PepTalk 2009

header.jpg

navigation.jpg

Overview | Short Courses |Day 1 | Day 2 | Day 3 | Download Brochure

Day Three

Wednesday, January 14

7:00am – 5:30pm Registration

7:30 Breakfast Workshop (Sponsorship Available)

8:15 Chairperson’s Remarks
Lisa Hardwick, Research Associate, Baxter BioPharma Solutions

Characterizing the Design Space: Perspective on QbD

8:20 Design Space for Lyophilization
Samir Sane, Ph.D., Group Leader and Principal Engineer, Global Manufacturing Sciences and Technology, Genentech
Lyophilization involves numerous input parameters pertaining to the process setpoints, equipment and product configuration. It is important to fully understand how all these inputs influence the key output parameters related to process dynamics (e.g. product temperature), finished product attributes (e.g. cake appearance and moisture content), and ultimately the biochemical quality and long-term stability of the drug product. FDA’s Quality by Design initiative and emphasis on characterizing the design space is an excellent opportunity to apply the science of lyophilization and consistently achieve the desired product quality, predictable process performance and manufacturing flexibility. This presentation will discuss the various considerations involved in developing a design space for lyophilization. Some specific examples pertaining to biopharmaceutical products will also be discussed. Attendees will learn about:

Perspectives on Quality by Design for lyophilized product manufacture
Heat & mass transfer phenomena in lyophilization
Critical process parameters in lyophilization
Dealing with lyophilization process excursions during routine production

8:50 Topic to be Announced

Two-Part Presentation:
Selection and Implementation of a New Container/Closure System for
an Isolator Filling Line

9:20 Part 1: Selection and Material Qualification of a New Container/Closure System
Edward K. White, Senior Validation Scientist, Baxter BioScience
Selection and Implementation of a new container/closure system is a complex process that covers multiple project phases. This section of the case study discusses the selection, implementation, and material qualification of the new container/closure system. Specifically:
Develop selection criteria for a new container/closure system
Screening studies to select the right container/closure system for your product
Extractables/Leachables Studies
Fragmentation/Penetrability Studies

9:50 Coffee Break

10:45 Part 2: Validation of a New Container/Closure System
Aldelberto A. Cordova, M.S., Senior Principal Engineer, Validation, Baxter BioScience
Once a decision on a new container closure system has been made, validation requirements need to be mapped out to successfully plan the container closure “qualification” strategy. Using a case study of a filling & lyophilization process transfer using a new container closure system, the requirements leading to and including the process validation will be presented.

Incorporating process into existing constraints
Sterilization
Buffer fill process validation
Media Fill
Process validation – conformance runs
Stability
Validation and Registration

11:15 Overfill in Lyophilized Products
Clea Talley, Senior Engineer, DPDD Drug Product Team Leader, Amgen

What are the requirements?
What is the USP guidance?
How best to optimize overfill or eliminate it altogether

11:45 Lyophilization Technology Transfer, Validation, and Deviation Management
Lisa Hardwick, Research Associate, Baxter BioPharma Solutions
Topics covered will be:

Cycle transfer/scale-Up
Process validation (Process verification)
Cycle deviations (during commercial production)

12:15 Close of Morning Session

12:30 Luncheon Workshop (Sponsorship Available) or Lunch on your Own

1:45 Chairperson’s Remarks
Palani Palaniappan, Ph.D., Senior Director, Pharmaceutical Sciences, Millennium Pharmaceuticals, a Takeda Oncology Company
New Technologies for Freeze-Drying

1:50 Novel Lyophized Delivery Systems - Beyond the Vial
Walter Pebley, Bs.Chem Engr, VP Business & Technical Development, Advanced & Specialty Products Division, Oregon Freeze Dry, Inc.
Lyophilization or low-temperature, low-pressure drying has the potential processing utility to deliver dosage forms beyond parenterals. Actual preparations for topical, implantable, sublingual or buccal, and vaginal delivery have been succesfully demonstrated and I would like to share these delivery applications. I have found in my 26 years applying the principles of lyophilization in a wide variety of research and commercial applications, tools for solving problems come from the most unlikely sources when we are exposed to new or not so obvious uses. The audience will have the opportunity to see lyophilization projects applied in such diverse fields as cosmetics, nano materials, propellents, medical devices, and potent API’s. These delivery case studies may provide a “nugget” that could assist them in their process problem solving.

2:20 Lyophilization of a Challenging Biological—Blood Platelets
Richard O. Cliff, EMTM, co-Founder and Vice President Operations, Cellphire, Inc.
The pursuit of successful lyophilization of blood platelets has gone on for over 50 years. The structural nature and inherent properties of this cell-like biological make for an uphill challenge. The platelet is sensitive to handling, temperature and additional biochemical cues that aren’t amenable to the classic challenges presented by lyophilization—namely processing, freezing, drying and rehydration. The current FDA-approved storage profile for platelets is on constant agitation at 22°C for no more than 7 days. For the vast number of platelet transfusions performed annually (10 million units US) the blood banking community has a constant need for more platelets, and with their short shelf-life nearly 20% of the donated product outdates. Our technical approach will be presented along with some data that may afford not only a solution for the transfusion market, but provide a path of delivering platelets and their contents for use in medical device and diagnostics.

2:50 Alternatives to Lyophilization
Jim Searles, Ph.D., Director of Development, Aktiv-Dry LLC
Selection of a drying process for a bulk or final finished product requires understanding of the available options. One must have a firm grasp of the required product attributes in order to define the process to best achieve them. Other constraints are often significant as well, such as which processes are already available within the company, and which have expertise readily at-hand. The purpose of this talk is to broaden the knowledge of alternatives to lyophilization including:

Conventional spray drying
Bubble drying(R)
Supercritical processes
Foam drying

These processes are often technically and economically superior to lyophilization, but are under-utilized due to lack of knowledge of how the processes work, where to find expertise, and the types of products for which they are appropriate. In this talk we will cover those basics.

3:20 Technology Spotlight
“Closed” Freeze Drying System for R&D and Process Development of Lyophilized Products
Joseph Brendle, Product Manager, W.L. Gore and Associates, Inc.
Many guidance documents recommend the use of closed systems wherever possible. Freeze-drying inherently requires an open system to allow for sublimation. An innovative technology allows for efficient freeze drying while completely containing and protecting product. When used in the development process of not fully characterized or potent products, this technology provides an alternative to capital-intensive containment methods or outsourcing.

3:35 Refreshment Break in the Exhibit Hall

4:15 Poster Awards in Exhibit Hall

Closing Case Studies

4:30 From Proteins and Model Membranes to Viruses: Strategies for Freeze-Drying Complex Biologics
Satoshi Ohtake, Ph.D., Formulation Scientist/Process Development Engineer, Aridis Pharmaceuticals
All of commercially-available vaccines are stored either under refrigerated conditions or frozen. Such stringent storage conditions place a strain on the storage and transport of vaccines, in addition to the added complexities of mass vaccination campaigns in regions lacking sufficient cold chain storage. Although, new vaccines are developed or re-engineered to improve safety and efficacy, the development of thermally stable vaccines has lagged behind. Development efforts to stabilize vaccines at room temperature include molecular/genetically-engineered vaccines, formulation improvements, and process optimization. This talk will focus on formulation approaches and challenges encountered when freeze-drying vaccines, in particular the difference in stabilizing non-enveloped and enveloped viruses. In addition, the stability of freeze-dried vaccines will be compared to those produced by spray-drying.

Case study comparing the stability of non-enveloped and enveloped viruses
The advantages and disadvantages associated with physico-chemical analysis and in vitro assay to determine the recovery of viral activity
Comparison of stability and recovery of viruses following freeze-drying and spray-drying

5:00 Development of the Stable Lyophilized Market Formulation of Hirudin
Tudor Arvinte, Ph.D., School of Pharmacy Geneva-Lausanne, Department of Pharmaceutics and Biopharmaceutics, University of Geneva; Chairman and Chief Executive Officer, Therapeomic, Inc.
Recombinant Hirudin HV1(1-65), rHir, is a potent thrombin inhibitor which is on the market in different countries in a lyophilized formulation. In this marketed formulation rHir is very stable chemically and physically at room temperature over years and also over weeks at 50°C. Initial standard lyophilized formulations of rHir were stable only at 4°C to 8°C and were not stable more than 1-2 weeks at room temperature. The talk will present aspects from the development of this lyophilized very stable formulation highlighting the importance of in-depth studies of hirudin biophysical and biochemical properties.