AN INTERVIEW WITH...
Interview Partner: Shawn Cain
Chief Operating Officer LSNE
In general, how has the lyophilization market JOHUNLK V]LY [OL SHZ[ Ä]L `LHYZ& /V^ OH]L [OLZL
changes allowed LSNE to better assist your clients?
Lyophilization development has evolved to take a more comprehensive approach to understanding the formulation of the drug product to be lyophilized. A few of the primary tools LSNE uses to develop pharmaceutically elegant lyophilized dosage forms are modulated Differential Scanning Calorimetry (mDSC) and Freeze Dry Microscopy (FDM). We also use a ‘vial thief’ which allows our scientists to remove samples during the course of the lyophilization cycle development run and obtain real time information about the product as it is going through the lyophilization process. We utilize a Quality by Design (QbD) approach to reduce the number of iterations required during the formulation and lyophilization cycle development phase to plan our development pathway to save our clients time and money while providing the best drug product presentation possible. The time spent obtaining a comprehensive \UKLYZ[HUKPUN VM [OL [OLYTHS WYVÄSL VM [OL MVYT\SH[PVU HUK P[Z MYLLaPUN point, glass transition temperature, collapse temperature, and eutectic temperature, allows LSNE to develop a robust/optimized lyophilization cycle. By optimizing the lyophilization cycle at an early stage of clinical development, a cost savings is realized by having a reduced lyophilization cycle time which will save our clients’ money throughout the product’s lifecycle. In addition to the reduced lyophilization cycle time, the optimized drug product has greater stability and this can be demonstrated at an earlier stage by conducting the required ICH Stability Studies with an advanced lyophilized Drug Product.
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lyophilization scale-up processes and larger scale GMP processes? What should a pharmaceutical manufacturer keep in mind when scaling up a lyophilization process?
Yes, transferring a lyophilization process from small scale development to a large scale clinical or commercial lyophilizer has some challenges. LSNE uses proprietary algorithms to transfer projects from lyophilization cycle development to large scale cGMP manufacturing. We have a ]HZ[ HTV\U[ VM L_WLYPLUJL PU LMÄJPLU[S` KL]LSVWPUN HUK VW[PTPaPUN lyophilization cycles in our development scale lyophilizers (down to 4.6 square feet) and transferring the lyophilization process to our largest cGMP lyophilizer (270 square feet). First and foremost it is critical to understand the capabilities of the large production lyophilizers and the WHYHTL[LYZ [OH[ JHU IL VI[HPULK ;OLZL WYV]PKL ZWLJPÄJ KLZPNU H[[YPI\[LZ critical to a successful transfer of the cycle. LSNE uses several types of
equipment and tools to evaluate this lyophilization process transfer, including thermocouples, capacitance manometers, Pirani gauges, and extensive analytical testing, to name a few.
For lyophilization cycles that have been developed by our clients or another CDMO, LSNE prefers to use a stepwise approach for the process transfer [V LUZ\YL HU LMÄJPLU[ WYVJLZZ H[ VUL VM V\Y [OYLL J.47 THU\MHJ[\YPUN facilities. During the transfer of a new lyophilization cycle developed by a 3rd party, a small scale non-GMP technical transfer run is conducted. As API or BDS is so valuable to our client’s development and clinical programs, we develop a plan with the client to minimize the amount of Drug Substance or API used. A preferred method is to add active vials to various areas of the development lyophilizer for testing; a standard approach is to place active vials in the front, back, left, right, top, middle, and bottom. To ensure the lyophilizer is simulating a full lyophilization run, we will add dunnage to load the rest of the lyophilizer’s shelves. The dunnage is typically the formulation without the active (placebo) or WFI. The info from this transfer run is discussed with the client and we may offer suggestions for further development/optimization. After the initial small scale technical transfer run has been successfully completed, LSNE will use its scale-up algorithms to develop a cycle for the larger production lyophilizers. Next, we will perform an engineering run, using the same Production units that will be utilized in the cGMP batches. This engineering Y\U YLK\JLZ YPZR HUK LUZ\YLZ HU LMÄJPLU[ HUK J.47 JVTWSPHU[ WYVJLZZ PZ PU place prior to the cGMP batch run. During the engineering run, not only is the lyophilization cycle itself evaluated, but all aspects of the process are HZZLZZLK" MYVT MVYT\SH[PVU [V ÄS[YH[PVU [V [OL ÄSSPUN VM [OL ]PHS [V LUZ\YL UV product adheres to the sides of the vial or near the stopper.
In particular, can you tell me how LSNE’s
technologies, services and experience can help a pharmaceutical manufacturer develop a robust lyophilization scale-up process that can be
quickly and economically transferred to a GMP manufacturing operation with little risk?
LSNE is an industry leader as a CMO with the largest number of lyophilizers in service in North America. We have multiple development lyophilizers ranging in size from 4.6 square feet to 14 square feet. We have the ability to run multiple formulations in identical development lyophilizers which greatly speeds up the formulation and lyophilization cycle development process. LSNE also has almost 20 years of experience in successfully developing over 400 lyophilization cycles for our clients. We have seen many complex formulations and families of molecules and have faced many technically challenging development projects.
Pharmaceutical Outsourcing | 26 | November/December 2016
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