TissueLAB: Company Profile by Jim Chrysagis

TECHNOLOGY FOR HUMAN TISSUE BANKS

MUSCOLOSKELETAL HUMAN ALLOGRAFTS

The Company Tissuelab S.p.A. was founded in 2003 with the aim to create a European Reference Centre for

research and development in biotechnologies and systems for reconstructive musculoskeletal surgery. Thanks to the cooperation with important companies operating in the Orthopaedic and in the Blood Banks fields, and to the technological know-how of their partners, Tissuelab has created in pharmaceutical grade laboratories for processing human osteotendineous tissue from donation, on behalf of Italian and foreign tissue Banks.

The processing facility is able to design and to formulate freeze-dried grafts such as: tissue

segments templates, demineralised bone matrices, for routine use in surgery, and specialty products worked out with a CNC equipment, in full respect of the quality and safety regulations.

stabilimento di S. Antimo - NAPOLI

The Process The complete process, starting from the plant to the manufacturing procedures, the quality

system and the management of the production is in accordance with the GMP standards for the manufacture of the pharmaceutical sterile products (Eudralex Vol.1 Medicinal Products for human and veterinary use: Good Manufacturing Practices Annex 1 Manufacture of sterile Medicinal Products) In particular:

Classified environments: the manufacture is carried out in environments with pharmaceutical

requirements, whose classification has been validated physically (particle counting, differential pressures between environments with different classification grade), microbiologically (environment validation “at rest” and “in operation” with air and surfaces biological monitoring) and operatively (fluxes diagrams for operators, materials and products).

The Safety System and equipment validation: the equipment and the crucial instrumentations are validated

according to the pharmaceutical standards following the IQ Protocols (Installation Qualifications), OQ Protocols (Operation Qualifications) and PQ Protocols (Performance Qualifications). Biological Banks (-80째C), autoclave, freeze-dryer, the demineralised bone powder machine, laminar flow equipment, cutting machine, etc. are part of these mentioned processes.

Process validation: Tissuelab has validated the

sterilization and viral inactivation process, the freeze-drying cycles and the tissue processing. Furthermore, the cleaning process of equipments, of the environments (microbiological and particulate analysis), and the autoclaving cycles for standard defined loads have been validated.

Terminal sterilization: the products undergo a viral inactivation and sterilization through the

Clearant method (sterilization with gamma rays at low temperatures with radioprotector soaking treatment) that guarantees a viral and microbiological safety as confirmed by ad hoc studies. The treatment performed in strict controlled conditions does not modify the biomechanical and biological integrity of the tissue. The sterility controls are performed in accordance to the European Pharmacopoeia for sterile medicines.

Mechanical and Biological Studies: the preservation of the mechanical and biological properties

of hard and soft tissues treated with Clearant method has been confirmed during the validation process. The maintenance of the osteoinductivity properties following demineralization, freeze-drying and sterilization has been evaluated see fig.1.

The Production Tissuelab manufactures a wide range of

human musculoskeletal tissues:

➢ Freeze-dried demineralised bone matrix (DBM) in granules and powder. Bone pastes and putties mixing the DBM with a carrier able to guarantee the suitable physical chemical and biological features the products. ➢ Soft tissues (ligaments and tendons), and hard tissues (cancellous and cortical bone) in different shape and size (chips, struts, cortical dowels, strips, blocks…). Hard tissues are presented in freeze-dried pharmaceutical form in a vacuum sterilized package , while the soft tissues are frozen at -80°C after sterilization. The Tissuelab process and the patent method of terminal sterilization/viral inactivation guarantees the maintenance of osteoconductive, osteoinductive and bio-mechanical properties of human tissues at the highest safety for the patients.

fig.1

Allograft and Substitute Characteristics Type of tissue:

Osteoconductive properties

Rejection

Synthetic