PHARMACEUTICAL QUALITY BY DESIGN (QbD)

SEMINARONPHARMACEUTICAL QUALITY BY DESIGN (QbD) : 

SEMINARONPHARMACEUTICAL QUALITY BY DESIGN (QbD) SHARAN KUMAR REDDY B M.PHARMACY(1ST SEMESTER) INDUSTRIAL PHARMACY ST.PETER’S INSTITUTE OF PHARMACEUTICALSCIENCES VIDHYANAGAR, HANAMKONDA-A.P(506001)

CONTENTS : 

CONTENTS INTRODUCTION OVERVIEW OF QbD QbD TOOLS CURRENT APPROACH VS QbD CONCLUSION REFERENCES

INTRODUCTION : 

INTRODUCTION The pharmaceutical Quality by Design (QbD) is a systematic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management.

SIGNIFICANCE OF QbD : 

SIGNIFICANCE OF QbD • Quality by Design means -designing and developing formulations and manufacturing processes to ensure a predefined quality • Quality by Design requires – understanding how formulation and manufacturing process variables influence product quality • Quality by Design ensures – Product quality with effective control strategy

OVER VIEW OF QbD : 

OVER VIEW OF QbD DEFINE target product Quality profile DESIGN formulation and process IDENTIFY critical material Attributes and critical process parameters CONTROL materials and process TARGET DESIGN IMPLEMENTATION

DEFINE TARGET PRODUCT QUALITY PROFILE : 

DEFINE TARGET PRODUCT QUALITY PROFILE A natural extension of Target Product Profile for product quality – Quality characteristics (attributes) that the drug product should possess in order to reproducibly deliver the therapeutic benefit promised in the label. Guide to establish formulation strategy and keep the formulation effort focused and efficient.

Target product quality profile : 

Target product quality profile Dosage Form Characteristics– Appearance, shape, size etc. Identity Strength Assay Uniformity Purity/Impurity Stability, and Dissolution/Disintegration – Pharmacokinetics and bioequivalence Others Target product quality profile includes CQAs of drug product Critical quality attributes (CQAs)

Example : 

Example

DESIGN FORMULATION AND PROCESS : 

DESIGN FORMULATION AND PROCESS Drug substance property

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Excipient Property Physical property – Particle size, shape, solid phase, moisture content, hygroscopicity, aqueous solubility, pKa, and density Chemical property – Chemical identity, purity, incompatibility with drug substance Biological property Mechanical property Excipient quality Drug excipient compatibility studies -Thermal analysis, isothermal stress etc

Design drug product : 

Design drug product

Process Selection based on Physical Properties : 

Process Selection based on Physical Properties

Identify Critical Material Attributes and Process Parameters : 

Identify Critical Material Attributes and Process Parameters Critical Material Attribute (CMA) – A physical, chemical, biological or microbiological property or characteristic of a material that should be within an appropriate limit, range, or distribution to ensure the desired product quality. Critical Process Parameter (CPP) – A process parameter whose variability has an impact on a critical quality attribute and therefore should be monitored or controlled to ensure the process produces the desired quality.

CMA and CPP example : 

CMA and CPP example

Design space : 

Design space Design Space– The multidimensional combination and interaction of input variables (e g. Material attributes) and process parameters that have been demonstrated to provide assurance of quality.

Design Space Determination: Blend Uniformity : 

Design Space Determination: Blend Uniformity 1. Prior knowledge and risk assessment to determine potential critical factors and responses - Factors: API and MCC particle sizes, load level, number of rotations - Response: Blend uniformity 2. DoE - Central composite response surface 3. Determine design space based on the outcome of DoE 4. Evaluate scale effect

CONTROL STRATEGIES : 

CONTROL STRATEGIES

Control Variability : 

Control Variability There is uncharacterized variability in the excipients and process – Level 1 handles variability by excessively testing – Level 2 handles variability by limited testing and establishing design space for critical material attributes and process parameters – Level 3 is a robust process that can ensure quality in the presence of uncharacterized variability.

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Reducing Product Variability Process (or Process Step) Input ProcessParameters Input Materials Product (or Intermediate) Process Variability

Quality by Design Tools : 

Quality by Design Tools Design of experiments (DoE) Risk assessment Process analytical technology (PAT)

Design of Experiments (DOE) : 

Design of Experiments (DOE) Structured, organized method for determining the relationship between factors affecting a process and the response of that process. DOE Methodology (1) Choose experimental design (e.g., full factorial, d-optimal) (2) Conduct randomized experiments (3) Analyze data (4) Create multidimensional surface model

Risk assessment : 

Risk assessment Risk – Risk is defined as the combination of the probability of occurrence of harm and the severity of that harm. Risk Assessment – A systematic process of organizing information to support a risk decision to be made within a risk management process. It consists of the identification of hazards and the analysis and evaluation of risks associated with exposure to those hazards

Formulation and process attributes : 

Formulation and process attributes

Process Analytical Technology(PAT) : 

Process Analytical Technology(PAT) A system for designing, analyzing, and controlling manufacturing through timely measurements (i.e., during processing) of critical quality and performance attributes of raw and in process materials and processes with the goal of ensuring final product quality. The term analytical in PAT is viewed broadly to include chemical, physical, microbiological, mathematical, and risk analysis conducted in an integrated manner.

Example: Current Tablet Production : 

Example: Current Tablet Production Raw Material Dispensing Blending Compression Identification Tests (Chemical Only) Test Product Quality for Release (Active Only) No Tests (Time Based) End-Product Focused Testing to Document Quality Process at Risk

PAT Tablet Production : 

PAT Tablet Production Compression Functional Tests (Chemical and Physical) Validate Process Control Control Blending (Particle Size & Disintegrant Distribution) Process Focused Mitigate the Process Risk Predictive Models

Current vs. QbD Approach to Pharmaceutical Development : 

Current vs. QbD Approach to Pharmaceutical Development

CONCLUSION : 

CONCLUSION Quality by Design define target product quality profile ,design and develop formulation and process to meet target product quality profile, Identify critical raw material attributes, process parameters, and sources of variability. PAT, DoE, and risk assessment are tools to facilitate the implementation of QbD. There is a need for vigorous and well funded research programs to develop new pharmaceutical manufacturing platforms.

REFERENCES : 

REFERENCES [1] ICH Guideline Q8 – Pharmaceutical Development, http://www.ich.org (10 Nov 2005). [2] U.S. Food and Drug Administration Guidance for Industry. PAT – A Framework for Innovative Pharmaceutical Development, Manufacturing and Quality Assurance, http://www.fda.gov/Cder/OPS/PAT.htm (Sep 2004). [3] J.C. Berridge An Update on ICH Guideline Q8 – Pharmaceutical Development, www.fda.gov/ohrms/dockets/AC/06/ slides/2006-4241s1_2.ppt, ISPE Vienna Congress 2006.

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