Lyophilized Drug Product Cake Appearance: What Is Acceptable?
Cake appearance is an important attribute of freeze-dried products, which may or may not be critical with respect to product quality (i.e., safety and efficacy). Striving for "uniform and elegant" cake appearance may continue to remain an important goal during the design and development of a lyophilized drug product. However, "sometimes" a non-ideal cake appearance has no impact on product quality and is an inherent characteristic of the product (due to formulation, drug product presentation, and freeze-drying process). This commentary provides a summary of challenges related to visual appearance testing of freeze-dried products, particularly on how to judge the criticality of cake appearance. Furthermore, a harmonized nomenclature and description for variations in cake appearance from the ideal expectation of uniform and elegant is provided, including representative images. Finally, a science and risk-based approach is discussed on establishing acceptance criteria for cake appearance.
Department of Formulation Sciences, Biopharmaceutical Development, MedImmune, 1 Medimmune Way, Gaithersburg, Maryland 20878. Electronic address: PatelSaj@medimmune.com.
Sajal Manubhai
SM
Patel
Baxter Medical Products R&D, Baxter Healthcare, Bloomington, Indiana 47403.
Steven L
SL
Nail
Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut 06269.
Michael J
MJ
Pikal
Clinical Supply and Transfer, Boehringer Ingelheim, Ingelheim am Rhein, Germany.
Raimund
R
Geidobler
Department of Pharmacy, Ludwig Maximilian University of Munich, Munich 81377, Germany.
Gerhard
G
Winter
Coriolis Pharma, Am Klopferspitz 19, Martinsried, Munich 82152, Germany.
Andrea
A
Hawe
Formulation Technologies, KBI Biopharma, Inc., Durham, North Carolina 27704.
Juan
J
Davagnino
Drug Product Development, Janssen R&D, Malvern, Pennsylvania 19355.
Shailaja
S
Rambhatla Gupta
D004339:Drug Compounding / Q000379:methods; D004355:Drug Stability; D005612:Freeze Drying / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D044367:Phase Transition; D011786:Quality Control
D004364:Pharmaceutical Preparations
amorphous; drying; formulation; freeze drying; glass transition; lyophilization; processing; protein formulation; stability