Institute for International Research

Monday, February 25th, 2008

AM Workshop:

Forced Degradation 101

8:30 Workshop Registration and Morning Coffee
9:00 Workshop Begins
10:30 30 Minute Networking Break
Developing a Forced Degradation Studies Best Practice at Schering-Plough    We have been developing a best practice document for conducting forced degradation studies on drug substance and drug product.  Our goal is to identify the most meaningful conditions for these studies based on the reactivity and physical properties of new drug candidates.  This presentation will cover data and lessons learned from our preliminary forced degradation studies performed with a model compound and emphasize on the key experiments for future compounds.  Specific emphasis will be placed on predicting drug stability and the role of these studies in both analytical method development and formulation development strategies.

• Identifying conditions for hydrolytic degradation with acid or base                                            
• Comparison of radical initiators including AIBN, Tween and KPS 
• Studying solvent effects on the oxidation of a model compound with hydrogen peroxide
• forced degradation studies
• When is enough, enough – how far should you go to degrade a compound?          

Gwendolyn Kuehl, PhD, Associate Principal Scientist, SCHERING-PLOUGH

Introduction to Photostability Forced Degradation Testing

• Master key concepts of ICH Q1B and Q5C photostability requirements for improved compliance
  
• Explore current available options in commercial photostability testing equipment, light sources and measurement
  
• Leverage practical considerations including sample presentation when conducting photo stability testing

Allen F. Zielnik, Chemistry Senior Consultant, ATLAS MATERIAL TECHNOLOGY LLC

Drug Product vs. Drug Substance Forced Degradation

Drug product forced degradation is not given as much focus as drug process forced degradation. It is a critical piece of development work, yet it is often an afterthought when developing a molecule. With every company performing drug product degradation differently, there are no clear testing guidelines to turn to.

• What is going on with drug products and forced degradation?
  
• What are the regulations?
  
• Uncover what forced degradation tests a drug product must undergo
  
• Explore what other companies are doing to test drug product forced degradation

Open Interactive Discussion on Forced Degradation Fundamentals

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PM Workshop:

Drug Excipient Interaction & Compatibility

12:30 Workshop Registration Begins
1:00 Workshop Begins
2:30 30 Minute Networking & Refreshment Break
4:00 Workshop Concludes

Fundamental Chemistry of Drug-Excipient Incompatibility

Drug-excipient incompatibility is caused by chemical and physical interactions between drug and excipients or reactive impurities in the excipients. Chemical interaction between drug and excipients or reactive impurities could induce new chemical entities in the final product, therefore it could compromise the safety and quality of a product. In order to effectively choose a stable formulation, one should be fully aware of the chemical characteristics of the drug and all intended excipients, and understand the potential chemical interactions between them. This presentation provides an overview of the fundamental chemistry of drug-excipient incompatibility with appropriate case studies. This knowledge is of help in designing effective drug excipient compatibility studies and in understanding formulation development problems related to drug-excipient compatibility issues.

Fenghe Qiu, PhD, Principal Scientist, Analytical Sciences, BOEHRINGER INGELHEIM

Drug Degradation in the Presence of Excipients

• Review the functional classes of excipients, examples of typical excipients in each class, and known problems associated with them
  
• Address issues of predictable incompatibilities such as the reaction of reducing sugars with drugs containing amine moieties, inclusion of excipients with humectant properties in formulations containing easily hydrolyzed drugs, peroxide impurities in PEGylated excipients and natural products, effectiveness of preservatives in excipients, etc.
  
• Examine alternative experimental strategies (isothermal and nonisothermal isoconversional solid state Arrhenius experiments, TAM, excipient-mediated acceleration or deceleration of solution degradation, oxidative stressing of solids)

William R. Porter, PhD, Associate Research Fellow, ABBOTT LABORATORIES

Open Interactive Discussion: Methods to Improve the Efficiencies in Excipient Prediction

Certain excipients that are very prone to initiating excipients, and you can measure trace reactive species in excipients to predict how the excipient will react with your formulation to cause degradation. By measuring the trace levels of reactive species in excipients, you can better predict how an excipient will react in your formulation.

• Predict how the excipient will interact with your API to make excipient selection more efficient
  
• Discover ways to predict if how different excipients will react with your compound
  
• Explore the relation of impurities to excipients as they relate to the stability of the drug