Abstract
This article describes and reviews the steps involved in risk assessment of the twenty-four (24) potential elemental impurities in pharmaceutical drug products, as per the permitted daily exposure limits. Screening and estimation of prescribed elemental impurities in pharmaceutical drug substances, inactive excipients and drug products by inductively coupled plasma mass spectrometry or inductively coupled plasma optical emission spectrometry and their controls involved are also reviewed, as referred in the general chapters <232> & <233> of the United States Pharmacopoeia, Q3D guideline for elemental impurities as per international conference on harmonization and q3d elemental impurities: guidance for industry as per U. S., Food and Drug Administration USFDA.
Keywords: Risk assessment, Elemental impurities (EIs), Screening and Control, International Conference on Harmonization (ICH) Q3D guideline, United States Pharmacopoeia (USP) General Chapter <232> & <233>.
Graphical Abstract
[1]
Teasdale, A.; Chéry, C.C.; Cook, G. Implementation of ICH Q3D elemental impurities guideline: challenges and opportunities. Pharm. Technol., 2015, 39(3)
[2]
Elemental Impurities: A Virtual Company Perspective. con-tract pharma; april- 2017. https://www.contractpharma.com/issues/2017-04-01/view_features/elemental-impurities-a-virtual-companyperspective/Accessed November 20, 2018,
[3]
Semiquantitative Screening of Pharmaceutical Antiviral Drugs
using the Agilent 7500ce ICP-MS in Helium Collision Mode, Application
Note, Rebeca Santamaria-Fernandez, Sheila Mer-son,
and Ruth Hearn, LGC, Queens Road, Teddington, Mid-dlesex,
TW11 0LY UK , 2015.
[4]
Implementation of ICH Q3D Elemental Impurities Guideline:
Challenges and Opportunities, PharmTech.com., 2015, 39(3)
[5]
United states pharmacopeia (usp), general chapter 231 - heavy metals. http://www.usp.org/chemical-medicines/elementalimpurities-updates Accessed On: November 20,, 2018.
[6]
United States Pharmacopeia (USP), General Chapter 232 - Elemental
Impurities – Limits. http://www.usp.org/chemicalmedicines/elemental-impurities-updates Accessed On: November 20, 2018.
[7]
united states pharmacopeia (usp), general chapter 233 - elemental impurities - procedures. http://www.usp.org/chemicalmedicines/elemental-impurities-updates Accessed On: November 20,, 2018.
[8]
International Conference on Harmonisation Q3D Guideline for
Elemental http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q3D/Q3D_Step_4.pdf Accessed On: November 20,, 2018.
[9]
Elemental Impurities in Drug Products – Guidance for Indus-try, https://www.fda.gov/downloads/-Drugs/Guidances/UCM509432.pdf Accessed On: November 20,, 2018.
[10]
US-FDA (U. S., Food and Drug Administration) Q3D Ele-mental
Impurities: Guidance for Industry https://www.fda.gov/-downloads/drugs/guidances/ucm371025.pdf Accessed On: November 20, 2018.
[11]
Implementation Strategy of ICH Q3D Guideline http://www.ema.-europa.eu/docs/en_GB/document_library/Scientific_guideline-/2017/03/WC500222768.pdf Accessed On: November 20,, 2018.
[12]
Presentation: Product risk assessment general approach, Q3D
training module 5, prepared by the Q3D implementation work-ing
group, International Council for Harmonisation of Tech-nical Requirements
for Pharmaceuticals for Human Use, 2015.
[13]
Schweitzer, M.G. presentation on implementation of ICH Q3D
FDA/PQRI Conference on Evolving Product Quality, 2014.
[14]
US-FDA (U. S., Food and Drug Administration) Guidance for
Industry: Container Closure Systems for Packaging Human Drugs
and Biologics – Guidance for Industry https://www.fda.gov/downloads/-drugs/guidances/ucm070551.pdfAccessed on: November 20,, 2018.
[15]
Li, G.; Schoneker, D.; Ulman, K.L.; Sturm, J.J.; Thackery, L.M.; Kauffman, J.F. Elemental impurities in pharmaceutical excipients. J. Pharm. Sci., 2015, 104(12), 4197-4206.https://www.sciencedirect.com/science/-article/pii/S0022354915000775#t0010
[http://dx.doi.org/10.1002/jps.24650] [PMID: 26398581]
[http://dx.doi.org/10.1002/jps.24650] [PMID: 26398581]
[16]
Jenke, D.; Rivera, C.; Mortensen, T.; Amin, P.; Chacko, M.; Tran, T.; Chum, J. Acompilation of metals and trace elements extracted from materials relevant to pharmaceutical applications such as packaging systems and devices. J. Pharm. Sci. Technol., 2015, 69, 1-48.
[17]
Jenke, D.R.; Stults, C.L.; Paskiet, D.M.; Ball, D.J.; Nagao, L.M. Materials in manufacturing and packaging systems as sources of elemental impurities in packaged drug products: a literature review. PDA J. Pharm. Sci. Technol., 2015, 69(1), 1-48.https://www.ncbi.nlm.nih.gov/pubmed/25691713
[http://dx.doi.org/10.5731/pdajpst.2015.01005] [PMID: 25691713]
[http://dx.doi.org/10.5731/pdajpst.2015.01005] [PMID: 25691713]
[19]
Teasdale, A; Chéry, CC; Cook, G; Glennon, J; Lee, CW; Harris, L. Implementation of ich q3d elemental impurities guideline: challenges and opportunities. Pharmaceutical technology march, 2015, 39(3)
[20]
Presentation: Calculation Options, Q3D training module 7, prepared
by the Q3D implementation working group, Interna-tional
Council for Harmonisation of Technical Requirements for Pharmaceuticals
for Human Use, 2015.
[21]
Brazilian Pharmacopeia - 5th Ed., Chapter 5.3.2.3 Limit test for
heavy metals, the assay method. National Sanitary Surveil-lance
Agency - ANVISA
, 2010.
[22]
Lewen, N.; Mathew, S.; Schenkenberger, M.; Raglione, T. A rapid ICP-MS screen for heavy metals in pharmaceutical compounds. J. Pharm. Biomed. Anal., 2004, 35(4), 739-752.
[http://dx.doi.org/10.1016/j.jpba.2004.02.023] [PMID: 15193718]
[http://dx.doi.org/10.1016/j.jpba.2004.02.023] [PMID: 15193718]
[23]
Prajapati, J. Challenges to conclude elemental impurities risk assessment for pharmaceutical dosage form and submission in regulatory dossier. J. Generic Med., 2017, 13(3) 174113431769924.
[24]
Nageswara Rao, R.; Talluri, M.V.N.K. An overview of recent applications of inductively coupled plasma-mass spectrometry (ICP-MS) in determination of inorganic impurities in drugs and pharmaceuticals. J. Pharm. Biomed. Anal., 2007, 43(1), 1-13.
[http://dx.doi.org/10.1016/j.jpba.2006.07.004] [PMID: 16891084]
[http://dx.doi.org/10.1016/j.jpba.2006.07.004] [PMID: 16891084]
[25]
Rury, M. The importance of method development for trace-element analysis by inductively coupled plasma–optical emission. Spectroscopy (Springf.), 2016, 31(5), 16-32.
[26]
Kallam, S.R.; Srikanth, J.; Prakash, K.V. development and validation of an inductively coupled plas-ma mass spectrometry (icpms) method for the determination of 17 trace metals in ingenol mebutate (api), iosr j. pharm. biological sci., 2016, 11(4), 6-11.www.iosrjournals.org
[27]
Støving, C.; Jensen, H.; Gammelgaard, B.; Stürup, S. Development and validation of an ICP-OES method for quantitation of elemental impurities in tablets according to coming US pharmacopeia chapters. J. Pharm. Biomed. Anal., 2013, 84, 209-214.
[http://dx.doi.org/10.1016/j.jpba.2013.06.007] [PMID: 23850936]
[http://dx.doi.org/10.1016/j.jpba.2013.06.007] [PMID: 23850936]
[28]
Sims, J.; Smith, A.; Patel, D.; Batchelor, R.; Carreira, J. Automated sample preparation for ICP analysis of active pharmaceutical ingredients and intermediates. J. Lab. Autom., 2011, 16(5), 377-380.
[http://dx.doi.org/10.1016/j.jala.2010.10.006] [PMID: 21906564]
[http://dx.doi.org/10.1016/j.jala.2010.10.006] [PMID: 21906564]
[29]
Venzago, C.; Popp, M.; Kovac, J.; Kunkel, A. Pharmacopeial requirements for elemental impurities: a novel approach to the trace determination of osmium by oxidative pressure vessel sample digestion and measurement using inductively coupled plasma mass spectrometry (ICP-MS) after complexation and stabilisation. J. Anal. At. Spectrom., 2013, 28(7), 1125-1129.
[http://dx.doi.org/10.1039/c3ja50040c]
[http://dx.doi.org/10.1039/c3ja50040c]
[30]
Matusiewicz, H. Wet digestion methods. Sample preparation for trace element analysis; Mester, Z; Sturgeon, R., Ed.; Elsevier: Amsterdam, 2003, Vol. XLI, pp. 193-234.
[http://dx.doi.org/10.1016/s0166-526x(03)41006-4]
[http://dx.doi.org/10.1016/s0166-526x(03)41006-4]
[31]
Axelsson, B.O.; Jörnten-Karlsson, M.; Michelsen, P.; Abou-Shakra, F. The potential of inductively coupled plasma mass spectrometry detection for high-performance liquid chromatography combined with accurate mass measurement of organic pharmaceutical compounds. Rapid Commun. Mass Spectrom., 2001, 15(6), 375-385.
[http://dx.doi.org/10.1002/rcm.238] [PMID: 11291114]
[http://dx.doi.org/10.1002/rcm.238] [PMID: 11291114]
[32]
Muller, A.L.H.; Muller, E.I.; Barin, J.S.; Flores, E.M.M. Microwave-assisted digestion using diluted acids for toxic element determination in medicinal plants by ICP-MS in compliance with United States pharmacopeia requirements. Anal. Methods, 2015, 7(12), 5218-5225.
[http://dx.doi.org/10.1039/C5AY00436E]
[http://dx.doi.org/10.1039/C5AY00436E]
[33]
Barin, J.S.; Mello, P.A.; Mesko, M.F.; Duarte, F.A.; Flores, E.M.M. Determination of elemental impurities in pharmaceutical products and related matrices by ICP-based methods: a review. Anal. Bioanal. Chem., 2016, 408(17), 4547-4566.
[http://dx.doi.org/10.1007/s00216-016-9471-6] [PMID: 27020927]
[http://dx.doi.org/10.1007/s00216-016-9471-6] [PMID: 27020927]
[34]
International Conference on Harmonisation (ICH) Validation of
analytical procedures: text and methodology: Q2(R1) http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q2_R1/Step4/Q2_R1 Guideline.pdf Accessed on: November 20,, 2018.
[35]
Presentation: Controls of Elemental Impurities, Q3D training
module 6, prepared by the Q3D implementation working group, International
Council for Harmonisation of Technical Requirements
for Pharmaceuticals for Human Use,, 2015.
[36]
Presentation: FDA Perspective and Expectations for Control of
Elemental Impurities in Drug Products, PQRI/USP Workshop on
Implementation Status of ICH Q3D Rockville, MD November 9-
10, http://pqri.org/wp-content/uploads/2016/11/4-EIFDAperspectivedPQRI.pdf Accessed on: November 20, 2018.
[37]
Brandon, E.F.; Oomen, A.G.; Rompelberg, C.J.; Versantvoort, C.H.; van Engelen, J.G.; Sips, A.J. Consumer product in vitro digestion
model: Bioaccessibility of contaminants and its application in
risk assessment., Regul. Toxicol. Pharmacol., 2006, 44(2), 161-171.
[http://dx.doi.org/10.1016/j.yrtph.2005.10.002] [PMID: 16337324]
[http://dx.doi.org/10.1016/j.yrtph.2005.10.002] [PMID: 16337324]
[38]
International Conference on Harmonisation (ICH) Specifi-Cations:
Test Procedures And Acceptance Cri-Teria For New Drug Substances
And New Drug Products: Chemical SubstanceS Q6A Current
Step 4 version, https://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q6A/Step4/Q6Astep4.pdf Accessed on: November 20, 2018.
[39]
Wollein, U.; Bauer, B.; Habernegg, R.; Schramek, N. Potential metal impurities in active pharmaceutical substances and finished medicinal products - A market surveillance study. Eur. J. Pharm. Sci., 2015, 77, 100-105.
[http://dx.doi.org/10.1016/j.ejps.2015.05.028] [PMID: 26036232]
[http://dx.doi.org/10.1016/j.ejps.2015.05.028] [PMID: 26036232]
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