GMP Flashcards
Manufacture
- Involves everything including:
○ Facilities
○ Materials
○ People
○ Methods
○ Tests
○ Packaging
○ Storage
Production: Distribution
Production
- Part of Manufacture, focuses only on:
○ Producing the actual medicine
○ Collecting materials
○ Making medicine
○ Testing
Packaging
Quality
- Pharmaceutical quality is the foundation that allows patients to have confidence in the safety and efficacy of medicinal products.
- The quality of a pharmaceutical product is defined by the quality of raw materials, equipment, and technical knowledge required to manufacture (including packaging) and supply of the medicinal product.
- Good manufacturing practice (GMP) is a system for ensuring that products are consistently produced and controlled as per quality standards.
Standards: BP, EP, USP, etc.
GMP definition
Good manufacturing practice (GMP) is a system for ensuring that products are consistently produced and controlled according to quality standards. It is designed to minimize the risks involved in any pharmaceutical production that cannot be eliminated through testing the final product.
What are the regulatory agencies?
EMA, MHRA, FDA, ICH, PICS.
GMP components
- Materials: Approved
- Machines: Qualified
- Processes: Validated
- Procedures/Methods: Validated
- People: Trained
- Facilities: Appropriate
- Traceability of manufactured products: Documentation
- Preventing cross-contamination: Mix-ups
- Complaint handling system
- Recall systems
Risk management
Importance of GMP standards
- Regulatory agencies produce guidelines to provide requirements that a manufacturer needs to meet to ensure their products are consistently high in quality, from batch to batch, for their intended use.
The main purpose is to prevent any harm from occurring to the patient.
Pharmaceutical Quality
All pharmaceutical processes are systems of inputs (variables) and outputs (responses). Experiments are conducted to identify the relationship between inputs and outputs.
Pharmaceutical Manufacture I
Conventional product development methodologies involve assessing the impact of one factor at a time (OFAT) approach whereby only one variable is changed at one time to assess its effect while the rest are kept constant.
Pharmaceutical Manufacture II
Quality by Design (QBD), on the other hand, is a systematic approach to product development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management (ICH Q8).
Advanced Manufacturing Approaches
Development efforts categorized into minimum, acceptable, and aspirational levels.
Statistical tools: design expert
Appropriate statistical software is used to formulate experiments called Design of Experiments (DOE).
QBD Case Study - Tablet Manufacture
- Identification of factors and responses.
- Design matrix.
- Statistical analysis.
- Identification of spaces.
- Statistically intensified technique involving:
○ Factorial analysis
○ Analysis of variance (ANOVA)
○ Principal component analysis (PCA)
○ Multiple regression
○ Response surface methodology (RSM) - Starts with brainstorming to list factors affecting CQA.
Uses quality investigation tools like Ishikawa Fishbone Diagram and FMEA.
CQA Classification
- RISK ASSESSMENT
○ Non-critical
○ High-risk
○ Key/critical
Assess impact on CQA.
Statistical Tools: Design expert - what do they do?
- Statistical software formulates experiments (DOE).
- Factors’ minimum and maximum levels are selected.
- Design matrix identifies responses.
Statistical analysis provides Quality Target Product Profile (QTPP).
What is Design Space divided into?
- Divided into:
○ Knowledge Space: High probability of deviations
○ Design Space: Proven acceptable range (PAR)
○ Control Space: Optimized normal range (NOR)
Design and control spaces reduce regulatory burden.
