FOURTH FNCA COORDINATORS MEETING March – 7, 2003 , Naha-shi , Okinawa , Japan FOURTH FNCA COORDINATORS MEETING - 2003 - QUALITY ASSURANCE ASPECT IN THE PRODUCTION OF PZC BASED 99MTC GENERATOR Le Van So Nuclear Research Institute, Dalat , Vietnam BASIC ELEMENTS OF QUALITY MANAGEMENT • Appropriate infrastructure i.e., Quality Policy and “Quality System” – – – – organizational structure procedures processes resources • Systematic action QA • Commitment and Involvement of top executives GMP Manufacturing QC Validation - Prospective - Concurrent - Retrospective Other Quality Aspect QA : is defined as the VALIDATION: sum total of the • Prospective Validation : arrangements made with Which is conducted prior to the object of ensuring that the commercial distribution of products will be of the a new RP or a RP made by a quality required for their new or revised process intended use • Concurrent Validation: Which is conducted for a GMP : is that part of QA process in which the RP is aimed at ensuring that being manufactured on a products are consistently production scale before manufactured to a quality completion of process appropriate to their intended use QC : is that part of GMP which is concerned with the sampling, specification and testing , and with the organization, documentation and release procedures which ensure that the necessary and relevant test are, in fact, carried out and that materials are not released for their intended use, nor products released for sale or supply, until their quality has been judged to be satisfactory validation studies • Retrospective Validation : Which is conducted for a RP already manufactured on a production scale basesd on accumulated production testing and control data OTHER QUALITY ASPECT: ( Functions&Responsibilities , Non conformances /corrective preventive action analysis …) ELEMENTS OF GMP Premises and Environment Equipment Personnel Documentation Manufacturing procedures – Raw materials – Processing procedures – In-process testing – Processing control – Labelling / packaging / Storage / Shipping Quality control Contract manufacture Import Consignment control 10 Product complaints / Recall 11 Internal audit system 12 Product evaluation and launch protocol Product evaluation – Pre-clinical studies - Clinical trial Product launch protocol – Registration – Market approval Ten Commandments of GMP – – – – – – – We should write procedures We should follow our written procedure We should document (record) our work We should validate our work We should design and build proper facilities and equipment We should maintain our facilities and equipment We should be competent (as a result of education, training and experience) – We should be clean – We should build in quality not test quality in your product – We should audit for compliance EVALUATION STUDIES ON THE PROCEDURE OF PZC BASED 99mTC GENERATOR PRODUCTION Outline of the technology for PZC based 99mTc generator production Table 1: Outline of the technologies for 99mTc generator production Fission based generator Raw materials (Commercia l products) and preparation Hot cell process -Fission Mo solution -Al2O3 adsorbent – Dispensing 99Mo stock solution 99 Gel based Generator - (n,γ)99Mo solution - Chemicals ZrOCl2,… PZCbased Generator - (n,γ)99Mo solution - PZC adsorbent Hot cell process (Finished generator assembling –Hot assembling) Inactive cleanroom process (Generator components assembling, Cold Assembling) – Dispensing 99Mo stock solution 99 – Mo adsorption on Alumina column – Chemical synthesis and preparation of gel powder – Dispensing gel and column loading – Dispensing 99Mo solution and 99 Mo adsorption – Column loading QA & GMP Requirements for a new (PZC based)procedure for 99m Tc generator production • Raw materials o Finished 99mTc generator product design and generator component preparation o PZC adsorbent ( Specification ) • Equipment and facilities o Mo-99 adsorption and PZC column loading machine o Hot cell facility arrangement – Manipulator and conveyor • Procedure (standard procedure) o Description of process 99 Mo Adsorption – – Loading 99Mo –PZC column – Generator component cold and hot assembling o Raw material control 99 – Mo Solution (radioactivity and Molybdenum content) – PZC and Al2O3 adsorbent (99Mo Adsorption capacity, 99mTc elution yield, Mo and Zr breakthrough , particle size, stability) – Generator components (column ,solution- line…) – Elution kit (saline and evaluated vials) o In-process control – Radioactivity of solution (pre-and post- adsorption) – pH of solution (pre- and post- adsorption) – Temperature and time of adsorption – Radiation protection monitoring • Quality Control o Product specification of Pertechnetate solution eluted from PZC based Tc-99m generator o Testing procedure (pH, Radiochemical purity, Radionuclide identification, o Radionuclidic purity, Chemical purity (Aluminium, Zirconium content , Sterility, Bacterial Endotoxin ) • Product evaluation and launch protocol o Pre-Clinical studies – Biological test (bio-distribution studies in test animal) – Toxicity test – Pharmacokinetics studies – Radiation safety – Environment assessment including waste disposal studies o Clinical trials o Product launch protocol – Registration – Market approval View publication stats ... STUDIES ON THE PROCEDURE OF PZC BASED 99mTC GENERATOR PRODUCTION Outline of the technology for PZC based 99mTc generator production Table 1: Outline of the technologies for 99mTc generator production. . .QUALITY ASSURANCE ASPECT IN THE PRODUCTION OF PZC BASED 99MTC GENERATOR Le Van So Nuclear Research Institute, Dalat , Vietnam BASIC ELEMENTS OF QUALITY MANAGEMENT • Appropriate infrastructure... Retrospective Other Quality Aspect QA : is defined as the VALIDATION: sum total of the • Prospective Validation : arrangements made with Which is conducted prior to the object of ensuring that the commercial