Introduction to Quality Control in Pharmaceutical Analysis
Pharmaceutical Analysis 2: Introduction to Quality Control
Page 1: Overview
Course: Pharmaceutical Analysis 2 (PHAN212)
Semester: 2nd Semester, SY 2023-2024
Focus: Quality Control
Page 2: Learning Outcomes
At the end of this unit, students are expected to:
Define and explain the core principles, objectives, and organizational structure of a Quality Control (QC) System.
Describe the benefits of quality control systems.
Differentiate between different control functions.
Discuss the significance of the different divisions within QC.
Demonstrate understanding of the International Council for Harmonisation (ICH) Quality Guidelines and their role in global pharmaceutical standardization.
Analyze the relationship between QC organizational functions and the implementation of ICH Quality standards within a laboratory environment.
Page 3: Definitions
Quality:
Definition: Quality is the combination of attributes or characteristics of a product which, when compared to a standard, serves as a basis for measuring the uniformity of the product and determines its degree of acceptability.
Control:
Definition: Control refers to the measures or steps that are used to prevent or eliminate drug risks/hazards to ensure the safety and effectiveness of a drug product.
Page 4: Quality Control
Definition: Quality Control is a tool that provides assurance that a product conforms to standards and specifications through a system of inspection, analysis, and action.
Operational Techniques:
Includes activities used to fulfill quality requirements and assure safe, pure, and effective drug products.
Philosophy: Quality is regarded as everybody's business within the organization.
Page 5: Quality Assurance (QA)
Definition: The sum total of organized activities intended to ensure that all active pharmaceutical ingredients meet the quality required for their intended use.
Planned Activities:
All activities implemented within a quality system aimed at fulfilling quality requirements for a product or service (ASQ definition).
Page 6: Comparison of QA and QC
QA | QC |
|---|---|
Set of preventive activities | Detection activities |
Ensures standards are followed | Defines the standards to be followed |
Process-oriented | Product-oriented |
Focus on defect prevention | Focus on defect identification |
Page 7: Quality Control System
Established at:
The conception of a new product, during batch production, and throughout the distribution of commercial products.
Components:
Combination of administrative and technical procedures necessary for producing and delivering a safe, pure, and effective product.
Page 8: Assurance by QC System
Quality Control System ensures that the drug product is:
Free from impurities.
Physically and chemically stable.
Contains the stated amount of active ingredient.
Provides optimal release of active ingredients upon administration.
Page 9: Benefits of Quality Control System
Minimizes or eliminates the risk of marketing unsafe products.
Guarantees conformance to regulatory requirements.
Ensures product efficacy.
Reduces operating costs.
Lowers operating losses.
Enhances employee morale.
Motivates the pharmaceutical/medical professions to sell or prescribe the products.
Page 10: Performance Improvement Process
Internal Process:
A process focused on improving the organization’s performance by learning best practices from better-performing entities, evaluating and building on relevant performances within the organization and others.
Page 11: Total Quality Management (TQM)
Definition: A management approach centered on quality, involving all members of an organization, aimed at long-term success through customer satisfaction and benefits to all members and society.
Page 12: Primary Elements of TQM
Elements not explicitly detailed in the transcript; typically include customer focus, continuous improvement, participation of all employees, and a process-oriented approach toward performance.
Page 13: Accreditation
Definition: Quality assessment with a judgment that an evaluated unit (program or organization) meets the required standards to operate in a particular system.
Duration: Accreditation typically granted for 4 to 10 years, subject to a cyclical reevaluation process.
Page 14: ISO Overview
Definition: ISO (International Organization for Standardization) is a voluntary, non-treaty federation of standard-setting bodies from around 130 countries. Founded in 1946-47, it facilitates international trade and cooperation in economic, intellectual, scientific, and technological aspects.
Page 15: Organization of Quality Control
Structure: Quality Control is defined by:
Specific functions and responsibilities.
Effective coordination.
Focused activities aimed at maintaining the highest product standards at the lowest cost.
Page 16: Common Divisions in a Manufacturing Firm
1. Finance.
2. Production.
3. Quality Assurance (QC).
4. Marketing (optional for third-party contract manufacturers).
Page 17: Organizational Chart of a Pharmaceutical Company
Departments include:
Research & Development, Operations, Quality Management, Sales, Finance, Regulatory, and several specialized divisions (Pharmaceutical Development, Materials Management).
Key Figures:
Chairman, President & CEO.
Illustration Note: Update of organizational structure as of 2012-08-20.
Page 18: Control Functions in QC
Control functions can generally be classified into four categories:
Analysis Function
Monitor Function
Record Review and Release Function
Audit Function.
Page 19: Analysis Function in QC
Purpose: Ensure product acceptability.
Activities include:
Testing raw materials, packaging components, and bulk products during processing, after packaging, and after distribution.
Analysis may also involve verification of products against complaints for validity and causes of deficiencies, followed by preventive actions.
Page 20: Monitor Function in QC
Purpose:
Sampling and examining materials to assure adherence to specifications.
Activities include:
Environmental monitoring in areas where pharmaceuticals, such as parenterals, are processed, focusing on microbial and particulate matter control.
Page 21: Record Review and Release Function
Purpose:
Ensure accuracy and completeness of records generated during production.
Process: Employing detailed checklists to facilitate record review before each lot release.
Page 22: Audit Function
Purpose:
Training employees on SOP compliance and understanding the procedures.
Goal: Identify areas where established SOPs are not followed, and report findings for corrective measures.
Page 23: Quality Control Divisions
The divisions within Quality Control include:
A. Materials Inspection Section
B. Analytical Laboratory
C. Biological Testing Laboratory
D. Quality Coordination Office
E. Specification and Analytical Development.
Page 24: Materials Inspection Section
Role: Inspectors must be experienced and familiar with material characteristics and sampling techniques.
Function Locations: Operations, warehouse, manufacturing, and packaging areas.
Page 25: Responsibilities of Materials Inspection Section
Sample and examine all raw materials received.
Conduct physical tests on all shipments of packaging materials and all manufacturing operations.
Periodically examine quality during storage, shipping, and distribution phases.
Perform independent audits from production personnel's work.
Page 26: Analytical Laboratory
Requirements: Located in a quiet area, protected from manufacturing noise/vibration.
Functions:
Conduct qualitative and quantitative analysis on raw materials, intermediates, and finished products.
Analysts must be proficient in gravimetric and volumetric analysis and skilled in using instruments for spectrometry, titrimetry, and chromatography.
Page 27: Biological Testing Laboratory
Staffing Requirements: Trained in microbiological procedures; a veterinarian is advised for animal care.
Facility Needs:
Specific rooms for biological tests and an animal house for species used in testing.
Page 28: Functions of Biological Testing Laboratory
Conduct microbiological/pharmacological assays, sterility, pyrogen, and bacteriological tests.
Perform environmental monitoring.
Page 29: Continuation of Functions of Biological Testing Laboratory
Includes the functions described above along with continued quality assessments across testing procedures.
Page 30: Specification and Analytical Development
Background: Requires knowledge in QC principles, analytical procedures, manufacturing, research, product development, and statistics.
Functions include:
Coordinate with various departments for product enhancement.
Establish specifications for raw and packaging materials.
Page 31: Functions Continued
Validate existing and tentative testing procedures.
Develop new assay methods for in-house use.
Improve specifications for quality characteristics of manufactured products.
Page 32: Quality Coordination Office
Accessibility: Should be easy to access for all manufacturing and packaging operations, focusing on documentation duties.
Functions include:
Maintain comprehensive records representing batch history.
Analyze product performance data through stability studies and returned goods reports.
Page 33: Additional Functions of Quality Coordination Office
Investigate customer complaints related to product quality and forward results for sales reporting.
Notify development groups regarding improvement suggestions.
Maintain and develop Standard Operating Procedures (SOPs).
Page 34: Continuing Functions of Quality Coordination Office
This section plays a pivotal role in ensuring quality through record keeping, investigations, compliance, and procedural development.
Page 35: Standards Setting Organizations (SSO)
Definition: An organization recognized for establishing standards either by:
i) ANSI-approved SSO or equivalent abroad,
ii) a government-sponsored organization not solely reliant on financial support from the government.
Page 36: Guidelines and Regulations
Sources include:
WHO pharmaceutical norms and standards,
FDA CGMP regulations,
AO 2012 – 0008 adoption of PIC/S GMP guides,
ICH standards, underlining the harmonization of regulations across different regions.
Page 37: International Council for Harmonization (ICH)
Formation: Established on October 23, 2015, as a non-profit under Swiss law.
Objective: To create uniform standards for drug registration and clinical use.
History: Initiated in the 1980s to promote a single market in pharmaceuticals; founding members include the US, Japan, and the EU leading the initial collaboration.
Page 38: Purpose of ICH
Promotion of public health through harmonization which includes:
Preventing unnecessary duplication of clinical trials and evaluations.
Facilitating development and manufacturing of new medicines.
Enhancing registration and supervision processes for new medicines.
Decreasing unnecessary animal testing while maintaining safety.
Page 39: ICH Membership
Founding Members:
Europe: European Commission
Japan: Ministry of Health, Labor and Welfare (MHLW); Pharmaceuticals and Medical Devices Agency (PMDA)
US: FDA
Observers: WHO, IFPMA, regulatory authorities.
Page 40: ICH Issuances
GCP (Good Clinical Practice): Allows clinical trials in one region to serve as valid in others through established common ethical standards.
CTD/eCTD (Common Technical Document): Collects quality, safety, and efficacy information in a harmonized format accepted across ICH regions.
Page 41: Medical Dictionary for Regulatory Activities (MedDRA)
Definition: A standardized terminology developed by ICH to streamline regulatory information sharing and is critical for documentation and monitoring post-marketing authorizations.
Guidelines Overview:
Safety: 14 guidelines
Quality: 23 guidelines
Efficacy: 21 guidelines
Multidisciplinary: 6 guidelines
Page 42: Overview of ICH Guidelines
Quality Guidelines encompass:
Quality: Stability studies, impurity thresholds, and flexible pharmaceutical approaches.
Safety: Evaluation of risks, including carcinogenic, genotoxic, and reprotoxicity aspects.
Efficacy: Conduct and reporting of clinical trials.
Multidisciplinary: Guidelines for terminology (MedDRA), CTD, and electronic standards for regulatory information transfer.
Page 43: Detailed ICH Quality Guidelines
Includes topics like:
Q2 Analytical validation
Q3A-Q3D Impurities
Q4B Apparatus for Dissolution Test and many others regarding pharmaceutical lifecycle and quality systems.
Page 44: Q4B-Annex 7 Dissolution Test General Chapter
Interchangeability Declaration:
ICH recommends using certain pharmacopoeial texts interchangeably with conditions specified for dissolution tests.
Calibration requirements for dissolution apparatus to comply with regional GMP requirements.
Page 45: ICH Quality Guidelines Continued
Focus on finished product control, compendial requirements for dosage forms, statistical quality control, stability studies, and validation procedures.
Page 46: Multimedia Supplement
Resource: Watch video on a related topic [YouTube link](https://www.youtube.com/watch?v=Zawu57zQpQM&pp=ygUqcXVhbGl0eSBjb250cm9sIGluIHBoYXJtYWNI dXRpY2FsIGluZHVzdHJ5).
Page 47: References
Jenkins, Glenn L, Jenkins Quantitative Pharmaceutical Chemistry, NY, McGraw, Latest Edition.
Watson, David G., Pharmaceuticals Analysis: A Textbook for Pharmacy Students & Pharmaceutical Chemist, 4th ed. 2017. Elsevier. ISBN: 978-0-7020-7029-7.
Page 48: Activities for Next Meeting
Quiz No. 1: Introduction to Quality Control
Assignment No. 1: ICH Quality Guidelines
Lecture Topic Next Meeting: Standards and Specification.
Page 49: Review Questions
Define cGMP.
Define and explain quality control in pharmacy.
Differentiate QA from QC.
Discuss the importance of quality in pharmaceutical products.
Define TQM.
What are the control functions in quality control?
Enumerate the benefits of a Quality Control System.
Discuss the importance of accreditation in an institution.
What is an SOP? Explain its importance in manufacturing procedures.
TRUE OR FALSE: Inspection stations are placed in the area of operation, warehouse, manufacturing, and packaging areas.
Page 50: Questions and Conclusion
Final Note: Open to any questions. Thank you for your attention!
Contact Information: smorencio@fatima.edu.ph, cgsabroso@fatima.edu.ph