Foundation for Product Development: Stability & Solubility Fingerprinting

OK…who knows what this molecule is?! Come on … you know it … you can do it … YES! That’s right! It’s 5-ethylene-glycol!!! Well, so … maybe only the Chemists got that one.

Everyone … step back (some more than others!): who remembers sitting in good ol’ Chemistry class and starring off into never-never land? Who remembers memorizing the structure of a molecule, but having no clue why you were memorizing it or why you were even taking chemistry!? I’ll admit it … I was one of those. I’m a Biologist at heart … I have always had a genuine interest in how our bodies work. But I have to be honest and say that I despised Chemistry and always said, (as my parents will clearly remember!), “when will I ever need this!?!?!” Looking back, I can honestly say I’m thankful that I pushed through my Chemistry courses in highschool and college because I have since landed myself in this wonderful Pharmaceutical/Biotech industry where Chemistry affects my job on a daily basis! Who would have thunk?!?!?! Do I fully understand Chemistry yet? NO. And I don’t think I ever will. BUT…do I have the utmost respect for it? Oh I sure do!

And I have the utmost respect for the many qualified and highly intelligent Chemists in my field! Including part of our wonderful McCormick LifeScience Consultants team, Indu Javeri, PhD.

Indu has her doctorate in Chemistry from the University of Oklahoma. She has 24 years of experience in the development of pharmaceuticals and biologics. She has served as a CEO for 18 years and during this tenure her company partnered with many companies to help develop their products and formed collaborations that have led to new intellectual properties several times. She also has developed a nanoparticle technology platform that targets and transforms approved pharmaceuticals as well as new chemical entities to treat patients with enhanced safety and efficacy. Under her leadership, the company grew from 3 MM to 13 MM in sales and became known for producing high-quality products under cGMPs for use in manufacturing clinical trials. She is known for driving product, process, and customer service improvement, while simultaneously building partnerships with key business decision makers. She has held both scientific and management positions in Biotech industry.

Take it Away Indu!

Having worked in the Pharmaceutical industry for the past 23 years, I have come to intimately learn how product development is handled for both NDA and generic/biosimilar products. There are some obvious differences; however, there are also many similarities.

Whether it’s a generic product or a new chemical entity, a formulator requires an understanding of the molecule’s strengths and weaknesses. Based on my experiences, preformulation development of a product is the foundation as it allows for exercising and flexing muscles for developing robust formulations.

Preformulation is like building a relationship with the molecule at an early stage of drug development programs for any pharmaceutical, biopharmaceutical generic and biosimilars. It provides a stability and solubility fingerprint that is unique to that molecule, by characterizing and understanding the features that need to be under control and the features that are noncritical to the overall quality of the product. It is very analogous to humans as each one of us has a unique fingerprint that constitutes individuality; similarly, each product under development has a unique fingerprint. It plays a significant role in anticipating formulation problems and identifying logical paths in both liquid and solid dosage forms.

The formulator/scientist uses the information generated during preformulation studies to develop effective formulations and dosage forms. In addition, once you understand your molecule, you can use the information to:

• Identify lead candidates
• Identify the most appropriate salt for development
• Determine feasibility of parental (liquid or lyophilized)
• Identify a method of stabilization
• Identify stability indicating assays
• Evaluate product consistency during process scale-up and/or manufacturing process changes
• Determine acceptable vehicles for solid dosage forms

Once you have developed a good understanding of the physicochemical relationships and characterization of a therapeutic candidate, make sure that you document all the details of your experiments and findings as it serves as a stepping stone for a logically designed product development program and allows for effective IND, NDA/ANDA submissions. The most important thing to keep in mind is that along with the fingerprinting and subsequent development of the product, a good knowledge of Regulatory and process validation will only help accelerate the time required for bringing an API to market.

• Early Preformulation studies are the building blocks for product development; make sure that you have a good understanding of the strength and weakness of the molecule
• Keep a good paper trail of everything you do; documentation is key to the successful development of a product
• Don’t forget to pay attention to Regulatory and Validation requirements for successful product development