COMPLEX GENERICS AS A TREND OF MODERN PHARMACEUTICAL DEVELOPMENT
DOI:
https://doi.org/10.22159/ijap.2024v16i3.49937Keywords:
Complex generics, Non-biological generic drugs, Innovative dosage forms, Nanodrugs, Pharmaceutical development, Dosage forms, StandardizationAbstract
In the perspective of the pharmaceutical industry development, manufacturers expand their product portfolios by updating generic drugs. Complex Generics (CG) or Nonbiological Generic Drugs (NBGD) contain known pharmaceutical substances are out of patent protection and are made by using new technologies, excipients, nanocarriers, dosage form modernization, etc. These drugs are developed in the patients’ interests to improve their life quality and increase drugs’ efficacy and safety.
The article discusses the categories and characteristics of CG, shows examples available on the pharmaceutical market, API and dosage forms. This article discusses approaches to quality control that pose challenges for developers and regulators. The fundamental importance of the innovative drugs manufacturing process and the ingredients standardization in the dosage forms formulations to create the standard product are indicated. First, a comprehensive control of polymers is required as an important tool to make the necessary pharmacokinetics. The influence degree on the API release and the effectiveness of dosage form (DF) depends on the polymer’s physicochemical characteristics. In this regard, it is important to create databases of these excipients accessible to developers containing information about properties, use, dosages and safety.
In view of the complexity structure and manufacturing processes of the NBGD and insufficiency of pharmacopeial requirements for standard approaches for resolving issues of comparability and bioequivalence the current regulatory documents should be expanded and revise for a correct quality assessment. There is a need to create new scientific and regulatory roadmaps for the development and approval of complex generic drugs.
Downloads
References
Rathi H, Biyani M. Knowledge, attitude, and perception of Indian population about generic versus branded medicines: a web-based study. Asian J Pharm Clin Res. 2021;14:95-8. doi: 10.22159/ajpcr.2021.v14i2.40088.
Gao. Highlights of GAO-18-80, a report to congressional requesters. Generic drugs. FDA should make public its plans to issue and revise guidance on nonbiological complex drugs; 2017. Available from: quality by design (QbD ). [Last accessed on 04 May 2023]
Barei F. The generic pharmaceutical industry: moving beyond incremental innovation towards re-innovation. GaBI J. 2013;2(1):13-9. doi: 10.5639/gabij.2013.0201.011.
Donnelly M, Tsakalozou E, Sharan S, Straubinger T, Bies R, Zhao L. Review of complex generic drugs delivered through the female reproductive tract: the current competitive landscape and emerging role of physiologically based pharmacokinetic modeling to support development and regulatory decisions. J Clin Pharmacol. 2020;60Suppl 2:S26-33. doi: 10.1002/jcph.1760, PMID 33274513.
Generic drugs market–global industry analysis, market size, share, growth, trends, region outlook, and segment forecasts; 2021-2030. Available from: https://www.precedenceresearch.com/generic-drugs-market. [Last accessed on 04 May 2023]
Drugs going generic in the next 5 y; 2018-2022. Available from: https://www.goodrx.com/healthcare-access/medication-education/drugs-going-generic-2018-2019-2020-2021-2022. [Last accessed on 04 Nov 2023]
Higgins Dunn N. The top 15 blockbuster patent expirations coming this decade; 2021. Available from: https://www.fiercepharma.com/special-report/top-15-blockbuster-patent-expirations-coming-decade. [Last accessed on 04 May 2023]
Charles SA. Supergenerics: a better alternative for biogenerics. Drug Discov Today. 2005;10(8):533-5. doi: 10.1016/S1359-6446(05)03410-0, PMID 15837591.
Product-specific guidances for generic drug development. Available from: https://www.fda.gov/drugs/guidances-drugs/upcoming-product-specific-guidances-complex-generic-drug-product-development. [Last accessed on 04 May 2023]
Curriculum materials for health care degree programs. Biosimilars. Available from: https://www.fda.gov/drugs/biosimilars/curriculum-materials-health-care-degree-programs-biosimilars#level1.
Saraf GJ, Burade KKB, Gonjari ID, Hosmani AH, Pawar AA. A review on advances in pharmaceutical co-crystal preparation routes, intellectual property perspective and regulatory aspects. Int J Curr Pharm Sci. 2022;14(5):4-12. doi: 10.22159/Ijcpr.2022v14i5.2038.
Desnita R, Noviana E, Zai K, Saifullah Sulaiman TN. An up-to-date review: microspheres as a new drug delivery system. Int J App Pharm. 2023;15(6):82-9. doi: 10.22159/ijap.2023v15i6.49120.
EMA. QRD general principles regarding the SmPC information for a generic/hybrid/biosimilar product. Energy Market Authority of Singapore/627621/2011 rev.1,18 June 2018. Human Medicines Evaluation Division. Available from: https://www.ema.europa.eu/en/documents/regulatory-procedural-guideline/quality-review-documents-general-principles-regarding-summary-product-characteristics-information-generic-hybrid-biosimilar-product_en.pdf. [Last accessed on 24 May 2023]
Generic and hybrid medicines. Available from: https://www.ema.europa.eu/en/human-regulatory/marketing-authorisation/generic-hybrid-medicines. [Last accessed on 04 May 2023].
Highlights of prescribing information. Abraxane® for injectable suspension (paclitaxel protein-bound particles for injectable suspension) (albumin-bound), for intravenous use. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/021660s047lbl.pdf. [Last accessed on 24 May 2023]
Highlights of prescribing information. Sandostatin® LAR depot (octreotide acetate) for injectable suspension, for gluteal intramuscular use. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021008s043lbl.pdf. [Last accessed on 24 May 2023]
Pigarova EA, Dzeranova LK. Sandostatin i sandostatin LAR pri metabolicheskikh, neyroendokrinnykh i onkologicheskikh zabolevaniyakh. Obes Metabol. 2011;8(1):26-30. doi: 10.14341/2071-8713-5188.
Highlights of prescribing information. Trelstar® (triptorelin pamoate for injectable suspension), for intramuscular use. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020715s040,021288s035,022427s015lbl.pdf. [Last accessed on 24 May 2023]
Highlights of prescribing information. Diprivan® (propofol injectable emulsion), for intravenous use. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/019627s069lbl.pdf. [Last accessed on 24 May 2023]
Highlights of prescribing information. Copaxone (glatiramer acetate) solution for subcutaneous injection. Available from: www.accessdata.fda.gov/drugsatfda_docs/label/2009/020622s057lbl.pdf. [Last accessed on 24 May 2023]
Barenholz Y. Doxil®-the first FDA-approved nano-drug: lessons learned. J Control Release. 2012;160(2):117-34. doi: 10.1016/j.jconrel.2012.03.020, PMID 22484195.
Highlights of prescribing information. Doxorubicin hydrochloride liposome injection, for intravenous use. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/050718Orig1s060lbl.pdf. [Last accessed on 24 May 2023]
Highlights of prescribing information. Lovenox (enoxaparin sodium injection) for subcutaneous and intravenous use. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020164s085lbl.pdf. [Last accessed on 24 May 2023]
Highlights of prescribing information. Ferrlecit (sodium ferric gluconate complex in sucrose), injection, for intravenous use. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/020955s020lbl.pdf. [Last accessed on 24 May 2023]
Lionberger R. Generic drugs in the 21st century: FDA’s actions create transparency and value for complex generic product development. Available from: https://www.fda.gov/drugs/news-events-human-drugs/generic-drugs-21st-century-fdas-actions-create-transparency-and-value-complex-generic-product. [Last accessed on 24 May 2023]
Medina JR, Cortes M, Romo E. Comparison of the USP apparatus 2 and 4 for testing the in vitro release performance of ibuprofen generic suspensions. Int J App Pharm. 2017;9(4):90-5. doi: 10.22159/ijap.2017v9i4.19926.
Stern S, Coghlan J, Krishnan V, Raney SG, Babiskin A, Jiang W. Research and education needs for complex generics. Pharm Res. 2021;38(12):1991-2001. doi: 10.1007/s11095-021-03149-y, PMID 34950975.
Kumar L, Deshpande A, Page A. Super generics/improved therapeutic entities: an approach to fulfil unmet medical needs and extending market exclusivity of generic medicines. Int J Pharm Pharm Sci. 2015;7(2):25-9.
Rajora A, Chhabra G. Quality by design approach: regulatory need, current, and future perspective. Asian J Pharm Clin Res. 2021;14(6):29-35. doi: 10.22159/ajpcr.2021.v14i6.33733.
Using the inactive ingredient database. Guidance for industry. United States Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER); 2019. Available from: https://www.fda.gov/media/128687/download. [Last accessed on 02 May 2023]
Key takeaways from the FDA complex generic drug product development workshop: part 1. Available from: https://lubrizolcdmo.com/blog/key-takeaways-from-the-2019-fda-complex-generic-drug-product-development-workshop-part-1/ [Last accessed on 02 May 2023]
Wang Y, Qin B, Xia G, Choi SH. FDA’s poly (Lactic-co-glycolic acid) research program and regulatory outcomes. AAPS J. 2021;23(4):92. doi: 10.1208/s12248-021-00611-y, PMID 34189655.
Michalski A, Brzezinski M, Lapienis G, Biela T. Star-shaped and branched polylactides: synthesis, characterization, and properties. Prog Polym Sci. 2019;89(001):159-212. doi: 10.1016/j.progpolymsci.2018.10.004.
Decision of the board of the Eurasian Economic Commission. On approval of the Guidelines for the pharmacokinetic and clinical study of the bioequivalence of liposomal drugs for intravenous administration. Available from: https://docseaeunion.org/docs/en-us/01527324/err_18092020_111. [Last accessed on 19 Mar 2024]
Key takeaways from the FDA complex generic drug product development workshop: part 2; 2020. Available from: https://lubrizolcdmo.com/blog/key-takeaways-from-the-2019-fda-complex-generic-drug-product-development-workshop-part-2/. [Last accessed on 02 May 2023]
Gaspar RS, Silva Lima B, Magro F, Alcobia A, da Costa FL, Feio J. Non-biological complex drugs (NBCDs): complex pharmaceuticals in need of individual robust clinical assessment before any therapeutic equivalence decision. Front Med (Lausanne). 2020;7:590527. doi: 10.3389/fmed.2020.590527, PMID 33330550.
Recommendation of the board of the Eurasian Economic Commission. Vol. N15; 2020. On guidelines for quality assessment and bioequivalence studies of certain groups of drugs. Available from: https://docs.eaeunion.org/docs/ru-ru/01427321/err_18092020_15. [Last accessed on 19 Mar 2024]
Lunawat S, Bhat K. Complex generic products: insight of current regulatory frameworks in US, EU and Canada and the need of harmonisation. Ther Innov Regul Sci. 2020;54(5):991-1000. doi: 10.1007/s43441-020-00114-6, PMID 31960290.
Generics market: focus on value-added medicines/supergenerics, 2019-2030; 2019. Available from: https://www.researchandmarkets.com/reports/4850776/generics-market-focus-on-value-added-medicines?utm_source=dynamicandutm_medium=BWandutm_code=chh3jtandutm_campaign=1315290+-+Global+Generics+Market+Outlook%2c+2019-2030%3a+Focus+on+Value-Added+Medicines%2fSupergenericsandutm_exec=joca220bwd. [Last accessed 04 May 2023]
Published
How to Cite
Issue
Section
Copyright (c) 2024 DEMINA N. B., BAKHRUSHINA E. O., ANUROVA M. N., MERKUSHOVA A. G., POMYTKINA M. V., RASTOPCHINA O. V., BARDAKOV A. I., KRASNYUK I. I.
This work is licensed under a Creative Commons Attribution 4.0 International License.
