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Research ArticleTechnology/Application

100% Control of Controlled Ice Nucleation Vials by Camera-Supported Optical Inspection in Freeze-Drying

Julian H. Lenger, Raimund Geidobler, Werner Halbinger, Ingo Presser and Gerhard Winter
PDA Journal of Pharmaceutical Science and Technology March 2022, 76 (2) 120-135; DOI: https://doi.org/10.5731/pdajpst.2020.012575
Julian H. Lenger
1Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-Universität München
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  • For correspondence: julian.lenger@bayer.com gerhard.winter@cup.uni-muenchen.de
Raimund Geidobler
2Pharmaceutical Development Biologicals, Boehringer Ingelheim Pharma GmbH & Co. KG; and
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Werner Halbinger
3Seidenader Maschinenbau GmbH (Körber AG)
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Ingo Presser
2Pharmaceutical Development Biologicals, Boehringer Ingelheim Pharma GmbH & Co. KG; and
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Gerhard Winter
1Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-Universität München
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  • For correspondence: julian.lenger@bayer.com gerhard.winter@cup.uni-muenchen.de
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References

  1. 1.↵
    1. Carpenter J. F.,
    2. Pikal M. J.,
    3. Chang B. S.,
    4. Randolph T. W.
    Rational Design of Stable Lyophilized Protein Formulations: Some Practical Advice. Pharm Res 1997, 14 (8), 969–975.
    OpenUrlCrossRefPubMedWeb of Science
  2. 2.↵
    1. Rey L.,
    2. May J. C.
    1. Pikal M. J.
    Mechanisms of Protein Stabilization during Freeze-Drying and Storage: the Relative Importance of Thermodynamic Stabilization and Glassy State Relaxation Dynamics. In Freeze-Drying/Lyophilization of Pharmaceutical and Biological Products, 2nd ed.; Rey L., May J. C., Eds.; CRC Press: London, New York, 2004.
  3. 3.↵
    1. Gervasi V.,
    2. Dall Agnol R.,
    3. Cullen S.,
    4. McCoy T.,
    5. Vucen S.,
    6. Crean A.
    Parenteral Protein Formulations: An Overview of Approved Products within the European Union. Eur. J. Pharm. Biopharm. 2018, 131, 8–24.
    OpenUrl
  4. 4.↵
    1. Constantino H. R.,
    2. Pikal M. J.
    1. Chang B. S.,
    2. Patro S. Y.
    Freeze-Drying Process Development for Protein Pharmaceuticals. In: Lyophilization of Biopharmaceuticals; Constantino H. R., Pikal M. J., Eds.; Springer: New York, 2004; pp 113–138.
  5. 5.↵
    1. Rambhatla S.,
    2. Pikal M. J.
    Heat and Mass Transfer Scale-Up Issues during Freeze-Drying, I: Atypical Radiation and the Edge Vial Effect. AAPS PharmSciTech 2003, 4 (2), 22–31.
    OpenUrl
  6. 6.↵
    1. Rambhatla S.,
    2. Ramot R.,
    3. Bhugra C.,
    4. Pikal M. J.
    Heat and Mass Transfer Scale-Up Issues during Freeze Drying: II. Control and Characterization of the Degree of Supercooling. AAPS PharmSciTech 2004, 5 (4), 54–62.
    OpenUrl
  7. 7.↵
    1. Patel S. M.,
    2. Pikal M. J.
    Emerging Freeze-Drying Process Development and Scale-up Issues. AAPS PharmSciTech 2011, 12 (1), 372–378.
    OpenUrlCrossRefPubMedWeb of Science
  8. 8.↵
    1. Awotwe-Otoo D.,
    2. Agarabi C.,
    3. Read E. K.,
    4. Lute S.,
    5. Brorson K. A.,
    6. Khan M. A.,
    7. Shah R. B.
    Impact of Controlled Ice Nucleation on Process Performance and Quality Attributes of a Lyophilized Monoclonal Antibody. Int. J. Pharm. 2013, 450 (1–2), 70–78.
    OpenUrl
  9. 9.↵
    1. Awotwe-Otoo D.,
    2. Agarabi C.,
    3. Read E. K.,
    4. Lute S.,
    5. Brorson K. A.,
    6. Khan M. A.
    Product and Process Understanding to Relate the Effect of Freezing Method on Glycation and Aggregation of Lyophilized Monoclonal Antibody Formulations. Int. J. Pharm. 2015, 490 (1–2), 341–350.
    OpenUrl
  10. 10.↵
    1. Esfandiary R.,
    2. Gattu S. K.,
    3. Stewart J. M.,
    4. Patel S. M.
    Effect of Freezing on Lyophilization Process Performance and Drug Product Cake Appearance. J. Pharm. Sci. 2016, 105 (4), 1427–1433.
    OpenUrl
  11. 11.↵
    1. Konstantinidis A. K.,
    2. Kuu W.,
    3. Otten L.,
    4. Nail S. L.,
    5. Sever R. R.
    Controlled Nucleation in Freeze‐Drying: Effects on Pore Size in the Dried Product Layer, Mass Transfer Resistance, and Primary Drying Rate. J. Pharm. Sci. 2011, 100 (8), 3453–3470.
    OpenUrlPubMed
  12. 12.↵
    1. Oddone I.,
    2. Pisano R.,
    3. Bullich R.,
    4. Stewart P.
    Vacuum-Induced Nucleation as a Method for Freeze-Drying Cycle Optimization. Ind. Eng. Chem. Res. 2014, 53 (47), 18236–18244.
    OpenUrl
  13. 13.↵
    1. Oddone I.,
    2. Van Bockstal P. J.,
    3. De Beer T.,
    4. Pisano R.
    Impact of Vacuum-Induced Surface Freezing on Inter- and Intra-Vial Heterogeneity. Eur J Pharm Biopharm 2016, 103, 167–178.
    OpenUrl
  14. 14.↵
    1. Patel S. M.,
    2. Bhugra C.,
    3. Pikal M. J.
    Reduced Pressure Ice Fog Technique for Controlled Ice Nucleation during Freeze-Drying. AAPS PharmSciTech 2009, 10 (4), 1406–1411.
    OpenUrlPubMed
  15. 15.↵
    1. Chakravarty P.,
    2. Lee R.,
    3. DeMarco F.,
    4. Renzi E.
    Ice Fog as a Means to Induce Uniform Ice Nucleation during Lyophilization. BioPharm Int. 2012, 25 (1).
  16. 16.↵
    1. Ling W.
    Controlled Nucleation During Freezing Step of Freeze Drying Cycle Using Pressure Differential Ice Crystals Distribution From Condensed Frost. US, US8875413 B2: Patent no, 2014.
  17. 17.↵
    1. Ling W.
    Controlled Nucleation During Freezing Step of Freeze Drying Cycle Using Pressure Differential Ice Fog Distribution. U.S. Patent US8839528B2, 2014.
  18. 18.↵
    1. Gitter J. H.,
    2. Geidobler R.,
    3. Presser I.,
    4. Winter G.
    A Comparison of Controlled Ice Nucleation Techniques for Freeze-Drying of a Therapeutic Antibody. J. Pharm. Sci. 2018, 107 (11), 2748–2754.
    OpenUrl
  19. 19.↵
    1. Geidobler R.,
    2. Mannschedel S.,
    3. Winter G.
    A New Approach to Achieve Controlled Ice Nucleation of Supercooled Solutions during the Freezing Step in Freeze‐Drying. J. Pharm. Sci. 2012, 101 (12), 4409–4413.
    OpenUrlPubMed
  20. 20.↵
    1. Gasteyer T. H., III;.,
    2. Sever R. R.,
    3. Hunek B.,
    4. Grinter N.,
    5. Verdone M. L.
    Method of Inducing Nucleation of a Material. U.S. Patent US9453675B2, 2016.
  21. 21.↵
    1. Kramer M.,
    2. Sennhenn B.,
    3. Lee G.
    Freeze-Drying Using Vacuum-Induced Surface Freezing. J. Pharm. Sci. 2002, 91 (2), 433–443.
    OpenUrlPubMed
  22. 22.↵
    1. Oddone I.,
    2. Barresi A. A.,
    3. Pisano R.
    Influence of Controlled Ice Nucleation on the Freeze-Drying of Pharmaceutical Products: The Secondary Drying Step. Int. J. Pharm. 2017, 524 (1–2), 134–140.
    OpenUrl
  23. 23.↵
    1. Geidobler R.,
    2. Konrad I.,
    3. Winter G.
    Can Controlled Ice Nucleation Improve Freeze-Drying of Highly-Concentrated Protein Formulations? J. Pharm. Sci. 2013, 102 (11), 3915–3919.
    OpenUrl
  24. 24.↵
    1. Fang R.,
    2. Tanaka K.,
    3. Mudhivarthi V.,
    4. Bogner R. H.,
    5. Pikal M. J.
    Effect of Controlled Ice Nucleation on Stability of Lactate Dehydrogenase during Freeze-Drying. J. Pharm. Sci. 2018, 107 (3), 824–830.
    OpenUrl
  25. 25.↵
    1. Oddone I.,
    2. Arsiccio A.,
    3. Duru C.,
    4. Malik K.,
    5. Ferguson J.,
    6. Pisano R.,
    7. Matejtschuk P.
    Vacuum-Induced Surface Freezing for the Freeze-Drying of the Human Growth Hormone: How Does Nucleation Control Affect Protein Stability? J. Pharm. Sci. 2020, 109 (1), 254–263.
    OpenUrl
  26. 26.↵
    1. Geidobler R.,
    2. Winter G.
    Controlled Ice Nucleation in the Field of Freeze-Drying: Fundamentals and Technology Review. Eur. J. Pharm. Biopharm. 2013, 85 (2), 214–222.
    OpenUrlCrossRefPubMed
  27. 27.↵
    1. Vollrath I.,
    2. Friess W.,
    3. Freitag A.,
    4. Hawe A.,
    5. Winter G.
    Comparison of Ice Fog Methods and Monitoring of Controlled Nucleation Success after Freeze-Drying. Int. J. Pharm. 2019, 558 18–28.
    OpenUrl
  28. 28.↵
    1. Searles J. A.,
    2. Carpenter J. F.,
    3. Randolph T. W.
    The Ice Nucleation Temperature Determines the Primary Drying Rate of Lyophilization for Samples Frozen on a Temperature-Controlled Shelf. J. Pharm. Sci. 2001, 90 (7), 860–871.
    OpenUrlCrossRefPubMedWeb of Science
  29. 29.↵
    1. Lin T. P.,
    2. Hsu C. C.,
    3. Kabakoff B. D.,
    4. Patapoff T. W.
    Application of Frequency-Modulated Spectroscopy in Vacuum Seal Integrity Testing of Lyophilized Biological Products. PDA J. Pharm. Sci. Technol. 2004, 58 (2), 106–115.
    OpenUrlAbstract/FREE Full Text
  30. 30.↵
    1. Singh S. N.,
    2. Kumar S.,
    3. Bondar V.,
    4. Wang N.,
    5. Forcino R.,
    6. Colandene J.,
    7. Nesta D.
    Unexplored Benefits of Controlled Ice Nucleation: Lyophilization of a Highly Concentrated Monoclonal Antibody Solution. Int. J. Pharm. 2018, 552 (1-2), 171–179.
    OpenUrl
  31. 31.↵
    1. Sane P.,
    2. Bogner R. H.,
    3. Bhatnagar B.,
    4. Tchessalov S.
    Reconstitution of Highly Concentrated Lyophilized Proteins: Part 1 Amorphous Formulations. J. Pharm. Sci 2020, 109 (5), 1681–1691.
    OpenUrl
  32. 32.↵
    1. Goshima H.,
    2. Do G.,
    3. Nakagawa K.
    Impact of Ice Morphology on Design Space of Pharmaceutical Freeze-Drying. J. Pharm. Sci. 2016, 105 (6), 1920–1933.
    OpenUrl
  33. 33.↵
    1. Nail S. L.,
    2. Searles J. A.
    Elements of Quality by Design in Development and Scale-Up of Freeze-Dried Parenterals. BioPharm Int. 2008, 21 (1), 40–45.
    OpenUrl
  34. 34.↵
    1. Sundaram J.,
    2. Shay Y. H. M.,
    3. Hsu C. C.,
    4. Sane S. U.
    Design Space Development for Lyophilization Using DOE and Process Modeling. BioPharm Int. 2010, 23 (9), 40–45.
    OpenUrl
  35. 35.↵
    1. Koganti V. R.,
    2. Shalaev E. Y.,
    3. Berry M. R.,
    4. Osterberg T.,
    5. Youssef M.,
    6. Hiebert D. N.,
    7. Kanka F. A.,
    8. Nolan M.,
    9. Barrett R.,
    10. Scalzo G.,
    11. Fitzpatrick G.,
    12. Fitzgibbon N.,
    13. Luthra S.,
    14. Zhang L.
    Investigation of Design Space for Freeze-Drying: Use of Modeling for Primary Drying Segment of a Freeze-Drying Cycle. AAPS PharmSciTech 2011, 12 (3), 854–861.
    OpenUrlPubMed
  36. 36.↵
    1. Patel S. M.,
    2. Pikal M. J.
    Lyophilization Process Design Space. J. Pharm. Sci. 2013, 102 (11), 3883–3887.
    OpenUrl
  37. 37.↵
    1. Awotwe-Otoo D.,
    2. Agarabi C.,
    3. Khan M. A.
    An Integrated Process Analytical Technology (PAT) Approach to Monitoring the Effect of Supercooling on Lyophilization Product and Process Parameters of Model Monoclonal Antibody Formulations. J. Pharm. Sci. 2014, 103 (7), 2042–2052.
    OpenUrl
  38. 38.↵
    1. Schersch K.,
    2. Betz O.,
    3. Garidel P.,
    4. Muehlau S.,
    5. Bassarab S.,
    6. Winter G.
    Systematic Investigation of the Effect of Lyophilizate Collapse on Pharmaceutically Relevant Proteins I: Stability after Freeze‐Drying. J. Pharm. Sci. 2010, 99 (5), 2256–2278.
    OpenUrlPubMed
  39. 39.↵
    1. Luoma J.,
    2. Ingham E.,
    3. Martinez C. L.,
    4. Allmendinger A.
    Comparison of Techniques to Control Ice Nucleation during Lyophilization. Processes 2020, 8 (11), 1439.
    OpenUrl
  40. 40.↵
    1. Wenzel T.,
    2. Gieseler M.,
    3. Gieseler H.
    Investigation of Two Different Pressure-Based Controlled Ice Nucleation Techniques in Freeze-Drying: The Integral Role of Shelf Temperature after Nucleation in Process Performance and Product Quality. J. Pharm. Sci. 2020, 109 (9), 2746–2756.
    OpenUrl
  41. 41.↵
    1. Roy M. L.,
    2. Pikal M. J.
    Process Control in Freeze Drying: Determination of the End Point of Sublimation Drying by an Electronic Moisture Sensor. PDA J. Pharm. Sci. Technol. 1989, 43 (2), 60–66.
    OpenUrlAbstract/FREE Full Text
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PDA Journal of Pharmaceutical Science and Technology: 76 (2)
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100% Control of Controlled Ice Nucleation Vials by Camera-Supported Optical Inspection in Freeze-Drying
Julian H. Lenger, Raimund Geidobler, Werner Halbinger, Ingo Presser, Gerhard Winter
PDA Journal of Pharmaceutical Science and Technology Mar 2022, 76 (2) 120-135; DOI: 10.5731/pdajpst.2020.012575

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100% Control of Controlled Ice Nucleation Vials by Camera-Supported Optical Inspection in Freeze-Drying
Julian H. Lenger, Raimund Geidobler, Werner Halbinger, Ingo Presser, Gerhard Winter
PDA Journal of Pharmaceutical Science and Technology Mar 2022, 76 (2) 120-135; DOI: 10.5731/pdajpst.2020.012575
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Keywords

  • Lyophilization
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