CONDITIONS AND PROCEDURES FOR IMPORTATION AND EXPORTATION

Transcription

1 CONDITIONS AND PROCEDURES FOR IMPORTATION AND EXPORTATION Raphaël BARDONNET October 2017 BIOBANK Limited company with capital of 1,399, Melun Company Register B Siret Code APE - NAF 2110Z ZA Lavoisier - 4, rue Lebon Presles en Brie - France Tel: (33) Fax: (33)

2 CONTENTS 1. REGULATORY AUTHORISATIONS Authorisations relating to BIOBank activities Authorisations relating to importation and exportation ORIGIN AND SELECTION OF TISSUES General presentation of the organisation Clinical selection Biological selection TRANSFORMATION OF BONE GRAFTS Principal of the Supercrit process Implementation Approval of the grafts before distribution RANGE OF PRODUCTS 9 5. TRACEABILITY OF PRODUCTS Information system Tissue traceability during transformation Traceability documents Biovigilance REGULATORY REQUIREMENTS FOR EXPORTATION Export to a member state of the EU or party to the EEA Export to a non-member country of the EU or EEA Conditions and procedures for importation and exportation 2

3 1. REGULATORY AUTHORISATIONS Authorisations relating to BIOBank activities BIOBank is a human origin bone tissue bank, authorised by the ANSM (French National Safety Agency for Health Products) to prepare, store, distribute and transfer viro-inactivated bone allografts for orthopaedic surgery and dental surgery. BIOBank covers the entire activities of a tissue bank as provided for in article L of the French Code of Public Health (authorisation since 29 September 2003), for taking charge of tissues collected for the deliverance of safe bone grafts. These stages mainly include the selection of donors in accordance with statutory clinical and biological criteria and the actual viro-inactivation of the bone grafts through implementation of the Supercrit process. All these operations are performed in accordance with the Rules of Good Practice for Tissue Banks set by the ANSM decision of 27 October 2010 and the Code of Public Health, the articles of which transpose European Directives 2004/23/EC, 2006/17/EC and 2006/86/EC. The BIOBank grafts come from femoral heads harvested exclusively from living donors during hip arthroplasties. All samples are obtained in France by orthopaedic surgeons within approved health institutions. As it is the case for all French tissue establishments, BIOBank holds a Single Authorisation, awarded by the ANSM, that relates on the one hand to the institute s activities and on the other to the preparation procedures implemented, grouped by families depending on the form of the grafts (anatomical, geometrical, granules, powders, plates). The BIOBank Single Authorisation, granted on 10 February 2017, bears number BT/16/O/014. Authorisations relating to importation and exportation As a European Tissue Establishment, BIOBank is authorised to export its products in the member states of the European Union (EU) and party to the European Economic Area (EEA). This authorisation extends to certain countries outside the EU and EEA. BIOBank also has authorisation to import femoral heads taken from living donors, with a view to re-exportation to the country of origin of bone grafts viro-inactivated by the Supercrit process. This authorisation is limited to the tissue establishments that have signed a contract with BIOBank, the implementation of which is subject to ANSM s prior authority. BIOBank is registered in the European Coding Platform for tissue establishments under number: FR07701T ( Conditions and procedures for importation and exportation 3

4 2. ORIGIN AND SELECTION OF TISSUES General presentation of the organisation The tissues processed by BIOBank are femoral heads harvested from patients during hip arthroplasties. Therefore, the removal of tissues is carried out in the context of a regulated surgical operation, ensuring optimal quality and asepsis. BIOBank supplies the orthopaedic surgeons with a special sterile sampling kit for gathering bone tissue and blood sampling that will enable serological screening for transmissible diseases. A specialised transporter undertakes the transit of the samples to BIOBank in refrigerated vehicles at a temperature of -20 C controlled by electronic temperature sensors. BIOBank directly undertakes the transformation, quality control and final checking stages. Final gamma ray sterilisation at 25 kgy is carried out by an accredited provider. H Clinical selection Removal Reception and control of collection Production and dispatch of sampling kits Biological selection Supercritical defatting Chemical inactivation Packing Sterilisation Approval and placing in storage H Distribution Implantation Conditions and procedures for importation and exportation 4

5 General presentation of the organisation Clinical selection is an essential stage in contributing to the safety of graft patients, collection team personnel and tissue banks. Its procedures are defined in the rules of good practices relating to human tissues harvested and used for therapeutic purposes. The exclusion criteria are established by the French Biomedicine Agency (ABM) and governed by the regulations. Conformity with these criteria and the detection of signs of a pathology that could contraindicate removal are aimed at the avoidance of the transmission of diseases from the donor to the recipient. Thus, the surgical team takes charge of each donor under the responsibility of the collecting orthopaedic surgeon who must: check the medical file of each donor, ensure that there are no regulatory contraindications for collecting the tissue, ensure the non-opposition of the donor to the removal for the purposes of therapeutic or scientific use, complete and sign the removal sheet that will accompany the tissue. Biological selection Its legal framework is governed by the health and safety rules set by the French Code of Public Health and the order of 23 December 2010 relating to screening for infectious diseases. The test report is certified by an approved analysis laboratory, mentions the techniques and reagents used and bears the signature of the person in charge of marker detection. It is passed to the removal surgeon in order that he or she may inform the donor of the results during a medical interview. This individual certificate of compliance is kept by BIOBank and at the disposal of the grafting surgeon on request. Table of infection markers looked for as part of the biological selection: Disease Infectious element Marker Hepatitis B HBV HBs ag, anti-hbc ab, anti-hbs ab Hepatitis C Infection by the HIV virus Infection by the HTLV virus Syphilis HCV HIV 1 and 2 HTLV I and II Treponema pallidum Anti-HCV ab anti-hiv ab and P24 ag Anti-HTLV I Ab Anti-treponemal Ab A serum bank is created for each serum analysed, identified and preserved at -20 C. The serum bank enables confirmation or additional biological tests to be carried out by the use of new screening techniques. Conditions and procedures for importation and exportation 5

6 3. TRANSFORMATION OF BONE GRAFTS The BIOBank Supercrit process is particularly suited to bone tissue and in particular to femoral heads, with the purpose of ensuring the maximum safety of the graft at microbiological level, whilst preserving the intrinsic biological and mechanical properties of the human bone tissue. Principal of the Supercrit process Various processing methods have been developed with the aim of devitalising the bone tissue. They generally associate a fat solvent to an oxidative treatment. In the classic procedures, the solvent (chloroform or acetone) is necessary to remove the fat from the bone tissue that contains numerous adipocytes in its medular cavities. The presence of a large quantity of lipids leads to poor wettability of the tissue, preventing or interfering with the action of the aqueous oxidisers. As their diffusion in the bone tissue is restricted, the volume of the bone fragments able to be treated effectively is low. In addition, the use of these fat removal solvents can leave undesirable toxic residues. In contrast, the BIOBank procedure is a method based on defatting the bone tissue by a non-toxic fluid, CO2 in supercritical state, together with chemical oxidation of the residual proteins contained in the pores of the cancellous tissue. The aim of this procedure, apart from viral inactivation, is to eliminate fats, cellular debris and medular proteins in order to leave the organo-mineral structure of the bone tissue, comprising carbonated apatite and type 1 collagen, perfectly preserved. Osteoconduction may then be done under the best conditions possible. Principle of the Supercrit technology: Beyond a critical pressure and temperature, CO2 is no longer in a gaseous or liquid state; it is in another state known as supercritical fluid. As a liquid, it has a higher density and consequently a higher solvent capacity. This property, that may be roughly proportional to the density, is thus variable as a function of the temperature and the pressure. The other interesting property of supercritical CO2 is that it demonstrates transportation properties similar to those of gases because of its low viscosity and raised diffusion ability. These two properties, higher diffusion and solvent power, make this fluid very useful for the extraction of compounds contained in a porous matrix such as cancellous bone tissue. CO2 in the supercritical state is often used as an extraction vehicle as it is natural, safe (non-toxic, noncorrosive, non-inflammable) easily available and cheap. In addition, its supercritical coordinates are soft (critical pressure 7.38 Mpa, critical temperature 31 C) and are easy to achieve. The critical temperature also enables non-denaturing of the biological molecules in the face of these conditions of temperature and pressure. This is an important property for the bone tissue, as any denaturing of the bone protein matrix could lead to collapse of the mechanical properties. Non-polar molecules, like hydrocarbons, oils and generally all lipids, are soluble in CO2 in the supercritical state. In contrast, polar molecules, amino acids and proteins are not very soluble. Conditions and procedures for importation and exportation 6

7 Supercritical CO2 is thus a compound that is particularly well suited to defatting cancellous bone tissue. PRESSURE REGULATION VALVE CYCLONIC SEPARATORS EXTRACTION AUTOCLAVE EXTRACTED FAT BONE TISSUE CONDENSER CO2 HEAT EXCHANGER CO2 PUMP Principle diagram of an extraction machine with supercritical CO2 Implementation The tissues are prepared in batches of several parts while the identification of each unit is meticulously respected. No mixing of products is done during the procedure. Between each operation, systematic visual inspection of the tissues is carried out by a qualified person in charge. Any handling of the tissues takes place in a laboratory specially designed for aseptic tissue processing. The work environment is made up of clean rooms with a controlled atmosphere, in a total area of 250 m2, fitted with high technicality special equipment. Trained and qualified personnel implement all stages of the BIOBank procedure with the exception of the gamma sterilisation. Conditions and procedures for importation and exportation 7

8 Synopsis of operations: Cryopreservation of femoral heads Mechanical preparation of cartilage slicing Extraction by supercritical CO 2 Mechanical finishing (heads, half-heads, granules, blocks, bone wedges) Chemical inactivation treatement Drying Frozen femoral half-head Primary packing in sachets Quality control Gamma sterilisation Sterilisation approval Secondary packing in box Treated femoral half-head Distribution The sterility of the finished products with a 10-6 SAL is achieved through radiation with gamma rays at a sterilising dose of 25 to 30 kgy on the grafts previously protected by a double primary packaging. This stage is carried out by a provider approved for the sterilisation of medical devices. A check of the sterilisation is carried out in accordance with standards EN 552 and ISO In addition to the efficacy of this final sterilisation procedure, the non-heating of the material and the absence of toxic residues are additional arguments that justify the choice of this technique. Conditions and procedures for importation and exportation 8

9 Approval of the grafts before distribution A systematic review of the production files is carried out under the responsibility of the BIOBank medical and technical manager. It results in authorisation to put them into storage and the availability of the grafts for therapeutic use. Distribution and transfer of the grafts are then carried out in accordance with the practitioners particular medical instructions, in accordance with regulations. 4. RANGE OF PRODUCTS The grafts present in various forms, belonging to 5 families of products approved by ANSM: Anatomical forms (PPT1) Granules (PPT5) Geometrical forms (PPT3) Powder forms (PPT6) Conditions and procedures for importation and exportation 9

10 The BIOBank grafts present in various forms suited to the various indications that the surgeon encounters for reconstituting the bone stock of his or her patients. Category Anatomical forms Geometrical forms Form - Complete femoral head - Femoral half-head - Bone wedges for 6, 8, 10, 12 and 14 osteotomy - 20x10x10 mm and 30x20x10 mm blocks Cancellous bone granules (3-4 mm) in vial - Volumes: 5, 7, 18 and 25 cc Cancellous bone granules (3-4 mm) in syringe Cancellous and cortico-cancellous bone powder in vial Cancellous and cortico-cancellous bone powders in syringe Bone plates - Volumes: 7, 18 and 25 cc mm powder, in 0.5, 1, 2 and 4 cc - 1 mm powder, in 0.5, 1, 2 and 4 cc mm powder, in 0.5, 1 and 2 cc - 15x10x4 mm and 22x12x5 mm cortico-cancellous bone block - 12x10 mm et 18x10 mm cortical bone plate 5. TRACEABILITY OF PRODUCTS Information system Tissue traceability is an essential element in the management of a tissue bank; it is managed by a specially designed information system and has the lockouts and access rights that are indispensible to a tissue bank. Tissue traceability during transformation Tissue traceability has three objectives: to ensure the traceability from the donor to the recipient; to preserve the donor and recipient s anonymity; to ensure BIOBank s activity data history. Conditions and procedures for importation and exportation 10

11 The recording by BIOBank of individual-related data is the subject of a licence granted by the CNIL (French Data Protection Authority). Tissue traceability is centred on a unique and anonymous ID number, allocated at the time of removal and supplemented by a product code depending upon the operation. The ID is supplemented by the Single European Code (SEC) imposed by directive EU 2015/565 of the European Commission of 8 April 2015 on the codification of products of human origin. Links are established between these different numberings as well as between the tissues and the preparation conditions (tissue file, production file, therapeutic products attached, consumables, etc.). These links enable the whole history of removal, selection, preservation, transformation, product disposal and biovigilance to be transmitted. The information necessary to traceability is transcribed on to labels and documents that accompany the tissues throughout their life cycle, whilst respecting the anonymity of the donor and the recipient. Traceability documents The documents enabling traceability of the bone grafts to be guaranteed in accordance with the regulatory provisions are included in the grafts outer packaging box: the Graft ID form, certified by the BIOBank medical responsible person in charge, including the information necessary for traceability (origin, characteristics, clinical data, serological screening results, preparation conditions, etc.); This form must be kept in the patient s medical file. the Implantation form, which should be filled in by the surgical team on the conditions of use and returned to BIOBank by mail or fax; This form must be returned to the tissue bank that has distributed the graft to the final user the traceability labels affixed to the graft to facilitate the keeping of the medical file and, if applicable, keeping a filing register. Biovigilance In accordance with national and european regulations relating to biovigilance, the biovigilance system depends on the reporting by the health professionals of: incidents, occurring during the chain linking removal to administration to the patients; adverse effects (however serious), observed among the living patient donors and the recipients. The surgical team that discovers the incident must, as soon as possible, draw up a statement with the assistance of their local biovigilance contact. The statement is forwarded to the relevant biovigilance department of the national competent authority. A copy of this form is sent to BIOBank. Conditions and procedures for importation and exportation 11

12 In all cases, the statement specifies the following elements of information: 1. the identity and details of the informants; 2. the products concerned (nature, ID number, product code, SEC); 3. the patient involved (donor or recipient); 4. the description of the incident or the adverse effect (date occurring, description, consequences); 5. the other recipients of the tissue concerned; 6. the actions implemented (description, persons informed). As soon as BIOBank is informed of the incident, an enquiry is started in order to understand the causes, correct the problem and avoid any repetition. Should non-compliant products be implicated, the tissue recall procedure will then be activated under the authority of the BIOBank medical responsible person in charge. The results of the enquiry and recall actions will be transmitted for information to the surgeon and to the health authorities. 6. REGULATORY REQUIREMENTS FOR EXPORTATION Export to a member state of the EU or party to the EEA As the BIOBank products are licensed by the ANSM, the competent French authority, exportation is possible without restriction to the States that are members of the EU or party to the EEA. The regulatory requirements that may be applicable originate in the recipient state that may impose particular measures for the entry of products of human origin on to its territory. These procedures are to be studied for each individual case. Export to a non-member country of the EU or EEA In accordance with decree no of 23 March 2017, the export of BIOBank products to a non-member country of the EU or EEA requires application to ANSM for the purpose of extending the BIOBank product export licence to the new consignee. The documents to be supplied are detailed in the ANSM decision of 2 July 2015: 1. Description of the transport conditions 2. Agreement or contract linking BIOBank and the consignee organisation 3. Labelling model attached to the packages 4. Details relating to the consignee: a. Name b. Name of the person in charge c. Legal status d. Address e. Country f. Telephone/fax nbr. g. address 5. Traceability document model Conditions and procedures for importation and exportation 12

13 ZA Lavoisier - 4 rue Lebon Presles en Brie - France Dental Backoffice: Orthopaedic Backoffice: Fax: commercial@biobank.fr DR1-GB