RADYOFARMASÖTİKLERİN KALİTE GÜVENCESİ VE KALİTE KONTROLÜ: GENEL BİR BAKIŞ

Öz

Amaç: Radyofarmasi, radyofarmasötik adı verilen, teşhis ve tedavi amaçlı kullanılan, farmasötik ve radyoaktif özellikleri bir arada taşıyan farmasötik formları inceleyen, geliştiren, kalite kontrollerini yapan, dağıtımı ve uygulaması ile uğraşan özel bir eczacılık alanıdır. Radyofarmasötikleri diğer konvansiyonel ilaçlardan ayıran en önemli fark; radyofarmasötiklerin radyonüklid içermesidir. Radyofarmasötikler insanlara uygulandığı için steril, pirojensiz, izotonik, izohidrik olmalı ve geleneksel ilaç için gerekli tüm kalite kontrol testlerine tabi olmalıdır. Ayrıca içerdikleri radyonüklid nedeniyle ek kalite kontrol testlerinin uygulanması da gereklidir. Bu derlemede radyofarmasötiklere uygulanan kalite kontrol testleri, hastane radyofarmasi laboratuvar tipleri ve İyi Radyofarmasi Uygulamaları (GRP) ele alınacaktır.
Sonuç ve Tartışma: Radyofarmasötikler, farmakopelerin ilgili bölümlerinde belirtilen standartlara uygun olarak hazırlanmalıdır. Her radyofarmasötik serisi için farmakopelerde belirtilen testler ve kayıtlar tutulmalıdır. Radyofarmasötiklerin üretimi ve hazırlanması, steril preparatlar için İyi Üretim Uygulamaları ve radyoaktif ürünler için GRP uyarınca yapılmalıdır. Ancak kalite kontrol testlerini geçen radyofarmasötikler, doz kalibratörlerinde doz ölçümleri yapıldıktan sonra hastalara verilebilir. Böylece hastanın güvenliği ve faydası maksimize edilirken risk minimuma indirilir. Yarı ömrü kısa olan bazı radyofarmasötikler kalite kontrol testleri tamamlanmadan kullanılmaktadır. Bu durumda kalite güvence sisteminin etkinliği ve devamlılığı uygun aralıklarla test edilmelidir. Hastane radyofarmasi laboratuvarları tarafından yapılan işlemlere göre uluslararası standartlar Seviye IA/B, Seviye IIA/B ve Seviye IIIA/B/C olarak belirlenmişitr. Radyofarmasötiklerin kalite güvencesi, GRP kapsamında yeterli sayıda eğitimli personel, kalibre ve kontrolleri yapılmış cihazlar, uygun maddeler ve her aşamada belirlenen testlerin yapıldığı ve sonuçların doğru ve düzenli olarak kayıt altına alındığı bir çalışma düzeni ile sağlanır.

Anahtar Kelimeler

• İyi radyofarmasi uygulamaları
• radyofarmasötikler
• radyofarmasi laboratuvarı
• kalite güvencesi
• kalite kontrol

QUALITY ASSURANCE AND QUALITY CONTROL OF RADIOPHARMACEUTICALS: AN OVERVIEW

Öz

Objective: Radiopharmacy is a special field of pharmacy that examines, develops, conducts quality controls, deals with distribution and application of pharmaceutical forms called radiopharmaceuticals that are used for diagnostic and therapeutic purposes, carrying pharmaceutical and radioactive properties together. Radiopharmaceuticals contain radionuclides. This is the most important difference that distinguishes radiopharmaceuticals from other conventional drugs. Since radiopharmaceuticals are administered to humans, they must be sterile, pyrogen-free, isotonic, isohydric, and subject to all quality control tests required for conventional drug. Also, additional quality control tests are required due to radionuclide they contain. In this review, quality control tests applied to radiopharmaceuticals, hospital radiopharmacy laboratory types and Good Radiopharmacy Practices (GRP) will be discussed.
Result and Discussion: Radiopharmaceuticals should be prepared in accordance with standards specified in relevant sections of pharmacopoeias. For each series of radiopharmaceuticals, tests prescribed in the pharmacopoeias and records must be kept. Production and preparation of radiopharmaceuticals should be carried out in accordance with Good Manufacturing Practices for sterile preparations and GRP for radioactive products. However, radiopharmaceuticals that pass quality control tests can be administered to patients after dose measurements are made in dose calibrators. Thus, the patient's safety and benefit are maximized, while the risk is minimized. Some radiopharmaceuticals with a short half-life are used before quality control tests are completed. In this case, the effectiveness and continuation of the quality assurance system should be tested at appropriate intervals. According to procedures performed by hospital radiopharmacy laboratories, international standards are determined as Level IA/B, Level IIA/B and Level IIIA/B/C. Quality assurance of radiopharmaceuticals is provided by a sufficient number of trained personnel within the scope of GRP, devices that have been calibrated and controlled, appropriate substances and a working order in which tests determined at each stage are made and results are recorded accurately and regularly.

Anahtar Kelimeler

• Good radiopharmacy practices
• radiopharmaceuticals
• radiopharmacy lab
• quality assurance
• quality control

Kaynakça

1. Ekinci, M., İlem-Özdemir, D. (2021). Radyofarmasötikler ve teranostikler. Journal of Literature Pharmacy Sciences, 10(1), 119-132. [CrossRef]
2. 2. Wadsak, W., Mitterhauser, M. (2010). Basics and principles of radiopharmaceuticals for PET/CT. European Journal of Radiology, 73(3), 461-469. [CrossRef]
3. 3. Shukla, J., Vatsa, R., Garg, N., Bhusari, P., Watts, A., Mittal, B.R. (2013). Quality control of positron emission tomography radiopharmaceuticals: An institutional experience. Indian Journal of Nuclear Medicine, 28(4), 200-206. [CrossRef]
4. 4. Guideline on Radiopharmaceuticals, CHMP, EMEA/CHMP/QWP/306970/2007 (draft released for consultation) Web site. (2007). From http://www.emea.europa.eu/pdfs/human/qwp/ 30697007en.pdf. Accessed: 17.01.2022
5. 5. European Pharmacopoeia. (2009). Radiopharmaceutical Preparations, Online 8.5.
6. 6. Saha, G.B. (2018). Nuclear Pharmacy. In: Fundamentals of Nuclear Pharmacy, 3rd ed, (pp. 185-202).
7. 7. Bringhammar, T., Zolle, I. (2007). Quality Assurance of Radiopharmaceuticals. In: Zolle, I. (Ed.), Technetium-99m Pharmaceuticals: Preparation and Quality Control in Nuclear Medicine, (pp. 67-75). Springer-Verlag Berlin Heidelberg.
8. 8. International Atomic Energy Agency Web site (2018). Quality control in the production of radiopharmaceuticals. From https://www-pub.iaea.org/MTCD/Publications/PDF/TE-1856web.pdf Accessed: 17.01.2021

9. 9. Pauwels, E.K.J. (2005). Radioactivity radionuclides radiation. European Journal of Nuclear Medicine and Molecular Imaging, 32, 628. [CrossRef]
10. 10. Kowalsky, R.J., Falen, S.W. (2013). Radiopharmaceuticals in Nuclear Pharmacy and Nuclear Medicine. American Pharmacists Association. APhA, 3rd ed, pp. 875.
11. 11. Skuldt, D.H. (2020). Nuclear Medicine. In: Webster, J.G. (Ed.), Minimally Invasive Medical Technology, 1st ed, (pp. 334). CRC Press.
12. 12. Biersack, H.J., Freeman, L.M., Zuckier, L.S., Grünwald, F. (2007). Clinical Nuclear Medicine. Springer Berlin Heidelberg, pp. 548.
13. 13. Saha, G.B. (2006). Physics and Radiobiology of Nuclear Medicine. 3rd ed, Springer-Verlag New York, pp. 320.
14. 14. Zanzonico, P. (2008). Routine quality control of clinical nuclear medicine instrumentation: A brief review. Journal of Nuclear Medicine, 49(7), 1114-1131. [CrossRef]
15. 15. Zimmerman, B.E., Cessna, J.T. (2000). Experimental determinations of commercial “dose calibrator” settings for nuclides used in nuclear medicine. Applied Radiation and Isotopes, 52(3), 615-619. [CrossRef]
16. 16. He, J., Tang, X., Gong, P., Wang, P., Wen, L., Huang, X., Han, Z., Yan, W., Gao, L. (2018). Rapid radionuclide identification algorithm based on the discrete cosine transform and BP neural network. Annals of Nuclear Energy, 112, 1-8. [CrossRef]
17. 17. Neacsu, B., Cimpeanu, C., Barna, C. (2013). Radionuclidic purity - An essential parameter in quality control of radiopharmaceuticals. Romanian Reports in Physics, 65(1), 155-167.
18. 18. L’Annunziata, M. (2003). Handbook of Radioactivity Analysis. 2nd ed, Academic Press, pp. 1326.
19. 19. Dash, A., Knapp, F.F., Pillai, M.R.A. (2013). 99Mo/99mTc separation: An assessment of technology options. Nuclear Medicine and Biology, 40(2), 167-176. [CrossRef]
20. 20. Molavipordanjani, S., Tolmachev, V., Hosseinimehr, S.J. (2019). Basic and practical concepts of radiopharmaceutical purification methods. Drug Discovery Today, 24(1), 315-324. [CrossRef]
21. 21. Vallabhajosula, S., Killeen, R.P., Osborne, J.R. (2010). Altered biodistribution of radiopharmaceuticals: Role of radiochemical/pharmaceutical purity, physiological, and pharmacologic factors. Seminars in Nuclear Medicine, 40(4), 220-241. [CrossRef]
22. 22. Hage, D.S. (2018). Chromatography. In: Rifai, N., Horvath, A.R., Wittwer, C.T., Hoofnagle, A. (eds), Principles and Applications of Clinical Mass Spectrometry: Small Molecules, Peptides, and Pathogens, (pp. 1-32), Elsevier Inc.
23. 23. Sherma, J. (2009). Thin layer radiochromatography. In: Cazes, J. (ed), Encyclopedia of Chromatography, 3rd ed, CRC Press.
24. 24. Kagan, I.A., Flythe, M.D. (2014). Thin-Layer Chromatographic (TLC) separations and bioassays of plant extracts to identify antimicrobial compounds. Journal of Visualized Experiments, 85, 51411. [CrossRef]
25. 25. Ullah, H., Ahmad, I., Rauf Khattak, M., Shah, S., Ahmad, S., Khan, K., Ahmad, S.Z. (2019). Evaluation of radiochemical purities of routinely used radiopharmaceuticals: Three years’ experience of a single institute. Iranian Journal of Nuclear Medicine, 27(1), 19-25. [CrossRef]
26. 26. Taşçı, C., Ülker, Ö., Ertay, T., Taner, M.S., Soylu, A., Berk, F., Erdoğan, S., Yürekli, Y., Aday, S., Ünak, P. (2003). Radyofarmasötikler için kalite kontrol yöntemleri kılavuzu. Turkish Journal of Nuclear Medicine, 12, 137-148.
27. 27. Wernick, M.N., Aarsvold, J.N. (2004). Emission Tomography: The Fundamentals of PET and SPECT. Elsevier Academic Press, pp. 576.
28. 28. Sandle, T. (2013). Sterility, sterilisation and sterility assurance for pharmaceuticals. Woodhead Publishing Series in Biomedicine. Woodhead Publishing, 1st ed, pp. 362.
29. 29. Blechová, R., Pivodová, D. (2001). Limulus amoebocyte lysate (LAL) test - an alternative method for detection of bacterial endotoxins. Acta Veterinaria Brno, 70(3), 291-296. [CrossRef]
30. 30. Putra, A.R., Lestari, E., Kurniasih, D., Karyadi, K., Sarmini, E., Aries, A. (2019). Applicability of bacterial endotoxin test (BET) for some radiopharmaceutical sterile kits by the use of tachypleus amebocyte lysate (TAL). Journal of Pharmaceutical Sciences and Community, 16(1), 20-28. [CrossRef]
31. 31. Mattsson, S., Johansson, L., Leide Svegborn, S., Liniecki, J., Noßke, D., Riklund, K. Å., Stabin, M., Taylor, D., Bolch, W., Carlsson, S., Eckerman, K., Giussani, A., Söderberg, L., Valind, S., ICRP (2015). Radiation dose to patients from radiopharmaceuticals: a compendium of current information related to frequently used substances. Annals of the ICRP, 44(2 Suppl), 7-321. [CrossRef]
32. 32. Janković, D., Maksin, T., Djokić, D., Milonjić, S., Nikolić, N., Mirković, M., Vranjes-Djurić, S. (2008). Particle size analysis: 90Y and 99mTc-labelled colloids. Journal of Microscopy, 232(3), 601-604. [CrossRef]
33. 33. Persico, M.G., Lodola, L., Buroni, F.E., Morandotti, M., Pallavicini, P., Aprile, C. (2015). 99mTc-human serum albumin nanocolloids: particle sizing and radioactivity distribution. Journal of Labelled Compounds and Radiopharmaceuticals, 58(9), 376-382. [CrossRef]
34. 34. Chourasia, M.K., Ashawat, M.S., Jain, N., Chalasani, K.B., Jain, R.K., Jain, A.K., Sabitha, M., Jain, S.K. (2003). Radiopharmaceuticals: Preparation, evaluation and applications. Indian Journal of Pharmaceutical Sciences, 65(5), 439-449.
35. 35. International Atomic Energy Agency Web site. (2010). Competency based hospital radiopharmacy Training. Training Course Series No. 39. Vienna. From https://www-pub.iaea.org/MTCD/Publications/PDF/TCS-39_web.pdf. Accessed: 27.01.2021
36. 36. Ertay, T., Yürekli, Y. (2017). Radyofarmasötiklerin kalite kontrolü. In: Ünak, P., Durmuş Altun, G., Teksöz, S., Biber Müftüler, Z. (eds), Uygulamalı Temel Radyofarmasi, (pp. 117-130). İstanbul: Nobel Tıp Kitabevleri.
37. 37. International Atomic Energy Agency Web site. (2008). Operational guidance on hospital radiopharmacy: A safe and effective approach. Vienna, pp. 1-90. From https://www-pub.iaea.org/MTCD/publications/PDF/Pub1342/Pub1342_web.pdf. Accessed: 23.01.2022
38. 38. Duatti, A., Bhonsle, U. (2013). Strengthening radiopharmacy practice in IAEA member states. Seminars in Nuclear Medicine, 43(3), 188-194. [CrossRef]
39. 39. European Association of Nuclear Medicine Web site. (2010). Guidance on current good radiopharmacy practice (cGRPP) for the small-scale preparation of radiopharmaceuticals. EANM Radiopharmacy Committee, pp. 1–14. From https://eanm.org/publications/guidelines/5_EJNMMI_Guidance_cGRPPfulltext_05_2010.pdf. Accessed: 16.01.2021
40. 40. Norenberg, J.P., Petry, N.A., Schwarz, S. (2010). Operation of a radiopharmacy for a clinical trial. Seminars in Nuclear Medicine, 40(5), 347-356. [CrossRef]
41. 41. Grecco, C.H.S., Vidal, M.C.R., Cosenza, C.A.N., Santos, I.J.A.L., Carvalho, P.V.R. (2012). New approach for safety management in radiopharmaceutical production facilities. Latin American Journal of Pharmacy, 31(8), 1199-1202.
42. 42. de Blois, E., de Zanger, R.M.S., Chan, H.S., Konijnenberg, M., Breeman, W.A.P. (2019). Radiochemical and analytical aspects of inter-institutional quality control measurements on radiopharmaceuticals. EJNMMI Radiopharmacy and Chemistry, 4(3), 1-13. [CrossRef]
43. 43. Taş, A., Özer, A.Y. (2020). Waste disposal and management in radiopharmaceuticals. FABAD Journal of Pharmaceutical Sciences, 45(1), 91-103.