FRESH PERSPECTIVES
Optimization of Primary Drying Time Using a Combination of ControLyo™ Nucleation on Demand and SMART™ Freeze Dryer Technology
Mark Shon SP Scientific
Given significant costs of producing a freeze-dried product (including equipment, utilities, etc.) along with the desire to decrease development timelines to get products on the market faster, reducing cycle development times and shortening the drying cycles are two significant financial drivers in today’s industry.
Current conventional cycle development still consists of a trial and error methodology. Based on knowledge of the critical temperature of a formulation (glass transition, Tg
’, or collapse temperature, Tc ), the goal is to narrowly control heat flow into the product to avoid the product temperature
exceeding this critical formulation temperature. Exceeding this could lead to melting or collapse of the freeze-dried cake, which compromises the quality attributes of the final drug product. Heat is generally added by shelf temperature adjustment and the process requires the development scientist to make a small change to the shelf temperature, then wait and watch the impact on product temperature. This process is repeated until the scientist finds a shelf temperature resulting in a product temperature close to the critical formulation temperature, controlled typically about 3-5°C below this critical temperature boundary (safety margin). It is also important to not allow this safety margin to be too large, as for each 1°C warmer the freeze dryer is run, primary drying can be reduced by up to 13%.
In practice, collaborations with large pharmaceutical companies have shown that it can take 8-10 attempts (or more) and an average of 60 days to develop a cycle for one product. If a company produces 6-8 new drugs a year that require freeze-drying, this could require the development of as many as 100 cycles per year.
Mark Shon is Vice President of Technology
Development for SP Scientific. His career includes over 20 years of managing businesses that
primarily develop and manufacture equipment for Life Sciences research, development and production. Previous positions include:
President, CEO Savant Instruments; President, CEO, E-C Apparatus; and Director of Business
Development for Thermo Fisher Scientific. Mark holds graduate degrees in Molecular/Cellular Biology and Business.
Fortunately, faster and less costly technology is available to develop an optimized cycle. SP Scientific’s Lyostar 3 development freeze dryer incorporates a technology called SMART™ freeze-drying. SMART™ was developed by the University of Connecticut and Purdue University through the Center for Pharmaceutical Processing Research (CPPR) and licensed to SP [1]. Given information that is readily available, such as the number of vials, fill volume, fill weight, freeze dryer chamber volume and most importantly, the critical formulation temperature, SMART™ does the following to optimize a cycle:
1. Selects an optimum freezing cycle based on whether the formulation is crystalline or amorphous. For crystalline products, it will automatically run a predefined annealing step.
2. Selects the optimum chamber pressure. 3. Automatically determines the target temperature of the product (between 3 to 5°C below Tc
).
4. Dynamically adjusts the shelf temperature during primary drying to keep the product at the pre-determined target temperature.
54 American Pharmaceutical Review | Fresh Perspectives 2013
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68 |
Page 69 |
Page 70 |
Page 71 |
Page 72 |
Page 73 |
Page 74 |
Page 75 |
Page 76 |
Page 77 |
Page 78 |
Page 79 |
Page 80 |
Page 81 |
Page 82 |
Page 83 |
Page 84 |
Page 85 |
Page 86 |
Page 87 |
Page 88 |
Page 89 |
Page 90 |
Page 91 |
Page 92