Skip to main content
Log in

Process analytical technology (PAT) for biopharmaceutical products

  • Review
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

The “Pharmaceutical Current Good Manufacturing Practices (CGMPs) for the 21st Century—A Risk Based Approach” initiative announced by the FDA in August 2002 to improve and modernize pharmaceutical manufacturing facilitated adoption of process analytical technology (PAT) by the pharmaceutical industry. The potential for improved operational control and compliance resulting from continuous real-time quality assurance was highlighted as a likely benefit that would result from PAT implementation. A considerable amount of work has been done on this topic by academic and industrial contributors in the last decade. In this paper, we will start with a brief overview of evolution of PAT concepts and a review of their application in the wider pharmaceutical industry. The rest of the paper focuses on PAT applications for biotech processes with emphasis on developments in the last five years. It is our observation that while significant advances have been accomplished with regard to our ability to analyze/monitor key process and quality attributes in the biotech industry, much more needs to be done with regard to utilizing the collected data for subsequent control of the process, to achieve optimum yield and product quality. The latter is necessary to achieve the benefits that will result from PAT implementation.

Ease of PAT implementation for some of the commonly used unit operations in biotech processes

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  1. U.S. Department of Health and Human Services, Food and Drug Administration (2002) http://www.fda.gov/Drugs/DevelopmentApprovalProcess/Manufacturing/QuestionsandAnswersonCurrentGoodManufacturingPracticescGMPforDrugs/UCM071836 Accessed 10 Feb 2010

  2. U.S. Department of Health and Human Services, Food and Drug Administration (2001) A presentation at the Advisory Committee for Pharmaceutical Science by Dr. Ajaz S. Hussain http://www.fda.gov/ohrms/dockets/ac/cder01.htm#Pharmaceutical%20Science Accessed 10 Feb 2010

  3. Hinz DC (2006) Anal Bioanal Chem 384:1036–1041

    Article  CAS  Google Scholar 

  4. Miller RW (2002) Am Pharm Rev 5(2):25–29

    Google Scholar 

  5. Miller RW (2003) Am Pharm Rev 6(1):52–61

    Google Scholar 

  6. U.S. Department of Health and Human Services, Food and Drug Administration (2002) Federal Register 67 (25) – Notice http://www.fda.gov/OHRMS/DOCKETS/98fr/020602e.pdf Accessed 19 Feb 2010

  7. U.S. Department of Health and Human Services, Food and Drug Administration (2003) Guidance for industry: PAT—a framework for innovative pharmaceutical, manufacturing and quality assurance http://www.fda.gov/ohrms/dockets/ac/03/briefing/3996B1_03_GFI-Pat.pdf Accessed 28 Dec 2009

  8. U.S. Department of Health and Human Services, Food and Drug Administration (2004) Guidance for industry: PAT—a framework for innovative pharmaceutical development, manufacturing and quality assurance http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm070305.pdf Accessed 28 Dec 2009

  9. Guidance for Industry: Q8(R2) Pharmaceutical Development, US Department of Health and Human Service, Food and Drug Administration (FDA). August, 2009. http://www.ich.org/LOB/media/MEDIA4986.pdf

  10. Rathore AS, Winkle H (2009) Nat Biotechnol 27:26–34

    Article  CAS  Google Scholar 

  11. Rathore AS (2009) Trends Biotechnol 27(9):546–553

    Article  CAS  Google Scholar 

  12. Van Hoek P, Hamrs J, Wang X, Rathore AS (2009) In: Rathore AS, Mhatre R (ed) Quality by design for biopharmaceuticals: Perspectives and case studies. Wiley Interscience

  13. Arora T, Greene R, Mercer J, Tsang P, Casais M, Feldman S, Look J, Lubiniecki T, Mezzatesta J, Pluschkell S, Rosolowsky M, Rathore AS, Schenerman M, Schofield T, Sheridan S, Smock P, Anliker S, McGarvey B, Meiklejohn B, Precup J (2009) Biopharm Int 22(11):26–36

    Google Scholar 

  14. Arora T, Greene R, Mercer J, Tsang P, Casais M, Feldman S, Look J, Lubiniecki T, Mezzatesta J, Pluschkell S, Rosolowsky M, Rathore AS, Schenerman M, Schofield T, Sheridan S, Smock P, Anliker S, Atkins L, McGarvey B, Meiklejohn B, Precup J (2010) Biopharm Int 23(1):26–36

    Google Scholar 

  15. Rathore AS (2009) Trends Biotechnol 27(12):698–705

    Article  CAS  Google Scholar 

  16. Scott B, Wilcock A (2006) J Pharm Sci Technol 60(1):17–53

    Google Scholar 

  17. Rathore AS, Gerhardt AS, Montgomery SH, Tyler SM (2009) Biopharm Int 22(1):36–44

    Google Scholar 

  18. Read EK, Park JT, Shah RB, Riley BS, Brorson KA, Rathore AS (2009) Biotechnol Bioeng 105(2):276–284

    Article  CAS  Google Scholar 

  19. Read EK, Park JT, Shah RB, Riley BS, Brorson KA, Rathore AS (2009) Biotechnol Bioeng 105(2):285–295

    Article  CAS  Google Scholar 

  20. Seely J (2005) In: Rathore AS and Sofer G (ed) Process validation in Manufacturing of Biopharmaceuticals Taylor and Francis

  21. Freund H, Sundmacher K (2008) Chem Eng Process 47:2051–2060

    CAS  Google Scholar 

  22. Koch MV (2006) Anal Bioanal Chem 384:1049–1053

    Article  CAS  Google Scholar 

  23. Simon H (1956) Process Applications of Analytical Instruments. Instrum Autom 29:1141–1145

    CAS  Google Scholar 

  24. Clevett KJ (1986) Process analyzer technology. Wiley-Interscience, New York

    Google Scholar 

  25. Koch KH (1997) Process analytical chemistry. Springer, New York

    Google Scholar 

  26. Chalmers JM ed (2000) Spectroscopy in process analysis. CRC Press, Boca Raton, FL

  27. Bakeev KA ed (2005) Process analytical technology: spectroscopic tools and implementation strategies for the chemical and pharmaceutical industries. Blackwell Publishing, Oxford

  28. Beebe KR, Blaser WW, Bredeweg RA, Chauvel JP, Harner RS, Lapack M, Leugers A, Martin DP, Wright LG, Yalvac ED (1993) Anal Chem 65(12):R199–R216

    Article  Google Scholar 

  29. Workman J, Koch M, Veltkamp DJ (2003) Anal Chem 75:2859–2876

    Article  CAS  Google Scholar 

  30. De Fatima L, de Lira B, Vasconcelos FVC, Pereira CF, Paim APS, Stragevitch L, Pimentel MF (2010) Fuel 89:405–409

    Article  CAS  Google Scholar 

  31. Prinsloo NM, Engelbrecht JP, Mashapa TN, Strauss MJ (2008) Appl Catal A-Gen 344:20–29

    Article  CAS  Google Scholar 

  32. Halstensen M, Bakker P, Esbensen KH (2006) Chemometr Intell Lab 84:88–97

    Article  CAS  Google Scholar 

  33. Seasholtz MB (1999) Chemometr Intell Lab 45:53–63

    Google Scholar 

  34. Fernandes HL, Raimundo IM, Pasquini C, Rohwedder JJR (2008) Talanta 75:804–810

    Article  CAS  Google Scholar 

  35. Qu H, Alatalo H, Hatakka H, Kohonen J, Louhi-Kulanen M (2009) J Cryst Growth 311:3466–3475

    Article  CAS  Google Scholar 

  36. Ward HW, Sistare FE (2007) Anal Chim Acta 595:319–322

    Article  CAS  Google Scholar 

  37. Junker BH, Wang HY (2006) Biotechnol Bioeng 95(2):226–261

    Article  CAS  Google Scholar 

  38. Medendorp J, Lodder RA (2006) AAPS Pharm Sci Tech 7(1):E1–E9

    Article  Google Scholar 

  39. Mantanus J, Ziemons E, Lebrun P, Rozet E, Klinkenberg R, Streel B, Eyrard B, Hubert P (2009) Talanta doi:10.1016/j.talanta.2009.10.019

  40. Akseli I, Cetinkaya C (2008) Int J Pharm 359:25–34

    Article  CAS  Google Scholar 

  41. Ho L, Muller R, Romer M, Gordon KC, Heinamaki J, Kleinebudde P, Pepper M, Rades T, Shen YC, Strachan CJ, Taday PF, Zeitler JA (2007) J Control Release 119:253–261

    Article  CAS  Google Scholar 

  42. Ghorab MK, Chatlapalli R, Hasan S, Nagi A (2007) AAPS Pharm Sci Tech 8(1) Article 23 doi:10.1208/pt0801023

  43. Li W, Bagnol L, Berman M, Chiarella R, Gerber M (2009) Int J Pharm 380:49–54

    Article  CAS  Google Scholar 

  44. Benedetti C, Abatzoglou N, Simard JS, McDermott L, Leonard G, Cartilier L (2007) Int J Pharm 336:292–301

    Article  CAS  Google Scholar 

  45. Sun C, Zang H, Liu X, Dong Q, Li L, Wang F, Su L (2009) J Pharm Biomed Anal doi:10.1016/j.jpba.2009.11.022

  46. Rosa SS, Barata PA, Martins JM, Menezes JC (2008) Talanta 75:725–733

    Article  CAS  Google Scholar 

  47. Paris I, Janoly-Dumenil A, Paci A, Mercier L, Bourget P, Brion F, Chaminade P, Rieutord A (2006) J Pharm Biomed Anal 41:1171–1178

    Article  CAS  Google Scholar 

  48. Lopez-Arellano R, Santander-Garcia EA, Andrade-Garda JM, Alvarez-Avila G, Garduno-Rosas JA, Morales-Hipolito EA (2009) Vib Spectrosc 51:255–262

    Article  CAS  Google Scholar 

  49. Tabasi SH, Moolchandani V, Fahmy R, Hoag SW (2009) Int J Pharm 382:1–6

    Article  CAS  Google Scholar 

  50. St-Onge L, Kwong E, Sabsabi M, Vadas EB (2004) J Pharm Biomed Anal 36:277–284

    Article  CAS  Google Scholar 

  51. Schellekens H (2009) Nephrol Dial Transplant 2(Suppl 1):i27–i36

  52. Kirdar AO, Chen G, Rathore (2010) Biotechnol Prog 26:527–531

    CAS  Google Scholar 

  53. Rathore AS, Sharma A, Chillin D (2006) Biopharm Int 19:48–57

    Google Scholar 

  54. Rathore AS, Wood R, Sharma A, Dermawan S (2008) Biotechnol Bioeng 101(6):1366–1374

    Article  CAS  Google Scholar 

  55. Rathore AS, Yu M, Yeboah S, Sharma A (2008) Biotechnol Bioeng 100(2):306–316

    Article  CAS  Google Scholar 

  56. Rathore AS, Parr L, Dermawan S, Lawson K, Lu Y (2010) Biotechnol Prog 26:448–457

    Google Scholar 

  57. Konstantinov K, Chuppa S, Sajan E, Tsai Y, Yoon S, Golini F (1994) Tibtech 12:324–333

    CAS  Google Scholar 

  58. Zhang J, Zhou H, Ji Z, Regnier F (1998) J Chromatogr B 707:257–265

    Article  CAS  Google Scholar 

  59. Chan C, Lo W, Wong KY (2000) Biosens Bioelectron 15:7–11

    Article  CAS  Google Scholar 

  60. Guenneugues P, Chibois S, Trystram G (1990) Food Control 1(4):236–241

    Article  Google Scholar 

  61. Armenta S, Garrigues S, Gauradia M, Rondeau P (2005) Anal Chem Acta 545:99–106

    Article  CAS  Google Scholar 

  62. Salgado AM, Folly ROM, Valdman B (2001) Sensor Actuator B 75:24–28

    Article  Google Scholar 

  63. Chen Y, Krol J, Huang W, Cino JP, Vyas R, Mirro R, Vaillancourt B (2008) Process Biochem 43:351–355

    Article  CAS  Google Scholar 

  64. Ferreira LS, Desouza MB, Folly ROM (2001) Sensor Actuator B 75:166–171

    Article  Google Scholar 

  65. Zeaiter M, Roger JM, Bellon-Maurel V (2006) Chemometr Intell Lab 80:227–235

    Article  CAS  Google Scholar 

  66. Triadaphillou S, Martin E, Montague G, Norden A, Jeffkins P, Stimpson S (2007) Biotechnol Bioeng 97(3):554–567

    Article  CAS  Google Scholar 

  67. Hofmann MC, Ellersiek D, Kensy F, Buchs J, Mokwa W, Schnakenberg U (2005) Sensor Actuator B 111–112:370–375

    Article  CAS  Google Scholar 

  68. Johansen C, Christensen LH, Nielsen J, Villadsen J (1992) Comp Chem Eng 16:S297–S304

    Article  CAS  Google Scholar 

  69. Tothill IE, Newman JD, White SF, Turner APF (1997) Enzyme Microb Tech 20:590–596

    Article  CAS  Google Scholar 

  70. Gordon SH, Green RV, Wheeler BC, James C (1993) Biotechnol adv 11:665–675

    Article  CAS  Google Scholar 

  71. Pescheck M, Schrader J, Sell D (2005) Bioelectrochemistry 67:47–55

    Article  CAS  Google Scholar 

  72. Heinzle E, Oeggerli A, Dettwiler B (1990) Anal Chim Acta 238:101–115

    Article  CAS  Google Scholar 

  73. Shu H, Hakanson H, Mattiason B (1995) Anal Chim Acta 300:227–285

    Article  Google Scholar 

  74. Chauvatcharins S, Seki T, Fujiyama K, Yoshida T (1995) J Ferment Bioeng 79(3):264–269

    Article  Google Scholar 

  75. Rhee J, Kang T (2007) Process Biochem 42:1124–1134

    Article  CAS  Google Scholar 

  76. Holm-Nielsen JB, Lomborg CJ, Oleskowicz-Popiel P, Esbensen KH (2008) Biotechnol Bioeng 99(2):302–313

    Article  CAS  Google Scholar 

  77. Tarkiainen V, Kotiaho T, Mattila I, Virkajarvi I, Aristidou A, Ketola R (2005) Talanta 65:1254–1263

    Article  CAS  Google Scholar 

  78. Cimander C, Carlsson M, Mandenius C (2002) J Biotechnol 99:237–248

    Article  CAS  Google Scholar 

  79. Appleqvist R, Hansen EH (1990) Anal Chim Acta 235:265–271

    Article  Google Scholar 

  80. Brooks SL, Ashby RE, Turner APF, Calder MR, Clarke DJ (1987/1988) Biosensor 3:45–56

    Article  CAS  Google Scholar 

  81. Rank M, Danielsson B (1992) Biosens Bioelectron 7:631–635

    Article  CAS  Google Scholar 

  82. Xie Y, Zeng H, Yao S, Wei W (1999) Talanta 50:1019–1025

    Article  CAS  Google Scholar 

  83. Zhang J, Xie Y, Dia X, Wei W (2001) J Microbiol Meth 44:105–111

    Article  CAS  Google Scholar 

  84. Morovjan G, Szakacs G, Fekete J (1997) J Chromatogr A 763:165–172

    Article  CAS  Google Scholar 

  85. Merbel NC (1997) Trends Anal Chem 16(3):162–172

    Article  Google Scholar 

  86. Kirdar AO, Green KD, Rathore AS (2008) Biotechnol Prog 24:720–726

    Article  CAS  Google Scholar 

  87. Macaloney G, Draper I, Preston J, Anderson KB, Rollins MJ, Thompson BG, Hall JW, McNeil B (1996) Trans I ChemE 74(c):212–220

    CAS  Google Scholar 

  88. Gnoth S, Jenzsch M, Simutis R, Lubbert A (2007) J Biotechnol 132:180–186

    Article  CAS  Google Scholar 

  89. Huang YL, Li SY, Dremel BAA, Bilitewski U, Schmid RD (1991) J Biotechnol 18:161–172

    Article  CAS  Google Scholar 

  90. Sarra M, Ison AP, Lilly MD (1996) J Biotechnol 51:157–165

    Article  CAS  Google Scholar 

  91. Guez JS, Cassar JPh, Wartelle F, Dhulster, Suhr H (2004) J Biotechnol 111:335–341

    Article  CAS  Google Scholar 

  92. Fehrenbach R, Comberbach M, Ptre JO (1992) J Biotechnol 23:303–314

    Article  CAS  Google Scholar 

  93. Taya M, Hegglin M, Prenosil JE, Bourne JR (1989) Enzyme Microb Tech 11:170–176

    Article  CAS  Google Scholar 

  94. Ruffieux P, Stockar UV, Marison IW (1998) J Biotechnol 63:85–95

    Article  CAS  Google Scholar 

  95. Navratil M, Norberg A, Lamben M, Mandenius C (2005) J Biotechnol 115:67–79

    Article  CAS  Google Scholar 

  96. Noll T, Biselli M (1998) J Biotechnol 63:187–198

    Article  CAS  Google Scholar 

  97. Mishima K, Mimura A, Takahara Y, Asami K, Hanai T (1991) J Ferment Bioeng 72(4):291–295

    Article  CAS  Google Scholar 

  98. Mishima K, Mimura A, Takahara Y (1991) J Ferment Bioeng 72(4):296–299

    Article  CAS  Google Scholar 

  99. Odman P, Johansen CL, Olsson L, Gernaey K, Lantz AE (2009) J Biotechnol 144:102–112

    Article  CAS  Google Scholar 

  100. Bachinger T, Riese U, Eriksson R, Mandenius C (2002) Biosens Bioelectron 17:395–403

    Article  CAS  Google Scholar 

  101. Kemp KB, Guan Y (1998) Thermochim Acta 309:63–78

    Article  CAS  Google Scholar 

  102. Goudar C, Biener R, Boisart C, Heidemann R, Piret J, Graaf A, Konstantinov K (2009) Metab Eng doi:10.1016/j.ymben.2009.10.007

  103. Kussow CM, Zhou W, David M, Gryte S, Hu W (1995) Enzyme Microb Tech 17:779–783

    Article  CAS  Google Scholar 

  104. Reinecke M, Scheper T (1997) J Biotechnol 59:145–153

    Article  CAS  Google Scholar 

  105. Renneberg R, Trott-Kriegeskorte, Lietz M, Jager V, Pawlowa M, Kaiser G, Wollenberger U, Schubert F, Wagner R, Schmid RD, Scheller FW (1991) J Biotechnol 21:173–186

    Article  CAS  Google Scholar 

  106. Vanderpol J, Spohn U, Eberhardt R, Gaetgens J, Biselli M, Wandrey C, Tramper J (1994) J Biotechnol 37:253–264

    Article  CAS  Google Scholar 

  107. Dremel BAA, Li SY, Schmid RD. Biosens Bioelectron 7:133-139

  108. Guez JS, Cassar JPh, Wartelle F, Dhulster, Suhr H (2009) Process Biochem 45(2):288–291

    Article  CAS  Google Scholar 

  109. Carvell JP, Dowd JE (2006) Cytotechnology 50:35–48

    Article  CAS  Google Scholar 

  110. Henry O, Kamen A, Perrier M (2007) J Process Contr 17:241–251

    Article  CAS  Google Scholar 

  111. Sitton G, Srienc F (2008) J Biotechnol 135:174–180

    Article  CAS  Google Scholar 

  112. Teixeira AP, Portugal CA, Carrinhas N, Dias JM, Crespo JP, Alves PM, Carrondo MJ, Oliveira R (2008) Biotechnol Bioeng 102:1098–1106

    Article  CAS  Google Scholar 

  113. Yigsaw Y, Piper R, Tran M, Shukla AA (2006) Biotechnol Prog 22:288–296

    Article  CAS  Google Scholar 

  114. Lorenz JK, Reo JP, Hendl O, Worthington JH, Petrossian VD (2009) Int J Pharm 367:65–72

    Article  CAS  Google Scholar 

  115. Maheshkumar S, Madhu GM, Roy S (2007) Sep Purif Technol 57:25–36

    Article  CAS  Google Scholar 

  116. Kuberkar V, Davis R (2001) J Membrane Sci 183:1–14

    Article  CAS  Google Scholar 

  117. Kuentz M, Rothlisberger D (2003) Eur J Pharm Biopharm 56(3):355–361

    Article  CAS  Google Scholar 

  118. Rodrigues LO, Cardoso JP, Menezes JC (2008) Biotechnol Prog 24:432–435

    Google Scholar 

  119. Bluma A, Hopfner T, Rudolph G, Lindner P, Beutel S, Hitzmann B, Scheper T (2009) J Cryst Growth 311(17):4193–4198

    Article  CAS  Google Scholar 

  120. Fujiwara M, Nagy ZK, Chew JW, Braatz RD (2005) J Process Contr 15(5):493–504

    Article  CAS  Google Scholar 

  121. Sharff A, Jhoti J (2003) Curr Opin Chem Bio 7:340–345

    Article  CAS  Google Scholar 

  122. Woerd M, Ferree D, Pusey M (2003) J Struct Biol 142:180–187

    Article  CAS  Google Scholar 

  123. Hansen CL, Skordalakes E, Berger JM, Quake SR (2002) Proc Natl Acad Sci 99:16531–16536

    Article  CAS  Google Scholar 

  124. Shall CA, Riley JS, Li E, Arnold E (1996) J Cryst Growth 165:299–307

    Article  Google Scholar 

  125. Jones WF, Wiencek JM, Darcey PA (2001) J Cryst Growth 232:221–228

    Article  CAS  Google Scholar 

  126. Shenoy B, Wang Y, Shan W, Margolin AL (2001) Biotech Bioeng 73:358–369

    Article  CAS  Google Scholar 

  127. Low DKR (1986) J Chem Tech Biotechnol 36:345–350

    CAS  Google Scholar 

  128. Cooley RE, Stevenson CE (1992) Process Control Qual 2:43–53

    CAS  Google Scholar 

  129. Fahrner RA, Lester PM, Blank GS, Reifsnyder DH (1998) J Chromatogr A 827:37–43

    Article  CAS  Google Scholar 

  130. Fahrner RA, Blank GS (1999) J Chromatogr A 849:191–196

    Article  CAS  Google Scholar 

  131. Barackman J, Prado I, Karunatilake C, Furuya K (2004) J Chromatogr A 1043:57–64

    Article  CAS  Google Scholar 

  132. Kim M, Chung H, Woo Y, Kemper MS (2007) Anal Chim Acta 587:200–207

    Article  CAS  Google Scholar 

  133. Park SC, Kim M, Noh J, Chung H, Woo Y, Lee J, Kemper MS (2007) Anal Chim Acta 593:43–53

    Google Scholar 

  134. Rathore AS, Li X, Bartkowski W, Sharma S, Lu Y (2009) Biotech Prog 25:1433–1439

    Article  Google Scholar 

  135. Mets H, Mader K (2008) Int J Pharm 364:170–175

    Article  CAS  Google Scholar 

  136. Nordon A, Littlejohn D, Dann AS, Jeffkins PA, Richardson MD, Stimpson SL (2008) Analyst 133:660–666

    Article  CAS  Google Scholar 

  137. Genin N, Rene F, Corrieu G (1996) Chem Eng Process 35:255–263

    Article  CAS  Google Scholar 

  138. Zhou GX, Ge Z, Dorwart J, Izzo B, Kupura J, Bicker G, Wyvratt J (2003) J Pharm Sci 92(5):1058–1065

    Article  CAS  Google Scholar 

  139. Velardi SA, Hamouri H, Barresi AA (2009) Chem Eng Res Des 87:1409–1419

    Article  CAS  Google Scholar 

  140. Gieseler H, Kessler WJ, Finson M, Davis SJ, Mulhall PA, Bons V, Debo DJ, Pikal MJ (2007) J Pharm Sci 96(7):1776–1793

    Article  CAS  Google Scholar 

  141. Barresi AA, Pisano R, Fissore D, Rasetto V, Vallan A, Parvis M, Galan M (2009) Chem Eng Process 48:408–423

    CAS  Google Scholar 

  142. Martin EB, Morris AJ (2002) J Biotechnol 99:223–235

    Article  CAS  Google Scholar 

  143. Kourti T (2004) Process Anal Technol 1:13–19

    Google Scholar 

  144. Barnes RJ, Dhanoa MS, Lister SJ (1993) J Infrared Spectrosc 1:185–186

    Article  CAS  Google Scholar 

  145. Roggo Y, Chalus P, Maurer L, Lema-Martinez C, Edmond A, Jent N (2007) J Pharm Biomed Anal 44:683–700

    Article  CAS  Google Scholar 

  146. Teixeira AP, Oliveira R, Alves PM, Carrondo MJT (2009) Biotechnol Adv 27:726–732

    Article  CAS  Google Scholar 

  147. Geladi P (2003) Spectrochim Acta B 58:767–782

    Article  CAS  Google Scholar 

  148. Pedersen DK (2002) PhD Thesis Spectroscopic and chemo metric exploration of food quality submitted to Department of Dairy and Food Science The Royal Veterinary and Agricultural University Denmark, 16-29

  149. Johnson R, Kirdar AO, Annamalai A, Ahuja S, Ram K, Rathore AS (2007) Biopharm Int 20:130–144

    CAS  Google Scholar 

  150. Kansakoski, Markku, Kurkinen, Marika, Weymarn, Niklas, Niemela, Pentti, Neubauer, Peter, Juuso, Esko, Eerikainen, Tero, Turunen, Seppo, Aho, Sirkka and Suhonen, Pirkko (2006) VTT Working Papers 1459-7683 http://www.vtt.fi/publications/index.jsp Accessed on 14 January 2010

  151. Wold S, Cheney J, Kettaneh N, McCready C (2006) Chemometr Intell Lab 84:159–163

    Article  CAS  Google Scholar 

  152. Vaidyanathan S, Arnold SA, Matheson L, Mohan P, McNeil B, Harvey LM (2001) Biotechnol Bioeng 74:376–388

    Article  CAS  Google Scholar 

  153. Undey C, Ertunc S, Cinar A (2003) Ind Eng Chem Res 42:4645–4558

    Article  CAS  Google Scholar 

  154. Moller SF, Von Frese J, Bro R (2005) J Chemometrics 19:549–563

    Article  CAS  Google Scholar 

  155. Kirdar AO, Conner JS, Baclaski J, Rathore AS (2007) Biotechnol Prog 23:61–67

    Article  CAS  Google Scholar 

  156. Gunther JC, Conner JS, Seborg DE (2007) Biotechnol Prog 23:851–857

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A. S. Rathore.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rathore, A.S., Bhambure, R. & Ghare, V. Process analytical technology (PAT) for biopharmaceutical products. Anal Bioanal Chem 398, 137–154 (2010). https://doi.org/10.1007/s00216-010-3781-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-010-3781-x

Keywords

Navigation