Review on the modern analytical advancements in impurities testing

Shumaila Anwar, Akbar Khan, Mariyum Jamal, Muhammad Zain Siddiqui

Article ID: 3159
Vol 6, Issue 1, 2025
DOI: https://doi.org/10.54517/aas3159
Received: 17 December 2024; Accepted: 26 March 2025; Available online: 2 April 2025; Issue release: 30 June 2025


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Abstract

Impurities in active pharmaceutical ingredients (APIs) and pharmaceutical drug products (DPs) lead to broader antithetical effects related to drug safety, efficacy, and regulatory compliance. This review discusses organic, elemental, and inorganic impurities, and residual solvents and stresses their impact on the quality of APIs and pharmaceutical DPs regarding patient safety. It endorses immensely developed contemporary analytical techniques like High-performance Liquid Chromatography (HPLC), and Gas Chromatography (GC), for organic impurities and discusses their hyphenated Mass Spectrometry (MS) chromatographic methodologies. Atomic Absorption Spectroscopy (AAS), Inductively Coupled Plasma (ICP) hyphenated with MS, and Optical Emission Spectroscopy (OES) techniques are discussed for mainly improved sensitivity and accuracy in the detection and identification of elemental and inorganic impurities. High-Resolution Mass Spectrometry (HRMS), Supercritical Fluid Chromatography (SFC), and ICP-hyphenated techniques alongside automation are among the emerging technologies that are discussed concerning their impending potential to solve intricacies related to complex drug matrices, challenging regulatory requirements, and new impurity profiles. The review underlines the discussion on harmonized global regulations and affordable access to advanced analytical techniques so that wider adoption is facilitated in the pharmaceutical industry. Imminent prospects are Artificial Intelligence (AI) incorporation, Machine Learning (ML), and green analytical methodologies to overcome the present confinements and to cater to the growing demands of the progressive pharmaceutical sector. This in-depth analysis is intended to help pharmaceutical stakeholders embrace novel impurity management approaches resulting in significantly enhanced drug quality and better healthcare outcomes on a global scale.


Keywords

organic impurities; elemental and inorganic impurities; residual solvents; HRMS; SFC; ICP-MS; ICP-OES; AI; ML; PAT


References

1. Ding B. Pharma Industry 4.0: Literature review and research opportunities in sustainable pharmaceutical supply chains. Process Safety and Environmental Protection. 2018; 119: 115-130. doi: 10.1016/j.psep.2018.06.031

2. Chakraborty Jyoti Joshi P. The Surging Relevance of Human Error in Pharmaceutical Manufacturing Sectors. International Journal of Science and Research (IJSR). 2023; 12(6): 1782-1791. doi: 10.21275/sr23614231626

3. Salgueiro L, Martins AP, Correia H. Raw materials: the importance of quality and safety. A review. Flavour and Fragrance Journal. 2010; 25(5): 253-271. doi: 10.1002/ffj.1973

4. Zhang K, Pellett JD, Narang AS, et al. Reactive impurities in large and small molecule pharmaceutical excipients – A review. TrAC Trends in Analytical Chemistry. 2018; 101: 34-42. doi: 10.1016/j.trac.2017.11.003

5. Abdin AY, Yeboah P, Jacob C. Chemical Impurities: An Epistemological Riddle with Serious Side Effects. International Journal of Environmental Research and Public Health. 2020; 17(3): 1030. doi: 10.3390/ijerph17031030

6. ICH Harmonized Tripartite Guideline. Impurities in New Drug Substances. Available online: https://database.ich.org/sites/default/files/Q3A%28R2%29%20Guideline.pdf (accessed on 15 December 2024).

7. ICH Harmonized Tripartite Guideline. Impurities in New Drug Products. Available online: https://database.ich.org/sites/default/files/Q3B%28R2%29%20Guideline.pdf (accessed on 15 December 2024).

8. ICH Harmonized Tripartite Guideline. Impurities: Guideline for Residual Solvents. Available online: https://database.ich.org/sites/default/files/ICH_Q3C-R8_Guideline_Step4_2021_0422_1.pdf (accessed on 15 December 2024).

9. ICH Harmonized Tripartite Guideline. Guideline for Elemental Impurities. Available online: https://database.ich.org/sites/default/files/Q3D-R1EWG_Document_Step4_Guideline_2019_0322.pdf (accessed on 15 December 2024).

10. Blessy M, Patel RD, Prajapati PN, et al. Development of forced degradation and stability indicating studies of drugs—A review. Journal of Pharmaceutical Analysis. 2014; 4(3): 159-165. doi: 10.1016/j.jpha.2013.09.003

11. Wang H, Chen Y, Wang L, et al. Advancing herbal medicine: enhancing product quality and safety through robust quality control practices. Frontiers in Pharmacology. 2023; 14. doi: 10.3389/fphar.2023.1265178

12. Vlčková HK, Pilařová V, Svobodová P, et al. Current state of bioanalytical chromatography in clinical analysis. The Analyst. 2018; 143(6): 1305-1325. doi: 10.1039/c7an01807j

13. Mekonnen BA, Yizengaw MG, Adugna KF. The clinical applications of drugs and their metabolites analysis in biological fluids and commonly used analytical techniques for bioanalysis: review. Frontiers in Analytical Science. 2024; 4. doi: 10.3389/frans.2024.1490093

14. Vora LK, Gholap AD, Jetha K, et al. Artificial Intelligence in Pharmaceutical Technology and Drug Delivery Design. Pharmaceutics. 2023; 15(7): 1916. doi: 10.3390/pharmaceutics15071916

15. Jena GK, Patra CN, Jammula S, et al. Artificial Intelligence and Machine Learning Implemented Drug Delivery Systems: A Paradigm Shift in the Pharmaceutical Industry. Journal of Bio-X Research. 2024; 7. doi: 10.34133/jbioxresearch.0016

16. Pokar D, Rajput N, Sengupta P. Industrial approaches and consideration of clinical relevance in setting impurity level specification for drug substances and drug products. International Journal of Pharmaceutics. 2020; 576: 119018. doi: 10.1016/j.ijpharm.2019.119018

17. Sangshetti JN, Deshpande M, Zaheer Z, et al. Quality by design approach: Regulatory need. Arabian Journal of Chemistry. 2017; 10: S3412-S3425. doi: 10.1016/j.arabjc.2014.01.025

18. Limpikirati PK, Mongkoltipparat S, Denchaipradit T, et al. Basic regulatory science behind drug substance and drug product specifications of monoclonal antibodies and other protein therapeutics. Journal of Pharmaceutical Analysis. 2024; 14(6): 100916. doi: 10.1016/j.jpha.2023.12.006

19. Đorđević S, Gonzalez MM, Conejos-Sánchez I, et al. Current hurdles to the translation of nanomedicines from bench to the clinic. Drug Delivery and Translational Research. 2021; 12(3): 500-525. doi: 10.1007/s13346-021-01024-2

20. Pognan F, Beilmann M, Boonen HCM, et al. The evolving role of investigative toxicology in the pharmaceutical industry. Nature Reviews Drug Discovery. 2023; 22(4): 317-335. doi: 10.1038/s41573-022-00633-x

21. Alsante KM, Huynh-Ba K, Baertschi SW, et al. Recent Trends in Product Development and Regulatory Issues on Impurities in Active Pharmaceutical Ingredient (API) and Drug Products. Part 1: Predicting Degradation Related Impurities and Impurity Considerations for Pharmaceutical Dosage Forms. AAPS PharmSciTech. 2013; 15(1): 198-212. doi: 10.1208/s12249-013-0047-x

22. Jamrógiewicz M, Pieńkowska K. Recent breakthroughs in the stability testing of pharmaceutical compounds. TrAC Trends in Analytical Chemistry. 2019; 111: 118-127. doi: 10.1016/j.trac.2018.12.007

23. ICH Harmonized Tripartite Guideline. Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances Q6A. Available online: https://database.ich.org/sites/default/files/Q6A%20Guideline.pdf (accessed on 15 December 2024).

24. ICH Harmonized Tripartite Guideline. Specifications: Test Procedures and Acceptance Criteria for Biotechnological/Biological Products: Q6B. Available online: https://database.ich.org/sites/default/files/Q6B%20Guideline.pdf (accessed on 15 December 2024).

25. Mande SR, Yelmame SS, Borse LB. A Review on Impurity Profiling in Pharmaceutical Substances. Asian Journal of Pharmaceutical Research and Development. 2024; 12(5): 46-51. doi: 10.22270/ajprd.v12i5.1477

26. Nordstrom FL, Sirota E, Hartmanshenn C, et al. Prevalence of Impurity Retention Mechanisms in Pharmaceutical Crystallizations. Organic Process Research & Development. 2023; 27(4): 723-741. doi: 10.1021/acs.oprd.3c00009

27. Maheshwari R, Todke P, Soni N, et al. Stability and Degradation Studies for Drug and Drug Product. Dosage Form Design Considerations. 2018; 1: 225-257. doi: 10.1016/b978-0-12-814423-7.00007-1

28. Vranić E. Basic principles of drug--excipients interactions. Bosnian Journal of Basic Medical Sciences. 2004; 4(2): 56-58. doi: 10.17305/bjbms.2004.3421

29. Kowalska J, Rok J, Rzepka Z, et al. Drug-Induced Photosensitivity—From Light and Chemistry to Biological Reactions and Clinical Symptoms. Pharmaceuticals. 2021; 14(8): 723. doi: 10.3390/ph14080723

30. Mejia JS, Gillies ER. Triggered degradation of poly(ester amide)s via cyclization of pendant functional groups of amino acid monomers. Polymer Chemistry. 2013; 4(6): 1969. doi: 10.1039/c3py21094d

31. Fortenberry A, Mohammad SA, Werfel TA, et al. Comparative Investigation of the Hydrolysis of Charge‐Shifting Polymers Derived from an Azlactone‐Based Polymer. Macromolecular Rapid Communications. 2022; 43(24). doi: 10.1002/marc.202200420

32. Brooks WH, Guida WC, Daniel KG. The Significance of Chirality in Drug Design and Development. Current Topics in Medicinal Chemistry. 2011; 11(7): 760-770. doi: 10.2174/156802611795165098

33. Ceramella J, Iacopetta D, Franchini A, et al. A Look at the Importance of Chirality in Drug Activity: Some Significative Examples. Applied Sciences. 2022; 12(21): 10909. doi: 10.3390/app122110909

34. Wu Y, Levons J, Narang AS, et al. Reactive Impurities in Excipients: Profiling, Identification and Mitigation of Drug–Excipient Incompatibility. AAPS PharmSciTech. 2011; 12(4): 1248-1263. doi: 10.1208/s12249-011-9677-z

35. Wasylaschuk WR, Harmon PA, Wagner G, et al. Evaluation of Hydroperoxides in Common Pharmaceutical Excipients. Journal of Pharmaceutical Sciences. 2007; 96(1): 106-116. doi: 10.1002/jps.20726

36. van der Waldt G. The judicious use of theory in social science research. The Journal for Transdisciplinary Research in Southern Africa. 2021; 17(1). doi: 10.4102/td.v17i1.1039

37. Cioc RC, Joyce C, Mayr M, et al. Formation of N-Nitrosamine Drug Substance Related Impurities in Medicines: A Regulatory Perspective on Risk Factors and Mitigation Strategies. Organic Process Research & Development. 2023; 27(10): 1736-1750. doi: 10.1021/acs.oprd.3c00153

38. Beard JC, Swager TM. An Organic Chemist’s Guide to N-Nitrosamines: Their Structure, Reactivity, and Role as Contaminants. The Journal of Organic Chemistry. 2021; 86(3): 2037-2057. doi: 10.1021/acs.joc.0c02774

39. ICH Harmonized Tripartite Guideline. Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk M7(R2). Available online: https://database.ich.org/sites/default/files/ICH_M7%28R2%29_Guideline_Step4_2023_0216_0.pdf (accessed on 15 December 2024).

40. Yu L, Liu S, Jia S, et al. Emerging frontiers in drug delivery with special focus on novel techniques for targeted therapies. Biomedicine & Pharmacotherapy. 2023; 165: 115049. doi: 10.1016/j.biopha.2023.115049

41. Kątny M, Frankowski M. Impurities in Drug Products and Active Pharmaceutical Ingredients. Critical Reviews in Analytical Chemistry. 2016; 47(3): 187-193. doi: 10.1080/10408347.2016.1242401

42. Maithani M, Raturi R, Sharma P, et al. Elemental impurities in pharmaceutical products adding fuel to the fire. Regulatory Toxicology and Pharmacology. 2019; 108: 104435. doi: 10.1016/j.yrtph.2019.104435

43. Inorganic Impurities. Available online: https://aurigaresearch.com/pharmaceutical-testing/inorganic-impurities/ (accessed on 15 December 2024).

44. FDA Guidance for Industry. ANDA Submissions - Refuse to Receive for Lack of Justification of Impurity Limits. Available online: https://www.fda.gov/files/drugs/published/ANDA-Submissions-%E2%80%94-Refuse-to-Receive-for-Lack-of-Justification-of-Impurity-Limits.pdf (accessed on 15 December 2024).

45. Mitra S, Chakraborty AJ, Tareq AM, et al. Impact of heavy metals on the environment and human health: Novel therapeutic insights to counter the toxicity. Journal of King Saud University - Science. 2022; 34(3): 101865. doi: 10.1016/j.jksus.2022.101865

46. Balali-Mood M, Naseri K, Tahergorabi Z, et al. Toxic Mechanisms of Five Heavy Metals: Mercury, Lead, Chromium, Cadmium, and Arsenic. Frontiers in Pharmacology. 2021; 12. doi: 10.3389/fphar.2021.643972

47. Balaram V. Environmental Impact of Platinum, Palladium, and Rhodium Emissions from Autocatalytic Converters—A Brief Review of the Latest Developments. In: Handbook of Environmental Materials Management. Springer; 2020.

48. Egorova KS, Ananikov VP. Toxicity of Metal Compounds: Knowledge and Myths. Organometallics. 2017; 36(21): 4071-4090. doi: 10.1021/acs.organomet.7b00605

49. Shibuya S, Watanabe K, Tsuji G, et al. Platinum and palladium nanoparticle‐containing mixture, PAPLAL, does not induce palladium allergy. Experimental Dermatology. 2019; 28(9): 1025-1028. doi: 10.1111/exd.13996

50. Genchi G, Carocci A, Lauria G, et al. Nickel: Human Health and Environmental Toxicology. International Journal of Environmental Research and Public Health. 2020; 17(3): 679. doi: 10.3390/ijerph17030679

51. Zhou S, Schöneich C, Singh SK. Biologics Formulation Factors Affecting Metal Leachables from Stainless Steel. AAPS PharmSciTech. 2011; 12(1): 411-421. doi: 10.1208/s12249-011-9592-3

52. Zhou S, Lewis L, Singh SK. Metal Leachables in Therapeutic Biologic Products: Origin, Impact and Detection. American Pharmaceutical Review. 2010; 13(4): 76-80.

53. Briffa J, Sinagra E, Blundell R. Heavy metal pollution in the environment and their toxicological effects on humans. Heliyon. 2020; 6(9): e04691. doi: 10.1016/j.heliyon.2020.e04691

54. Strickley RG. Solubilizing Excipients in Oral and Injectable Formulations. In: Pharmaceutical Research. Springer; 2004.

55. The United States Pharmacopeia Chapter <467> Residual Solvents. Available online: https://doi.usp.org/USPNF/USPNF_M99226_08_01.html (accessed on 15 December 2024).

56. Welton T. Solvents and sustainable chemistry. Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences. 2015; 471(2183): 20150502. doi: 10.1098/rspa.2015.0502

57. Witschi C, Doelker. Residual solvents in pharmaceutical products: acceptable limits, influences on physicochemical properties, analytical methods and documented values. European Journal of Pharmaceutics and Biopharmaceutics. 1997; 43(3): 215-242. doi: 10.1016/S0939-6411(96)00037-9

58. Khalikova M, Jireš J, Horáček O, et al. What is the role of current mass spectrometry in pharmaceutical analysis? Mass Spectrometry Reviews. 2023; 43(3): 560-609. doi: 10.1002/mas.21858

59. Kabir ER, Moreino SS, Sharif Siam MK. The Breakthrough of Biosimilars: A Twist in the Narrative of Biological Therapy. Biomolecules. 2019; 9(9): 410. doi: 10.3390/biom9090410

60. Rantanen J, Khinast J. The Future of Pharmaceutical Manufacturing Sciences. Journal of Pharmaceutical Sciences. 2015; 104(11): 3612-3638. doi: 10.1002/jps.24594

61. Pauli GF, Chen SN, Simmler C, et al. Importance of Purity Evaluation and the Potential of Quantitative 1H NMR as a Purity Assay. Journal of Medicinal Chemistry. 2014; 57(22): 9220-9231. doi: 10.1021/jm500734a

62. Coskun O. Separation Tecniques: Chromatography. Northern Clinics of Istanbul. 2016. 3(2): 156-160. doi: 10.14744/nci.2016.32757

63. Ramraje GR, Patil SD, Patil PH, et al. A brief review on: Separation techniques chromatography. Asian Journal of Pharmaceutical Analysis. 2020; 10(4): 231-238. doi: 10.5958/2231-5675.2020.00041.1

64. Beccaria M, Cabooter D. Current developments in LC-MS for pharmaceutical analysis. The Analyst. 2020; 145(4): 1129-1157. doi: 10.1039/c9an02145k

65. Zhou L, Mao B, Reamer R, et al. Impurity profile tracking for active pharmaceutical ingredients: Case reports. Journal of Pharmaceutical and Biomedical Analysis. 2007; 44(2): 421-429. doi: 10.1016/j.jpba.2006.11.004

66. Bachhav R, Khirnar A, Bachhav P, et al. Recent Approaches of Impurity Profiling in Pharmaceutical Analysis: A Concise Review. Medicinal & Analytical Chemistry International Journal. 2024; 8(1): 1-14. doi: 10.23880/macij-16000191

67. Liu G, Zhu B, Wang F, et al. Quantitative analysis of impurities in leucomycin bulk drugs and tablets: A high performance liquid chromatography-charged aerosol detection method and its conversion to ultraviolet detection method. Journal of Pharmaceutical and Biomedical Analysis. 2021; 202: 114148. doi: 10.1016/j.jpba.2021.114148

68. Cramers CA, Janssen H-G, van Deursen MM, et al. High-speed gas chromatography: an overview of various concepts. Journal of Chromatography A. 1999; 856(1-2): 315-329. doi: 10.1016/S0021-9673(99)00227-7

69. Maggio RM, Calvo NL, Vignaduzzo SE, et al. Pharmaceutical impurities and degradation products: Uses and applications of NMR techniques. Journal of Pharmaceutical and Biomedical Analysis. 2014; 101: 102-122. doi: 10.1016/j.jpba.2014.04.016

70. Shen JX, Liu G, Zhao Y. Strategies for improving sensitivity and selectivity for the quantitation of biotherapeutics in biological matrix using LC-MS/MS. Expert Review of Proteomics. 2015; 12(2): 125-131. doi: 10.1586/14789450.2015.1024225

71. Vosough M, Salemi A, Rockel S, et al. Enhanced efficiency of MS/MS all-ion fragmentation for non-targeted analysis of trace contaminants in surface water using multivariate curve resolution and data fusion. Analytical and Bioanalytical Chemistry. 2024; 416(5): 1165-1177. doi: 10.1007/s00216-023-05102-x

72. FDA. Liquid Chromatography-Electrospray Ionization-High Resolution Mass Spectrometry (LC-ESI-HRMS) Method for the Determination of Nitrosamine Impurities in Metformin Drug Substance and Drug Product. Available online: https://www.fda.gov/media/138617/download (accessed on 15 December 2024).

73. Kaufmann A. High Mass Resolution Versus MS/MS. Comprehensive Analytical Chemistry. 2012; 58: 169-215. doi: 10.1016/b978-0-444-53810-9.00001-8

74. Yamin TS, Madmon M, Hindi A, et al. Enhanced LC-ESI-MS/MS Sensitivity by Cationic Derivatization of Organophosphorus Acids. Molecules. 2023; 28(16): 6090. doi: 10.3390/molecules28166090

75. Tamara S, den Boer MA, Heck AJR. High-Resolution Native Mass Spectrometry. Chemical Reviews. 2021; 122(8): 7269-7326. doi: 10.1021/acs.chemrev.1c00212

76. Saito M. History of supercritical fluid chromatography: Instrumental development. Journal of Bioscience and Bioengineering. 2013; 115(6): 590-599. doi: 10.1016/j.jbiosc.2012.12.008

77. Roskam G, van de Velde B, Gargano A, et al. Supercritical Fluid Chromatography for Chiral Analysis, Part 1: Theoretical Background. LCGC Europe. 2022; 35(3): 83-92. doi: 10.56530/lcgc.eu.ou1980m2

78. De Klerck K, Mangelings D, Vander Heyden Y. Supercritical fluid chromatography for the enantioseparation of pharmaceuticals. Journal of Pharmaceutical and Biomedical Analysis. 2012; 69: 77-92. doi: 10.1016/j.jpba.2012.01.021

79. Chennuru LN, Choppari T, Duvvuri S, et al. Enantiomeric separation of proton pump inhibitors on new generation chiral columns using LC and supercritical fluid chromatography. Journal of Separation Science. 2013; 36(18): 3004-3010. doi: 10.1002/jssc.201300419

80. Yang Y, Liang Y, Yang J, et al. Advances of supercritical fluid chromatography in lipid profiling. Journal of Pharmaceutical Analysis. 2019; 9(1): 1-8. doi: 10.1016/j.jpha.2018.11.003

81. Babij NR, McCusker EO, Whiteker GT, et al. NMR Chemical Shifts of Trace Impurities: Industrially Preferred Solvents Used in Process and Green Chemistry. Organic Process Research & Development. 2016; 20(3): 661-667. doi: 10.1021/acs.oprd.5b00417

82. Douvris C, Vaughan T, Bussan D, et al. How ICP-OES changed the face of trace element analysis: Review of the global application landscape. Science of The Total Environment. 2023; 905: 167242. doi: 10.1016/j.scitotenv.2023.167242

83. Sturgeon R. ATOMIC ABSORPTION SPECTROMETRY | Vapor Generation. Encyclopedia of Analytical Science; 2005.

84. Ferreira SLC, Bezerra MA, Santos AS, et al. Atomic absorption spectrometry – A multi element technique. TrAC Trends in Analytical Chemistry. 2018; 100: 1-6. doi: 10.1016/j.trac.2017.12.012

85. Planeta K, Kubala-Kukus A, Drozdz A, et al. The assessment of the usability of selected instrumental techniques for the elemental analysis of biomedical samples. Scientific Reports. 2021; 11(1). doi: 10.1038/s41598-021-82179-3

86. Ward RJ, Crichton RR. Iron: Properties and Determination. Encyclopedia of Food and Health; 2016.

87. Wilschefski S, Baxter M. Inductively Coupled Plasma Mass Spectrometry: Introduction to Analytical Aspects. Clinical Biochemist Reviews. 2019; 40(3): 115-133. doi: 10.33176/aacb-19-00024

88. Aleluia ACM, Nascimento M de S, dos Santos AMP, et al. Analytical approach of elemental impurities in pharmaceutical products: A worldwide review. Spectrochimica Acta Part B: Atomic Spectroscopy. 2023; 205: 106689. doi: 10.1016/j.sab.2023.106689

89. FDA Guidance for Industry. Elemental Impurities in Drug Products Liquid. Available online: https://www.fda.gov/media/98847/download (accessed on 15 December 2024).

90. EMA. ICH Guideline Q3D (R2) on Elemental Impurities Step 5. Available online: https://www.ema.europa.eu/en/documents/scientific-guideline/international-conference-harmonisation-technical-requirements-registration-pharmaceuticals-human-use-ich-q3d-elemental-impurities-step-5-revision-2_en.pdf (accessed on 15 December 2024).

91. Agatemor C, Beauchemin D. Matrix effects in inductively coupled plasma mass spectrometry: A review. Analytica Chimica Acta. 2011; 706(1): 66-83. doi: 10.1016/j.aca.2011.08.027

92. Fernández-Sánchez ML. Atomic Emission Spectrometry—Inductively Coupled Plasma. Reference Module in Chemistry, Molecular Sciences and Chemical Engineering; 2018.

93. Gholap AD, Uddin MJ, Faiyazuddin M, et al. Advances in artificial intelligence for drug delivery and development: A comprehensive review. Computers in Biology and Medicine. 2024; 178: 108702. doi: 10.1016/j.compbiomed.2024.108702

94. Háda V, Bagdi A, Bihari Z, et al. Recent advancements, challenges, and practical considerations in the mass spectrometry-based analytics of protein biotherapeutics: A viewpoint from the biosimilar industry. Journal of Pharmaceutical and Biomedical Analysis. 2018; 161: 214-238. doi: 10.1016/j.jpba.2018.08.024

95. Gupta DK, Tiwari A, Yadav Y, et al. Ensuring safety and efficacy in combination products: regulatory challenges and best practices. Frontiers in Medical Technology. 2024; 6. doi: 10.3389/fmedt.2024.1377443

96. Mascarenhas-Melo F, Diaz M, Gonçalves MBS, et al. An Overview of Biosimilars—Development, Quality, Regulatory Issues, and Management in Healthcare. Pharmaceuticals. 2024; 17(2): 235. doi: 10.3390/ph17020235

97. Bayne ACV, Misic Z, Stemmler RT, et al. N-nitrosamine Mitigation with Nitrite Scavengers in Oral Pharmaceutical Drug Products. Journal of Pharmaceutical Sciences. 2023; 112(7): 1794-1800. doi: 10.1016/j.xphs.2023.03.022

98. Timpe C, Stegemann S, Barrett A, et al. Challenges and opportunities to include patient‐centric product design in industrial medicines development to improve therapeutic goals. British Journal of Clinical Pharmacology. 2020; 86(10): 2020-2027. doi: 10.1111/bcp.14388

99. Huanbutta K, Burapapadh K, Kraisit P, et al. Artificial intelligence-driven pharmaceutical industry: A paradigm shift in drug discovery, formulation development, manufacturing, quality control, and post-market surveillance. European Journal of Pharmaceutical Sciences. 2024; 203: 106938. doi: 10.1016/j.ejps.2024.106938

100. Gimpel AL, Katsikis G, Sha S, et al. Analytical methods for process and product characterization of recombinant adeno-associated virus-based gene therapies. Molecular Therapy - Methods & Clinical Development. 2021; 20: 740-754. doi: 10.1016/j.omtm.2021.02.010

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