Post-Market in vitro bioequivalence study of innovator and generic Gefitinib tablets: evaluation of JKN medicine quality

  • Fitri Nurhayati Pharmacy Doctoral Program, Faculty of Pharmacy, Universitas Pancasila, Jakarta, 12640, Indonesia.
  • Yusi Anggriani Center for Pharmaceutical Policy, Management, and Services Studies (CEPHAS), Faculty of Pharmacy, Universitas Pancasila, Jakarta, 12640, Indonesia
  • Elisna Syahruddin Division of Thoracic Oncology Department of Pulmonology Respiratory Medicine Faculty of Medicine, Universitas Indonesia Persahabatan National Respiratory Referral Hospital, Jakarta, 13230, Indonesia
  • Rizka Andalucia Directorate of Pharmaceutical Management and Service, Indonesian Ministry of Health, Jakarta, 12950, Indonesia
  • Jarir Ath-Thobari Faculty of Pharmacy, University of Gajah Mada, Yogyakarta, 55281, Indonesia
  • Esti Mulatsari Pharmacy Undergraduate Program, Faculty of Pharmacy, Universitas Pancasila, Jakarta, 12640, Indonesia
DOI: https://doi.org/10.35814/jifi.v22i1.1593

Abstract

Gefitinib is one of Tyrosine Kinase Inhibitors (TKIs), as first line therapy for Non-Small Cell Lung Cancer (NSCLC) with positive EGFR mutation. Gefitinib started to be accommodated in Jaminan Kesehatan Nasional (JKN) insurance in 2015 with the innovator gefitinib and was replaced by a generic product in middle of 2021. This research was conducted to see whether the quality of generic gefitinib equivalent to the innovator through post-market in vitro bioequivalence test. Assay method refers to previous research by Sandhya et al 2013 wih High Performance Liquid Chromatography (HPLC), while the dissolution test method is in accordance with the Food and Drug Association (FDA) 2010. We collected innovator from the official distributor and 3 batches (all batches that have been used in JKN program) of generic product from hospitals where lung cancer therapy services were provided. We evaluated the dissolution profile with similarity and unsimilarity factors and assess based on standard specification of dissolution profile that informed in innovator’s BPOM-approved brochure (avarage of 6 samples > 85% and no individual result < 75% at 45 minutes). The assay results met the requirements of ± 5% of what is stated on the label. Although dissolution profile of generic and innovator were not equal through difference and similarity factors calculation, but one batch of generics met dissolution profile standard of innovator. So, both generic and innovator drug met the standards of assay and dissolution, even though the dissolution profile were not equivalent.

References

[1]. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May 4;71(3):209–49. http://doi.org/10.3322/caac.21660

[2]. Syahruddin E, Wulandari L, Sri Muktiati N, Rima A, Soeroso N, Ermayanti S, et al. Uncommon EGFR mutations in cytological specimens of 1,874 newly diagnosed Indonesian lung cancer patients. Lung Cancer: Targets and Therapy. 2018 Mar;Volume 9:25–34. http://doi.org/10.3322/10.2147/LCTT.S154116

[3]. Arora A, Scholar EM. Role of Tyrosine Kinase Inhibitors in Cancer Therapy. Journal of Pharmacology and Experimental Therapeutics. 2005 Dec;315(3):971–9. http://doi.org/10.1124/jpet.105.084145

[4]. Ettinger DS, Wood DE, Aisner DL, Akerley W, Bauman JR, Bharat A, et al. Non–Small Cell Lung Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology. Journal of the National Comprehensive Cancer Network. 2022 May;20(5):497–530. http://doi.org/10.6004/jnccn.2022.0025

[5]. Fitri N, Yusi A, Elisna S, Hesty Utami R, Tri K. Cost-effectiveness analysis of tyrosine kinase inhibitors (erlotinib vs. gefitinib vs. afatinib) in non-small-cell lung cancer. J Appl Pharm Sci. 2021 Apr 5; http://doi.org/10.7324/JAPS.2021.110411

[6]. Menteri Kesehatan Republik Indonesia. Keputusan Menteri Kesehatan Republik Indonesia Nomor HK.02.02/MENKES/523/2015 . 2015.

[7]. Sarnianto P, Firdaus F, Farahiyah R, Aji Punto Baskoro M, Aulia Rizkita E. Kualitas dan Potensi Beberapa Kaplet/Tablet/Kapsul Antibiotik Pemenang e-Katalog 2017, Obat Sejenis Pengganti dan Originatornya (The Quality and Potency of Several Antibiotic Caplets/ Tablets/Capsules of e-Catalogue 2017, Their Substitutes and Originators). JURNAL ILMU KEFARMASIAN INDONESIA. 2022;20(1):128–35.

[8]. BPOM RI. Peraturan Kepala Badan Pengawas Obat dan Makanan Nomor 28 Tahun 2017. 2017;

[9]. Sandhya V, Varasala SM, Mangamma K. ANALYTICAL METHOD DEVELOPMENT AND VALIDATION FOR THE ESTIMATION OF GEFITINIB BY RP-HPLC METHOD IN TABLET DOSAGE FORM. Int J Pharm Biol Sci [Internet]. :2230–7605. Available from: www.ijpbs.comorwww.ijpbsonline.com

[10]. European Medicines Agency. Gefitinib Mylan Assessment Report [Internet]. 2018. Available from: www.ema.europa.eu/contact

[11]. BPOM RI. Peraturan Badan Pengawas Obat dan Makanan No 11 Tahun 2022 Tentang Tatalaksana Uji Bioekuivalensi. 2022.

[12]. Alshehri S, Alanazi A, Elzayat EM, Altamimi MA, Imam SS, Hussain A, et al. Formulation, In Vitro and In Vivo Evaluation of Gefitinib Solid Dispersions Prepared Using Different Techniques. Processes. 2021 Jul 14;9(7):1210. http://doi.org/10.3390/pr9071210

[13]. Colgan S, Faasse K, Martin LR, Stephens MH, Grey A, Petrie KJ. Perceptions of generic medication in the general population, doctors and pharmacists: a systematic review. Available from: http://bmjopen.bmj.com/

[14]. Siahaan SAS, Usia T, Pujiati S, Tarigan IU, Murhandini S, Isfandari S, et al. Pengetahuan, Sikap, dan Perilaku Masyarakat dalam Memilih Obat yang Aman di Tiga Provinsi di Indonesia. Jurnal Kefarmasian Indonesia. 2017 Aug 28;7(2).

[15]. European Medicines Agency. ICH Topic Q2 (R1) Validation of Analytical Procedures: Text and Methodology. 1995.

[16]. Departemen Kesehatan Republik Indonesia. Farmakope Indonesia Edisi IV. 1994.

[17]. U.S. Department of Health and Human Services Food and Drug Administration. Guidance for Industry: Dissolution testing of Immediate Release Solid Oral Dossage Form. 1997.

[18]. Badan Pengawas Obat dan Makanan. Iressa 250 mg Tablet Assesment Report [Internet]. 2018 [cited 2024 Apr 8]. Available from: https://registrasiobat.pom.go.id/files/assesment-reports/obat_baru/Iressa%20Tablet%20salut%20selaput%20250%20mg_Gefitinib_DKI1235300217A1_2020.pdf.

[19]. Ngwuluka NC, Olorunfemi PO, Ochekpe NA. Post-market in vitro bioequivalence study of six brands of ciprofloxacin tablets/caplets in Jos, Nigeria [Internet]. 2009. Available from: http://www.academicjournals.org/SRE

[20]. Dasari T, Kala SLJ, Nadendla RR. In process quality control tests of solid dosage forms: a comprehensive review. Scholars Academic Journal of Pharmacy. 2017;

[21]. Badan Pengawas Obat dan Makanan. Buku Pedoman Uji Disolusi dan Tanya Jawab. 2014 [cited 2024 Apr 26]. Available from: https://standarobat.pom.go.id/storage/book/Buku_Pedoman_Uji_Disolusi_dan_Tanya_Jawab.pdf

[22]. Hasnida A, Kok MO, Pisani E. Challenges in maintaining medicine quality while aiming for universal health coverage: a qualitative analysis from Indonesia. BMJ Glob Health. 2021 May 28;6(Suppl 3):e003663. http://doi.org/10.1136/bmjgh-2020-003663

[23]. Aini N, Saraswati RD, Octoberia IS. Profil Disolusi Terbanding, Penetapan Kadar, Dan Kualitas Fisik Tablet Atorvastatin Inovator, Generik Bernama Dagang, Dan Generik. Indonesian Pharmaceutical Journal. 2015;5(2):90–7.

[24]. Putri RA. Uji Disolusi, Uji Difusi (in–vitro) dan Penetapan Kadar Tablet Ranitidin Generik dan Generik Bermerek. [Jakarta]: Universitas Islam Negeri Syarif Hidayatullah Jakarta; 2016.

[25]. KS NS, K GP, Verma R, Ananthakrishna P, Kumar L. Validation of HPLC Method for Quantitative Determination of Gefitinib in Polymeric Nanoformulation. Pharm Chem J. 2017 May 17;51(2):159–63. https://doi.org/10.1007/s11094-017-1575-6

[26]. Chow S. Bioavailability and bioequivalence in drug development. WIREs Computational Statistics. 2014 Jul 10;6(4):304–12. https://doi.org/10.1002/wics.1310
Published
2024-04-30
How to Cite
NURHAYATI, Fitri et al. Post-Market in vitro bioequivalence study of innovator and generic Gefitinib tablets: evaluation of JKN medicine quality. JURNAL ILMU KEFARMASIAN INDONESIA, [S.l.], v. 22, n. 1, p. 137-146, apr. 2024. ISSN 2614-6495. Available at: <http://jifi.farmasi.univpancasila.ac.id/index.php/jifi/article/view/1593>. Date accessed: 21 dec. 2024. doi: https://doi.org/10.35814/jifi.v22i1.1593.
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Vol 22 No 1 (2024): JIFI
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