Institute of Nuclear Science and Technology
Radioisotope Production Division (RIPD)Phone: 880-2-7789816, Fax: 880-2-7789337
- Production & quality control of radioisotopes and radiopharmaceuticals
- Research & development in the field of new radioisotopes and radiopharmaceuticals
- Tc-99m Production
Instant 99mTc Production
- RIPD started producing instant 99mTc by irradiating natural MoO3 in the research reactor in 1987. A plant for production of instant 99mTc by solvent extraction was installed at RIPD by the former GDR under the Technical Cooperation Project of the IAEA. In this system the relative differences in the distribution coefficients of pertechnetate and molybdate for methyl ethyl ketone (MEK) was used as the basis of separation in the solvent extraction generator. Pertechnetate is preferentially extracted into MEK from alkaline molybdate solution. Produced 99mTc was routinely used in three nuclear medical centers located in Dhaka until 1997. Instant Tc-99m was not suitable for sending to hospitals remote from Dhaka due to its short half life.
- 99Mo/99mTc-Generator Production
- In order to get rid off the problem of sending instant 99mTc to remote nuclear medicine centers of the country, a plant for production of column chromatographic 99mTc-generator was installed at RIPD through an IAEA Technical Project with the technological assistance from BRIT, India. RIPD produced four generators (15 GBq each) per batch fortnightly since 1998 and 105 batches of 99mTc-generator had been produced in this plant and supplied to the four nuclear medicine centers of the country. The user’s responses regarding the performances of these generators and quality of TcO4 - obtained from these generators were quite satisfactory.
- This 99mTc-generator plant is capable of producing only four generators per batch but the country’s weekly demand is 17 generators. In order to meet the country’s entire demand, a new plant has been installed at RIPD on May 2005 which was going for routine operation from October 2005. This plant has been designed and installed in a collaboration with the German company Hans Waelischmiller GmbH and RIPD with the financial assistance from the IAEA.
- A computer controlled on-line sterile filtration and loading system for production of 99mTc-generator has been developed and used in this plant. This plant is capable of producing 50 generators (15GBq) per batch and this generator production facility complies with the cGMP for radiopharmaceuticals.
- A special type of filter is used for the on-line filtration. This filter is a combination of hydrophilic and hydrophobic membranes which allows passage of both aqueous solution and air. The same type of filtration unit is used in the generator assembly for terminal filtration.
- The main obstacle in development of the on-line loading system was the existence of the air filter at one of the inlet needles of the generator hardware. This difficulty has been overcome by the introduction of a pneumatically controlled glass column adopter. First, the loading solution is transferred to the adaptor and then the adopter is pneumatically connected to the on-line system.
- This new plant consists of two hot cells. One is used for chemical processing and dispensing of 99Mo solution and the other hot cell is used for sterile filtration and generator loading. Usually radioisotope hot cells are maintained under negative pressure to protect the release of any radionuclide during operation, but for aseptic loading of the generator positive pressure is required. To overcome this difficulty, a laminar flow module is installed above the loading area of the hot cell which provides class 100 clean environments during loading process and the overall pressure of the hot cell is maintained negative.
- This chromatographic 99mTc-generator production is based on fission produced 99Mo. The main features of this generator are: (1) cold generator assembling (2) dry-column generator (3) terminal filtration (4) small elution volume (minimum volume for full elution is 3 ml) (5) elution volume can be selected by volume controller (6) adequate radiation protection for the users (7) sterile and non-pyrogenic 99mTc eluate (8) re-useable generator hardware etc.
- The generators produced at RIPD are comparable with the best quality generators available in the world market. This facility enables Bangladesh to produce high quality 99mTc-generator locally.
- 131I Production
- A plant for production of 131I has been installed at RIPD in 1987. I-131 is produced by irradiatingTeO2 target in the 3MW TRIGA Mark-II Research Reactor. Te-130 (natural abundance 33.4%) captures neutron to produce 131Te, which transforms into 131I by beta emission.
- TeO2 in a finely crystalline form sealed in quartz ampoule is irradiated in the reactor and after two days of cooling it is heated at about 730oC. Iodine -131 is released and transferred by air stream into a trap filled with Na2CO3/NaHCO3 buffer or 10 mM NaOH solution. More than 99% of the iodine is absorbed as sodium iodide at pH 7 to 9. This plant has the capacity of processing 370 GBq of 131I per batch.
- RIPD produces 131I every week and the quality of the I-131 (radiochemical purity, radionuclidic purity, pH range etc.) was found within permissible limit. The produced isotope is supplied to the nuclear medicine centers for diagnostic and therapeutic applications. The users responses are satisfactory.
- 131I Capsule production
- 1.85, 2.78 and 3.70 GBq of 131I capsules are used for thyroid ablation therapy and 37-74 MBq of 131I capsules are used for diagnosis in the nuclear medicine centers. Present demand of 131I therapeutic capsules in the country is about 56 GBq/week.
- In order to produce 131I capsules locally, a plant has been installed at RIPD in 2001. The facility can be used for the production of both diagnostic and therapeutic capsules. Inert filling material of the capsules is mixture of dry Na2HPO4, ascorbic acid and Na2S2O3 powder in 10:1:1 ratio.
- Kit Production
- RIPD is going to establish a facility for the production of Tc-99m in-vivo kits, which are the essential precursors of Tc-99m radiopharmaceuticals. The local production of cold kit would help to cut import. The facility will be established under the ADP project of the government. A supporting IAEA TC project has been also under taken in this regards.
- Quality Assurance (QA) and Good Manufacturing Practices (GMP) at RIPD
- The practice of radiopharmacy is a part of the broader practice of nuclear medical diagnosis, which itself may be treated as a quality system. The aspect that is designed to ensure that radiopharmaceuticals are safely and reproducibly prepared and handled in hospitals to a standard appropriate to their intended use
- The quality of radiopharmaceuticals may affect not only the safety of the patient but also the outcome of the diagnostic or therapeutic procedure. QA is the responsibility of the organization to determine that systems, facilities and written procedures are both adequate and followed in order to assure that products will meet, in the final dosage form all the applicable specifications. QA becomes an overseeing function, often auditing operations to determine the procedures and systems are suitable and if not, to recommend the required changes. GMP is that part of quality assurance which ensures that products are consistently produced and controlled to the quality standards appropriate to the intended use.
- RIPD has written QA program which includes information pertaining to organizational structure, personnel, premises, processing/formulation, quality control testing etc. This QA program complies with the “Guide lines for good manufacturing practices of radiopharmaceuticals2” and “Quality Assurance (QA) Manual for Radiopharmaceuticals3” published under the East Asia and Pacific Regional Technical Co-operation Project (RAS/2/009) of the IAEA.
- Research and Development of PZC based Tc-99m Generator.
- Research on the Development of new Diagnostic and Therapeutic Radiopharmaceuticals.
- RIPD substituted import of Tc-99m generators and I-131 solution by local production.
- Completed the three IAEA Technical Cooperation Project and one IAEA Technical Cooperation Project is ongoing.
- BGD/4/006 Starting date: 1986; Completion date: 1988
- BGD/4/014 Starting date: 1991; Completion date: 1996
- BGD/2/010 Starting date: 2003; Completion date: 2005
- BGD/2/011 Starting date: 2006 (ongoing)
- A new Tc-99m generator production plant has been installed at RIPD in 2005. A computer controlled on-line production system has been developed in this facility in a joint venture among RIPD, the IAEA and HWM, Germany. This facility has a production capacity of 50 generators per batch and complies with the cGMP for radiopharmaceuticals. This plant is now used for weekly production of Tc-99m generators.
I-131 production line has been renovated under another ADP project of the government. Two processing units have been installed in the same production hot cell for alternate use. This line is in use for weekly production of I-131 solution
- Facility for the Production of Tc-99m Generator (old)
- Facility for the Online Production of Tc-99m Generator (new)
- Facility for the Production of Iodine-131 Solution
- Facility for the Production of Iodine-131 Capsules
- Facility for the Production of Hippuran
- Facility for Animal Testing
- HVAC (Humidity, ventilation and air cooling) facility
- QC laboratory (well equipped)
- Production of Lu-177 Radiopharmaceuticals for therapeutic use.
- Production of PET Radiopharmaceuticals for diagnostic use.
- Upgrading the Radioisotope Production facility.
- Indexed journals
- M. Anwar Hossain, Renata Mikolajczak and M. Z. Abedin, Evaluation of quality control tests for Sodium Pertechnetate (99mTc) injection in reference to European & United States Pharmacopoeia, Bangladesh Journal of Nuclear Medicine, Vol. 10, No.1, p 74-76, 2007..
- Md. Mustafizur Rahman, “Arsenic Contamination in Environmental Water and Ground Water in Bangladesh and Its Removal from these Waters for Getting Safe Drinking Water”, The Rotary-No-Tomo (In Japanese), Vol. 54, No. 1, PP. 12-14, January, 2006.
- Md. Mustafizur Rahman, Yasushi Seike and Minoru Okumura, “Concentrations of Arsenic in Brackish Lake Water: Application of Tristimulus Colorimetric Determination”, Analytical Sciences, Vol. 22, No. 3, PP. 475-478, March, 2006.
- Md. Mustafizur Rahman, Kaoru Fujinaga, Yasushi Seike and Minoru Okumura, “A Simple in situ Visual and Tristimulus Colorimetric Method for the Determination of Trace Arsenic in Environmental Water after Its Collection on a Mercury(II)-Impregnated Paper”, Analytical Sciences, Vol. 20, No.1, PP. 165-170, January, 2004.
- M. Zainul Abedin, M. Azizul Haque, Mahbubul Haque, M. Ramzan Ali and Anwar Hossain, Md. Abdur Razzaque and M Abul Hashem Bhuiyan, Manufacture of 4KT lead pot from recyclled lead containers for thetrapy dose I-131 supply, AERE Technical Report, 2004-2005.
- M. Zainul Abedin, M. Azizul Haque, M. Ramzan Ali, Anwar Hossain, Momtaz F. Waheed and Rabeya Akhter, Tc-99m Generator Production at RIPD during 2005, AERE Technical Report, 2004-2005 .
- M. Z. Abedin, M. A. Haque, M. R. Ali, A. Hossain, R. Akhter and R. Mondal, Installation, Commissioning & Testing of new Tc-99m generator production plant at RIPD, AERE Technical Report, 2004-2005.
- M. Zainul Abedin, M. Azizul Haque, M. Anwar Hossain, Momtaz F. Waheed, Rabeya Akhter and M. Abdur Razzaque, Uninterrupted Prduction and Supply of I-131 in the year 2005, AERE Technical Report, 2004-2005.
- M. Z. Abedin, M. A. Haque, M. F. Waheed and R. Akhter and M. A. Hossain Installation of 2nd Furnace and Radioisotope I-131 Production at RIPD during 2004, AERE Technical Report, 2004-2005.
- M. Zainul Abedin, M. Azizul Haque, M. Ramzan Ali, Anwar Hossain, M. F. Waheed and Rabeya Akhter, Production of chromatographic Tc-99m Generators in RIPD during the year 2004, AERE Technical Report, 2004-2005 (in Print).
- M. Z. Abedin, Kanai Lal Chakraborti, and Lyzu Yasmin, Determination of Antimony in Tc-99m Generator shielding, AERE Technical Report, 2003.
- M. Z. Abedin, Kanai Lal Chakraborti, Azizul Haque, Anwar Hossain and Lyzu Yasmin, Production of I-131 And Its Quality Control, AERE Technical Report, 2003.
- M. Z. Abedin, H. Rahman Miah, Azizul Haque, M. Ramzan Ali and Anwar Hossain, Production of chromatographic Tc-99m Generators in RIPD, AERE Technical Report, 2003
- Conference papers
- M.Anwar Hossain, Momtaz F. Waheed, Abdur Razzaque, Lyzu Yasmin, Rabeya Akhter, Md. Mustafizur Rahman, M.Ramjan Ali, M.Azizul Haque and M.Zainul Abedin, New Tc-Generator Production Facility in Bangladesh: Adherence to QA and GMP for Radiopharmaceuticals, Abstract published in the proceedings 12thnational conference of Soc. of Nuclear Medicine, Bangladesh, 30 March, 2007.
- Momtaz F. Waheed, M.Anwar Hossain, Abdur Razzaque, Lyzu Yasmin, Rabeya Akhter, Md. Mustafizur Rahman, M.Ramjan Ali, M.Azizul Haque and M.Zainul Abedin, Utilization of 3MW TRIGA Mark-II Research Reactor for Radioiodine Production in Bangladesh, Abstract published in the proceedings 12thnational conference of Soc. of Nuclear Medicine, Bangladesh, 30 March, 2007
- M.A. Hossain, M.A. Haque, M.A. Razzaque, Rabeya A., M.F. Waheed, M.Z. Abedin. “Dry distillation of 131I during phase transition of irradiated natural TeO2”, Abstract published on the Bangladesh J. of Nucl Med,Vol 9.No 1, p 73 27-28 January, 2006.
- M. Z. Abedin and M.A. Haque: Trends in indigenous radioisotope and radiopharmaceutical production in Bangladesh. Accepted for presentation in the International Symposium on Trends in radiopharmaceuticals (ISTR-2005). Vienna, Austria, 14-18 Nov., 2005.
- M. Z. Abedin, M.A. Haque, R.U. Mondal and W.G. Wagner: Development of on-line system for production of 99Mo/99mTc-generator. Presented at the 3rdAnnual Conference of the Association of Nuclear Medicine Physicians of India in collaboration with Society of Nuclear Medicine (I) Northern Chapter, Srinagar, Kashmir (India), 30thSept. – 2ndOct., 2005.
- A Haque and M.A. Haque: Irradiation of targets for production of target in the TRIGA reactor facility in Bangladesh: Presented in the IAEA/RCA Meeting on Target Irradiation for Production of Isotopes. Jakarta, Indonesia, Sept. 05-09, 2005.
- M.A. Haque: Safety training of employees at RI facility in Bangladesh. Presented at the International Seminar on Operation and Maintenance of Nuclear Facilities Courses, Takai, Japan, Sept. 26 to Oct. 07, 2005.
- M.A. Haque: Operation and maintenance and safety aspects of RI facility in Bangladesh. Presented at the International Seminar on Operation and Maintenance of Nuclear Facilities Courses, Takai, Japan, Sept. 26 to Oct. 07, 2005.
- L. Yasmin, M. Azizul Haque, M. Z. Abedin and M.K. Pramanik, Quantification of Bacterial Endotoxin in Na99mTcO4samples eluted from RIPD-99mTc Generators, 9thNational Conference of Bangladesh Society of Nuclear Medicine, 9thJanuar, 2004, Dhaka, Bangladesh (Printed in the Conference proceedings).
- M. Azizul Haque, M. A. Hossain, L. Yasmin, Momtaz F. Waheed, R. Akhter and M. Z. Abedin, Installation of new I-131 production System & its performance, 9thNational Conference of Bangladesh Society of Nuclear Medicine, 9th January, 2004, Dhaka, Bangladesh (Printed in the Conference proceedings).
- Azizul Haque, M. Ramzan Ali, M.Z. Abedin, Mahbubul Haque, M.H. Rahman Miah and A.O.M. Abdul Ahad, Design and Development of new Hardware for Column Chromatographic 99mTc-Generators, 9th National Conference of Bangladesh Society of Nuclear Medicine, 9th January, 2004, Dhaka, Bangladesh (Printed in the Conference proceedings).
- M. Zainul Abedin, M.A. Haque, H.R.Miah, Anwar Hossain, Lyzu Yasmin, M.A. Razzaque and K.L. Chakrabarti, Some Experiences on Chromatographic Tc-99m Generator Production, International Conference on Current Trends in Radiopharmaceuticals, October 21-23,2003, PINSTECH and NORI, Islamabad, Pakistan, (Printed in the Conference proceedings).
- M. Zainul Abedin, Ms. Lyzu Yasmin H. Rahman, Anwar Hossain, K.L. Chakrabarti, Quality Assurance of RIPD Tc-99m Generators, 2nd AGM of ARCCNM and 8thNational Conference of SNMB, 6-8 February, Dhaka, Bangladesh, Abstract printed in Bangladesh Journal of Nuclear Medicine, Vol. 6, No.1, p. 72, 2003.