Cpk process capability used in pharma .pdf

pharma

1. Prepared By, Starlin
Cpkin the
Pharmaceutical
Industry

2. Prepared By, Starlin
Detailed Explanation of Cpk
The Process Capability Index (Cpk) is a measure that
evaluates how well a process is performing in terms of
meeting the specified product quality standards.
It compares the allowable limits (based on product
specifications) to the actual variability (spread of the
process) and gives a value that indicates how well the
process can stay within these limits.

3. Prepared By, Starlin
CpkFormula and Components
The formula for calculating Cpkis:
??????????????????=min(
??????????????????−??????​
3??????
,
??????−??????????????????
3??????
)
Where:
USL (Upper Specification Limit): The maximum
value allowed for a product characteristic (e.g.,
tablet weight, concentration of active ingredient).

4. Prepared By, Starlin
CpkFormula and Components (contd)
LSL (Lower Specification Limit): The minimum
value allowed for the product characteristic.
μ (Mean): The average of all data points from
the process.
σ (Standard Deviation): A measure of how
spread out the data is, indicating the variability
in the process.

5. Prepared By, Starlin
CpkFormula and Components (contd)
The Cpkis calculated by determining the
number of standard deviations the process
mean is away from the nearest specification
limit.
The process with a higher Cpkis considered
more capable, meaning it’s more likely to
produce products that meet the specifications.

6. Prepared By, Starlin
Steps to Interpret Cpk
Process Mean (μ): This is the center of the distribution,
representing the typical or average value of the process.
Specification Limits (USL and LSL): These are the acceptable
range for product attributes (such as weight, potency, or
concentration).
Standard Deviation (σ): This measures how much the process
output varies from the mean. A smaller standard deviation
means the process is more consistent.

7. Prepared By, Starlin
Steps to Interpret Cpk
If Cpkis high, it suggests that the process
produces products with minimal variation
and is well-centered between the
specification limits.
If Cpkis low, it indicates more variation
and possible defects.

8. Prepared By, Starlin
Step-by-Step Calculation of Cpk:

9. Prepared By, Starlin
Example Scenario
Let's walk through a pharmaceutical
example: a company is producing tablets,
and one of the critical quality attributes is
the weight of the tablets.

10. Prepared By, Starlin
Example Scenario (Contd)
Tablet Weights (mg): 496, 497, 495, 502,
501, 498, 500, 501, 499, 497
Target Weight (μ): 500 mg
Lower Specification Limit (LSL): 490 mg
Upper Specification Limit (USL): 510 mg

11. Prepared By, Starlin
Step 1: Calculate the Mean (μ)
The mean is the average of the tablet weights. The
formula for the mean is
??????=
∑??????
�
Where: X = individual tablet weights
n = number of samples (in this case, 10 tablets)
The tablet weights are: 496, 497, 495, 502, 501, 498, 500,
501, 499, 497.

12. Prepared By, Starlin
Step 1: Calculate the Mean (μ)
??????=
496+497+495+502+501+498+500+501+499+497
10
??????=
4995​
10
=499.5�??????

13. Prepared By, Starlin
Calculate the Standard Deviation (σ)
The formula for standard deviation is:
??????=
∑(??????
??????−??????)
2
??????
Where: ??????
??????= each individual tablet weight
μ = mean
n = number of samples

14. Prepared By, Starlin
Calculate the Standard Deviation (σ)

15. Prepared By, Starlin
Calculate the Standard Deviation (σ)
∑(??????
??????−??????)
2
=12.25+6.25+20.25+
6.25+2.25+2.25+0.25+2.25+0.25+
6.25=58.50

16. Prepared By, Starlin
Calculate the Standard Deviation (σ)
Now, divide by the number of samples (n =
10) and take the square root:
??????=
58.50
10
=5.85≈2.42�??????

17. Prepared By, Starlin
Step 3: Calculate Cpk
The formula for calculating Cpkis:
??????????????????=min(
??????????????????−??????​
3??????
,
??????−??????????????????
3??????
)
USL = 510 mg
LSL = 490 mg
μ = 499.5 mg
σ = 2.42 mg

18. Prepared By, Starlin
Step 3: Calculate Cpk
Cpkfor USL:
??????????????????−??????
3σ
=
510−499.5
3×2.42
=
10.5
7.26
≈1.45

19. Prepared By, Starlin
Step 3: Calculate Cpk
Cpk for LSL:
??????−??????????????????
3σ
=
499.5−490
3×2.42
=
9.5
7.26
≈1.31

20. Prepared By, Starlin
Step 3: Calculate Cpk
Finally, take the minimum of the two
values:
??????????????????=min(1.45,1.31)=1.31

21. Prepared By, Starlin
Step 4: Interpretation
Cpk= 1.31 means that the process is capable of
producing tablets within the specification
limits with a good level of consistency, but
there is still room for improvement.
Typically, a Cpkgreater than 1.33 is
considered acceptable for a process to meet
specifications consistently.

22. Prepared By, Starlin
Impact of Cpk on
Pharmaceutical
Processes

23. Prepared By, Starlin
Consistency in Active Ingredient Dosage
Consistency is key in pharmaceutical
manufacturing, as variations in weight
could impact the dosage of the active
pharmaceutical ingredient (API),
potentially leading to under-dosing or
overdosing.

24. Prepared By, Starlin
Compliance with Regulatory Requirements
Regulatory bodies like the FDA or EMA set strict
requirements for pharmaceutical manufacturing
processes. A high Cpkdemonstrates the
company’s ability to maintain consistent quality
and meet these regulatory requirements. A Cpkof
1.33 or higher is often considered the minimum
acceptable standard in pharmaceutical production.

25. Prepared By, Starlin
Reduction in Scrap and Rework
With a high Cpk, fewer products are
outside the specified limits, which means
less waste and fewer products that need to
be reprocessed or discarded. This leads to
cost savings and improved efficiency.

26. Prepared By, Starlin
Product Stability and Safety
Especially for sterile injectables, a high
Cpkensures that parameters such as pH,
concentration, and sterility are consistently
within acceptable limits, ensuring the
safety and efficacy of the product.

27. Prepared By, Starlin
Consequences of a Low Cpk
Increased Risk of Non-Compliance:
Regulatory bodies will likely flag a process
with a low Cpk, which may result in
increased scrutiny, delays in product
release, and possible regulatory actions.

28. Prepared By, Starlin
Consequences of a Low Cpk
Quality Control Issues: More out-of-specification
products will be produced, leading to higher
rejection rates and potentially impacting patient
safety due to incorrect dosage.
Higher Production Costs: Increased waste, rework,
and process downtime contribute to higher costs.

29. Prepared By, Starlin
Thank You
Prepared by,
Starlin
Ph. No: [phone]
Email: [email protected]