Cpk <1.33, Now What? A Commercial Quality Perspective

Paul Stojanovski Vice President, Product and Process Robustness ,Global Quality Teva Pharmaceuticals

The views expressed herein are the views of the presenter only and not those of any company, employer, or organization associated with the presenter.

Process Capability A Quality Tool

Process Capability – A Quality Tool

Process Capability a Quality Tool for: 1. Risk Assessment

2. Root Cause investigation 3. CAPA Effectiveness 4. Product Continuous Improvement

The Process

Data Collection

Data Collection: 1) Product Development Reports – R&D

a) Critical Process Parameters (CPP) b) Critical Quality Attributes (CQA) c) Critical Material Attributes (CMA)

2) Commercial batch manufacturing information a) Specifications b) Batch data on CQA’s

3) Calculation of CpK’s on CQA’s affecting product performance:

a) OSD Immediate release i. Assay, CU, Dissolution, water content, blend uniformity

Assessment Process

Assessment Process

Case Study • Product: Extended release tablets

• Product strengths: 500 mg, 750 mg and 1000 mg

• Additional information: New product, launched in 2013

• Product history: No history of OOS and OOT investigations

• Dissolution data for active ingredient for release, presented below. What does the data tell us?

Dissolution

testing

interval

1 hour 3 hours 6 hours 9 hours 12 hours 20 hours Assay CU Water

Content

Individual

strengths Cpk values

(target Cpk > 1.33) 1000 mg 4.00 5.00 1.1 0.66 0.73 13.00 4.09 9.52 5.44 750 mg 4.00 3.63 2.96 3.03 2.44 5.44 3.78 7.24 4.68 500 mg 3.00 2.82 2.06 1.92 1.90 3.62 1.1 4.26 8.57

Case Study – Assay 500 mg

Case Study • Product: Extended release tablets

• Product strengths: 500 mg, 750 mg and 1000 mg

• Additional information: New product, launched in 2013

• Product history: No history of OOS and OOT investigations

• Dissolution data for active ingredient for release, presented below. What does the data tell us?

Dissolution

testing

interval

1 hour 3 hours 6 hours 9 hours 12 hours 20 hours Assay CU Water

Content

Individual

strengths Cpk values

(target Cpk > 1.33) 1000 mg 4.00 5.00 1.1 0.66 0.73 13.00 4.09 9.52 5.44 750 mg 4.00 3.63 2.96 3.03 2.44 5.44 3.78 7.24 4.68 500 mg 3.00 2.82 2.06 1.92 1.90 3.62 1.1 4.26 8.57

Case Study #1 – Dissolution 1000mg

Enhanced Root Cause Analysis

Data Evaluation: 1. Product Development – R&D 2. Validation 3. Commercial batch manufacturing information 4. Specifications 5. Equipment information 6. Change Controls 7. Quality Infractions

a. Deviations b. Laboratory Investigations c. Complaints d. Adverse Reactions

8. Stability

Remediation Plan

Continuous Process Verification (CPV)

What is Continued Process Verification?

Proactive approach. Identify issue before it becomes serious Quality problem.

Use existing data to predict product performance and draw conclusions.

Apply standard methodology, based on science and statistics.

Perform Holistic evaluation.

Contribute to Process sustainability.

Culture of Continuous Improvement.

Utilization of Annual Product Review data

Summary

Summary

• Use Process Capability evaluation as an assessment tool • CQA’s affected by lower CpK’s lead to CPP’s or CMA’s to

be investigated • Process capability can assure CAPA effectiveness after

remediation • Link process to Annual Product Review to utilize data

available and establish a Proactive Product Control System to prevent product failure

• Continuous Improvement of processes to enhance Quality, Business and most importantly patient service

Title THANK YOU