Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411815EnglishN2026August14Healthcare
Quality by Design (QbD)-Based Regulatory Dossier Preparation of Imiglucerase: A Review
English0106Harshada R. KhadeEnglish Shilpa PiseEnglish
The concept of Quality by Design (QbD) enables the incorporation of scientific knowledge and risk management during the development of drugs. Imiglucerase is a recombinant biological enzyme that serves in the treatment of Type 1 Gaucher disease and thus calls for a thorough analysis regarding quality. This paper provides an analysis of the use of QbD in preparing the regu latory dossier of this product. This involves an overview of several aspects including the Quality Target Product Profile (QTPP), Critical Quality Attributes (CQAs), Critical Material Attributes (CMAs), Critical Process Parameters (CPPs), risk assessment and control strategy of Imiglucerase development. The relevance of the Common Technical Document (CTD) and electronic Com mon Technical Document (eCTD) in compiling quality, nonclinical and clinical information about the drug will also be addressed in the paper.
EnglishQuality by Design (QbD), Imiglucerase, Regulatory Affairs, Regulatory Dossier, Common Technical Document (CTD), Critical Quality Attributes (CQAs), Critical Process Parameters (CPPs), Critical Material Attributes (CMAs), Quality Risk Management
(QRM), Biopharmaceuticals.http://ijcrr.com/abstract.php?article_id=4915http://ijcrr.com/article_html.php?did=4915
1. International Council for Harmonisation. ICH Q8(R2): Pharma ceutical Development [Internet]. Geneva: ICH; 2009 [cited 2026 Jun 28]. Available from: https://database.ich.org/sites/default/ files/Q8_R2_Guideline.pdf
2. U.S. Food and Drug Administration. Pharmaceutical Quality Resources [Internet]. Silver Spring (MD): U.S. Food and Drug Administration; [cited 2026 Jul 01]. Available from: https:// www.fda.gov/drugs/pharmaceutical-quality-resources
3. International Council for Harmonisation. ICH Q9(R1): Quality Risk Management [Internet]. Geneva: ICH; 2023 [cited 2026 Jul 03]. Available from: https://database.ich.org/sites/default/files/ ICH_Q9_Guideline.pdf
4. Rathore AS, Winkle H. Quality by Design for Biopharmaceuti cals. Nature Biotechnology. 2009;27(1):26-34. Available from: https://www.nature.com/articles/nbt0109-26
5. European Medicines Agency. Cerezyme (Imiglucerase): Euro pean Public Assessment Report (EPAR) [Internet]. Amsterdam: European Medicines Agency; [cited 2026 Jul 06]. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/ cerezyme
6. Sanofi. Cerezyme® (Imiglucerase) Prescribing Information [In ternet]. Bridgewater (NJ): Sanofi; [cited 2026 Jul 08]. Available from: https://products.sanofi.us/cerezyme/cerezyme.html
7. International Council for Harmonisation. ICH M4: Organisa tion of the Common Technical Document for the Registration of Pharmaceuticals for Human Use [Internet]. Geneva: ICH; [cited 2026 Jul 10]. Available from: https://database.ich.org/sites/de fault/files/M4_R3 Guideline.pdf
8. Grangeia HB, Silva C, Simões SP, Reis MS. Quality by De sign in Pharmaceutical Manufacturing: A Systematic Review. European Journal of Pharmaceutical Sciences. 2020. Avail able from: https://www.sciencedirect.com/science/article/pii/ S092809871930379X
9. Yu LX, Amidon G, Khan MA, et al. Understanding Pharmaceuti cal Quality by Design. The AAPS Journal. 2014. Available from: https://link.springer.com/article/10.1208/s12248-014-9598-3
10. Lionberger RA, Lee SL, Lee L, Raw A, Yu LX. Quality by De sign: Concepts for ANDAs. The AAPS Journal. 2008. Available from: https://link.springer.com/article/10.1208/s12248-008 9036-2
11. International Council for Harmonisation. ICH Q5E: Compa rability of Biotechnological/Biological Products Subject to Changes in Their Manufacturing Process [Internet]. Geneva: ICH; 2005 [cited 2026 Jul 12]. Available from: https://database. ich.org/sites/default/files/Q5E_Guideline.pdf
12. U.S. Food and Drug Administration. Biosimilar Guidances [In ternet]. Silver Spring (MD): U.S. Food and Drug Administra tion; [cited 2026 Jul 14]. Available from: https://www.fda.gov/ drugs/biosimilars/biosimilar-guidances
13. International Council for Harmonisation. ICH Q6B: Specifica tions: Test Procedures and Acceptance Criteria for Biotechno logical/Biological Products [Internet]. Geneva: ICH; 1999 [cit ed 2026 Jul 16]. Available from: https://database.ich.org/sites/ default/files/Q6B_Guideline.pdf
14. U.S. Food and Drug Administration. Electronic Common Tech nical Document (eCTD) [Internet]. Silver Spring (MD): U.S. Food and Drug Administration; [cited 2026 Jul 18]. Available from: https://www.fda.gov/drugs/electronic-regulatory-submis sions-and-review/electronic-common-technical-document-ectd
15. U.S. Food and Drug Administration. Search for Pharmaceutical Quality Documents [Internet]. Silver Spring (MD): U.S. Food and Drug Administration; [cited 2026 Jul 21]. Available from: https://www.fda.gov/drugs/pharmaceutical-quality-resources/ search-pharmaceutical-quality-documents
16. ter Horst JP, Turimella SL, Metsers F, Zwiers A. Implementation of Quality by Design (QbD) Principles in Regulatory Dossiers of Medicinal Products in the European Union (EU) Between 2014 and 2019. Ther Innov Regul Sci. 2021;55(3):583-590. doi:10.1007/s43441-020-00254-9 [cited 2026 Jun 25]. Available from: https://link.springer.com/article/10.1007/s43441-020 00254-9
17. Luciani F, Galluzzo S, Gaggioli A, Kruse NA, Venneugues P, Schneider CK, et al. Implementing quality by design for biotech products: Are regulators on track? mAbs. 2015;7(3):451-455. do i:10.1080/19420862.2015.1023058 [cited 2026 Jun 28]. Avail able from: https://pmc.ncbi.nlm.nih.gov/articles/PMC4623250/
18. Rathore AS. Roadmap for implementation of Quality by De sign (QbD) for biotechnology products. Trends Biotechnol. 2009;27(9):546-553. doi:10.1016/j.tibtech.2009.06.006 [cited 2026 Jul 03]. Available from: https://www.sciencedirect.com/ science/article/pii/S0167779909001188
19. European Medicines Agency. Quality: Quality by Design (QbD) [Internet]. Amsterdam: European Medicines Agency; [cited 2026 Jul 06]. Available from: https://www.ema.europa.eu/en/ human-regulatory-overview/research-and-development/scien tific-guidelines/quality-guidelines/quality-quality-design-qbd
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411815EnglishN2026August14Healthcare
Global Comparison of ART Influence on Mental Health: A Narrative Review
English0713Maria SkorupaEnglish Malgorzata KurowskaEnglish Malgorzata ZiolekEnglish Milena WatekEnglish Tomasz PiszczekEnglish Jagoda KuniewiczEnglish Michal TokarczykEnglish Kinga KarczewskaEnglish Julia KuczkowskaEnglish Andrzej SamujlikEnglish
People living with HIV (PLWH) experience a higher prevalence of depression (31%) and anxiety (15–40%) than the general population. Although antiretroviral therapy (ART) has transformed HIV into a manageable chronic condition, its impact on mental health remains complex and may vary by adherence, regimen characteristics, and socioeconomic context. This narrative re view synthesizes evidence from six geographically and socioeconomically diverse cohorts (comprising over 300,000 individuals across the United States, China, Japan, Kazakhstan, Rwanda, and Tanzania) to evaluate the relationship between ART param eters and psychiatric outcomes. A search of PubMed/MEDLINE and Google Scholar identified observational and prospective studies published between 2012 and 2024. Synthesized findings reveal consistent associations between mental health and ART engagement, though non-causal in design. In LMICs and youth cohorts (e.g., Rwanda, 37% suboptimal adherence; Tanzania, n = 407) depressive symptoms, anxiety, and elevated systemic inflammatory markers (CRP, sTNFR-II) correlated with lower adherence. Conversely, US population-level data indicated lower odds of mood disorders among ART recipients compared to untreated individuals, while Japanese prospective data demonstrated improved sleep and quality-of-life scores following regi men simplification to single-tablet regimens. Evidence suggests that the psychological benefits of ART depend heavily on adher ence thresholds (≥90%) and regimen tolerability rather than treatment initiation alone. Potential underlying pathways include viral suppression and reduced neuroinflammation, alongside psychosocial gains such as enhanced self-efficacy and healthcare engagement. Given the observational nature of most data, ART should be viewed as a contributing factor rather than a direct cure for psychiatric burden. Integrating routine mental health screening into HIV care may optimize both virological adherence and psychological well-being globally.
EnglishAntiretroviral therapy (ART), Mental health, People living with HIV (PLWH), Adherence, Global health, Depressionhttp://ijcrr.com/abstract.php?article_id=4919http://ijcrr.com/article_html.php?did=4919
1. World Health Organization [Internet]. Geneva: World Health Organization; 2024 [cited 2026 Jun 8]. HIV data and statistics. Available from: https://www.who.int/teams/global-hiv-hepa titis-and-stis-programmes/hiv/strategic-information/hiv-data and-statistics
2. Remien RH, Stirratt MJ, Nguyen N, Robbins RN, Pala AN, Mel lins CA. Mental health and HIV/AIDS: the need for an integrat ed response. AIDS. 2019 Jul 15;33(9):1411-1420. doi: 10.1097/ QAD.0000000000002227.
3. Rezaei S, Ahmadi S, Rahmati J, Hosseinifard H, Dehnad A, Aryankhesal A, et al. Global prevalence of depression in HIV/ AIDS: a systematic review and meta-analysis. BMJ Support Palliat Care. 2019 Dec;9(4):404-412. doi: 10.1136/bmjsp care-2019-001952.
4. Gamaldo CE, Gamaldo A, Creighton J, Salas RE, Selnes OA, David PM, et al. Evaluating sleep and cognition in HIV. J Ac quir Immune Defic Syndr. 2013 Aug 15;63(5):609-616. doi: 10.1097/QAI.0b013e31829d63ab.
5. Pence BW, Miller WC, Whetten K, Eron JJ, Gaynes BN. Preva lence of DSM-IV-defined mood, anxiety, and substance use disorders in an HIV clinic in the Southeastern United States. J Acquir Immune Defic Syndr. 2006 Jul;42(3):298-306. doi: 10.1097/01.qai.0000219773.82055.aa.
6. Elbirt D, Mahlab-Guri K, Bezalel-Rosenberg S, Gill H, Attali M, Asher I. HIV-associated neurocognitive disorders (HAND). Isr Med Assoc J. 2015 Jan;17(1):54-59.
7. HIV.gov [Internet]. Washington (DC): U.S. Department of Health and Human Services; 2023 [cited 2026 Jun 8]. A Time line of HIV and AIDS. Available from: https://www.hiv.gov/hiv basics/overview/history/hiv-and-aids-timeline
8. Palella FJ, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, et al. Declining morbidity and mortality among pa tients with advanced human immunodeficiency virus infection. N Engl J Med. 1998 Mar 26;338(13):853-860. doi: 10.1056/ NEJM199803263381301.
9. Gandhi RT, Landovitz RJ, Sax PE. Antiretroviral Drugs for Treatment and Prevention of HIV in Adults: 2024 Recommenda tions of the International Antiviral Society–USA Panel. JAMA. 2025 Feb 18;333(7):609-628. doi: 10.1001/jama.2024.24543.
10. Kenedi CA, Goforth HW. A systematic review of the psychiatric side-effects of efavirenz. AIDS Behav. 2011 Nov;15(8):1803 1818. doi: 10.1007/s10461-011-9939-5.
11. Zareifopoulos N, Lagadinou M, Karela A, Pouliasi F, Econo mou I, Tsigkou A, et al. Efavirenz as a psychotropic drug. Eur Rev Med Pharmacol Sci. 2020 Oct;24(20):10729-10735. doi: 10.26355/eurrev_202010_23433.
12. Llibre JM. Neuropsychiatric Adverse Events with Dolutegravir and Other Integrase Strand Transfer Inhibitors. AIDS Rev. 2019 Jul-Sep;21(3):148-156. doi: 10.24875/AIDSREV.19000023.
13. Carr A, Samaras K, Burton S, Law M, Freund J, Chisholm DJ, et al. A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors. AIDS. 1998 May 7;12(7):F51-F58. doi: 10.1097/00002030 199807000-00003.
14. Working Group on Modelling of Antiretroviral Therapy Moni toring Strategies in Sub-Saharan Africa, Phillips A, Shroufi A, Vojnov L, Cohn J, Roberts T, et al. Sustainable HIV treatment in Africa through viral-load-informed differentiated care. Nature. 2015 Dec 3;528(7580):S68-S76. doi: 10.1038/nature16046.
15. Walmsley SL, Antela A, Clumeck N, Duiculescu D, Eberhard A, Gutierrez F, et al. Dolutegravir plus abacavir–lamivudine for the treatment of HIV-1 infection. N Engl J Med. 2013 Nov 7;369(19):1807-1818. doi: 10.1056/NEJMoa1215541.
16. Tsai AC, Bangsberg DR, Frongillo EA, Hunt PW, Muzoora C, Martin JN, et al. Food insecurity, depression and the modifying role of social support among people living with HIV/AIDS in rural Uganda. Soc Sci Med. 2012 Jun;74(12):2012-2019. doi: 10.1016/j.socscimed.2012.02.033.
17. British HIV Association [Internet]. London: British HIV Associ ation; 2019 [cited 2026 Jun 8]. BHIVA guidelines for the routine investigation and monitoring of adult HIV-1-positive individu als. Available from: https://www.bhiva.org/file/DByfVvXvA faSe/Guidelines-for-the-routine-investigation-and-monitoring of-adult-HIV-1-positive-individuals-2019.pdf 18. Ba DM, Risher KA, Ssentongo P, Zhang Y, Dai Q, Liu G, et al. Human Immunodeficiency Virus (HIV) Treatment With Antiret roviral Therapy Mitigates the High Risk of Mental Health Disor ders Associated With HIV Infection in the US Population. Open Forum Infect Dis. 2023 Oct 12;10(11):ofad555. doi: 10.1093/ ofid/ofad555. 19. Da W, Li X, Qiao S, Zhou Y, Shen Z. Antiretroviral thera py and mental health among people living with HIV/AIDS in China. Psychol Health Med. 2020 Jan;25(1):45-52. doi: 10.1080/13548506.2019.1616101.
20. Yoshino Y, Wakabayashi Y, Kitazawa T. Changes in health and sleep quality after anti-retroviral treatment modification in Japanese people living with HIV. J Infect Chemother. 2023 Oct;29(10):948-952. doi: 10.1016/j.jiac.2023.06.009.
21. Mergenova G, Davis A, Gilbert L, El-Bassel N, Terlikbayeva A, Primbetova S, et al. Mental health and cognition in relation to adherence to antiretroviral therapy among people living with HIV in Kazakhstan: a cross-sectional study. J Int AIDS Soc. 2024 Jul;27(Suppl 3):e26320. doi: 10.1002/jia2.26320.
22. Smith Fawzi MC, Ng L, Kanyanganzi F, Kirk C, Bizimana J, Cyamatare F, et al. Mental Health and Antiretroviral Adherence Among Youth Living With HIV in Rwanda. Pediatrics. 2016 Oct;138(4):e20153235. doi: 10.1542/peds.2015-3235.
23. Memiah P, Nkinda L, Majigo M, Humwa F, Haile ZT, Muthoka K, et al. Mental health symptoms and inflammatory markers among HIV infected patients in Tanzania. BMC Public Health. 2021 Jun 10;21(1):1113. doi: 10.1186/s12889-021-11064-5.
24. Mudra Rakshasa-Loots A, Whalley HC, Vera JH, Cox SR. Neu roinflammation in HIV-associated depression: evidence and fu ture perspectives. Mol Psychiatry. 2022 Sep;27(9):3619-3632. doi: 10.1038/s41380-022-01619-2.
25. Johnson MO, Neilands TB, Dilworth SE, Morin SF, Remien RH, Chesney MA. The role of self-efficacy in HIV treatment adher ence: validation of the HIV Treatment Adherence Self-Efficacy Scale (HIV-ASES). J Behav Med. 2007 Oct;30(5):359-370. doi: 10.1007/s10865-007-9118-3.
26. Katz IT, Ryu AE, Onuegbu AG, Psaros C, Weiser SD, Bangsberg DR, et al. Impact of HIV-related stigma on treatment adherence: systematic review and meta-synthesis. J Int AIDS Soc. 2013 Nov 13;16(3 Suppl 2):18640. doi: 10.7448/IAS.16.3.18640