Meeting Solid Dose Formulation Challenges

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Alyson Craig
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1 Streamlining (Fast Tracking) Solid Dosage Form Development Tony Carpanzano, B.S., R. Ph. Director, Research & Development Streamlining (Fast Tracking) Solid Dosage Form Development Meeting Solid Dose Formulation Challenges

2 New Development Project UPPER MANAGEMENT: Here s your challenge.. I want it done fast, I want it done right, and I want it at low cost! New Development Project UPPER MANAGEMENT: Here s your challenge.. I want it done fast, I want it done right, and I want it at low cost! Experienced Formulator:.. You can have any two options..

3 Best Response Focusing attention to several key points in formulation development will aid in Fast tracking a product, keeping costs to a minimum, and establish a solid foundation for fulfilling regulatory requirements (QBD). Seven Basic Habits of Highly Effective Be Proactive Begin with the end in mind Put first things first Think win-win Synergize Sharpen the saw

4 Seven Basic Habits of Highly Effective Be Proactive Systematic Approach Begin with the end in mind Put first things first Think win-win Synergize Sharpen the saw Seven Basic Habits of Highly Effective Be Proactive Systematic Approach Begin with the end in mind Pre-defined objectives Put first things first Think win-win Synergize Sharpen the saw

5 Seven Basic Habits of Highly Effective Be Proactive Systematic Approach Begin with the end in mind Pre-defined objectives Put first things first Product & Process Think win-win Synergize Sharpen the saw Seven Basic Habits of Highly Effective Be Proactive Systematic Approach Begin with the end in mind Pre-defined objectives Put first things first Product & Process Think win-win Process Control Synergize Sharpen the saw

6 Seven Basic Habits of Highly Effective Be Proactive Systematic Approach Begin with the end in mind Pre-defined objectives Put first things first Product & Process Think win-win Process Control Good science and quality risk management Synergize Sharpen the saw Seven Basic Habits of Highly Effective Be Proactive Systematic Approach Begin with the end in mind Pre-defined objectives Put first things first Product & Process Think win-win Process Control Good science and quality risk management Synergize Production efficiency, post launch mgmt. Sharpen the saw Continual improvement

7 Solid Dose Formulation Challenges Solid Dose Formulation Challenges Formulation and Manufacturing process NDA Innovator has a high degree of freedom ANDA Generic companies have a much lesser degree of freedom Regulatory / compendial issues Cost issues Patent / legal issues QBD FDA requirements have mandated a more comprehensive (exhaustive) development process Data driven formulation and process selection Burden? Opportunity? Advantage?

8 Solid Dose Formulation Challenges - API Physical form Crystalline, amorphous, polymorphic (patented?) Oil, waxy, or low melting solid Cohesive requires high energy input to disperse and achieve uniformity may stick to punches Poor flow may lead to poor weight/hardness/content uniformity Low density Fluffy, fly-away, difficult to handle safety Solid Dose Formulation Challenges - API Not compressible May require extensive processing and/or large amounts of excipients to form a tablet Solubility High solubility not usually an issue for IR, but can be an issue for ER Low solubility generally an issue Hygroscopic Unstable Sensitive to moisture, heat, light, oxygen or other components

9 Solid Dose Formulation Challenges Dosage Form Dosage form Tablet (IR, MR, fast dissolve), capsule or soft gel Therapeutic Dosage level High dose tablet size try to keep excipient levels as low as possible need high functionality Low dose uniformity typically wet granulation is the process of choice, high functionality excipients offer alternatives Compatibility of needed excipients with API Binders, diluents, Coatings functional or cosmetic Key Points for Development

10 The Fast Track Target product profile Clearly defined expectations SMART Literature search Patents can help or be misleading Related compounds and drug products Chemistry, PDR Unusual or proprietary excipients The Fast Track Pre-Formulation do the homework Characterize the API Risk Assessments for API attributes on drug product CQA s Characterize the Reference Label Drug (generics) Reverse engineering Formulation Gain insight to process Have a thorough understanding of the proposed excipients functionalities and limitations

11 The Fast Track Excipient selection Understand stability impact Known API interactions and incompatibilities Rationale for excipient selection RLD (generics) QBD Risk assessment for selected excipients Functionality or data driven Process Selection The Fast Track Understand stability impact Process conditions to avoid (heat, moisture, shear, atmosphere) Rationale for process selection RLD (generics) QBD Risk assessment for selected process Functionality or data driven

12 The Fast Track Initial Formulation Prototypes Physical characterization In-vitro characterization Microbiological evaluation Accelerated stability Pilot-Bio study Stability in proposed commercial packaging Updated risk assessment for formulation The Fast Track Prototype Process Evaluate & identify key processing steps Conduct pilot-scale studies Propose PAT where appropriate Updated risk assessment for process

The Fast Track Scale-up / Commercial Process Assessment of key process steps Evaluate PAT where appropriate Define process control strategy Updated risk

13 The Fast Track Scale-up / Commercial Process Assessment of key process steps Evaluate PAT where appropriate Define process control strategy Updated risk assessment Packaging Stability of commercial package(s) Post launch product lifecycle management PAT data, yield analysis Continual improvement QUESTIONS

Application of Quality by Design (QbD) in product development. James E. Polli September 16, 2015

Application of Quality by Design (QbD) in product development James E. Polli jpolli@rx.umaryland.edu September 16, 2015 Pharmaceutical Equivalence Same active ingredient(s) Same dosage form Same route