The difference in characteristics between two items known as variation. This variation may be due to substandard quality of raw material, carelessness on the part of operator, fault in machinery system etc. Variation in quality is of types: 1.Variation by chance 2. Assignable cause

1. DISCOVER . LEARN . EMPOWER
Sources of quality variation,
control of quality variation.
UNIVERSITY INSTITUTE OF PHARMA
SCIENCES
Pharm D
Pharmaceutical Analysis-I (21PST-324)
Mr. Yunes Alsayadi

2. Variation in quality
The difference in characteristics between two
items known as variation. This variation may
be due to substandard quality of raw material,
carelessness on the part of operator, fault in
machinery system etc. Variation in quality is of
types:
1.Variation by chance
2. Assignable cause

3. TYPES OF VARIATIONS
 In variation by chance, variation occurs due to
defect in machine, Raw material or any other
factors.
Assignable cause is due to nonrandom cause like:
Difference in quality of raw material.
Difference in machines.
Difference in operators.
Difference of time.

4. Key Areas of Variation
 Materials
 Equipment
 Environment
 Process
 Personnel

5. 40-70% of Variability Comes from
People
Training
Poor Procedures
Processing procedures
not well understood
Procedures are not
adequate when steps are
critical.
Leading to poor execution
(lack of procedural
control)
Work environment
Monitoring training
effectiveness
Lack of skill sets
Attrition (acquisitions,
mergers etc.)
No cross functional
training
Inadequate resources
Lack of manufacturing
theory

6. Equipment
Lack of adequate Preventive Maintenance
Lack of adequate Calibration
Disregard for limitations imposed by OQ/PQ
Unclear functional/operational requirements

7. Measurement and Data
Misinterpretation
Wrong application (Informatics)
Too much data (changes knowledge base)
Sample scheme inadequate
Human error
Inappropriate interface with process and
equipment
Incorrect process attribute
Inadequate analytical qualification

8. Environmental Issues
Inadequate or poor understanding and control
Humidity Control – Sensitivity of specialized
dosage forms
Seasonal variation
Needs for specialized equipment
Sensitive processes (Coating)
Insufficient resources for Environmental
Controls (when necessary)

9. Materials
Inherent variability in components
Inadequate monitoring of quality attributes for
functional properties
Poor characterization and monitoring of excipient
quality and its impact on product quality and
processability
Poor understanding of component variability on PV and
process ability .
Alternate supplier qualification
Multivariate interactions – Impact possibilities are
numerous – Solving one problem may not address
some unknowns because of MV nature of variations

10. Process
Static manufacturing process vs. adjustable
manufacturing process to accommodate material
variability
Not developed to be robust
Complexity of product
Formulation not suitable for manufacturing
process used (equipment)
Poor design (people unfriendly)
In general, Manual vs. Automated operations
more prone to mistakes.

11. Operator Error
Performing ad hoc changes
Poor follow up of SOPs
Poor documentation practices
Poor supervisory controls
Limited training effectiveness using current
methodologies

12. Packaging
Inadequate understanding of packaging
material characteristics
Unintended changes in packaging components
(affecting the PV) downstream
Inadequate communication of changes in pkg
components and lack of understanding of its
(unintended but adverse) impact on drug
product quality
Lack of supplier change communication

13. Components
Undefined physical properties – Not
measured, not known
Robust during design does not hold up later
Poor characterization of functional properties
of excipients with API (compatibility)
Change in supplier (qualification)

14. Laboratory Controls
Ambiguity in method instructions – Room for
various interpretation
Multiple sources of (critical) reagents for test
method
Inadequate training of analyst and – Poor
monitoring of the effectiveness of training
Poor maintenance and calibration of
instruments

15. Assignment
• How to control quality variations in
Pharmaceuticals?

16. Expected Questions
• Mention a detailed notes on quality
variations, their sources?
• Variations are of two types: mention them.
Give a short note on controlling quality
variations.

17. THANK YOU
For queries
Email: yunes.r18@cumail.in