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Review ArticleReview

Advice on Degradation Products in Pharmaceuticals: A Toxicological Evaluation

Sâmia Rocha de Oliveira Melo, Maurício Homem-de-Mello, Dâmaris Silveira and Luiz Alberto Simeoni
PDA Journal of Pharmaceutical Science and Technology May 2014, 68 (3) 221-238; DOI: https://doi.org/10.5731/pdajpst.2014.00974
Sâmia Rocha de Oliveira Melo
Faculty of Health Sciences, University of Brasilia, Brasília, Brazil
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  • For correspondence: samiamelo@gmail.com
Maurício Homem-de-Mello
Faculty of Health Sciences, University of Brasilia, Brasília, Brazil
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Dâmaris Silveira
Faculty of Health Sciences, University of Brasilia, Brasília, Brazil
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Luiz Alberto Simeoni
Faculty of Health Sciences, University of Brasilia, Brasília, Brazil
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References

  1. 1.
    International Conference on Harmonisation (ICH). Harmonised Tripartite Guideline: Impurities in New Drug Products Q3B (R2) (Revised Guideline), 2006.
  2. 2.
    1. Smith R. J.,
    2. Webb M. L
    1. Martin G. E.
    A Systematic Approach To Impurity Identification. In Analysis of Drug Impurities, Smith R. J., Webb M. L, Eds.; Blackwell Publishing: Iowa, 2007; pp 124–155.
  3. 3.
    Agência Nacional de Vigilância Sanitária (ANVISA). RE 01/2005: Guia para a realização de estudos de estabilidade. Ministério da Saúde: Brasil, July 29, 2005.
  4. 4.
    Health Canada. Draft Guidance for Industry - Impurities in Existing Drug Substances and Products. (Last modification 2010/06/16). Guideline: Genotoxicity: A Standard Battery for Genotoxicity Testing of Pharmaceuticals. ICH Topic S 2 B, 2010.
  5. 5.
    1. Roy J.
    Pharmaceutical impurities—a mini-review. AAPS PharmSciTech 2002, 3 (2), 1–8.
    OpenUrl
  6. 6.
    1. Ahuja S.,
    2. Alsante K. M.
    1. Ahuja S.
    Overview: Isolation and Characterization of Impurities. In Handbook of Isolation and Characterization of Impurities in Pharmaceuticals, Ahuja S., Alsante K. M., Eds.; Academic Press: San Diego, 2003; pp 1–24.
  7. 7.
    1. Robinson D. I.
    Control of genotoxic impurities in active pharmaceutical ingredients: a review and perspective. Org. Process Res. Dev. 2010, 14 (4), 946–959.
    OpenUrl
  8. 8.
    1. Jacobson-Kram D.,
    2. McGovern T.
    Toxicological overview of impurities in pharmaceutical products. Adv. Drug Del. Rev. 2007, 59 (1), 38–42.
    OpenUrlPubMed
  9. 9.
    ICH. Assessment and control of DNA reactive (mutagenic) impurities in pharmaceuticals to limit potential carcinogenic risk. Draft Guideline, 2013.
  10. 10.
    1. Basak A. K.,
    2. Raw A. S.,
    3. Al Hakim A. H.,
    4. Furness S.,
    5. Samaan N. I.,
    6. Gill D. S.,
    7. Patel H. B.,
    8. Powers R. F.,
    9. Yu L.
    Pharmaceutical impurities: regulatory perspective for Abbreviated New Drug Applications. Adv. Drug Del. Rev. 2007, 59 (1), 64–72.
    OpenUrlPubMed
  11. 11.
    1. Singh S.,
    2. Handa T.,
    3. Narayanam M.,
    4. Sahu A.,
    5. Junwal M.,
    6. Shah R. P.
    A critical review on the use of modern sophisticated hyphenated tools in the characterization of impurities and degradation products. J. Pharm. Biomed. Anal. 2012, 69, 148–173.
    OpenUrlPubMed
  12. 12.
    1. Alsante K. M.,
    2. Ando A.,
    3. Brown R.,
    4. Ensing J.,
    5. Hatajik T. D.,
    6. Kong W.,
    7. Tsuda Y.
    The role of degradant profiling in active pharmaceutical ingredients and drug products. Adv. Drug Deliv. Rev. 2007, 59 (1), 29–37.
    OpenUrlCrossRefPubMed
  13. 13.
    1. Baertschi S. W.,
    2. Alsante K. M.,
    3. Reed R. A.
    1. Baertschi S. W.,
    2. Jansen P. J.,
    3. Alsante K. M.
    Stress testing: a predictive tool. In Pharmaceutical Stress Testing: Predicting Drug Degradation. Drugs and the Pharmaceutical Sciences, 2nd ed.; Baertschi S. W., Alsante K. M., Reed R. A., Eds.; Informa Healthcare: New York, 2011; pp 10–48.
  14. 14.
    1. Reynolds D. W.,
    2. Facchine K. L.,
    3. Mullaney J. F.,
    4. Alsante K. M.,
    5. Hatajik T. D.,
    6. Motto M. G.
    Conducting forced degradation studies. Pharm. Technol. 2002, February, 48–56.
  15. 15.
    1. Huynh-Ba K.
    1. Waterman K. C.
    Understanding and predicting pharmaceutical product shelf-life. In Handbook of Stability Testing in Pharmaceutical Development, Huynh-Ba K., Ed.; Springer: New York, 2009; pp 115–135.
  16. 16.
    Drug Degradation Database. CambridgeSoft Corporation: 2004. Available at http://d3.cambridgesoft.com/.
  17. 17.
    1. Huynh-Ba K.
    1. Baertschi S. W.
    Forced Degradation and Its Relation to Real Time Drug Product Stability. In Pharmaceutical Stability Testing To Support Global Markets, Huynh-Ba K., Ed.; Springer: New York, 2010; pp 107–116.
  18. 18.
    FDA.Guidance for Industry Analytical Procedures and Methods Validation. Chemistry, Manufacturing, and Controls Documentation (Draft Guidance), 2000.
  19. 19.
    1. Garg A.,
    2. Solas D. W.,
    3. Takahashi L. H.,
    4. Cassella J. V.
    Forced degradation of fentanyl: Identification and analysis of impurities and degradants. J. Pharm. Biomed. Anal. 2010, 53 (3), 325–334.
    OpenUrlPubMed
  20. 20.
    1. Baertschi S. W.
    Analytical methodologies for discovering and profiling degradation-related impurities. Trends Anal. Chem. 2006, 25 (8), 758–767.
    OpenUrl
  21. 21.
    1. Lukulay P.,
    2. Hokanson G.
    A perspective on reconciling mass balance in forced degradation studies. Pharm. Technol. 2005, 29 (10), 106–112.
    OpenUrl
  22. 22.
    1. Demond W.,
    2. Kenley R. A.,
    3. Lokensgard D.,
    4. Weilersbacher G.,
    5. Herman K.
    Orthogonal HPLC methods for quantitating related substances and degradation products of pramlintide. AAPS PharmSciTech 2000, 1 (1), 50–59.
    OpenUrl
  23. 23.
    1. Liu D. Q.,
    2. Kord A. S.
    Analytical challenges in stability testing for genotoxic impurities. Trends Anal. Chem. 2013, 49, 108–117.
    OpenUrl
  24. 24.
    1. Elder D.,
    2. Snodin D.,
    3. Teasdale A.
    Control and analysis of hydrazine, hydrazides and hydrazones—genotoxic impurities in active pharmaceutical ingredients (APIs) and drug products. J. Pharm. Biomed. Anal. 2011, 54 (5), 900–910.
    OpenUrlPubMed
  25. 25.
    1. Argentine M. D.,
    2. Owens P. K.,
    3. Olsen B. A.
    Strategies for the investigation and control of process-related impurities in drug substances. Adv. Drug Deliv. Rev. 2007, 59 (1), 12–28.
    OpenUrlPubMed
  26. 26.
    1. Snodin D.,
    2. Vudathala G.
    Genotoxic impurities: a case for regulatory rethink. AAPS Mag. 2009, 20–27.
  27. 27.
    1. Klaassen C. D.
    1. Klaunig J. E.,
    2. Kamendulis L. M.
    Chemical Carcinogens. In Casarett & Doull's Toxicology: The Basic Science of Poisons, Klaassen C. D., Ed.; McGraw-Hill: New York, 2008.
  28. 28.
    1. Müller L.,
    2. Mauthe R. J.,
    3. Riley C. M.,
    4. Andino M. M.,
    5. Antonis D. D.,
    6. Beels C.,
    7. DeGeorge J.,
    8. De Knaep A. G.,
    9. Ellison D.,
    10. Fagerland J. A.,
    11. Frank R.,
    12. Fritschel B.,
    13. Galloway S.,
    14. Harpur E.,
    15. Humfrey C.D.N.,
    16. Jacks A. S.,
    17. Jagota N.,
    18. Mackinnon J.,
    19. Mohan G.,
    20. Ness D.K,
    21. O'Donovan M.R.,
    22. Smith M.D.,
    23. Vudathala G.,
    24. Yotti L.
    A rationale for determining, testing, and controlling specific impurities in pharmaceuticals that possess potential for genotoxicity. Regul. Toxicol. Pharmacol. 2006, 44 (3), 198–211.
    OpenUrlCrossRefPubMedWeb of Science
  29. 29.
    ICH. Harmonised Tripartite Guideline: Guideline for Residual Solvents ICH Q3C(R5) (Revised Guideline), 2011.
  30. 30.
    CHMP Guideline on the Limits of Genotoxic Impurities. CPMP/SWP/5199/02 EMEA/CHMP/QWP/251344/2006, 2006.
  31. 31.
    1. McGovern T.,
    2. Jacobson-Kram D.
    Regulation of genotoxic and carcinogenic impurities in drug substances and products. Trends Anal. Chem. 2006, 25 (8), 790–795.
    OpenUrl
  32. 32.
    1. Kean T.,
    2. Miller J.,
    3. Skellern G.,
    4. Snodin D.
    Acceptance criteria for levels of hydrazine in substances for pharmaceutical use and analytical methods for its determination. Pharmeur. Sci. Notes 2006, 2, 23–33.
    OpenUrl
  33. 33.
    1. Dolan D. G.,
    2. Naumann B. D.,
    3. Sargent E. V.,
    4. Maier A.,
    5. Dourson M.
    Application of the threshold of toxicological concern concept to pharmaceutical manufacturing operations. Regul. Toxicol. Pharmacol. 2005, 43 (1), 1–9.
    OpenUrlCrossRefPubMedWeb of Science
  34. 34.
    1. Bercu J. P.,
    2. Hoffman W. P.,
    3. Lee C.,
    4. Ness D. K.
    Quantitative assessment of cumulative carcinogenic risk for multiple genotoxic impurities in a new drug substance. Regul. Toxicol. Pharmacol. 2008, 51 (3), 270–277.
    OpenUrlCrossRefPubMed
  35. 35.
    1. Kroes R.,
    2. Renwick A.,
    3. Cheeseman M.,
    4. Kleiner J.,
    5. Mangelsdorf I.,
    6. Piersma A.,
    7. Schilter B.,
    8. Schlatter J.,
    9. van Schothorst F.,
    10. Vos J.
    Structure-based thresholds of toxicological concern (TTC): guidance for application to substances present at low levels in the diet. Food Chem. Toxicol. 2004, 42 (1), 65–83.
    OpenUrlCrossRefPubMedWeb of Science
  36. 36.
    1. Raillard S. P.,
    2. Bercu J.,
    3. Baertschi S. W.,
    4. Riley C. M.
    Prediction of drug degradation pathways leading to structural alerts for potential genotoxic impurities. Org. Process Res. Dev. 2010, 14 (4), 1015–1020.
    OpenUrl
  37. 37.
    Zeneth. Lhasa Limited: 2012. Available at http://www.lhasalimited.org/products/zeneth.htm.
  38. 38.
    1. Snyder R. D.,
    2. Smith M. D.
    Computational prediction of genotoxicity: room for improvement. Drug Discov. Today 2005, 10 (16), 1119–1124.
    OpenUrlCrossRefPubMedWeb of Science
  39. 39.
    1. Muster W.,
    2. Breidenbach A.,
    3. Fischer H.,
    4. Kirchner S.,
    5. Muller L.,
    6. Pahler A.
    Computational toxicology in drug development. Drug Discov. Today 2008, 13 (7–8), 303–310.
    OpenUrlCrossRefPubMedWeb of Science
  40. 40.
    1. Dobo K. L.,
    2. Greene N.,
    3. Fred C.,
    4. Glowienke S.,
    5. Harvey J. S.,
    6. Hasselgren C.,
    7. Jolly R.,
    8. Kenyon M. O.,
    9. Munzner J. B.,
    10. Muster W.,
    11. Neft R.,
    12. Reddy M. V.,
    13. White A. T.,
    14. Weiner S.
    In silico methods combined with expert knowledge rule out mutagenic potential of pharmaceutical impurities: an industry survey. Regulatory Toxicology and Pharmacology 2012, 62 (3), 449–455.
    OpenUrlPubMed
  41. 41.
    1. Fioravanzo E.,
    2. Bassan A.,
    3. Pavan M.,
    4. Mostrag-Szlichtyng A.,
    5. Worth A. P.
    Role of in silico genotoxicity tools in the regulatory assessment of pharmaceutical impurities. SAR QSAR Environ. Res. 2012, 23 (3-4), 257–277.
    OpenUrlPubMed
  42. 42.
    1. Valerio L. G.,
    2. Cross K. P.
    Characterization and validation of an in silico toxicology model to predict the mutagenic potential of drug impurities. Toxicol. Appl. Pharmacol. 2012, 245, 209–211.
    OpenUrl
  43. 43.
    1. Benigni R.,
    2. Bossa C.
    Structure alerts for carcinogenicity, and the Salmonella assay system: a novel insight through the chemical relational databases technology. Mutat. Res. 2008, 659 (3), 248–251.
    OpenUrlCrossRefPubMedWeb of Science
  44. 44.
    GESTIS Database. Institute of Occupacional Safety and Health (IFA). Sankt Augustin, Germany.
  45. 45.
    1. Giordani A.,
    2. Kobel W.,
    3. Gally H. U.
    Overall impact of the regulatory requirements for genotoxic impurities on the drug development process. Eur. J. Pharm. Sci. 2011, 43 (1), 1–15.
    OpenUrlPubMed
  46. 46.
    NIOSH Database. Centers for Disease Control and Prevention: Atlanta, GA. Available at http://www.cdc.gov/niosh/npg/.
  47. 47.
    Pharmapendium Database. Elsevier: 2011. Available at http://www.elsevier.com/online-tools/pharmapendium.
  48. 48.
    Toxinet Database. U.S. National Library of Medicine: Bethesda, MD. Available at http://toxnet.nlm.nih.gov/.
  49. 49.
    1. Jena G.,
    2. Kaul C.,
    3. Ramarao P.
    Genotoxicity testing, a regulatory requirement for drug discovery and development: Impact of ICH guidelines. Indian J. Pharmacol. 2002, 34 (2), 86–99.
    OpenUrl
  50. 50.
    ANVISA. Gerência de Avaliação de Segurança e Eficácia – GESEF. Guia para a condução de estudos não clínicos de segurança necessários ao desenvolvimento de medicamentos. Ministério da Saúde: Brasil, 2010.
  51. 51.
    FDA. Bacterial Reverse Mutation Test. Toxicological Principles for the Safety Assessment of Food Ingredients: Redbook 2000, 2003; pp 44–67.
  52. 52.
    1. Tejs S.
    The Ames test: a methodological short review. Environ. Biotechnol. 2008, 4 (1), 7–14.
    OpenUrl
  53. 53.
    FDA. In vitro Mammalian Chromossomal Aberration Test—Toxicological Principles for the Safety Assessment of Food Ingredients: Redbook 2000, 2003; pp 68–76.
  54. 54.
    FDA. Mouse Lymphoma Thymidine Kinase Gene Mutation Assay Toxicological Principles for the Safety Assessment of Food Ingredients: Redbook 2000, 2003; pp 77–86.
  55. 55.
    FDA. Mammalian Erythrocyte Micronucleus Test. Toxicological Principles for the Safety Assessment of Food Ingredients: Redbook 2000, 2003; pp 87–96.
  56. 56.
    ICH. Harmonised Tripartite Guideline: Guidance on genotoxicity testing and data interpretation for pharmaceuticals intended for human use ICH S2(R1), 2011.
  57. 57.
    1. Vijayan M.,
    2. Deecaraman M.,
    3. Pudupalayam K. T.
    In vitro genotoxicity of piperacillin impurity-A. African J. Biotech. 2007, 6 (18).
  58. 58.
    Impurities in drug substances and drug products. In USP 33–NF 28, 2010; pp R-1097.
  59. 59.
    1. Calixto J. B.,
    2. Siqueira Junior J. M.
    Desenvolvimento de medicamentos no Brasil: desafios. Gaz. Méd. Bahia 2008, 78 (1).
  60. 60.
    1. Yu L. X.
    Pharmaceutical quality by design: product and process development, understanding, and control. Pharm. Res. 2008, 25 (4), 781–791.
    OpenUrlCrossRefPubMed
  61. 61.
    WHO Expert Committee on Specifications for Pharmaceutical Preparations. Stability Testing of Active Pharmaceutical Ingredients and Finished Pharmaceutical Products. WHO Technical Report Series—953 (43rd 722 Report), 2009.
  62. 62.
    The Association of South East Asian Nations (ASEAN). ASEAN Guideline on Stability Study of Drug Product (Revised Guideline), 2005.
  63. 63.
    Cooperation Council for The Arab States of the Gulf (GCC). The GCC Guidelines for Stability Testing of Active Pharmaceutical Ingredients (APIs) and Finished Pharmaceutical Products (FPPs). Version 3.0 (Revised Guideline), 2011.
  64. 64.
    Department of Health Republic of South Africa (MCC), Medicine Control Council. Stability, 2011.
  65. 65.
    ICH Harmonised Tripartite Guideline: Impurities in New Drug Substances Q3A (R2) (Revised Guideline), 2008.
  66. 66.
    ICH. Harmonised Tripartite Guideline: Stability Testing of New Drug Substances and Products Q1A (R2) (Revised Guideline), 2003.
  67. 67.
    ICH. Harmonised Tripartite Guideline: Photostability Testing of New Drug Substances and Products ICH Q1B, 1999.
  68. 68.
    ICH. Harmonised Tripartite Guideline: Stability Testing for New Dosage Forms ICH Q1C, 1997.
  69. 69.
    ICH. Harmonised Tripartite Guideline: Evaluation of Stability Data ICH Q1E, 2004.
  70. 70.
    Agência Nacional de Vigilância Sanitária (ANVISA) RE 01/2005 (July 29th, 2005): Guia para a realização de estudos de estabilidade. Ministério da Saúde, Brasil, 2005.
  71. 71.
    1. Frimpter G. W.,
    2. Timpanelli A. E.,
    3. Eisenmenger W. J.,
    4. Stein H. S.,
    5. Ehrlich L. I.
    Reversible “Fanconi syndrome” caused by degraded tetracycline. JAMA 1963, 184 (2), 111–113.
    OpenUrlCrossRefPubMedWeb of Science
  72. 72.
    1. Machado F. C.,
    2. Demicheli C.,
    3. Garnier-Suillerot A.,
    4. Beraldo H.
    Metal complexes of anhydrotetracycline. 2. Absorption and circular dichroism study of Mg (II), AMID, and Fe (III) complexes. Possible influence of the Mg (II) complex on the toxic side effects of tetracycline. J. Inorg. Biochem. 1995, 60 (3), 163–173.
    OpenUrlCrossRefPubMedWeb of Science
  73. 73.
    1. Mendez A.,
    2. Chagastelles P.,
    3. Palma E.,
    4. Nardi N.,
    5. Schapoval E.
    Thermal and alkaline stability of meropenem: degradation products and cytotoxicity. Int. J. Pharm. 2008, 350 (1–2), 95–102.
    OpenUrlCrossRefPubMed
  74. 74.
    1. Chatzitakis A.,
    2. Berberidou C.,
    3. Paspaltsis I.,
    4. Kyriakou G.,
    5. Sklaviadis T.,
    6. Poulios I.
    Photocatalytic degradation and drug activity reduction of Chloramphenicol. Water Res. 2008, 42 (1–2), 386–394.
    OpenUrlPubMed
  75. 75.
    1. Karimi M. A.,
    2. Mazloum-Ardakani M.,
    3. Mashhadizadeh M. H.,
    4. Banifatemeh F.
    Simultaneous kinetic spectrophotometric determination of hydrazine and isoniazid using H-point standard addition method and partial least squares regression in micellar media. Croat. Chem. Acta 2009, 82 (4), 729–728.
    OpenUrl
  76. 76.
    1. Castell J.,
    2. Miranda M.,
    3. Morera I.
    Photolytic degradation of ibuprofen. Toxicity of the isolated photoproducts on fibroblasts and erythrocytes. Photochem. Photobiol. 2008, 46 (6), 991–996.
    OpenUrl
  77. 77.
    1. Caviglioli G.,
    2. Valeria P.,
    3. Brunella P.,
    4. Sergio C.,
    5. Attilia A.,
    6. Gaetano B.
    Identification of degradation products of ibuprofen arising from oxidative and thermal treatments. J. Pharm. Biomed. Anal. 2002, 30 (3), 499–509.
    OpenUrlCrossRefPubMedWeb of Science
  78. 78.
    1. Connors K. A.,
    2. Amidon K. L.,
    3. Stella V. J.
    Chemical Stability of Pharmaceuticals, 2nd ed.; Wiley: New York, 1986.
  79. 79.
    1. Lima D. M.,
    2. dos Santos L. D.,
    3. Lima E. M.
    Stability and in vitro release profile of enalapril maleate from different commercially available tablets: possible therapeutic implications. J. Pharm. Biomed. Anal. 2008, 47 (4–5), 934–937.
    OpenUrlPubMed
  80. 80.
    1. Quaglia M. G.,
    2. Farina A.,
    3. Donati E.,
    4. Cotechini V.,
    5. Bossu E.
    Determination of MPTP, a toxic impurity of pethidine. J. Pharm. Biomed. Anal. 2003, 33 (1), 1–6.
    OpenUrlPubMed
  81. 81.
    1. Florey K.
    1. Gröningsson K.,
    2. Lindgren J.,
    3. Lundberg E.,
    4. Sandberg R.,
    5. Wahlén A.
    Lidocaine base and hydrochloride. In Analytical Profiles of Drug Substances, Florey K., Ed.; Academic Press: Orlando, FL, 1985; Vol. 14, pp 207–243.
    OpenUrl
  82. 82.
    1. Powell M. F.
    Stability of lidocaine in aqueous solution: effect of temperature, pH, buffer, and metal ions on amide hydrolysis. Pharm. Res. 1987, 4 (1), 42–45.
    OpenUrlCrossRefPubMedWeb of Science
  83. 83.
    National Toxicology Program (NTP). Toxicology and Carcinogenesis Studies of 2,6-xylidine (CAS No.87-62-7) in Charles River CD Rats (Feed Studies). NTP: Research Triange Park, NC, 1990. Available at http://ntp.niehs.nih.gov/ntp/htdocs/LT_rpts/tr278.pdf.
  84. 84.
    1. Ciavarella A. B.,
    2. Gupta A.,
    3. Sayeed V. A.,
    4. Khan M. A.,
    5. Faustino P. J.
    Development and application of a validated HPLC method for the determination of gabapentin and its major degradation impurity in drug products. J. Pharm. Biomed. Anal. 2007, 43 (5), 1647–1653.
    OpenUrlPubMed
  85. 85.
    1. Bakshi M.,
    2. Singh S.
    Development of validated stability-indicating assay methods—critical review. J. Pharm. Biomed. Anal. 2002, 28 (6), 1011–1040.
    OpenUrlCrossRefPubMed
  86. 86.
    1. Dobo K. L.,
    2. Greene N.,
    3. Cyr M. O.,
    4. Caron S.,
    5. Ku W. W.
    The application of structure-based assessment to support safety and chemistry diligence to manage genotoxic impurities in active pharmaceutical ingredients during drug development. Regul. Toxicol. Pharmacol. 2006, 34 (3), 282–293.
    OpenUrl
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PDA Journal of Pharmaceutical Science and Technology: 68 (3)
PDA Journal of Pharmaceutical Science and Technology
Vol. 68, Issue 3
May/June 2014
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Advice on Degradation Products in Pharmaceuticals: A Toxicological Evaluation
Sâmia Rocha de Oliveira Melo, Maurício Homem-de-Mello, Dâmaris Silveira, Luiz Alberto Simeoni
PDA Journal of Pharmaceutical Science and Technology May 2014, 68 (3) 221-238; DOI: 10.5731/pdajpst.2014.00974

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Advice on Degradation Products in Pharmaceuticals: A Toxicological Evaluation
Sâmia Rocha de Oliveira Melo, Maurício Homem-de-Mello, Dâmaris Silveira, Luiz Alberto Simeoni
PDA Journal of Pharmaceutical Science and Technology May 2014, 68 (3) 221-238; DOI: 10.5731/pdajpst.2014.00974
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Keywords

  • Degradation products
  • Toxicity
  • Regulatory guides and standards
  • Safety
  • Quality

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