wpe6E.jpg (10092 bytes)

Lecturer (IAEA Expert Mission)

19-23 JUNE 2000





1. Radiation sterilization of tissue


2. Disposal of waste tissues


During the masters degree program in Bangkok Biomaterial Center, BBC arranged the expert visit of Dr. Nazly Hilmy to give lectures on tissue banking related topics and evaluate the progress of the IAEA fellows.


The main objectives were the improvement of knowledge on Quality system in tissue banking, prepare Quality System Documents and to prepare some research proposals.

Lecture topic: Importance of Quality Assurance System in tissue banking

A total quality system to achieve an international recognized standards.

Unless uniform donor screening, procurement, processing, packaging, management and the distribution of tissue allografts is achieved, with the performance audited by a competent authority, the international acceptance of the product cannot be achieved.

A fundamental parameter in achieving guaranteed sterilization of tissue is the accurate measurement of total bioburden and radiation sterilization dose required to achieve the appropriate sterility assurance level (SAL).

Definitions for tissue bank and tissue banking.

Tissue banking is general term of activities of retrieval, processing, storage and distribution of human tissues for medical use.

Tissue banks is the formally organized entities those activities.

Definitions for quality, control, assurance, quality assurance of tissue.

Quality: The degree of excellence

Control: To check, to verify


Positive statement intended to give confidence

To make certain

To guarantee

The Quality Assurance of a Tissue: Formal guarantee of degree of excellent of tissues and their capability and characteristic to fulfill the demand upon it at the least possible cost.

Importance of having international standards for a tissue bank.

Exchange of tissue allografts between countries, regional, international without fear of grafts quality.

Exchange of tissue bank staffs (International/regional)

Accreditation of new tissue bank by international/regional committee.

Training and exchange of experiences.

New established tissue bank can benefit expertise of another regional tissue bank.


Introduction to Quality system, Quality Assurance and Quality Control.

Quality Assurance (ISO 9000):

All those planned and systematic actions necessary to provide adequate confidence that the finished tissues will satisfy given requirements for quality.

Quality Control:

The operational techniques and activities that are used to fulfill requirements for quality.

Aim of quality assurance system in tissue banking.

Assessment of the actual quality of the tissues.

Correction of any observed defects and prevention of potential defect.

Systematic problem solving.

To reduce the gap ABNA to zero.

Systematic pathway of problem solving.

Problem identification.

Problem prioritization.

Problem analysis.

In-depth study of the problem.

Identification of remedial action.

Implementation of remedial action.

Monitoring and reevaluation of the problem.

Importance of standardization and quality management in tissue banking.

Harmonization of standards and guidelines.

Progress in medical and technical sciences related to tissue banking.

International co-operation and networking.

Increasing demand for human and biological tissue.

Increasing risk of virus infections.

General standards for tissue banking.

General standards are intended to be applicable to any and all forms of tissue banking activities.

Current thinking of diversified group of experienced practitioner of tissue banking.

Reviewed regularity.

Generally published by association.

General standards/guidelines for tissue banking.

American Association of Tissue Banks (1998).

Joint Musculo Standards of EATB and EAMTB (European Association of Musculoskeletel Transplantation)

American Red Cross Tissue Service.

EATB General Standards of Tissue Bank.

Australian Orthopedic Association: National Guidelines for Bone and Tissue Banking.

An Australian Code of Practice for transplantation of cadaveric organs and tissues: National Health and Medical Research Councils.

IAEA guideline: Multi-media distance learning package on tissue banking.

Good Manufacturing Practices (GMP)


Lecture topic: Implementation of Quality Assurance in tissue banking

Definitions of Medical Devices (ISO 11137,97)

Any instrument used for

Diagnosis, prevention, monitoring, treatment of disease.

An injury or handicap

Investigation, replacement or modification of anatomy or physiological process

Control of conception.

ISO 9000, Definitions:

Quality: The totally of features and characteristics of a product that bear on its ability to satisfy stated or implied needs.

Quality Manual: A document stating the quality policy, quality system of an organization.

Quality Audit: A systematic and independent examination to determine whether quality activities and related results comply with planned arrangements and whether this arrangements are implemented effectively and are suitable to achieve objectives.

Quality Surveillance: The continuing monitoring and verification of the status of the procedures, methods, conditions, processes, products and analysis of records in relation to stated references to ensure that specified requirements for quality are being met.

Quality Policy: The overall quality intentions and direction of an organization as regards quality, as formally expressed by top management.

Quality Management: That aspect of the overall management function that determines and implements the quality policy.

Quality System: The organization structure responsibility, procedures, processes and resources for implementing quality management.

Quality Control: The operational techniques and activities that are used to fulfill requirements for quality.

Quality Assurance: All those planned and systematic actions necessary to provide adequate confidence that a product or service will satisfy given requirements for quality.

Role of tissue bank.


Adequate supply of high quality transplanted tissues of various shape and size.

Allow patients accessibility to grafts regardless of their economic status.

Efficient in all steps of activity.

Introduction to Quality Manual

Documented quality system that reflects the current management, organization, policy, procedures. This may be one document supported by several tiers of documents, each tier becoming progressively more details.

Purpose of the Manual: To describe the policies and management system used in achieving the quality of supplied tissue grafts.

Responsibility of Quality Assurance Department:

Documentation and data control.

Product identification, traceability, segregation.

Inspection sampling and test procedure.

Specifications for raw and packaging materials.

Calibration and maintenance of test equipment.

Initial and periodic process validation study.

Stability testing, recall and quality audit of intermediate and finished product.

Preservation of records and samples.

Staff training.

Procedural Manual:

Procedural manual is intended to outline the acceptable methods for donor selection procurement, processing, storage and distribution of tissue grafts. It is used as a guide for tissue bank personnel. It is open to be revised and validated. It is the source of work instruction or SOP's.

Good Manufacturing Practice (GMP)


Learning to work efficiently and accurately in hygienic condition.

Products meet the qualification of the international standard for producing sterile medical products.

Products meet the consumer qualification.

Basic principals of GMP and Quality Assurance.

An integrated system of design, manufacture and quality assurance.

Suitable premises, equipment and materials.

Trained personnel.

Documented procedure for all functions affected quality.

Appropriate batch and product records.

Adequate transport and storage.

A recall system.

System for review and audit of the operation of GMP.

Parameters monitored in quality assurance.

Raw and packaging materials qualification.

Tissue processing equipment (calibration and validation)

Environmental monitoring

Standard operating procedure manuals and updates.

Tissue storage devices.

Tissue labeling.

Tissue sterilization with gamma rays

Release of all materials for use in tissue processing.

Final tissue release for distributions.


Importance of documentation.

Documentation is a good record keeping practice, from raw material acquisition, processing, labeling, distribution and recall.


To define tissue bank system of information and control.

Minimize risk of misinterpretation and error.

Provide unambiguous procedure.

Facilitate checking of calculations.

Lecture topic: Batan research tissue bank:


Flow of raw materials and processing.

Raw material qualification.

Parameters monitored in quality assurance.

National network in Indonesia.

Processing and distribution.

Adverse reactions

Lecture topic: Disposal of waste tissues.

Definition for waste tissue.

Waste tissues of the tissue bank are tissues and materials come from procurement and processing of tissues.

Source of waste: Waste tissue and waste materials.

Waste materials and other resources of wastes.

Waste materials from Procurement:

Living donor: used gauze, clothes, plastic pack

Cadaveric donor: Tissue pieces, used gauze, cotton. Papers, catheter, disposal syringe,

razor used for shaving hairs, blood contaminated materials.

Waste materials from processing:

Tissues such as left over pieces of bone, soft tissues, muscles, sawdust from bone

cutting. Materials contaminated from cleaning bench, saw. Knife, vessel and


Expired tissues.

Invalid tissues: Tissues with positive results from serological and microbiological assay.

Materials discarded from microbiological test such as culture media, pieces of tissues, gauze, cotton etc.

All materials should be autoclaved prior to disposal. Expired and invalid tissues should be documented prior to disposal.

Hazard of tissue bank wastes.

Contaminated waste tissues and materials can lead to transmission of diseases to the tissue bank worker and general public.

All waste materials and tissues should be wrapped pack and disposed carefully.

Collection and disposal of wastes.

Waste should be collected into plastic bags immediately after procurement and processing.

Wet waste should be wrapped in multi layer plastic bags.

Sharp objects must be placed in a special envelope and labeled before disposal.

All waste can be incinerate or buried.

Bury the waste tissue in a special land.

Never send the waste to dumping site of ordinary rubbish.


Lecture topic: Amnion membrane and techniques in conducting research on amnion.

Definition for amnion.

Amnion is a collagen rich, thin transparent and tough membrane, lining the chorion leave and placenta that produces the amniotic fluid at the earliest period of fetus.

Consists of five layers with thickness of 0.02 to 0.5 mm. They are epithelium, basement membrane, compact layer, fibroblast layer, spongy layer.

Types of amnion grafts.

Viable: Fresh, short-term storage at 40C.

Cryopreservation at -700C with 10% bovine serum, 15% Glycerol

Non-viable: Freeze/air dried and then sterilized by gamma irradiation


Quality control of fresh amniotic membrane.

Donor: well screened.

Organoleptic: 1. Colourless, clear and transparent

2. Meconium stained placenta should be discarded

Serological test: HIV, Hepatitis B/C

Swab Test: exclusion criteria

Contaminated by pathogenic bacteria will be discarded.

Processing steps.

Amnion membrane is separated from chorion and extraneous tissue. Washed in clean water to eliminate blood clot and keep in sterile solution in sterile bag at 40C. Transfer to the tissue bank. Washed four times in saline/sterile water and immerse in 0.05% NaOCl for 10-15 minutes. Washed in sterile water four times. Mounting on sterile cotton gauze under laminar flow bench. Mounting on freeze dryer rack and then deep freeze (-400C) over night or air dried under laminar flow bench. Lyophilization until water content: 7% or less and cut according to size. Triple packing in polyethylene pouch. Sterilization by gamma irradiation at dose of 25kGy. Store at room temperature or less, protect from light.

Biological functions and benefit of amnion for clinical use.

Control of bacterial flora.

Reduction of fluid loss.

Promotion of healing.

Stimulation and protection of epithelization and granulation and neo vascularization.

Protection of nerve ending and blood vessel.

Tight adherence to the wound surface, increase in mobility.

Help in prediction of readiness for grafting.

Preparation of skin defects for closure.

Ability to decrease pain.

Physical and biomechanical properties.

Excellent adherent and easily conforms to body contour.

Absence of immunologic reactions.

Healing effects: antibacterial, angiogenetic, better vascularization, enhancement of formation granulation and epithelization.

Thin, semi-permeability, elasticity, translucence membrane.

Effective barrier to reduce to reduce heat, fluid and protein loss.

Good patient acceptability and permit early mobilization.

Reduction of pain and analgesics.


Lecture topic: Techniques in conducting research studies on amnion.

Problem criteria.

Mechanics of amnion membrane.

Clinical effects.

Supporting and packaging materials.

Aging and expiration date.

Quality control of amnion grafts.

Lecture topic: Sterilization tissue graft

Introduction to radiation sterilization.

Alpha radiation (particle)

Beta radiation/electron (particle)

Gamma irradiation