CAPA in the Pharmaceutical and Biotech Industries

How to Implement an Effective Nine Step Program

J Rodriguez

• Publisher: Woodhead Publishing
• Year: 2015
• ISBN:
  9781908818379
• Topic: Medicine
• Subtopic: Pharmacology

CAPA in the Pharmaceutical and Biotech Industries: How to Implement an Effective Nine Step Program contains the most current information on how to implement, develop, and maintain an effective Corrective Action and Preventive Action (CAPA) and investigation program using a nine step closed-loop process approach for medical devices and pharmaceutical and biologic manufacturers, as well as any anyone who has to maintain a quality system.This book addresses how companies often make the mistake of fixing problems in their processes by revising procedures or, more commonly, by retraining employees that may or may not have caused the problem. This event-focused fix leads to the false assumption that the errors have been eradicated and will be prevented in the future. The reality is that the causes of the failure were never actually determined, therefore the same problem will recur over and over. CAPA is a complete system that collects information regarding existing and potential quality problems. It analyzes and investigates the issues to identify the root cause of nonconformities. It is not just a quick-fix, simple approach, it is a process and has to be understood throughout organizations.

• Provides an understanding of the principles and techniques involved in the effective implementation of a CAPA program, from the identification of the problem, to the verification of preventive action
• Emphasis is placed on the practical aspects of how to perform failure investigations and root cause analysis through the use of several types of methodologies, all explained in detail
• Provides effective methods to use with a Corrective Action system to help quality professionals identify costly issues and resolve them quickly and appropriately

1

Understanding the FDA’s CAPA requirements and regulations

Abstract

This chapter explains how to understand the United States Food and Drug Administration (FDA) regulations and requirements related to investigations and to corrective actions and preventive actions (CAPA), annual product reviews (APRs), and most importantly, how to interpret FDA regulations as well as ISO 13485 requirements.

It is important to develop an understanding of how to interpret the regulations, because CAPA requirements continue to be misunderstood, and as a result, CAPA continues to be the number one issue cited during FDA inspections.

In addition, a review of the FDA’s current inspectional approach for medical device, pharmaceutical, and biologics manufacturers is also included in order to provide some key points related to what the FDA will be looking for during an inspection. Learning how to interpret the regulations, and the FDA’s inspectional approach, will enable manufacturers to be better prepared and therefore avoid any reports of inspectional observations issued by the FDA or any regulatory actions relating to good manufacturing practices brought by the FDA, such as 483 observations, warning letters, consent decrees, export bans, and injunctions.

Keywords

21 CFR; 21 CFR part 820; Abbreviated inspection; Adverse effects; Analysis; Annual product review (APR); Approving; Auditing; Biologics; CFR (code of federal regulations); Changes; Complaints; Compounding products; Concessions; Corrective actions and preventive actions (CAPA); Current good manufacturing practice (CGMP); Detection; Effectiveness; FDA (U.S. Food and Drug Administration); Identification; Improvement; Inspection; Investigation; Management review; Measurement; Medical devices; Nonconforming product; Occurrence; Pharmaceutical; Potential; Prevention; Preventive actions; Procedures; Products; Quality; Quality by design; Quality control unit; Quality data; Quality problem; Quality record; Quality systems inspectional technique (QSIT); Records; Recurrences; Rejecting; Remedial correction; Reports; Returned product; Risk assessment; Risk management; Root-cause investigation; Statistical methodology; Strength; Timeliness; Trending; Validating; Verification

Part I. 21 CFR part 820.100 for medical devices

Exhibit 1.1 Overview of part 820.100 requirements

Subpart J. Corrective and preventive action

Section 820.100 Corrective and preventive action

1. Each manufacturer shall establish and maintain procedures for implementing corrective and preventive action. The procedures shall include requirements for:

a. Analyzing processes, work operations, concessions, quality audit reports, quality records, service records, complaints, returned product, and other sources of quality data to identify existing and potential causes of nonconforming product, or other quality problems. Appropriate statistical methodology shall be employed where necessary to detect recurring quality problems;

b. Investigating the cause of nonconformities relating to product, processes, and the quality system;

c. Identifying the action(s) needed to correct and prevent recurrence of nonconforming product and other quality problems;

d. Verifying or validating the corrective and preventive action to ensure that such action is effective and does not adversely affect the finished device;

e. Implementing and recording changes in methods and procedures needed to correct and prevent identified quality problems;

f. Ensuring that information related to quality problems or nonconforming product is disseminated to those directly responsible for assuring the quality of such product or the prevention of such problems; and

g. Submitting relevant information on identified quality problems, as well as corrective and preventive actions, for management review.

2. All activities required under this section, and their results, shall be documented (http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=820&showFR=1&subpartNode=21:8.0.1.1.12.10).

Part II. 21 CFR Part 211: current good manufacturing practice for finished pharmaceuticals

Exhibit 1.2 Overview of part 211 requirements

Subchapter C. Drugs: general

Subpart B. Organization and personnel

Section 211.22 Responsibilities of quality control unit

1. There shall be a quality control unit that shall have the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging material, labeling, and drug products, and the authority to review production records to assure that no errors have occurred or, if errors have occurred, that they have been fully investigated. The quality control unit shall be responsible for approving or rejecting drug products manufactured, processed, packed, or held under contract by another company.

2. Adequate laboratory facilities for the testing and approval (or rejection) of components, drug product containers, closures, packaging materials, in-process materials, and drug products shall be available to the quality control unit.

3. The quality control unit shall have the responsibility for approving or rejecting all procedures or specifications impacting on the identity, strength, quality, and purity of the drug product.

4. The responsibilities and procedures applicable to the quality control unit shall be in writing; such written procedures shall be followed (http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=211.22).

Subpart J. Records and reports

Section 211.192 Production record review

All drug product production and control records, including those for packaging and labeling, shall be reviewed and approved by the quality control unit to determine compliance with all established, approved written procedures before a batch is released or distributed. Any unexplained discrepancy (including a percentage of theoretical yield exceeding the maximum or minimum percentages established in master production and control records) or the failure of a batch or any of its components to meet any of its specifications shall be thoroughly investigated, whether or not the batch has already been distributed. The investigation shall extend to other batches of the same drug product and other drug products that may have been associated with the specific failure or discrepancy. A written record of the investigation shall be made and shall include the conclusions and follow-up (http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=211.192).

Subpart J. Records and reports

Section 211.180 General requirements

5. Written records required by this part shall be maintained so that data therein can be used for evaluating, at least annually, the quality standards of each drug product to determine the need for changes in drug product specifications or manufacturing or control procedures. Written procedures shall be established and followed for such evaluations and shall include provisions for:

a. A review of a representative number of batches, whether approved or rejected, and, w...

Table of contents

• Cover image
• Title page
• Table of Contents
• Related titles
• Copyright
• Dedication
• Biography
• Preface
• Introduction
• 1. Understanding the FDA’s CAPA requirements and regulations
• 2. Implementing a CAPA program: Going back to basics
• 3. The nine-step CAPA program
• 4. Step 1: identification of the event and writing a proper problem statement
• 5. Step 2: risk assessment and impact assessment
• 6. Step 3: evaluate event and initiate remedial actions (correction)
• 7. Step 4: data gathering and analysis
• 8. Step 5: investigation
• 9. Step 6: part I—root cause analysis
• 10. Step 7: corrective and preventive action plans
• 11. Step 8: implement and follow-up on action plans
• 12. Step 9: verification of effectiveness
• 13. Examples of procedures
• Conclusion: requirements for an effective CAPA program
• Normative references
• Glossary
• Bibliography
• Index
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