON
A person who is authorized to perform designated functions for which he or she is trained and qualified.
SAFETY
A quality of tissue indicating handling according to standards and substantial freedom from the potential for harmful effects to recipients.
SATELLITE FACILITY
A facility operated or owned by the tissue bank and located in a physically separate location from its primary address, and where any tissue banking activities occur or where any tissue banking services are provided.
SECONDARY PACKAGE
The barrier that surrounds the primary package (e.g., the tissue can be sterile tissue inside, aseptically processed tissue, recovered, or acquired tissue.)
SEMEN (R)
The fluid of man’s reproductive system consisting of spermatozoa and secretions of accessory glands.
SEMEN DONOR (R)
A man who donates semen for use in artificial insemination or assisted reproductive technology procedures where the recipient is not a sexually intimate partner. A semen donor can be further categorized as a directed donor or an anonymous donor but is not a client depositor.
SERIES OF STANDARDS
A group of standards related to a particular topic presented as a capitalized heading (e.g., B2.000) followed by indented subsections (e.g., B2.100, B2.120, B2.121). The heading and everything indented under it are considered part of the series.
SERVICES TO DONOR FAMILIES
A defined policy or support program describing tissue donation follow-up offered to the authorizing person (or party). This may include written communications regarding: potential uses of tissue; recovery outcome information; bereavement information and support; provision of a copy of the document of gift/authorization: and/or guidance describing how to contact the tissue bank if any questions arise regarding the donation. Frequency of follow-up and program maintenance is at the discretion of the tissue bank, however, periodic evaluation of services is required.
SHALL
Used to indicate a mandatory standard, same as MUST.
SHOULD
Used to indicate a recommendation; advisory, indicating a commonly accepted activity for which there may be effective alternatives.
SIGNATURE
A record is signed when it has been authenticated or adopted by the signer by means in writing, or an electronic signature, symbol, sound, process or recording pursuant to applicable law.
SKIN (S)
A membranous soft tissue type that includes, but is not limited to epidermis and dermis.
SKIN PREP
The application of antiseptic solution to decontaminate the skin. This is a continuous process that is performed without delay between steps; it does not include shaving hair, although this can be done if preferred. Unless otherwise qualified/validated, the manufacturer’s written recommendations must be followed, including that the antiseptic solution should remain in place for the recommended contact time and be allowed to air dry completely before the surgical drapes are placed.
STANDARD OPERATING PROCEDURES MANUAL (SOPM)
A group of standard operating procedures (SOPs) detailing the specific policies of a tissue bank and the procedures used by the staff/personnel to carry out the functions of the tissue bank.
STANDARDS
AATB Standards for Tissue Banking
STATIC
At-rest condition during aseptic processing where the controlled environment is complete with equipment installed and operating in a manner agreed upon, but with no personnel present [ISO 14644-1].
STERILE
For tissue, the absence of detectable, viable, microorganisms (refer to ANSI/AAMI ST67:2011). For reagents, supplies, materials and equipment, free from viable microorganisms.
STERILITY ASSURANCE LEVEL (SAL)
The probability of a single viable microorganism occurring on a product after sterilization (refer to ANSI/AAMI ST67:2003).
STERILIZATION
A validated process used to render tissue free from viable microorganisms (refer to ANSI/AAMI ST67:2003) including spores.
STOCK RECOVERY
Retrieval of tissue that has not left the direct control of the tissue bank (manufacturer), i.e., the tissue is located on the premises owned, or under the control of, the tissue bank (manufacturer), and no portion of the affected tissue has been released for use. Reference 21 CFR Part 7, 7.3(k).
STORAGE
The maintenance of tissue for future use.
STRUCTURAL SUPPORT
Those tissue grafts that contribute biomechanical strength to a surgical construct.
SUMMARY OF RECORDS
A condensed version of the donor testing and eligibility determination records. This can be combined with the package insert.
SURGICAL BONE (SB)
Any bone from a living donor for allogeneic use such as a femoral head removed during surgery.
TERMINAL STERILIZATION
A validated process whereby tissue within its final sterile barrier system (e. g., package, container) is sterilized (refer to ANSI/AAMI ST67:2011).
THIRD PARTY RECORDS
Records produced by an entity not involved in tissue recovery, acquisition, or donor screening. Examples of third party records include: hospital medical records; emergency medical services records; coroner/medical examiner records; prenatal records, and police reports.
TISSUE
A functional group of cells. The term is used collectively in Standards to indicate both cells and tissue.
TISSUE BANK
An entity that provides or engages in one or more services involving tissue from living or deceased persons for transplantation purposes. These services include obtaining authorization and/or informed consent, assessing donor eligibility, recovery, collection, acquisition, processing, storage, labeling, distribution and dispensing of tissue.
TISSUE DISPENSING SERVICE
Any entity that receives, stores, and provides tissue directly to an end-user for transplantation. Tissue dispensing services may or may not be tissue banks, depending on what other functions they perform.
TISSUE DISTRIBUTION INTERMEDIARY
An intermediary agent who acquires and stores tissue for further distribution and performs no other tissue banking functions.
TISSUE IDENTIFICATION NUMBER
Any unique combination of letters, numbers, and/or symbols assigned to tissue and linked to a donor, from which the complete history of the recovery, collection or acquisition, processing, packaging, quarantine, labeling, storage, distribution and dispensing of tissue can be traced. Identical tissue processed under the criteria defined in ‘‘lot’’ may be assigned the same tissue identification number.
TOLERANCE LIMITS
The limits that define a range of acceptable values that are established for each testing procedure which, when exceeded, require the implementation of corrective actions designed to produce results within the acceptable range in future tests.
TOTAL ISCHEMIC TIME (C, V)
The time interval from asystole to subjecting tissue to disinfection solution. This is the sum of warm ischemic time and cold ischemic time.
TRACEABILITY
The ability to locate tissue during any step of its donation, recovery, collection, or acquisition, processing, testing, storage, distribution or disposition. It implies the capacity to identify the medical facility receiving the tissue and, at the medical facility, the ability to identify the recipient.
TRANSFER (R)
The placement of human reproductive tissue into a human recipient (R).
TRANSPLANTATION
The transfer of an allograft or autograft to a recipient.
TRANSPORT MEDIUM
Any microbiological medium capable of maintaining cellular viability during the transport of a culture from field to laboratory.
TRANSPORT SYSTEM
The combination of the packaging system and the container utilized to transport tissue.
VALIDATION
Confirmation through the provision of documented objective evidence that predefined specifications have been fulfilled and can be consistently reproduced.
VALVED CONDUIT (C)
An allograft heart valve with an attached length of cardiac outflow tract (aortic or pulmonic).
VARIANCE
A departure from Standards that is pre-approved by the AATB Board of Governors prior to implementation.
VASCULAR TISSUE (V)
Tissue type that includes, but is not limited to arterial grafts and vein grafts.
VEIN GRAFT (V)
A segment of vein that is recovered, processed and preserved.
VERIFICATION
The confirmation by examination and provision of objective evidence that specified requirements have been fulfilled.
VERIFIED COPY
A copy of a death certificate without the raised seal but issued by an authorizing agency.
VETERINARY USE
Treatment of a condition or disease in a non-human animal.
WARM ISCHEMIC TIME (C)
The time interval from asystole to subjecting cardiac tissue to cold rinse (or transport) solution at recovery.
WARM ISCHEMIC TIME (V)
The time interval from asystole to subjecting vascular tissue to transport solution and wet ice temperatures at recovery.
WET ICE TEMPERATURES
Temperatures ranging from above freezing (0°C) to 10°C.
WITNESS
An individual who signifies in writing, or in electronically recorded format, that he or she has observed the execution or verbal authorization of the document of gift/authorization or informed consent. The witness’ signification must be contemporaneous with execution and the witness must be identified by name, address and/or such other contact information as is relevant and feasible. A witness should not be an employee or agent of the tissue bank or requesting entity.
AAMI
Association for the Advancement of Medical Instrumentation
AATB
American Association of Tissue Banks
ANSI
American National Standards Institute
AORN
Association of periOperative Registered Nurses
ASQ
American Society for Quality
ASTM
ASTM International, formerly known as the American Society for Testing and Materials (ASTM), is a globally recognized leader in the development and delivery of international voluntary consensus standards
CAP
College of American Pathologists
CBER
Center for Biologics Evaluation and Research
CDC
Centers for Disease Control and Prevention
CFR
Code of Federal Regulations. Published by the Office of the Federal Register, National Archives and Records Administration, Washington, DC
e.g.
exempli gratia; for example, such as; the list is not finite
FDA
The United States Food and Drug Administration
i.e.
id est; that is; indicates a finite list
ISO
International Organization for Standardization
USP
United States Pharmacopeia
The purpose of a tissue bank shall be clearly
formulated and documented
The tissue bank shall state whether it is a freestanding entity or part of an
institution
The tissue bank shall have a BLANK that may consist of a Board of Trustees, Board of Governors, Board of Directors or a designated responsible individual in whom policy-making authority resides, unless otherwise provided by the institution of which it is a part.
Governing Body
This Board or designated individual shall determine the BLANK to be pursued by the tissue bank.
scope of activities
The Governing Body shall designate one or more senior employees as
management with executive responsibility
Issues of liability, ethical considerations, fiduciary responsibility, and compliance with applicable laws and regulations, these Standards, and the tissue bank’s SOPM shall be the responsibility of the
Governing Body and management with executive responsibility.
A tissue bank SHOULD establish and maintain a mechanism to access
medical, technical, and scientific advice as needed. Decisions SHALL be documented.
Satellite facilities SHALL be operated in accordance with the
tissue bank’s SOPM
What are some types of tissue banking activities or services?
1) donor referral;
2) authorization;
3) informed consent;
4) donor eligibility assessment;
5) recovery, collection, and/or acquisition;
6) post-delivery functions;
7) laboratory services (see exception at B1.600);
8) testing services;
9) processing;
10) storage;
11) tissue release;
12) distribution; and/or
13) consignment.
Written agreements or contracts shall
indicate the nature of the relationships, division of tasks performed, division of issues of liability, specific responsibilities of each party and a summary of the protocols and procedures relating to the services provided. The tissue bank shall maintain a copy of each such agreement, which shall be made available for review if requested by AATB inspectors. Compliance with Standards by all parties shall be required and documented in a quality agreement.
A tissue bank that recovers tissue that is processed and/or distributed by another tissue bank shall be responsible for being in compliance with these Standards for all operations it performs. This includes, but is not limited to, the requirement to have a Medical Director; unless the tissue bank that recovers tissue and the tissue bank responsible for the processing and/or distribution of such tissue have a written agreement that defines the responsibilities of the processing tissue bank’s Medical Director to provide required oversight over donor screening and donor testing*, to follow applicable standards in Section D and Appendix II, and to share records (see D4.300). A tissue bank that recovers tissue is not required to audit its contracted tissue bank processor(s).
A tissue bank that BLANK tissue recovered and/or distributed by another tissue bank shall be responsible for being in compliance with these Standards for all operations it performs. The tissue BLANK organization must bear the burden of proof, and document in writing, that operations performed by other organizations prior to the receipt of tissue for BLANK were performed in a manner consistent with these Standards as well as the BLANK tissue bank’s requirements.
processes, processing, processing, processing
A tissue bank that BLANKS tissue recovered and/or processed by other tissue banks shall be responsible for being in compliance with AATB Standards for all operations it performs. The BLANK must also bear the burden of proof, and document in writing, that operations performed by other organizations prior to its receipt of tissue for BLANK were performed in a manner consistent with AATB Standards. Any records necessary to demonstrate compliance shall be readily accessible to the BLANK tissue bank.
distributes, distributor, distribution, distributing
If an AATB-accredited tissue bank obtains from and processes tissue for a tissue bank not accredited by the AATB that is located outside of the United States (U.S.), do the the requirement for compliance with Standards apply to the foreign tissue bank if the processed tissues will not be distributed within, or to, the U.S?
No
All tissues imported from entities that do not follow AATB Standards shall be appropriately BLANK throughout import, storage, processing, and export.
quarantined
The AATB-accredited tissue bank must verify that the foreign tissue bank not accredited by the AATB complies with
regulations of the governmental authority having jurisdiction in their country for the functions they perform.
How frequently does the accredited tissue bank have to verify (via audits and inspections) that that its contracted entities comply with AATB Standards, laws, and regulations?
at least biennially (once every 2 years)
The tissue bank must ensure (and maintain documentation of activities obtained by either paper audit or on-site audit) that a laboratory performing donor infectious disease testing for the tissue bank is:
1) registered with the FDA as a tissue establishment and lists ‘testing’ as a function;
2) using the appropriate FDA-licensed, approved, or cleared donor screening tests;
3) following manufacturers’ instructions for these tests; 4) certified in accordance with the Clinical Laboratory Improvement Amendments of 1988 (42 U.S.C. 263a) and 42 CFR part 493, or has met equivalent requirements as determined by the Centers for Medicare and Medicaid Services;
5) retaining donor infectious disease test run records for ten years; and
6) aware of the requirement of the tissue bank to comply with D4.240.
Who shall ensure the establishment of the tissue bank’s policy and objectives for, and commitment to, quality, and shall ensure that the quality policy is understood, implemented, and maintained at all levels of the organization?
Management with executive responsibility
What must a tissue bank have in place in the event of a merger, acquisition, or dissolution?
Contingency Plan
The tissue bank shall have a Medical Director who maintains a valid medical license from any state or U.S. territory (or for international members, the physician must maintain an equivalent medical license). He/she should have training and experience in evaluating and determining donor eligibility particularly with regard to infectious diseases or use a Medical Advisory Committee or consultants to assist in those areas. Unless….
An AATB-accredited tissue bank recovering tissue for an AATB-accredited processing tissue bank may fulfill this requirement by securing a written agreement with the processing tissue bank that defines the responsibilities of the processing tissue bank’s Medical Director to provide required oversight over donor screening and donor testing operations conducted by the recovery tissue bank.
Who is responsible for establishing donor eligibility criteria?
Medical Director overseeing the tissue bank
Who establishes policies and procedures regarding adverse outcomes?
Medical Director overseeing the tissue bank
Who is responsible for notifying appropriate parties of the availability of positive infectious disease test results, and for reporting positive test results when required?
Medical Director overseeing the tissue bank
Who has the responsibility for assuring compliance with the SOPM regulatory requirements?
Quality assurance program personnel
Who is responsible for managing audits?
Quality assurance personnel
Who has the responsibility and authority to approve or reject tissue, as well as discontinue processing and/or release of tissue when deviations from SOPM warrants?
The individual responsible for the quality review
Documentation must be made concurrent with each significant step and must include, but not be limited to:
1) information from the donor referral source;
2) donor eligibility assessment information;
3) record of informed consent, or document of gift/authorization;
4) donor physical assessment or physical examination, and donor identification;
5) tissue recovery or collection, transport, and processing;
6) quarantine and infectious disease testing;
7) in-process testing;
8) record review;
9) tissue labeling, storage, release, and distribution;
10) quality control; and
11) services to donor families.
Records must include
the responsible party(ies) and must delineate the dates, times, and locations of subsequent procedures as well as the individuals performing them in order to facilitate traceability.
Results of laboratory tests used to determine final release of tissue for transplantation (e.g., sterility testing and testing for residual water, ethylene oxide, residual calcium) shall be maintained by
the tissue bank that determines the suitability of the allograft for distribution (‘‘distributor’’).
Records of the informed consent, documents of gift/authorization, and records pertaining to donor eligibility, recovery, collection, acquisition, processing, storage, date of distribution, QA, and identity of person/entity to whom distributed, shall be retained at least
10 years beyond the date of distribution, date of transplantation (if known), date of disposition, or date of expiration of the tissue (whichever is latest) or longer if required by applicable laws and regulations.
Donor eligibility records of dura mater donors shall be retained
indefinitely
Tissue banks that have their tissues processed by another agency must assure that processing and QC records are retained for at least
10 years.
The reproductive tissue bank should maintain current donor and client depositor addresses until tissues are
used or destroyed.
A tissue bank’s records management system shall identify tissue by use of
a unique identifier
Laboratory and QC specimens related to a donor shall also be
traceable to the donor
Revisions to paper records shall be made with a single line drawn through the altered text. The revision shall be initialed and dated by the individual making the revision. Additions to a completed record shall be initialed and dated by the individual making the additions.
Records additionally shall include the following information:
1) ABO/Rh, if available;
2) date/time of asystole;
3) date/time of recovery of the heart (time when subjected to cold rinse solution);
4) date/time of subjection of cardiac tissue to disinfection solution;
5) start and stop times when tissue was subjected to disinfection solution; and
6) date/time: a) when preservation began; and b) when placed in final container.
3) date/time vascular tissues subjected to perfusion solution;
4) date/time vascular tissues placed in transport solution and subjected to wet ice temperatures;
5) date/time of subjection of vascular tissue to disinfection solution;
6) start and stop times when tissue was subjected to disinfection solution; and
7) date/time (a) when preservation began and (b) when placed in final container.
What records need to be maintained for reproductive tissue?
Donor records shall include documentation of informed consent, relevant medical records, results of all laboratory screening tests, and outcome of prior assisted reproductive technology procedures (if known) including number of successful pregnancies and any reports that would affect the donor’s eligibility. Records shall also include personal attributes of the donor such as: height, weight, eye color, hair color, complexion, racial group, and/or body type.
Monetary compensation or other valuable consideration, including goods or services, shall not be offered to a donor, authorizing person, the donor’s estate, or any other third party acting on behalf of the donor, except in the following instances:
1) the tissue bank may reimburse responsible third parties for costs directly associated with a donation; or 2) the tissue bank may reimburse living donors for costs associated with an acceptable donation, including compensation for restoration of lost earnings when directly attributable to donation, if and as authorized by law.
(R) The reproductive tissue bank may provide monetary compensation to donors of reproductive tissue if
the compensation is compliant with professional standards of practice.
A policy shall be established requiring the donor always be treated with
A policy shall be established requiring the donor always be treated with
This authorization shall be expressed in a document of gift/authorization, the original or a copy of which shall be maintained in the donor’s record at the tissue bank responsible for
recovery, as well as in the donor’s record at the tissue bank whose Medical Director is responsible for the donor eligibility determination.
True or False: In cases where a donor has executed a document of gift it may be acted upon (permits recovery) provided it meets applicable laws and regulations.
True
When a document of authorization is used it must contain the following signatures and related information:
1) the authorizing person’s signature and: name, mailing address (NOTE: If requested by the authorizing person, only an email address may be documented as the address but, in such cases, the authorizing person should permit its use and should be informed that if the email address changes or if email communication is blocked, there may be no effective forwarding or receipt of information.); phone number, and relationship to the donor;
2) the donation coordinator’s signature and the date, identity of their organization, the signature of each witness if witnessing is required by law or regulation, documentation that the Core Elements were used, and a statement granting authorization for tissue recovery
Legal authorization can be obtained using different methods. When authorization is obtained:
In person, by telephone, by facsimile, or using electronic transmission (e-mail)
What are the Core Elements?
1) the name of the Donor;
2) the name, mailing address, and telephone number of the authorizing person, and his/her relationship to the donor
3) an explanation that the tissue is a gift, and that neither the donor’s estate nor the authorizing person will receive monetary compensation or valuable consideration for it;
4) a description of the general types of tissue to be recovered;
5) a description of the permitted use(s) of the recovered tissues (i.e., transplant, therapy, research, or education);
6) an explanation that recovery of tissue requires the following actions, and the document of gift/authorization thus specifically authorizes: a) access to, and required disclosure of, the Donor’s medical and other relevant records; b) testing and reporting for transmissible diseases; c) the removal of specimens which may include, but are not limited to blood or tissue samples for the purposes of biopsy or other testing necessary for determination of donor eligibility; d) the release to the tissue bank of any and all records and reports of a Medical Examiner, Coroner or Pathologist (e.g., autopsy report); and e) such other requirements as may be applicable for the specific donation or tissue bank, such as transport of the donor’s body, archiving of samples, photographic or other imaging, etc.
7) contact information for the organization represented by the donation coordinator; and
8) any additional information required by laws or regulations.
9) Any explanation required by law, such as an explanation that multiple organizations (nonprofit and/or for profit) may be involved in facilitating the gift(s) and/or reference to the possibility that tissue may be distributed internationally, must be included.
The following information should be provided to an authorizing person:
1) a general description of the recovery e.g., timing, relocation of donor if applicable, contact information, etc.;
2) an explanation that costs directly related to the evaluation, recovery, preservation, and placement of the tissues will not be charged to the family;
3) an explanation regarding the impact the donation process may have on burial arrangements and on appearance of the donor’s body; and
4) an explanation that the document of authorization is available.
When is it required to obtain blood from the birth mother?
When a donor is 28 days of age or less
Is the authorizing person able to revoke or amend the gift made by the donor?
No
In cases where the gift is authorized by a donor’s own document of gift (i.e., first person consent), including a document of gift recorded in a donor registry…
law mandates notification, such notification shall be made pursuant to law.
Prior to transport of the donor’s body or recovery, the donation coordinator should attempt to notify the person who would have been an authorizing person had no gift been made during the life of the donor or the person who is authorized to make arrangements for final disposition. The information to be provided in the notification should contain, at a minimum…
the Core Elements of authorization
The donation coordinator should inquire during the notification whether the notified person is aware of any revocation or refusal made by
the donor
Recovery may proceed only after…
good faith efforts to notify an appropriate person of the gift fail to result in actual notification within a time frame compatible with the successful recovery of the tissue, and the attempt to notify shall be documented.
Donor eligibility criteria shall be established by
the Medical Director of the tissue establishment responsible for the determination of donor eligibility (ref. Section 1271.50) and shall not conflict with these Standards.
Is documentation of a physical exam and DRAI required for an autologous donor?
No
True or False: The health status of the infant(s) shall be assessed in regard to information that could affect the quality or safety of the birth tissue for transplantation.
True
Heart donors shall also be evaluated for the risk of
Chagas’ Disease
Potential skin donors shall be evaluated on an individual basis by chart review and visual assessment for size, current medical status, and…
skin condition
What is the age limit for autologous tissue donation?
No age limit
What is the age limit for the birth mother for birth tissue donation?
There is no age limit for the birth mother, however, policies and procedures shall be written regarding gestational age limits.
Semen donors shall be younger than…years of age to minimize the risk of genetic anomalies except with the written agreement of the user physician
40
Oocyte donors shall be younger than… years, unless an exception has been made by the Medical Director with documented agreement of the user physician.
35
Prior to the recovery of tissue from a deceased donor, a physical…
assessment shall be performed by a responsible person.
Tissue shall be rejected if the recent ante-mortem or postmortem physical assessment identifies evidence of:
high risk behavior and signs of HIV infection or hepatitis infection; other viral or bacterial infections; or, signs of trauma or infection to the body where recovery of tissue is planned.
If any of the following signs are observed or noted in any other available record, and are deemed to be an indication of these risks, then the tissue shall be rejected:
1) physical evidence for risk of sexually transmitted diseases such as genital ulcerative disease, herpes simplex, chancroid (genital lesions);
2) physical evidence for risk of, or evidence of, syphilis (genital lesions, rash, skin lesion [non-genital]);
3) for a male donor, physical evidence consistent with anal intercourse including perianal condyloma (insertion trauma, perianal lesions);
4) physical evidence of non-medical percutaneous drug use such as needle tracks (and/or non-medical injection sites), including examination of tattoos (which may be covering needle tracks);
5) disseminated lymphadenopathy (enlarged lymph nodes);
6) unexplained oral thrush (white spots in the mouth);
7) blue or purple spots consistent with Kaposi’s sarcoma (blue/purple [gray/black] spots/lesions);
8) physical evidence of recent tattooing, ear piercing, or body piercing (tattoos/piercings should be described);
9) unexplained jaundice, hepatomegaly, or icterus.
Note: Hepatomegaly may not be apparent in a physical assessment unless an autopsy is performed (enlarged liver, jaundice, icterus);
10) physical evidence of sepsis, such as unexplained generalized rash/generalized petechiae, or fever (rash); 11) large scab consistent with recent smallpox immunization (scab);
12) eczema vaccinatum (lesion,scab); 13) generalized vesicular rash, generalized vaccinia (rash); 14) severely necrotic lesion consistent with vaccinia necrosum (lesion); and/or 15) corneal scarring consistent with vaccinial keratitis (abnormal ocular finding, scarring).
a physical examination of the birth mother must be performed during admission for delivery or within
14 days prior to delivery.
A physical examination must be performed on all anonymous and directed semen and oocyte donors. A repeat physical examination shall be performed on anonymous semen donors at least every
A physical examination must be performed on all anonymous and directed semen and oocyte donors. A repeat physical examination shall be performed on anonymous semen donors at least every
A physical examination shall be performed by the Medical Director or licensed physician designee, or by a physician involved with the individual’s medical care, or designee as permitted by law prior to…
the donation of tissue from a potential living donor
A physical assessment shall be performed by a responsible person prior to…
recovery of tissue from a deceased donor
A documented dialogue (DRAI) shall be conducted with the
donor (if living) or the deceased donor’s next of kin, the nearest available relative, a member of the donor’s household, other individual with an affinity relationship (caretaker, friend, significant life partner) and/or the primary treating physician
For all donors one month (28 days) of age or less, the infant and the birth mother shall be screened for
risk of relevant communicable disease agents and diseases (RCDADs) and the birth mother’s blood must be tested
The tissue bank shall have a policy for obtaining information from the patient’s physician as to whether the autologous donor is at high risk for
viral hepatitis or HIV infection.
The donor risk assessment interview of the birth mother shall be obtained, or previous donor risk assessment interview information verified, no more than BLANK days prior to delivery. If this interview is performed after delivery it must be completed within BLANK days of delivery.
14
Prior to tissue donation, a preliminary review of readily available relevant medical records shall be conducted by a trained individual. This review shall include but may not be limited to:
Prior to tissue donation, a preliminary review of readily available relevant medical records shall be conducted by a trained individual. This review shall include but may not be limited to:
(A) Except for skin, autologous donation should not be undertaken when the autologous donor has, or is being treated for, bacteremia or other significant bacterial infection that can be associated with bacteremia, unless
such tissue will be secondarily sterilized prior to transplantation or treated in such a manner to minimize microbial contamination.
Infectious disease testing of donor blood specimens shall be performed for each tissue donor on a specimen collected at the time of donation or within
7 days prior to or after donation
If the donor is one month (28 days) of age or less, a blood specimen from the birth mother must be collected within
7 days prior to or after tissue donation and tested instead of a specimen from the infant donor
For anonymous and directed oocyte donors, the blood specimen must be collected within
30 days prior to oocyte collection, or within 7 days post donation.
Samples for infectious disease testing of anonymous and directed semen donors must be obtained within
7 days of initial semen collection
Tissue from a donor who is older than 12 years of age shall be determined to be not suitable for transplantation if blood loss is known or suspected to have occurred and there has been transfusion/infusion of more than
2,000 milliliters (mL) of blood (e.g., whole blood, or red blood cells) or colloids within 48 hours; or more than 2,000 mL of crystalloids within one hour; or any combination thereof, prior to asystole or the collection of a blood specimen, whichever occurred earlier unless: 1) a pre-transfusion or pre-infusion blood specimen from the tissue donor is available for infectious disease testing; or 2) an algorithm is utilized that evaluates the volumes administered in the 48 hours prior to collecting the blood specimen from the tissue donorto ensure that there has not been plasma dilution sufficient to affect test results.
Tissue from a donor who is 12 years of age or less who has been transfused or infused at all, shall be determined to be not suitable for transplantation unless
a pre-transfusion or pre-infusion blood specimen from the tissue donor is available for infectious disease testing, or an algorithm is utilized that evaluates the volumes administered in the 48 hours prior to collecting the blood specimen from the tissue donor to ensure that there has not been plasma dilution sufficient to affect test results.
Testing used for donor eligibility shall be performed by laboratories that are registered with
FDA as a tissue establishment for testing and are either certified to perform such testing on human specimens in accordance with Clinical Laboratory Improvement Amendments of 1988 (42 U.S.C. 263a) and 42 CFR part 493, or that have met equivalent requirements as determined by the Centers for Medicare and Medicaid Services.
Results of initial infectious disease and/or confirmatory testing shall be used as one component of determining
donor eligibility
If a laboratory that performs organ donor testing performs the initial testing in duplicate or triplicate, the tissue bank must obtain and review the results of
all individual tests performed
All tissue from donors who test repeatedly reactive on a required screening test shall be
quarantined and shall not be used for transplantation.
Donor sample testing shall be performed, and test results interpreted according to the
manufacturer’s instructions in the package insert for the particular infectious disease marker.
Excluding autologous, embryo donor, and client depositor tissue, all human tissue intended for transplantation shall be from donors who are tested and found to be negative for:
1) antibodies to the human immunodeficiency virus, type 1 and type 2 (anti- HIV-1 and anti-HIV-2);
2) nucleic acid test (NAT) for HIV-1; 3) hepatitis B surface antigen (HBsAg);
4) nucleic acid test (NAT) for the hepatitis B virus (HBV); 5) total antibodies to hepatitis B core antigen (anti-HBc—total, meaning IgG and IgM);
6) antibodies to the hepatitis C virus(anti-HCV);
7) nucleic acid test (NAT) for HCV;
8) syphilis (a non-treponemal or treponemal-specific assay may be performed).
Donors of viable leukocyte-rich tissue (e.g., semen, certain (CT)) shall also be tested and found to be negative for antibodies to
human T-lymphotropic virus type I and type II (anti-HTLV-I and anti-HTLV-II).
For tissue establishments located within the United States (U.S.), all living donors, excluding autologous donors, shall be tested and found to be negative for
WNV NAT when recovery, collection, or acquisition occurs from June 1st through October 31st every year.
For tissue establishments located outside the U.S. importing tissues to the U.S., all living donors, excluding autologous donors, shall be tested year-round and found to be negative for WNV NAT.
In addition to the infectious disease tests listed above, all anonymous and directed semen and oocyte donors shall undergo testing for Neisseria gonorrhea and Chlamydia trachomatis. If the reproductive tissue is collected by a method that ensures freedom from contamination of the tissue by infectious disease organisms that may be present in the genitourinary tract, then these tests are not required.
All donated semen from anonymous donors shall be frozen and quarantined for at least 6 months. After such time and prior to release of semen, the donor shall be retested for anti-HIV-1, HIV-1 NAT, antiHIV-2, HBsAg, anti-HBc, HBV NAT, anti-HCV, HCV NAT, antiHTLV-I, anti-HTLV-II, syphilis, and for anti-CMV.
Oocyte donor tissue is not subject to
quarantine and the donor is not subject to repeat testing.
“Appropriate measures” meansv
using available resources to accomplish the testing. If the client depositor cannot be tested due to death or inability to locate the person, directed or anonymous donation of the embryos can still be completed.
Positive test results shall be
reported to state and/or local health department(s) as required by law or regulation, the donor (if living), and/or the authorizing person (if donor is deceased)
A policy shall be established to collect and preserve serum, plasma, or hematopoietic tissue samples from donors for an appropriate duration after the
recovery, collection, or acquisition date as/if prescribed by a quality, safety, and legal risk assessment conducted by the tissue bank to mitigate the establishment’s specific risk exposure.
Prior to enrollment of a donor in the sperm donor program, his semen shall be tested for sperm quality and found acceptable for such parameters as
sperm motility, concentration, and post-thaw motility. Donors shall be excluded unless the specimen meets criteria set by the Medical Director and, when appropriate, the Medical Advisory Committee.
True or False: If any tissue bank determines a donor to be ineligible, this determination must be communicated in writing to the tissue bank that recovered tissues, and the tissue bank that recovered tissues must share this information with all establishments that are known to have recovered tissues, or to have received recovered tissues, from the same donor.
True
Are tests performed after tissue has been disinfected or subjected to processing considered relevant donor records to the tissue bank that recovered? Would these results be shared with the tissue banks who received recovered tissues?
No
Detailed records of the tissue donation shall be maintained that include information regarding
relevant packaging, transportation, and, when applicable, donor reconstruction steps.
All critical supplies, reagents, materials, and equipment approved for use for recovery, collection, or acquisition shall be identified and specifications (e.g., sterile where applicable) shall be
documented
What needs to be recorded in regards to reagents, supplies, and materials?
the type, quantity, manufacturer, lot number, date of receipt, and expiration date or manufacturing date (as applicable)
Do tissue banks need to maintain records on supplies?
The tissue bank shall maintain records of all supplies, reagents, materials, and equipment from receipt through period of time used. All reagents, supplies, materials and equipment shall be used and stored in accordance with manufacturers’ instructions, unless qualified/validated for intended use or storage.
Do sterilization steps need to be documented?
Yes
True or False: Newer stock rotation items should be used first and not used if expired or quality has been compromised.
False
What is the importance of using unique donor identifiers?
Donor identifiers allow for tracing of the tissue from the donor and to final disposition of each tissue with confidentiality.
What are some ways to verify the identity of a patient?
hospital wristband, medical examiner number, driver’s license, or government issued identification with photograph
Who is responsible for verifying a patient’s identity for autologous and surgical bone recovery?
Identification of the donor shall be the responsibility of the hospital staff involved with the recovery.
Who is responsible for verifying a patient’s identity for birth tissue recovery?
Identification of the birth mother shall be the responsibility of the hospital staff, or the tissue bank staff member involved with acquisition.
Recovery, collection, or acquisition shall be performed using what kind of technique?
aseptic or clean techniques appropriate to the specific tissue type and intended use. Tissue must be labeled using a donor identifier and a description according to the SOPM.
If recovery is to be delayed for a deceased donor, the donor’s body should be
refrigerated/cooled as specified in the tissue-specific standards.
Recovery from one donor shall be the exclusive activity taking place at one time at a recovery site to prevent…
cross-contamination or mix-ups
True or False: Two tissue recoveries can occur simultaneously in the same room.
False
Tissue recovery shall not occur after
embalming procedures have begun (i.e., injection of embalming fluid, application of drying agents either internally or topically).
Is pooling allowed in tissue banking?
No. Pooling tissue from multiple donors shall not occur during recovery, collection, acquisition or storage
Cardiac tissue and vascular tissue recovery and processing time limits (i.e., warm and cold ischemic time, disinfection time, and the perfusion time [specific to vascular tissues]) shall be established by
each individual tissue bank; however, the upper time limits for initiation of recovery of specific tissue types shall not be exceeded.
Warm ischemic time (C, V) shall not exceed
24 hours from asystole if the donor’s body was cooled (e.g., application of sufficient amounts of wet ice or a cooling blanket, cold weather conditions) or refrigerated within 12 hours of asystole. The time limit shall not exceed 15 hours if the donor’s body was not cooled or refrigerated. If the donor’s body is cooled for a period of time then not cooled for a period of time, the time period the donor’s body is not cooled cannot exceed 15 cumulative hours.
Perfusion time shall not exceed
12 hours from asystole
The skin prep shall begin within
24 hours of asystole provided the donor’s body was cooled (e.g., application of sufficient amounts of wet ice or a cooling blanket, cold weather conditions) or refrigerated within 12 hours of asystole. The skin prep shall begin within 15 hours of death if the deceased donor’s body has not been cooled or refrigerated. If the donor’s body is cooled for a period of time then not cooled for a period of time, the time period the donor’s body is not cooled cannot exceed 15 cumulative hours.
Prior to recovery, the recovery site must be evaluated for suitability using pre-established criteria designed to control…
contamination and cross-contamination
All tissue shall be recovered in an aseptic or clean fashion using standard surgical preparation with
sterile packs, instrumentation, and technique.
The recovery site evaluation must be documented, however, if the recovery site is an operating room in a heath care facility…
no documented site evaluation is required.
What are the Recovery Site Suitability Parameters?
1) size/space;
2) lighting;
3) plumbing and drainage for the intended use;
4) the physical state of the facility (i.e., state of repair);
5) ventilation;
6) cleanliness of room and furniture surfaces;
7) pests;
8) traffic;
9) location;
10) other activities occurring simultaneously;
11) sources of contamination; and
12) the ability to appropriately dispose of biohazardous waste and handle contaminated equipment.
All working surfaces (e.g., back table, Mayo stand, recovery table) used during recovery must be decontaminated using a
bactericidal/antimicrobial agent. All cleansing and disinfecting events performed by tissue bank personnel shall be documented.
Technician gowning, gloving, and movement shall be accomplished with the same diligence as used routinely for
operative procedures. Aseptic technique shall be followed.
What shall be worn during the time of the surgical scrub?
A head cover, eye shields and mask shall be worn at the time of scrub, and a Sterile gown and gloves shall be donned after the scrub/wash.
Cleansing, preparing (i.e., skin prep), and draping the skin shall be accomplished with the same diligence as used routinely for operative procedures. Unless otherwise qualified/validated, agents used shall be
antimicrobial skin preparation products, as specified in the SOPM, and shall be used in accordance with manufacturers’ guidelines/instructions.
What kind of specific tissue recovery operations control contamination and cross- contamination?
Some examples include: sequencing of the tissue recovery, use of well-defined zone recovery techniques, and isolation draping in the presence of trauma. Areas of skin that have abrasions or puncture wounds should be avoided. All tissue shall be recovered using aseptic technique.
What tissues require cultures to be obtained at recovery?
MS, OA, S, SB
True or False: If the birth tissue delivery location is an operating room or a designated delivery room in a specialized health care facility, no documented site evaluation is required, however, any other location of delivery must meet the requirements at D5.500 and D5.510. Such an evaluation must be documented.
True
Are birth tissue cultures obtained before or after acquisition?
If performed, the technique used to obtain cultures prior to acquisition shall be appropriate and performed according to written instructions
Recovery records for allogeneic tissue shall include, but not be limited to:
1) name, and address of the recovery agency;
2) date, time and staff involved in all significant steps performed during the recovery (documentation shall be as per C1.100);
3) location and assessment of the suitability of the recovery site;
4) documentation of the physical assessment or physical examination;
5) documentation of any errors, accidents, or deviations that occurred;
6) donor name, age, and sex;
7) the type, lot number, manufacturer, and expiration date of critical reagents, supplies and materials, and the identification of equipment, used to recover, rinse, and/or transport tissue; and
8) specific tissue recovered; and
9) other available relevant medical records.
The following information regarding autologous tissue recovery shall be documented:
1) name and address of the institution in which the autologous tissue was recovered;
2) date and time the autologous tissue was recovered; 3) name of the physician recovering the autologous tissue;
4) donor name, age, sex, and hospital medical record number and/or social security number; and
5) type of tissue recovered.
Details of the delivery and post-delivery time period through acquisition shall be documented in the donor’s record. These records shall include, but not be limited to the: 1) birth mother’s name;
2) infant donor’s gestational age;
3) name and address of the health care facility and the identification of the delivery environment/location;
4) date and time of the delivery;
5) the physician or other authorized practitioner involved with the delivery, or designee as permitted by law;
6) information to allow tracking of critical reagents, supplies and materials provided by the tissue bank;
7) specific tissue(s) acquired;
8) other available relevant medical records; and
9) documentation of any errors, accidents, or deviations that occurred.
Immediately following recovery of each individual tissue at the recovery site, how should the recovered tissue be packaged?
individually and aseptically wrapped or enclosed and shall be immediately labeled with the unique donor identifier and the description according to the SOPM. Tissue shall be maintained at defined environmental temperatures until the time of transport to the processing center. Maintenance of such temperatures shall be documented. The receptacle/transport package must be designed to prevent contamination of the contents and allow for aseptic presentation of the tissue at the time of processing.
The package shall be labeled immediately with definitive autologous donor identifying information such as the patient’s name, hospital registration number, security number, birth date, etc., and shall be prominently labeled…
“FOR AUTOLOGOUS USE ONLY.’’
What kind of solution should recovered cardiac tissue be rinsed and packaged in?
Recovered cardiac tissue shall be rinsed and packaged in an isotonic, sterile solution such as normal saline, lactated Ringer’s solution, PlasmaLyte®, transplant organ perfusate (e.g., Belzer’s UW solution, Collin’s solution) or tissue culture media, immediately following recovery. The volume of the transport solution should be adequate to cover the entire heart, including the vessels and valves. The type, lot number, manufacturer, and expiration date shall be documented.
Immediately following recovery, vascular tissue shall be gently flushed and packaged in…
an isotonic sterile solution such as tissue culture media. Normal saline solution should not be used. The type, lot number, manufacturer, and expiration date of all reagents used for recovery and packaging shall be documented.
Recovered skin tissue shall be packaged in…
a sterile solution immediately following recovery or packaged by another method that maintains the integrity of the tissue for its intended use (e.g., decellularized dermis). If in solution, the volume of transport solution must be adequate to cover the entire skin. The type, lot number, manufacturer, and expiration date(s) shall be documented.
Transportation temperatures do not require verification if the packaging and transport conditions have been
validated to maintain the required environmental conditions, including temperatures.
The receptacle/transport package for tissue transport must indicate…
'’DONATED HUMAN TISSUE’’ is enclosed and must include the name and address of the originating agency and processing center (if different).
All human tissue processed or shipped prior to determination of donor eligibility must be
under quarantine, accompanied by records assuring identification of the donor and indicating that the tissue has not been determined to be suitable for transplantation (e.g., ‘‘Quarantine’’; “Donor Eligibility Has Not Been Completed’’; and ‘‘Not Suitable for Transplant in its Current Form’’)
When wet ice temperatures would be injurious to the tissue recovered (A, LD, CT), it may be transported at appropriate temperatures and within time limits that maintain the
quality of the tissue for its intended use.
The transport package (C, V) shall be transported at wet ice temperatures. Time of acceptance of the tissue into the processing center shall be documented. Cardiac tissue and vascular tissue shall be received at the processing location within sufficient time following recovery to allow for the start of
disinfection within the established cold ischemic time limit.
The recovered MS tissue shall be wrapped in an aseptic fashion with at least one
moisture barrier and shall be transported at wet ice temperatures or colder
The maximum time that recovered tissue shall remain at wet ice temperatures, prior to either processing or freezing, shall be no longer than a time limit established by
a validated procedure that maintains tissue quality
If the tissue is to be cryopreserved, the skin transport package shall be transported at what temperature?
wet ice temperatures or packaged by another method that maintains the quality of the tissue for its intended use.
Unless there is a specific request from a medical examiner, pathologist, or a funeral home, the surgical incision(s) shall be
closed in an aesthetic fashion and the deceased donor’s body prepared for the next portion of the recovery or for transportation to an appropriate facility
Reconstruction should employ techniques consistent with what guidelines?
funeral home guidelines and/or medical examiner or pathologist requests. Documentation of donor reconstruction (if applicable) and disposition of the donor’s body shall be maintained in the donor’s record.
Storage, including temporary storage, of recovered, acquired, or collected tissue shall be in conformance with storage temperature and monitoring expectations provided by the tissue bank that will
process the tissue.
Adequate controls must exist to prevent
mix-ups, contamination, cross-contamination, and ensure tissue is identified as acceptable or unacceptable during all stages of recovery, receipt, storage, processing and distribution.
If physical segregation is deemed unnecessary, justification must be established, and must include a risk assessment and use of a validated electronic system. Considerations for the risk assessment shall include:
1) potential severity of impact if controls fail to prevent mix-up, contamination or cross-contamination;
2) probability of failure to occur;
3) likelihood of identifying a failure before it reaches a customer;
4) existing controls to prevent failure; and
5) back-up plan for failure of validated electronic system.
The SOPM must address when the segregation of tissue during storage is indicated and how it will be appropriately segregated to avoid contamination, cross-contamination and mix-ups.
Considerations for assessment of risk include, where applicable:
1) donor infectious disease test results are unavailable or this testing will not be performed;
2) the intended use of the tissue is primarily for transplantation or is restricted to research or education; 3) autologous tissue is segregated from allogeneic tissue;
4) the donor has been determined to be ineligible;
5) the ability of packaging and labeling to withstand storage temperatures, and/or
6) the ability to decontaminate storage equipment or the storage area should an accident occur.
Appropriate segregation must include considerations above and storage must be in clearly defined and labeled areas (shelves or compartments) of the storage equipment or storage area
Freezers and refrigerators used for storing tissue shall be regularly maintained, calibrated, and monitored according to written
QC procedures
Approval or rejection of the receipt of tissue into the processing or storage facility must be documented. The receipt and movement into storage, to immediate processing or to removal, shall be documented, including, at a minimum:
1) the condition of the transport package;
2) confirmation each tissue is labeled with a tissue identification number, or other traceable unique identifier;
3) evidence proper environmental conditions were maintained (e.g., presence/absence of ice/coolant). Refer to H3.300;
4) the date and time of receipt and movement; and
5) personnel involved.
Except for reproductive tissue, each unit of tissue shall be assigned a tissue identification number, which shall serve to
relate the tissue to the donor from whom it was recovered or acquired and the associated records at any phase (e.g., quarantined, unprocessed, processed inventory) of the operation. Tissue units shall be assigned the same tissue identification number only if they are identical and processed as a lot.
Can a unique identifier for reproductive tissue include the directed donor’s or client depositor’s name?
Yes
For donors and client depositors giving multiple specimens, do tissue banks use the same unique identifier for all collection dates?
No, for donors and client depositors giving multiple specimens, a secondary code shall be used to distinguish between dates of collection. The reproductive tissue bank that collects and processes the reproductive tissue shall be identified by name, code, or other identifier on the final container.
Is pooling from multiple donors during processing, preservation, or storage allowed?
No
If autologous tissue is not to be processed, it should be retained in its
original wrapping.
(C, V) Processing shall include a disinfection period followed by
rinsing, packaging, and preservation
What is required in a tissue evaluation that describes the attributes of each allograft?
A standardized evaluation and classification system is required that describes the attributes of each allograft. A detailed description of the condition of the allograft shall be recorded in the permanent donor processing records. The allograft evaluation system shall be made available to the implanting surgeon. (C, V, OA)
Except for reproductive tissue, when tissues are exposed to the environment during processing, these activities shall be consistent with the requirements of
aseptic processing.
Without a subsequent validated microbial inactivation process, aseptic processing shall be performed in a
a certified and qualified bacteriologically and climate-controlled environment.
Adequate processing environmental control is defined by justifying and documenting the following:
1) type and frequency of environmental monitoring;
2) when the samples are to be taken (e.g., during or at the conclusion of operations);
3) sampling locations and number of sites to be sampled;
4) sample duration;
5) sample size (e.g., surface area, air volume);
6) action and alert levels for test results; and
7) potential corrective actions when alert and/or action levels are exceeded
All critical supplies, reagents, materials, and equipment approved for use for processing and preservation shall be identified and specifications (e.g., sterile where applicable) documented. It is expected that the tissue bank has the ability to link all supplies, reagents, materials, and equipment to
tissue processed over the period of time they were in use.
All non-disposable surgical instruments and mechanical/electrical equipment used in tissue processing shall be
cleaned, decontaminated, and, where applicable sterilized, between use for tissue from different donors according to written procedures.
A record shall be made of all reagents, supplies, and materials following receipt including, as applicable, the…
the type, quantity, manufacturer, lot number, date of receipt, and expiration date or manufacturing date (as applicable).
For non-disposable surgical instruments and mechanical/electrical equipment deemed critical, written procedures must be prepared and methods shall be
validated, to prevent contamination or cross-contamination during processing. Adequate controls must exist to prevent mix-ups between acceptable and unacceptable items.
Reagents, supplies, and materials with expiration dates or production dates shall be stored in a manner to facilitate
inventory rotation. Items not bearing an expiration or production date shall be labeled with the date of acquisition and stored in a manner to facilitate inventory rotation. Older items should be used first and not used if expired or quality is compromised.
The container shall…
maintain its integrity, withstand sterilization and storage conditions, not produce toxic residues during storage, and maintain tissue quality through the labeled expiration date. Containers shall not interfere with the effective use of appropriate agents applied to sterilize or disinfect the tissue.
If ethylene oxide is used to sterilize processing or packaging components that come in contact with the allografts (e.g., disinfection jars or packaging pouches), residues of
ethylene oxide, ethylene glycol, and ethylene chlorohydrin should be evaluated.
(C, V) Final packaging containers shall be adequate for use at defined storage temperatures and documented to remain stable and impervious to microbial particles under normal environmental conditions at the specified temperature and throughout the recommended
thawing regimen.
Containers shall be stored under quarantine until the containers have been
tested, sampled, or examined, as appropriate, and released for use. Containers not meeting specifications shall not be used.
Time limits and/or other valid process control end points or limits for the completion of each phase of processing and preservation shall be
established and validated with reference to tissue quality. Additionally, a time limit and temperature for pre-processing quarantine storage that address tissue quality must be established and justified.
(C, V) Disinfection of cardiac and vascular tissue shall be accomplished via a time specific, validated process (disinfection time). The total ischemic time shall not exceed
48 hours
(R) After collection, analysis shall be performed within an appropriate time period, and processing, if performed, shall be initiated within a time period appropriate for retention of functional quality, as specified in the
SOPM
(S) When preservation of cellular viability is desired, processing of skin shall be initiated within
10 days of recovery, provided the skin is placed in tissue storage media that is replaced at least every 72 hours.
If the media for skin preservation is not changed, processing shall be initiated within
96 hours of recovery
(C, V, OA, S) To prevent drying and possible cellular and extracellular matrix deterioration, the tissue shall be kept moist at all times during processing using a
sterile solution/medium. If drying does not impact quality for intended use (e.g., decellularized dermis), the requirement to prevent drying is not applicable.
When applicable, the type, amount, concentration, and method of incorporation/addition of all media, cryoprotectants, and any other additives used in processing shall be specified in the
SOPM. This information about the allograft shall be made available to the implanting/transplanting physician, upon request.
Process control procedures shall be designed to assure that tissue has the intended…
identity, characteristics, and quality
The tissue bank shall determine when, which, and how controls are to be performed
e.g…. residual moisture testing, microbial cultures of tissue, solutions, packaging, equipment, pH measurements, or post thaw sperm quality). Sampling for in-process controls shall be designed to be representative of the materials to be evaluated.
True or False: Tissue dimensions do not matter because each recipient is a different height and weight.
False. Tissue banks that process tissue shall include in their SOPM a description of the final types of tissue, any specifically required or specifically prohibited dimensions or characteristics, and the means used to assess these characteristics. At or near the end of processing, tissue shall be evaluated according to these procedures to determine whether it is in conformance with the SOPM. Relevant tissue dimensions or characteristics shall be recorded. All tissue deemed to be out of conformance shall not be released for transplantation.
Tissue measurement shall be performed and documented and must include the…
quantity or other characteristics of the tissue expressed as applicable (e.g. volume, weight, dimensions, cell density, number of viable cells or a combination of these).
(C) Allograft heart valve grafts shall be inspected, evaluated, and sized by internal valve annulus diameter, and recorded in…
millimeters (mm)
The length of the aortic conduit, main pulmonary artery, and the left and right pulmonary arteries shall be recorded in…
millimeters (mm) or centimeters (cm).
(V) Vascular tissue grafts shall be inspected, evaluated, and sized by diameter and recorded in
millimeters (mm)
The length of the vascular segment shall be recorded in…
centimeters (cm)c
(MS) Unless bone is treated by a validated process to reduce minerals, representative samples of each lot shall be tested for…
residual calcium by a standard method
Residual calcium content for bone labeled as demineralized shall not exceed
8% by a standard method.
For bone that has been subjected to a demineralization process with a residual calcium content target that exceeds 8% when tested, the tissue must not be labeled as….
demineralized and should be labeled as partially demineralized to describe the extent of demineralization.
Records of in-house laboratory testing shall include, at a minimum:
1) sample source and quantity;
2) tissue identification number;
3) test date and identification of the person performing the test;
4) assay methods;
5) calculations, graphs, and charts, if used;
6) test results as well as interpretation of results;
7) testing or standardization of reference standards, reagents, or standard solutions; and
8) record review by an individual other than the operator generating the records to ensure compliance with Standards.
Each lyophilization cycle shall be monitored and recorded for
shelf temperature, condenser temperature, and vacuum
Residual moisture measurement shall not exceed
a limit linked to tissue quality
If a residual moisture limit has been established for finished tissue, the container shall maintain the limit for the duration of the
expiration period
Except for reproductive tissue, tissue to be cryopreserved must be frozen at a controlled and monitored, predetermined rate with compensation for
heat of crystallization/latent heat of fusion to a predetermined end-point
What information must be maintained about cryopreserved tissue?
Documentation of the concentrations of cryoprotectant and nutrient or isotonic solutions in the cryopreservative solution shall be maintained. When applicable, procedures for cryopreservation shall be established and the method controlled to maintain tissue quality.
Procedures for cryopreservation of reproductive tissue shall be established and documented. If a controlled rate chamber is being utilized, the thermal profile for each
cryopreservation cycle shall be logged with the specimen records.
Upon termination of the freezing program, the cryopreserved tissue shall immediately be placed in
storage. Temperature fluctuation and cycling should be avoided.
Procedures for the preservation of tissue by chemical means shall be validated and documented. When chemical preservation has been used, what kind of document shall indicate so?
package insertc
Individual processing facilities shall establish, validate, and document disinfection or sterilization regimens and microbial surveillance methods. The SOPM shall establish a list of organisms that necessitate discard, sterilization and/or disinfection of tissue. The list shall be based upon not only the category type of tissue but also the
method by which the tissue was processed (e.g., cryopreserved MS tissues that cannot be sterilized and can only be disinfected and rendered culture negative).
What organisms for C, V, CT tissue are considered to be pathogenic, highly virulent microorganisms that shall result in tissue discard unless treated with a disinfection or sterilization process validated to eliminate the infectivity of such organisms? (C, V, CT)
1) Clostridium;
2) fungi (yeasts, molds); and
3) Streptococcus pyogenes (group A strep.).
What organisms for MS, OA tissue are considered to be pathogenic, highly virulent microorganisms that shall result in tissue discard unless treated with a disinfection or sterilization process validated to eliminate the infectivity of such organisms?
(MS, OA)
1) Clostridium; and
2) Streptococcus pyogenes (group A strep.).
What organisms for Skin tissue are considered to be pathogenic, highly virulent microorganisms that shall result in tissue discard unless treated with a disinfection or sterilization process validated to eliminate the infectivity of such organisms? (S)
1) Clostridium;
2) Enterococcus sp.;
3) fungi (yeasts, molds);
4) gram negative bacilli;
5) Staphylococcus aureus; and
6) Streptococcus pyogenes (group A strep.).
What is used to reduce or eliminate bioburden?
Non-terminal irradiation. A dose is selected to reduce or eliminate bioburden. The selected dose shall be justified and any claims made must be supported by data. The type of irradiation shall be indicated on the container label or package insert of all tissue exposed to non-terminal irradiation.
What are the most common sources of ionizing radiation?
Cobalt 60, electon beam, and X-ray
Identification of the irradiation source, the dosimetry, and completed certificate of irradiation shall be documented in the
processing record
What shall the sterilization dose be capable of achieving?
The sterility assurance level (SAL)
The type of irradiation shall be indicated on the
container label or package insert of all tissue exposed to irradiation.
What size/weight category is “very small” tissue?
<100 mg
What size/weight category is “small” tissue?
<10 grams
What size/weight category is “medium” tissue?
10-100 grams
What size/weight category is “large” tissue?
> 100 grams
What is the residual level in parts per million of Ethylene oxide in very small tissue (<100 mg)?
2,500 ppm
What is the residual level in parts per million of Ethylene oxide in small tissue (<10 g)?
250 ppm
What is the residual level in parts per million of Ethylene oxide in medium tissue (10-100 g)?
100 ppm
What is the residual level in parts per million of Ethylene oxide in large tissue (>100 g)?
25 ppm
What is the residual level in parts per million of Ethylene Chlorohydrin in very small tissue (<100 mg)?
2500 ppm
What is the residual level in parts per million of Ethylene Chlorohydrin in small tissue (<10 g)?
250 ppm
What is the residual level in parts per million of Ethylene Chlorohydrin in medium tissue (10-100 g)?
100 ppm
What is the residual level in parts per million of Ethylene Chlorohydrin in large tissue (>100 g)?
25 ppm
What is the residual level in parts per million of Ethylene Glycol in very small tissue (<100 mg)?
5000 ppm
What is the residual level in parts per million of Ethylene Glycol in small tissue (<10 g)?
5000 ppm
What is the residual level in parts per million of Ethylene Glycol in medium tissue (10-100 g)?
2000 ppm
What is the residual level in parts per million of Ethylene Glycol in large tissue (>100 g)?
500 ppm
What may be used as disinfectants of bone in a validated processing procedure? (MS)
Iodophors, ethanol, and other solvent/detergent combinations. In any instance where a chemical disinfectant or antibiotic agent is used, the container label or the package insert shall identify presence of possible trace residuals.
What other agents may be used as disinfection agents? (BT, MS)
Other agents such as heat, ultraviolet radiation, or exposure to antibiotics may be used as disinfection agents. Procedures for processing with such agents shall be documented and validated to ensure consistency in tissue processing.
Processing and preservation records shall include the following:
1) processing dates and responsible processing personnel;
2) tissue identification number(s) and type(s) of tissue being processed;
3) tissue measurements (e.g., weight, dimensions, volume), as appropriate;
4) expiration, where applicable;
5) type and quantity of tissue sampled for in-process controls;
6) final disposition of each tissue obtained and/or processed; and
7) the type, lot number, manufacturer (unless recorded in other records), and expiration date, where applicable, of critical reagents, supplies and materials, and the identification of critical equipment, used to process and/or preserve tissue.
Human tissue shall be quarantined until the tissue is either determined to be
suitable for processing, transplantation or another appropriate disposition is accomplished.
All tissue shall be quarantined until the following criteria for donor eligibility are satisfied
1) all required infectious disease testing has been completed, reviewed by the responsible person, and found to be negative or non-reactive; and
2) donor screening has been completed, reviewed by the responsible person, and determined to indicate freedom from risk factors for and clinical evidence of HIV, hepatitis B, and/or hepatitis C infection.
Tissue shall be quarantined at any phase of the operation when its release could affect the…
safety, effectiveness, or quality of the tissue, and subsequently, the health of the recipient.
What tissue shall be quarantined?
1) tissue that is pending completion of processing, packaging, preservation, or labeling and final-release-approval signature;
2) tissue recovered, collected, or acquired from donors not meeting established donor eligibility criteria, including unacceptable test results;
3) tissue involved in a recall pending investigation, documentation, and resolution;
4) tissue failing to meet technical or quality assurance specifications;
5) tissue pending discard as medical waste; and
6) tissue returned by a consignee, pending evaluation.
Quarantine records for tissue quarantined post-release shall indicate
the reason for quarantine and the final disposition of the tissue. Release dates or disposal dates shall be indicated as well.
Each tissue bank shall establish acceptable temperature-range limits for the storage of tissue before and after processing in accordance with
with these Standards, applicable laws and regulations and in consideration of tissue quality and the packaging system for the tissue.
(A) Storage temperatures and conditions shall be the same as for comparable
allogeneic tissue. Any exception shall require written approval of the Medical Director of the tissue bank.
(MS, OA)
Processed frozen or cryopreserved musculoskeletal tissues shall be stored at temperatures of
-40°C or colder.
Temporary storage of processed frozen or cryopreserved musculoskeletal tissue between -20°C and -40°C is limited to
six months total.
(C, V) Cryopreserved cardiac tissue and vascular tissue allografts shall be maintained at temperatures of
-100°C or colder
(R) Reproductive tissues shall be stored
either in liquid nitrogen or in the vapor phase of liquid nitrogen.
(S) Frozen or cryopreserved skin shall be stored at ultra-low
-40°C or colder temperatures.
What temperature should Lyophilized, dehydrated, or desiccated tissue be stored at?
ambient temperature or colder.
What shall be utilized to document temperatures and to alert staff when temperatures have strayed outside acceptable limits?
A temperature monitoring system
If storage utilizes liquid nitrogen, what shall be monitored and documented at an interval specified in the SOPM?
either liquid nitrogen levels or temperature
What is the storage temperature for birth tissue?
Established by the tissue bank
What types of storage conditions are used for birth tissue?
Frozen, refrigerated, cryopreserved, lyophilized, dehydrated, desiccated
What types of storage conditions are used for cardiac and vascular tissue?
Frozen, cryopreserved
What is the storage temperature for cardiac and vascular?
-100°C or colder
What types of storage conditions are used for cellular tissue (CT)?
Refrigerated, Frozen, cryopreserved
What is the storage temperature for frozen or cryopreserved cellular tissue?
Established by the tissue bank
What is the storage temperature for refrigerated cellular tissue?
Above freezing (0°C) to 10°C
What types of storage conditions are used for musculoskeletal tissue (MS) and osteoarticular graft (OA)?
Refrigerated, Frozen, cryopreserved (temporary storage for 6 months or less), Frozen, cryopreserved (long term storage), Lyophilized, dehydrated, desiccated
What is the storage temperature for refrigerated MS tissue?
Above freezing (0°C) to 10°C
What is the storage temperature for frozen or cryopreserved (temporary storage for 6 months or less) MS tissue?
-20°C or colder to -40°C (this is warmer than -40°C but colder than -20°C)
What is the storage temperature for frozen or cryopreserved (long term storage) MS tissue?
40°C or colder
What is the storage temperature for lyophilized, dehydrated, or desiccated MS tissue?
Ambient
What is the storage temperature for reproductive tissue?
LN2 (Liquid or Vapor Phase)
What types of storage conditions are used for Reproductive tissue (R)?
Frozen, cryopreserved
What types of storage conditions are used for Skin (S)?
Refrigerated, Frozen, cryopreserved, Lyophilized, dehydrated, desiccated
What is the storage temperature for refrigerated skin?
Above freezing (0°C) to 10°C
What is the storage temperature for frozen and cryopreserved skin?
-40°C or colder
What is the storage temperature for lyophilized, dehydrated, and desiccated skin?
Ambient
Is ambient temperature monitoring required for lyophilized, dehydrated, or desiccated tissue?
No
Policies and procedures shall be developed for the emergency transfer of tissue to designated alternative storage facilities and for alternative monitoring methods in the event of
mechanical failure or loss of coolant. These shall include specification of tolerance limits or temperatures and time limits after which the initiation of the emergency transfer is required. Actions to be taken when limits have been exceeded shall also be specified in the SOPM.
The maximum storage period for tissue shall be appropriate to
the type of tissue, method of preservation, required storage temperature, packaging, and processing, as well as to its intended application.
Who shall be informed of any expiration dates?
The implanting physician
(A) Autologous skin that has not been processed or preserved should be stored refrigerated for no longer than
14 days
Each donor record shall contain a disposition/release statement and signature of both
the Medical Director or licensed physician designee who is assuming responsibility for donor eligibility determination and, if different, the individual(s) responsible for reviewing all technical and quality control specifications. If processing was performed, there shall be documentation of a review by designated personnel of all technical and quality control specifications. An SOPM shall clearly define the responsibilities of each reviewer.
Although the donor risk assessment interview may be preliminarily reviewed by technical staff to evaluate acceptability for recovery, acquisition, collection, or processing, tissue shall not be released for transplantation without determination of donor eligibility by
the Medical Director or licensed physician designee.
The donor eligibility review shall include, but is not limited to these records:
1) acceptability of the authorization or informed consent;
2) suitability of the recovery site, delivery environment, or where collection took place;
3) pertinent information from the medical records generated at the time of death, including any pathology and laboratory reports, physician summaries, and transfusion/infusion information;
4) the donor risk assessment interview; 5) all results of laboratory testing relevant to donor eligibility;
6) any plasma dilution calculations used to determine the acceptability of the blood sample used for testing;
7) all relevant culture results up to and through the completion of recovery (e.g., blood cultures, if performed; pre-sterilization/pre-disinfection cultures, if available);
8) applicable time limits for tissue recovery;
9) pertinent circumstantial and donor screening information relayed to tissue bank staff; 10) results of the physical assessment or physical examination;
11) the autopsy report, or a summary of findings, if an autopsy was performed; and
12) any other information gathered for the purposes of disease screening as required by Standards and applicable laws or regulations.
The birth mother’s risk for transmissible disease shall be evaluated for HIV, HBV, HCV and other infectious agents when indicated in the case of pediatric donors who…
have been breastfed within the past 12 months and/or are 18 months of age or less
The infant and the birth mother shall be screened for risk of relevant communicable disease agents and diseases (RCDAD) and the mother’s blood must be tested for all donors who are how old?
For all donors one month (28 days) of age or less
When no third party records are available that can be used to establish a likely cause of death, and if no autopsy was performed, what must be included in the donor record?
a certified copy of the death certificate. If it is not possible to obtain a certified copy, a verified copy of the death certificate must be included in the donor record.
Is a certified or verified copy of the death certificate required when third party records are available that can be used to establish a likely cause of death, or if an autopsy was performed?
No, it is voluntary
If it is determined that an autopsy was not performed due to infectious disease risk or, if an autopsy was performed, if any special precautions were taken that would suggest risk of a communicable disease in the donor…
this information should be considered
In the case of suspected Sudden Unexpected Infant Death (SUID), should an autopsy be performed?
Yes, an autopsy should be performed and results reviewed to confirm the cause of death.
What shall happen after the dura matter has been recovered?
After the dura mater has been recovered, a qualified pathologist shall perform an examination of the donor’s brain. Following fresh examination, the brain should be fixed and sliced, gross examination of the entire brain should be conducted (including multiple cross sections), and multiple specimens of tissue should be obtained (from different parts of the brain, e.g., frontal and occipital lobes) for histological examination. The gross and histologic findings must be assessed for any evidence suggestive of transmissible spongiform encephalopathy (TSE).
Tissue shall not be distributed from a donor who, or a donor whose birth mother, has engaged in behaviors defined as…
high risk for transmission of relevant communicable disease agents or diseases (RCDADs). This information shall be obtained via a donor risk assessment interview, physical assessment or physical examination, and by review of other available relevant medical records.
The Medical Director or licensed physician designee shall not determine an allogeneic donor eligible with any of the following findings:
1) evidence of significant active infection at the time of donation for relevant communicable disease agents or diseases (RCDADs). These include, but are not limited to: septicemia, viral disease (e.g., HIV, viral hepatitis, West Nile virus, rabies, Ebola virus disease, Zika virus infection, etc.), human transmissible spongiform encephalopathies, untreated syphilis, clinically active tuberculosis, leprosy (Hansen’s disease) or systemic mycosis; and/or 2) risk factors for relevant communicable disease agents or diseases (RCDADs) as specified in Appendix II. (R) Semen donors shall not exhibit an infectious skin disease that creates a risk of contamination of the semen. For all reproductive tissue donors, there shall not be evidence of infection within the past twelve months with Chlamydia trachomatis and/or Neisseria gonorrhea unless the reproductive tissues are collected by a method that ensures freedom from contamination of the tissue by infectious disease organisms that may be present in the genitourinary tract.
In addition to the infectious disease risk review, the Medical Director shall establish criteria and evaluate tissue donors for conditions that may adversely affect the safety or utility of the specific types of tissue processed and/or distributed by the tissue bank. Such conditions include, but are not limited to
1) history of autoimmune diseases;
2) current or prior diagnosis of malignancy and the evaluation shall include the type of malignancy, clinical course, and treatment prior to acceptance;
3) ingestion of, or exposure to, toxic substances;
4) genetic, metabolic, traumatic, or infectious diseases that may adversely affect the quality of specific tissues;
5) previous surgery; and
6) diseases of unknown etiology.
Disposition of allogeneic tissue shall be based upon the interpretation of all infectious disease test results and shall be as follows:
1) Human tissue shall be determined not to be suitable for transplantation if from a donor whose specimen has tested repeatedly reactive on an FDA-licensed, approved, or cleared donor screening test for anti-HIV-1, anti- HIV-2, HBsAg, antiHBc, or anti-HCV. When a birth mother’s specimen is used for testing, these same rules apply. 2) Viable leukocyte-rich tissue (e.g., semen) shall be determined not to be suitable for transplantation if from a donor whose specimen has tested repeatedly reactive (RR) on an FDA-licensed, approved, or cleared donor screening test for anti-HTLV-I or anti-HTLV-II. The eligibility of other human tissue for transplantation from donors whose specimens test RR for anti-HTLV-I or anti-HTLV-IIshall be determined by the Medical Director. Note: Law and/or regulation, including, where applicable, foreign laws and/ or regulations, may differ in regard to a RR HTLV antibody test result and how this impacts the suitability of the donor’s tissues for transplantation. 3) Human tissue shall be determined not to be suitable for transplantation if from a donor whose specimen had a final test result of positive, repeat reactive, or repeatedly reactive on a screening test using a NAT assay. When a birth mother’s specimen is used for testing, these same rules apply. 4) If a laboratory that performs organ donor testing performs the initial testing in duplicate or triplicate, the tissue bank must obtain and review the results of all individual tests performed. If any one of those initial tests is reactive or positive, the tissue shall be determined not suitable for transplantation. 5) Tissue from a donor reactive for syphilis using an FDA-licensed, cleared, or approved non-treponemal screening assay may be used for transplantation only if the sample is found to be negative using an FDA-licensed, cleared or appro
Tissue from an anonymous semen donor who tests reactive for an active, acute infection with cytomegalovirus (CMV)…
shall not be deemed suitable for use. Tissue from an anonymous semen donor determined to be in a latent CMV status may be acceptable.
What must be noted in the processing records in order for tissue to be released for transplantation?
Tissue may be released for transplantation only with notation in processing records by responsible persons that tissue produced meets technical specifications set forth in the SOPM (e.g., dimensions, quality) and that processing was performed according to the SOPM. There must be a signature by technical staff indicating that all technical elements were reviewed.
For contractual processing arrangements, tissue shall be released for transplantation by the distributing tissue bank only with a signature and written disposition/release statement or equivalent documentation from the processing center indicating that all quality measures were reviewed and determined to be acceptable according to the written SOPM. The written disposition/release statement or equivalent documentation shall indicate that the following conditions, at a minimum, have been met:
1) review of tissue processed for consistency with specific tissue requirements; 2) review of all processing and packaging bacteriologic testing results for completeness and acceptability; 3) review for completeness and acceptability of any test or environmental testing results generated; 4) review of all lot numbers and expiration dates recorded for verification of completeness and that all were within acceptable ranges (e.g., recovery kits, culture media, processing solutions); 5) review of all processing records for completeness and accuracy, and verification that tissue was processed in accordance with the SOPM and met defined specifications; 6) review and comparison of tissue obtained and units produced from each tissue for verification that the disposition of each tissue recovered, acquired, or collected is traceable; 7) verification that all (if any) error and accident reports potentially related to the safety or quality of the tissue to be released are resolved and corrections made where appropriate; 8) verification that all processing was accomplished within time limits specified in the SOPM and within applicable technical specifications in the SOPM (e.g., acceptable residual moisture, irradiation exposure limits, temperatures, and freezing curves); and
9) if tissue was recovered or collected by another entity, verification that the shipment was acceptable when it arrived at the processing center (e.g., with respect to temperature and time limits). (A) If autologous tissue is processed, the autograft may be released for clinical use only upon notation in processing records by technicians or their supervisor that processing was performed according to the SOPM. There must be a signature by technical staff indicating that all technical elements were reviewed.
Except for reproductive tissue, tissue shall not be released for transplantation without a signed disposition/release statement from the responsible person(s) at the site of distribution, indicating that, at some time prior to release, all quality measures were performed and found acceptable according to the written SOPM. The written disposition/release statement or equivalent documentation shall indicate that the following conditions, at a minimum, have been met:
1) review of tissue processed for consistency with specific tissue requirements;
2) review and comparison of tissue obtained and grafts produced from tissue for verification that the Disposition of tissue recovered is traceable;
3) verification that all (if any) error and accident reports, potentially related to the safety or quality of the tissue from each donor, are resolved and corrections made where appropriate;
4) verification that all processing was accomplished within time limits specified in the SOPM and within applicable technical specifications in the SOPM (e.g., acceptable residual moisture, irradiation exposure limits, temperatures, and freezing curves);
5) if tissue was recovered by another entity, verification of the acceptability of the shipment upon arrival at the processing center (e.g., with respect to temperature and time limits);
6) verification that the Medical Director or licensed physician designee has made a decision regarding donor eligibility and that all directives of the Medical Director regarding the donor were implemented; and
7) verification that final labeling of tissue was performed in accordance with SOPM and Standards.
(R) Reproductive tissue shall not be released for clinical use without a signed, written disposition/release statement of the person responsible for authorizing release, at the site of processing, indicating that all quality measures were reviewed and found acceptable according to the written SOPM. This includes, but is not limited to:
1) review of donor age and of tissue processed for consistency with specific tissue requirements;
2) record and verification that all lot numbers and expiration dates were complete and that all were within acceptable ranges (e.g., cryopreservation media);
3) review of all processing records for completeness and accuracy and verification that the tissue was processed in accordance with the SOPM and meets defined technical specifications;
4) review of tissue obtained and specimens produced from each collection for verification that the disposition of each tissue specimen is traceable;
5) verification of resolution of all error or accident reports (if any) potentially related to the safety or quality of the tissue;
6) verification that all processing was accomplished within time limits specified in the SOPM and within applicable technical specifications in the SOPM (e.g., ejaculate volume, sperm motility, concentration, morphology, and post-thaw motility);
7) if reproductive tissue was collected by another entity, verification of the time of receipt at the reproductive tissue bank and condition of the sample upon receipt; and
8) verification that the Medical Director has made a decision regarding donor eligibility and that all directives of the Medical Director regarding the donor were implemented.
Pre-established release criteria based on tissue utility must be developed. If tissue other than reproductive tissue is distributed or dispensed for transplantation, there shall be in each instance, documentation of:
1) donor eligibility and tissue processing information available at the time of release. All donor eligibility requirements in F1.100 must be met with the exception of a review of the autopsy report (if applicable) and pending culture results;
2) Medical Director or licensed physician designee review of all relevant information present;
3) approval of the release by the Medical Director or licensed physician designee;
4) a written statement issued to the end-user physician indicating what information required by the SOPM and/or these Standards is available and what information is not available for review, and when it is expected that the information will be available; and
5) a statement from the end-user physician indicating his/her understanding that the tissue is being released using available information.
Relevant final results shall be forwarded promptly
to the end-user physician upon completion of testing. Documentation of the release based on tissue utility shall be maintained in the donor record. These records shall be maintained together or summarized in a log.
(R) Release of reproductive tissue may be considered in the special cases of:
1) reproductive tissues from client depositors known to be reactive on tests for antiHIV-1, anti-HIV-2, anti-HCV, HBsAg, or any other test, excluding CMV, without subsequent negative confirmative testing as approved by the Medical Director; or
2) reproductive tissues from client depositors that have not been tested or do not meet current Standards; or
3) directed donors who have completed all required testing and screening according to Standard but:
a) had reactive test results; or
b) are determined ineligible according to screening criteria. In the case of release for one of the three circumstances listed above, the following documentation is required (refer to G3.210 and G3.220 for labeling requirements):
1) a written statement signed by a responsible person at the reproductive tissue bank disclosing the deviation(s) from Standards and description of potential risks to the recipient; and
2) acknowledgement from the medical provider indicating he/she:
a) has received the written statement from the reproductive tissue bank and acknowledges the deviation(s) from Standards;
b) has had ample opportunity to discuss the implication(s) with a responsible person at the reproductive tissue bank and other medical authorities;
c) agrees to fully explain the implication(s) to the recipient and provide her ample opportunity to ask questions and consult with experts of her choice; and
d) will document informed consent from the recipient.
If donor reproductive tissue is to be released before completion of the donor eligibility assessment, the tissue must be kept in
quarantine during shipment. The labeling must include a statement that the donor eligibility assessment, has not yet been completed. It must also include a statement indicating the reproductive tissue must not be transplanted or transferred until the donor eligibility assessment, is complete.
Tissue failing any portion of the review process shall be maintained in quarantine pending
resolution or disposal and shall not be released for transplantation. Unexplained discrepancies or deviations from specifications shall be fully investigated and documented.
If a donor is deemed ineligible as a result of donor eligibility assessment or disease screening procedures, the finding shall be specifically stated in the donor record and in the release/disposition decision statement, and this determination must be described and communicated in writing in a timely manner to the tissue bank that recovered tissue. If the tissue is to be made available for nonclinical purposes from a donor who has been determined to be ineligible based on the results of required testing and/or screening, it must be labeled:
1) ‘‘For Nonclinical Use Only’’; and 2) with the biohazard legend. (SB) Permanent and temporary deferrals of living surgical bone donors and the reason(s) for such deferral shall be documented in the donor record.
True or False: A list of labels used shall be maintained, as well as an example of every label that is utilized by the tissue bank.
True
Who is required to communicate changes regarding labels?
Dates of use (start and discontinuance) shall be recorded. Changes pertaining to labels and communicating changes shall be expected from tissue banks that supply labels to other tissue banks and tissue distribution intermediaries.
Labels shall be designed and qualified to be…
legible, indelible, and affixed firmly to the container under anticipated storage conditions for length of use. All labeling claims shall be clear, accurate, substantiated, and not misleading.
There shall be SOPs established and followed to ensure that approved labels, labeling, and packaging materials are used for tissue. Tissue labeling shall be documented at each step e.g.,
unprocessed, in-process quarantined, rejected, released.
If a sampling plan is used, it must follow a statistically valid method, such as ANSI/ASQ Z1.4:
Sampling Procedures and Tables for Inspection by Attributes
True or False: The storage area for labels and labeling materials shall be clearly identified. Access should be restricted to authorized personnel only. This is not applicable to labels included in tissue recovery packs.
True
As each type of label is removed from inventory, one label shall be retained for the
archives and the surplus labels shall be discarded. The label list and the SOPM shall be updated accordingly.
Except for autologous tissue and reproductive tissue, container labels shall include:
1) the tissue identification number;
2) descriptive name of the tissue and other information necessary for selection or use (e.g., size, right/left, medial/lateral, anterior/posterior);
3) expiration date (if applicable), including the month, day, and year or, if only the month and year are used, the expiration date must be clearly described in labeling as occurring at the beginning or the end of the month;
4) storage conditions, including recommended storage temperature and/or storage temperature range;
5) quantity or other characteristics of tissue expressed as applicable (e.g., volume, weight, dimensions, cell density, number of viable cells or a combination of these);
6) a reference to the package insert.
The following information shall be included on the container label unless space limitations require use of a corresponding insert:
1) disinfection or sterilization procedure utilized (if applicable);
2) preservative (if utilized) and/or method of preservation (if applicable);
3) potential residues of processing agents/solutions (e.g., antibiotics, ethanol, ethylene oxide, dimethylsulfoxide); and
4) name(s) and address(es) of tissue bank(s) responsible for determining donor eligibility, processing and distribution. Should more than two tissue banks be involved, the name of all tissue banks are required but the address is only required for the tissue bank determining donor eligibility.
(A) The following information shall be included on the container label for autologous tissue unless space limitations require use of a corresponding insert:
1) the donor classification statement ‘‘AUTOLOGOUS DONOR’’; 2) definitive autologous donor identifying information such as the patient’s hospital identification number, social security number, birth date, etc.; 3) alabel or attached tag ‘‘FOR AUTOLOGOUS USE ONLY’’; and 4) if infectious disease testing or donor screening is not complete or has not been performed, a label indicating ‘‘NOT EVALUATED FOR INFECTIOUS SUBSTANCES’’ is required; or 5) if infectious disease testing was performed and any results were positive, or if donor screening was performed and risk factors identified, then labeling with a ‘‘BIOHAZARD’’ label is required.
(R) Cryocontainers (e.g., vials, straws or ampules) shall be labeled so as to identify:
1) donor or client depositor unique identifier and/or other code that can be used by the reproductive tissue bank to identify the date the specimen was cryopreserved and the stage of development at cryopreservation, where applicable; and
2) name, initials, or other code that can be used to identify the reproductive tissue bank at which the specimen was processed.
A summary of records is not required if
donor eligibility determination is not required (i.e., autologous tissue and certain types of reproductive tissue).
A summary of records is required when donor eligibility assessment has been completed and shall include:
1) a statement that the tissue was prepared from a donor determined to be eligible based on the results of screening and testing. All results of relevant communicable disease tests performed on specimens from the donor and used for release of tissue shall be listed. Relevant tests include those tests that are required (see D4.230). For example, the CMV test result used must be listed for reproductive tissue. If a test for anti-HTLV I and/or anti-HTLV II was performed it must be reported;
2) the name and address of the establishment that made the donor eligibility assessment; and
3) a statement that the communicable disease testing was performed by a laboratory registered with FDA to perform donor testing and certified to perform such testing on human specimens in accordance with the Clinical Laboratory Improvement Amendments of 1988 (CLIA) and 42 CFR part 493, or that has met equivalent requirements as determined by the Centers for Medicare and Medicaid Services (CMS).
(R) A statement noting the reason for the determination of ineligibility in the case of tissue from a directed donor who is ineligible based on screening and/or testing. The summary of records may be included in the package insert. The package insert shall contain the following information:
1) a statement limiting use to specific health professionals (e.g., physicians, dentists, and/ or podiatrists);
2) a statement that the tissue is intended for use in one patient, on a single occasion only, or as is applicable for reproductive tissue;
3) known contraindications (if any) to the use of the tissue;
4) warnings and list of known possible significant adverse reactions;
5) a statement that adverse outcomes potentially attributable to the tissue must be reported promptly to the tissue supplier;
6) presence of known sensitizing agents (if any);
7) a statement that indicates that the tissue may transmit infectious agents;
8) a statement, if applicable, that the tissue may not be sterilized or re-sterilized.
9) dosage information (if applicable);
10) description of how the tissue was supplied (e.g., frozen, lyophilized, irradiated, demineralized or partially demineralized, see E2.612); 11) type of antibiotics present (if applicable);
12) concentration of preservative(s) and/or cryoprotectant(s) in final package solution (if applicable);
13) instructions for opening the package and/or container;
14) instructions for preparation of tissue for transplantation;
15) expiration time of tissue following reconstitution (upon preparation for use);
16) instructions indicating that once a container seal has been compromised, the tissue shall be either transplanted, if appropriate, or otherwise discarded;
17) acceptable storage conditions and tolerance limits;
18) special instructions required for the particular tissue, when applicable (e.g., ‘‘DO NOT FREEZE,’’ “DO NOT X-RAY,” “DO NOT IRRADIATE”);
19) a statement that it is the responsibility of the tissue dispensing service, tissue distribution intermediary, and/or end-user clinician to maintain tissue intended for transplantation in appropriate storage condi
(C, V) Inserts for cardiac tissue and vascular tissue shall contain the following additional information:
1) warning against using a graft if there is evidence that the container has broken or the contents have thawed;
2) statement that the end-user may not subject the tissue to sterilization (e.g., DO NOT STERILIZE the allograft by any method. Exposure of the allograft and the packaging to irradiation, steam, ethylene oxide, or other chemical sterilants will render the allograft unfit for use);
3) donor age (and blood type, if available);
4) date of dissection or preservation;
5) tissue warm ischemic time;
6) tissue cold ischemic time;
7) graft sizes (e.g., diameter and length);
8) graft physical descriptions and evaluations, including description of imperfections and evaluation criteria;
9) the type of cryoprotectant (if applicable) and clear statement regarding the possibility of residuals;
10) a description of the temperature-sensitive nature of the grafts; and
11) instructions for preparation of tissue for use.
Center-specific protocols shall be established for control of proper thawing, removal of cryoprotectant, and restoration of isotonic balance within the cryopreserved tissue. These protocols shall be provided with each cardiovascular allograft distributed for transplantation.
Reproductive tissue in the following categories require additional information in package inserts as listed below:
1) If the intended recipient is the sexually intimate partner of the gamete provider(s): 1) If the intended recipient is the sexually intimate partner of the gamete provider(s):
Note: a Summary of records is not required for this category.
a) For all reproductive tissue, include the statement: ‘‘For use by Sexually Intimate Partner Only.’’
b) For all reproductive client depositors who were not tested or screened using all parameters required for either a semen or egg donor, including the required tests and time limits for donor testing, include the statements:
1. ‘‘Not evaluated for Infectious Substances’’; and
2. ‘‘WARNING: Advise Recipient of Communicable Disease Risks.’’
c) For all reproductive client depositors who have reactive or positive test results:
1. biohazard symbol; and
2. ‘‘WARNING: Reactive test results for (insert name of test).’’
Reproductive tissue in the following categories require additional information in package inserts as listed below:
2) If the intended recipient is NOT the sexually intimate partner of either gamete provider, the following labeling is required in addition to a summary of records: 2) If the intended recipient is NOT the sexually intimate partner of either gamete provider, the following labeling is required in addition to a summary of records:
a) Directed donors (semen, oocyte, and/or embryo) with reactive test results: 1. biohazard symbol; 2. ‘‘WARNING: Reactive test results for (insert name of test)’’; and 3. ‘‘WARNING: Advise Recipient of Communicable Disease Risks.’’ b) Directed donors (semen, oocyte, and/or embryo) determined to be ineligible based upon risk factors for or clinical evidence of relevant communicable disease agents or diseases, including the physical examination: 1. biohazard symbol; and 2. “WARNING: Advise Recipient of Communicable Disease Risks.’’
Reproductive tissue in the following categories require additional information in package inserts as listed below:
If the intended recipient is NOT the sexually intimate partner of either gamete provider, and the tissue is from anonymous or directed embryo donors in cases where the gamete provider(s) was (were) not initially tested as donors, but were re-tested following 6-month quarantine, include the statement: 3) If the intended recipient is NOT the sexually intimate partner of either gamete provider, and the tissue is from anonymous or directed embryo donors in cases where the gamete provider(s) was (were) not initially tested as donors, but were re-tested following 6-month quarantine, include the statement: ‘‘Advise recipient that screening and testing of the donor(s) were not performed at the time of cryopreservation of the reproductive tissue, but have been performed subsequently.’’ (Note: A summary of records is not required for this category, however, a summary of the test results must be included.)
Reproductive tissue in the following categories require additional information in package inserts as listed below:
4) If the intended recipient is NOT the sexually intimate partner of a gamete provider who initially cryopreserved reproductive tissue as a client depositor but was subsequently screened and tested as a directed donor in cases where additional collections are unavailable, include the statement: 4) If the intended recipient is NOT the sexually intimate partner of a gamete provider who initially cryopreserved reproductive tissue as a client depositor but was subsequently screened and tested as a directed donor in cases where additional collections are unavailable, include the statement: “Advise recipient that screening and testing of the donor(s) were not performed at the time of cryopreservation of the reproductive tissue, but have been performed subsequently.”
Reproductive tissue in the following categories require additional information in package inserts as listed below:
5) Reproductive tissue intended for research: 5) Reproductive tissue intended for research: a) Client depositor reproductive tissue when gamete provider(s) were not tested or screened using all parameters required for either a semen or egg donor, including the required tests and time limits for donor testing, or donor (anonymous or directed) tissue has not completed 6- month quarantine release requirement: 1. ‘‘For Non-Clinical Use Only’’; and 2. ‘‘Not evaluated for Infectious Substances.’’ b) Anonymous donor tissue that has completed 6-month quarantine release requirement: 1. ‘‘For Non-Clinical Use Only.’’ c) Client depositor or donor (anonymous or directed) tissue from gamete provider(s) who had reactive test results OR have been determined to be ineligible: 1. biohazard label; 2. ‘‘For Non-Clinical Use Only’’; and 3. if applicable, ‘‘WARNING: Reactive test results for (insert name of test).’’
The transport package label shall include the following information:
1) name, address and telephone number of the distribution facility;
2) name and address of the destination;
3) unless the shipment contains reproductive tissue, prominent identification of contents as ‘‘DONATED HUMAN TISSUE.’’;
4) recommended storage conditions;
5) validated expiration date/time of the transport package when the storage temperature must be controlled;
6) type and quantity (when the quantity is applicable) of refrigerant or other hazardous materials enclosed in the transport package; and
7) any special handling instructions, when applicable (e.g., “DO NOT FREEZE,” “DO NOT X-RAY,” “DO NOT IRRADIATE”).
Labels for international shipments shall contain all of the information required for domestic shipments; however, information may be modified to meet requirements of the federal government and those of the
receiving country.
Provision of tissue for transplantation shall be restricted to
hospitals, free-standing medical facilities, tissue banks, tissue dispensing services, and end-users (e.g., physicians, dentists, podiatrists or other medical professionals) for use in recipients with the veterinary use exception that follows.
Human tissue for transplantation shall not be offered, distributed or dispensed for veterinary use unless
such use is specifically granted in a document of gift/authorization or in a record of informed consent.
(R) Reproductive tissue shall be released for use by the client depositor or the client depositor’s
sexually intimate partner only
A client depositor who requests that his/her reproductive tissue be distributed to a recipient, who is not the client depositor or who is not the sexually intimate partner of the client depositor, shall be treated as a
directed donor(s). All directed donor(s) must be fully tested and screened in a manner consistent with donor protocols and these Standards.
True or False: There is a limit to the number of offspring allowed by a gamete donor through a given a reproductive tissue bank.
(R) A written policy addressing limitation of the number of offspring by a gamete donor shall be established. The policy shall include the upper limits deemed acceptable to the reproductive tissue bank and shall describe the methods that will be used to comply
True or False: When a tissue bank distributes tissue obtained from another tissue bank or tissue distribution intermediary, all accompanying original labeling materials or other enclosures shall be distributed with the tissue.
True
Donor risk assessment, tissue-related information, and tissue processing details shall be made available to the end-user upon request, except
such information that may infringe upon the confidentiality of donor information.
Records shall be maintained by the tissue bank that distributes tissue (including unfinished or as yet unreleased tissue) to other entities. These records shall be designed to permit tissue to be traced from the donor to a consignee or end-user, and from a consignee or end-user back to the donor. Tissue distribution records shall include:
1) date of order placement;
2) name and address of consignee;
3) name of individual placing the order;
4) type and quantity of tissue ordered;
5) information pertaining to tissue shipped including:
a) identification number(s) of tissue(s);
b) collection and/or expiration date of tissue;
c) date of shipment;
d) type of refrigerant, and quantity of refrigerant when applicable, in the shipment;
e) mode of transportation and/or courier; and
f) name of the staff member filling the order.
6) identifying information, if available, about the intended recipient.
The tissue bank shall establish recipient…
follow-up data collection protocols, and procedures to evaluate information received.
All requests for human tissue intended for research use shall be submitted in writing. The request shall indicate the type of tissue requested and how it will be used as well as
the name, address and affiliation of the principal investigator accepting responsibility for receipt of the tissue.
Any specifically required solutions not readily available to the end-user that are needed to prepare the tissue for use shall
be made available to the utilizing facility.
A tissue bank shall establish a policy authorizing or prohibiting the return of tissue in its
original, unopened container.
