Process Control

Question 1

Continuous (FDA)/ On going (EMA) Process Verification Process Control

Answer 1

Ensure process quality, Increase process knowledge, Process stability, Process capability and Supports continuous improvement

Question 2

FDA Continued Process Verification

Answer 2

Ongoing collection and analysis of process data related to quality. Ensures cGMP adherence (detects variability), identifies problem and corrective action. Ensures quality attributes maintained at parameters at process qualification stage

Question 3

Data collected in FDA Continued Process Verification

Answer 3

Trends in process; incoming materials, components, in-process materials and finished products quality

Question 4

Ultimate Purpose of FDA Continued Process Validation

Answer 4

Establishes routine levels and frequency of sampling,. monitoring and statistical analysis

Question 5

EMA Ongoing Process Verification

Answer 5

Monitors product quality to ensure controlled state is maintained throughout lifecycle, process trends. Verification reviewed periodically, better understands product performance. Incremintal changes overtime

Question 6

Control Strategy Outline

Answer 6

Product design conclusion, validated by pharmacovigilance. Planned set of controls derived from current performance ensures product quality. Focus on; CQA, CPP and material attributes

Question 7

Critical Quality Attribute (CQA) [ICH Q8]

Answer 7

Physical, chemical, biological, microbiological characteristics within an approved range to ensure product quality

Question 8

Critical Process Parameters (CPP) [ICH Q8]

Answer 8

Process parameters variability has an impact on CQA should be monitored/controlled for desired quality. Measured during manufacturing

Question 9

CQAs Examples

Answer 9

Physical attributes, Id, Impurity assay, content uniformity, water uniformity and microbial limits. Measured during batch release testing

Question 10

CPPs Examples

Answer 10

Agitation Rate, Drying Rate, Temp

Question 11

Raw Material Attributes Outline

Answer 11

Physical, chemical, biological and microbiological characteristics of input materials within an appropriate limit. Ensures desired output quality. Tested in incoming inspection

Question 12

In Process Control (IPCs) Outline

Answer 12

Measured during manufacturing ensures quality maintained

Question 13

Control Chart Outline

Answer 13

Indicates when process is out of control to identify special-cause variation. Demonstrates consistency and stability. Evals effectiveness of process change

Question 14

Common Cause Variation Outline

Answer 14

Chance variation inherent in any process. Process can still be in statistical control with a common cause variant

Question 15

Special Cause Variation Outline

Answer 15

Variation that causes inconsistency in process. If present, then process can’t be in control

Question 16

Control Chart Ideal

Answer 16

Data evenly distributed across Mean line

Question 17

Control Chart Lines: 6+ data points consecutively ascending/descending from mean line

Answer 17

Process is not in control

Question 18

Control Chart 8+ consecutive points above/below mean line

Answer 18

Process is not in control

Question 19

Control chart; 2+ datapoints, 2 SDs from mean line

Answer 19

Process is out of control

Question 20

Capability Analysis (CP/CPK) Outline

Answer 20

Process variability over long period of time, all external influences present. Goal: quantifiable measure of meeting specification. Eliminates special cause variation

Question 21

Importance of Capability Analysis

Answer 21

Compares process against predefined targets, identify process related problems. Used as benchmark for comparison (competitors, progress, ect)

Question 22

Capability Analysis Ideal

Answer 22

Bar chart of normal distribution

Question 23

If CP/CPK > 1

Answer 23

Process is capable/performing

Question 24

If CP/CK = 1

Answer 24

Process is barely capable/performing

Question 25

If CP/CPK < 1

Answer 25

Process isn't capable/performing

Question 26

Risk Management Tools

Answer 26

Flow charts, Check sheets, Cause-effect diagram (Fishbone), Fault tree analysis and Failure model effect analysis (FMEA)

Question 27

Cause and Effect Diagram (Fishbone) Outline

Answer 27

Relationships between problems and possible causes. Problems: man, machine, material, method, measurement, 'mother nature'

Question 28

Failure Mode Effect Analysis (FMEA) Outline

Answer 28

Identifies way process/product to fail and plan to prevent failures. Determines actions to eliminate occurance and potential effects. Evaluates risk priority number

Question 29

Risk Priority Number

Answer 29

severity X occurrence probability X detection difficulty