Checking effectiveness of the CAPA ?

👉management process is business critical
👉Is top management involved
👉 Are there any drifts from SOP
👉Does change in personnel impact the process
Effectiveness Check
👉Are timelines always met
👉Is there a trending of the effectiveness of CAPAs
👉Is business impact assessed periodically
👉Carry out a gap analysis, use checklist approach

Benefits of CAPA?

👉 Quality📦💰
👉Detected problems do not recur
 👉🏻Deficiencies are permanently corrected
 👉Potential failures are prevented from occurring
 👉Reduction in batch failures
👉Reduction in customer complaints 👉Compliance
 👉Reduced chances of regulatory penal actions
👉CAPA commitments for inspection observations are met adequately
 👉Reduced adverse inspection comments👉Continuous🤔 Improvement
👉Manufacturing process becomes more robust

 👉Right First ⏰Time batches increases
 👉Risks brought under control
👉Increased customer satisfaction assured💊💊💊🙏💊💊💊

Corrective Action and Preventive Action (CAPA)?

what is a CAPA, Its Initiation, Closure and Verification, Information and documents related to CAPA. 📌Corrective Action
Action taken to rectify, fix or correct a specific deviation, defect or undesirable situation.
📌Preventive Action
Action taken to eliminate the cause of deviation, defect, or other undesirable situation in order to prevent the future occurrence of such or similar an event.
Initiation of CAPA:
🔑The initiation of CAPA requires submission of source document by concerned Department Head to QA.
🔑Department Head shall decide the need for CAPA with Head QA.
🔑 The Department Head shall get a CAPA form issued from QA. QA shall write the source document name and Source document number on the form before issue of form.
🔑 Department Head shall fill the CAPA form as under.
A) Date CAPA initiated
B) Proposed completion date
C) Select the department initiating the CAPA by making a √ mark in appropriate box.
D) Select the relevant system affected by making a √ mark in appropriate box. If none of the systems printed are affected select Not applicable. If any other system other than those mentioned is affected, write the system in blank spaces provided.
E) Write in brief the CAPA description from the source document and corrective and preventive action details.
F) The Department Head shall write their name with signature and date.
🔑The department head shall send the CAPA form to QA.
🔑GM QA / Designee shall allot a reference number to the CAPA form and make relevant entries in the CAPA log. Forward the CAPA form to the concerned department.
🔑The CAPA shall be numbered serially in the calendar year for each department with an identification code of department. A typical CAPA form shall be numbered as
CAPA/XXX/YYY/ZZ
Where,
XXX: department code.
YYY: serial number, commencing at 001 for each department in calendar year.
ZZ: Last digit of a calendar year.
e.g. CAPA/PRD/007/13 represents the 7th CAPA from production department in calendar year 2013🏃🏼🏃🏼🏃🏼🏃🏼🏃🏼🏃🏼🏃🏼🏃🏼🏃🏼🏃🏼🏃🏼CAPA Closure and Verification🎈🎈🎈📑
📌On completion of actions, the department head shall certify that the proposed CAPA is completed and implemented along with associated actions.
📌 QA shall verify the implementation and completion of CAPA with review of supporting documents and certify the same.
📌Any change proposed as a result of CAPA shall be through the SOP on Change Control Reference of the same shall be mentioned in the CAPA format.
📌All Change Controls, Deviations, Discrepancy, Incident Reports giving rise to CAPA shall be addressed through CAPA form.
📌 All facility up-gradations / Capital purchase requirements / major changes in quality system and compliance to regulatory commitments giving rise to CAPA shall be addressed through CAPA form.
📌The record of each CAPA shall be maintained.
📌 Copy of the completed CAPA shall be provided to the concerned Dept. Head by QA Department Head shall compile the CAPA information and submit the summary to the Management during GMP Committee meeting / Management Review Meeting.
📌Management shall review / verify the same quarterly in Management Review Meeting.
📌Information and documents related to CAPA drawn from internal audits, external/ Customer audits and regulatory inspections are considered confidential and can only be made available to regulatory review when approved by Director technical and Vice President QA.
Source documents of CAPA are identified as:
• GMP Investigations
• Deviations
• Change control
• Laboratory (OOS) Investigations
• Internal Audit Reports
• External / Customer Audits
• Annual Product Reviews
• Regulatory Inspection Reports
• Management Action Plans
• Changes in regulatory / Pharmacopoeia requirements
• Product Failures
• Complaints
• Product recall
• Returned Goods
• Incidence Reports
• Discrepancies& Dears allways refer your availability SOP

Five CAPA Tips?

U.S. Food and Drug Administration (“FDA”) inspects current Good Manufacturing Practice (“cGMP”) requirements for nearly two decades, I find myself repeating certain things to companies. Most often, the issues I repeat relate to Corrective and Preventive Action (“CAPA”) systems. CAPA systems are a focal point in FDA inspections precisely because they are the process that manufacturers follow in case something goes wrong. In the same way that a person’s character may be understood by trial through adversity, quality system auditors and FDA investigators understand a company’s operations through its CAPA system.

👇🏼By following five essential steps, companies can be CAPA compliant and ensure a successful audit or inspection.

👉🏻A CAPA system is not only a regulatory mandate, it is the means by which a company may improve its quality system to minimize risks and avoid problems. A properly designed CAPA system provides a process by which a company can proactively and retroactively correct problems identified through the quality system. This requires a robust dataset to detect problems, a measured approach to finding solutions, a careful implementation of those solutions, and documentation to memorialize and communicate the changes made to others.

👉🏻FDA investigators focus on CAPA during inspections because it is a roadmap to identify potential and existing problems at a company. CAPA documentation provides FDA investigators, auditors, and executive management a means to review problems. Therefore, effective management of the CAPA system is critical to compliance. By following five essential steps, companies can be CAPA compliant and ensure a successful audit or inspection.

🔊1. Implement a CAPA System and Document CAPA procedures

👉🏻The first step may seem obvious, but it is essential to establish a CAPA system and document all CAPA procedures. Despite its obviousness, the failure to either have a CAPA process, or failing to document or establish CAPA procedures, is one of the most common issues noted by the FDA. The lack of a documented CAPA system was the second most common observation by FDA investigators in fiscal year 2010 (trailing first place by a single observation) and was noted in more than half of all Warning Letters citing a CAPA violation between 2008 and 2009.

👉🏻The failure to have a CAPA system may result from being unaware of FDA and European Union requirements or may arise as a result of the product’s questionable regulatory status, such as software or in vitro diagnostic tests.1 Or these failures may occur in firms with a mature, robust quality system, where the firm relies on a contract manufacturer or fails to adequately integrate a newly acquired company within the firm’s quality system. As a result, firms must conduct due diligence when partnering with a contract manufacturer or acquiring a new company. A lack of CAPA procedures in a potential acquisition must be identified and implementing such procedures must be a priority after the purchase is complete. Facilities should be thoroughly reviewed after integration to ensure CAPA compliance.

🔊2. Analyze Quality Data Using Statistical Methodology to Identify Quality Problems

👉🏻The second step to CAPA compliance is to use statistical methodology to analyze quality data and identify quality problems. The regulation identifies the following types of quality data that should be reviewed: process; work operations; concessions; quality audit reports; quality records; service records; complaints; and returned product.2 In selecting quality data to analyze, it is critical to include data sources and elements that are both internal and external to the company. In addition, companies should be attentive to quality data on manufacturing processes and nonconformances. Both of these data sets have been noted on FDA Warning Letters.

👉🏻Complaints, in particular, should be given special attention. Complaints are a direct indicator of problems with distributed product, and should be analyzed through the CAPA system as appropriate. The FDA has made clear on multiple occasions that it views complaints as a CAPA data source, and that failure to address customers’ problems may result in a warning letter.

👉🏻Investigators and auditors often judge a firm’s quality system based on a review of its CAPA log. Therefore, it is imperative to implement and then record all changes in methods and procedures in the CAPA log. While the number of CAPAs alone may be misleading, it is important to note the key role that the CAPA log plays during an investigation. Therefore, firms should consider whether to address minor quality issues through another process or to elevate the issue to implement a CAPA process. Firms should also keep in mind that a single quality issue may spawn multiple CAPAs to facilitate implementing the necessary changes. Manufacturers should make it a priority to evaluate the number of CAPAs generated and analyze that information to determine if there is adequate quality assurance. A periodic review of the CAPA log will provide a broad view of how the system is running.

🔊3. Investigate and Identify the Cause of Quality Problems

👉🏻Manufacturers should promptly investigate the cause of quality problems. The FDA will take note if a firm has identified a problem but failed to conduct a detailed investigation to determine the root cause of the issue. Firms should conduct efficient and meaningful investigations by utilizing a systematic and orderly method. For example, firms should establish a documented investigation procedure that is implemented every time a problem arises. The investigation should be conducted by trained investigators. Firms should also employ a flexible CAPA closure target dating method that incorporates triaging based on risk. CAPAs that can be tied directly to nonconforming finished product should be given a priority.

👉🏻In the beginning, the company should articulate a clear and complete statement of the problem. It is essential to identify the issue so that it may be properly addressed. The company must then invest the appropriate time and resources into conducting a thorough investigation, implementing the firm’s documented investigation procedure. The investigation should be documented carefully. In addition to the investigation, the manufacturer should consider the impact of the issue on its products globally. Use of statistics and trending analysis are vital tools in determining the scope and impact of the problem. It is imperative that the company contemplates the relationship that poor practices have with nonconforming product. Ultimately, the investigation must analyze the root cause of the issue, and identify actions needed to correct and prevent the recurrence of quality problems.

👉🏻Finally, companies should avoid common mistakes that result in an incomplete investigation of the problem. Companies sometimes use training as a scapegoat, or as a cure-all, and the FDA will be unsatisfied without a proper investigation to support a “training-only” solution. Moreover, jumping to a first or obvious cause of a problem without an actual investigation is another cause for concern. Even if a problem has what appears to be a clear cause, firms should implement investigation procedures to ensure that the actual cause (or causes) of the issue has been identified and eliminated. A failure to test assumptions may result in dire consequences, both in terms of product quality and FDA compliance with CAPA procedures.

🔊4. Verify or Validate Corrective or Preventive Actions to Ensure the Effectiveness of Those Actions and to Ensure that the Actions Taken Do Not Result in an Adverse Impact on Finished Devices

👉🏻A common mistake companies make is the failure to check effectiveness after implementing a correction or preventive action. Once an investigation is complete and the root cause has been identified, it is imperative that any corrective or preventive actions be validated following implementation to ensure the actions are effective and do not introduce new problems.

👉🏻To identify and implement a plan is simply not enough; effective follow-up to ensure that the plan is addressing the problem and is not creating any new problems is indispensable. Companies should always be cognizant that fixing one problem may create another. With this in mind, any changes to the production process that fix an issue should also be viewed as a potential source of new problems. Therefore, after preventive or corrective actions have been taken, companies must ensure that not only the original problem has been solved but also that no new problems have arisen as a result of that action.

🔊5. Implement and Record Changes in Methods and Procedures as Part of Actions Taken and Disseminate Those Records to Management and Quality Assurance Personnel

👉🏻Any changes to methods and procedures must be appropriately memorialized in writing and must be reviewed by management and quality assurance personnel. The FDA highlights the importance of management review in its “QSIT Manual” by instructing investigators to examine the review schedule to determine if management reviews are sufficiently frequent enough to keep management “informed of ongoing quality issues and problems.” Indeed, if management is unaware of quality issues, that is a red flag for the FDA that the firm is not reviewing quality control as frequently as it should.

👉🏻Moreover, frequently conducting management reviews is not enough. Management reviews must also include a discussion of the substantive information on CAPAs to ensure that management is involved in implementing and validating corrective procedures. Effective managerial review of the CAPA process will help ensure that appropriate follow-up occurs. A best practice would be to include a managerial follow-up report on all CAPA issues that documents the investigation, actions implemented, and the validation of those actions to ensure that the problem was addressed and that no new problems arose. Active managerial involvement in the CAPA process will help promote allocation of adequate resources to address significant action and provide an incentive to follow-up on outstanding issues and close-out CAPAs in a timely manner.

👉🏻By implementing a rigorous CAPA process that analyzes quality data, contains a thorough investigatory procedure, validates the effectiveness of actions taken in response to issues, and then records any changes in methods and procedures, and subsequently disseminating that information to management and personnel will help ensure CAPA compliance. Incorporating these tips are valuable to ensuring an effective quality system. This will, in turn, ensure that FDA inspections and other audits go as smoothly as possible💊💊💊🙏🏽💊💊💊

Overview of a CAPA program

Overview of a CAPA program

Introduction

Our objective is to identify problems in a timely manner, to correct them and to prevent their re-occurrence. As a corollary to this, we want to foresee potential issues and ward them off before they become real. The ultimate goal is for the laboratory operation to become self-correcting.

To be successful, management has put into place a corrective-and-preventative actions (CAPA) system. Any CAPA system must work effectively and its “effectiveness” must be measured. It must also work efficiently. The CAPA program itself should not become a problem. The yoke of the CAPA program should be light and easy to bear.

Management Commitment to Quality

Commercial off-the-shelf software is available to facilitate the administration of the CAPA program and is designed around many of the common industry needs.2 Such software programs help one to log and track CAPAs, responsible persons, effectiveness checks, completion dates, etc. and have many desirable attributes. The essential ingredients for implementing an effective CAPA program are, however, not the tools used. Rather, they are (1) knowing what you want the CAPA program to do and (2) having an environment (quality culture) in which to install the program that will support and promote it and allow it to change. This is what we mean by “Management’s Commitment to Quality”. In this way, the CAPA program is no different from any other quality system in place at the compliant facility.

Management puts the process into place, funds it, oversees, and tends to it. It is important to note that it is Management’s commitment and not the Quality Assurance group’s commitment we are talking about. Management has the resources, vision, and a vested interest and puts a Quality Assurance group into place as one, albeit important, “cog in the wheel”

Roles and Responsibilities

Understanding “who is responsible for what” in the CAPA program is critical and our approach is simple: Management has the resources and sets the goals and therefore must drive the CAPA program. To do this, in part, Management puts a Quality Assurance program in place. Quality Assurance performs audits, finds problems, and reports them to Management. Management must “own” the problems as well as their solutions. It is not the job of the QA group to “fix” the problems (although they may make suggestions), since to do so would create a conflict of interest much like the fox guarding the chicken coop. Rather, an independent QA group plus a strong and actively-engaged Management work together to bring about the desired improvements.

Management and QA work together to approve the written procedures (SOPs) to be followed in the conduct of the CAPA program, including how the program is to be audited, how CAPA data are to be shared across the company, how CAPAs are to be reported to Management, approved, and ultimately “closed” and so on.

To effectively implement the CAPA program, everyone must “buy-in.” For each corrective and preventative action (CAPA), Management identifies the “responsible” person or persons who will work to close-out the CAPA. Such individuals typically report to Management, have an intimate knowledge of the problem that has been cited for CAPA (they may in fact have caused it) and can significantly contribute to its solution. In the “no-fault” culture we promote, we are not looking to blame. The responsible person plays a key role in helping to determine the root cause and will take actions to ensure improvement. They do not do this alone.

Another prominent role is that of CAPA coordinator. This role is two-fold: (1) to coordinate the activities required to ultimately close-out (finalize) the CAPA; and (2) to help manage and improve the CAPA program. The position is noted on the organizational chart, has an associated job description, and is tied to specific job training that is documented in the employees’ training binder. The task is shared by two individuals: One from the lab side (typically at the group leader level) and the other from the QA side (typically an experienced auditor).

The CAPA coordinators conduct regularly scheduled meetings (called CAPA meetings) where they invite responsible persons to enter into a brainstorming session in order to determine root causes and corrective and preventative actions. Present also is an experienced QA auditor, who determines an “effectiveness check” on the CAPA, communicates this to the group, and ensures that such checks are done according to schedule.

All employees must know that they are an integral part of the CAPA program and that they will be treated fairly. Having a mechanism in place by which any employee can contest the legitimacy of any CAPA finding is a cornerstone.

Leadership

Managing the CAPA program requires leadership skills. The approach must be risk-based while simultaneously building credibility with employees and outside auditors. This is done by (1) making decisions based on complete and good data; and (2) following up with a high level of consistency and transparency. It is essential that Leadership provide the program with a high-visibility, while protecting client confidentiality. The CAPA program must function as a “performance driver” using terms, definitions, and actions that are clear-cut for all employees to understand and that facilitate meaningful training. Managing is just one part, albeit an important part, of implementing an effective CAPA program.

The Quality Systems Approach

The quality systems approach to organizing and managing an operation that will comply with regulatory requirements is standard practice in the Pharmaceutical and Medical Device industries, and is well documented in the literature.3

A quality system is a portion of the larger operation that you want to bring under control via a system of management. For example, lab management decides to use only a qualified instrument in the conduct of an experimental study. Next, the decision is made to identify this instrument as “qualified,” to maintain an instrument logbook on it, along with a calibration schedule, etc. They soon find they need to do this on a number of instruments and determine that each instrument qualification shall follow a standard operating procedure and be documented in the same way –they are scaling this operation up. They consider all the details that must go in to ensure that laboratory instruments, associated documentation, reference standards, etc. are meeting all pre-determined criteria for performance, reliability, compliance with regulations: in short, “Quality.” They call this quality system “Metrology” and hire or train a Metrologist to manage it.

The quality systems together form a platform on which to conduct quality regulated laboratory work.

Written Procedures (SOPs)

Standard Operating Procedures (SOPs) provide a basis for setting expectations, organizing lab and study activities, maintaining qualified equipment and instruments, conducting training and auditing of laboratory and the administrative functions (e.g. Document Control). Table 1 provides a listing of some of the key SOPs (by title) in place to support the CAPA program. Having good written procedures in place is critical. The CAPA program generates data used by Management to decide on who should be trained on SOPs and how frequently, how to improve, add or delete written procedures, (including the SOP on the CAPA program) and how to improve training on written procedures. Every employee either working in the lab or providing support to the GMP/GLP program must be trained on the CAPA program. Training on procedures that are specific to experimental studies such as analytical (test) methods and study protocols or Metrology, Quality Assurance or Document Control may be aimed at employees working in these areas. The old adage “say what you are going to do and then do what you say” is akin to writing good procedures, performing quality audits against these procedures and taking corrective and preventative actions when such audits reveal a failure to follow these procedures and/or flawed procedures.

Quality Metrics

By “quality metric,” we mean a quantitatively measurable attribute or parameter that we wish to optimize that reports back on the work product, process or personnel. Quality metrics often have assigned pre-defined acceptance criteria, target values, or specifications. Furthermore, the numerical value assigned to that “specification” will often be set through a program of Quality Risk Management.

Quality metrics are monitored in our work flow at strategic positions. It is not possible in an article of this length to show all the details. However, Figure 4 should suffice to make that point. In Figure 4, we’ve shown a few positions (P1 – P7) in the work flow of an experimental study where we find it strategic to take CAPA data specific to the quality metric “conformance with the GMP or GLP study protocol.” Referring to the figure, the study begins with the study protocol and ends with the archiving of all study materials. At P1, the Principal Scientist checks that participating scientists are trained in the protocol; at P2, the Sample Coordinator checks that all samples, test articles, control articles, and standards have been properly received and are stored under those conditions specified in the protocol; at P3, QA checks that analysts are using only those analytical test methods called for in the protocol and that those methods have been properly validated or verified, the analyst checks that all system suitability results, and reportable test results meet any/all specifications called out in the protocol; at P4, QA checks that there were no unapproved deviations from the protocol; at P5, QA checks that any/all CAPAs generated in the conduct of the study have been closed out; at P6, QA checks that the data report has been written in conformance to the protocol; at P7, QA checks that the study has been archived in accordance with protocol.

Monitoring other quality metrics, such as “proper recording and storage of raw data,” is done similarly and a diagram of the work flow through the lab that is not study-specific would also follow the same logic.

Numerous quality systems are put into place at the laboratory to facilitate hitting the target or optimal value of each quality metric. The CAPA quality system is put into place to identify when the target was not hit, why, who are responsible, and what should be done about it. These concerns translate in CAPA lingo to deviation, root cause, responsible person, corrective action, preventative action, and effectiveness check. The effort is made to ensure that the quality metrics used by the lab point to high-level company goals so that they are meaningful. Working together, Quality Assurance and Management define the set of quality metrics or standards to which to hold the lab to.

Managing CAPAs

Managing CAPAs involves logging, reporting, closing, and trending. The CAPA log is the repository of all the data gathered, mostly by the QA group, on all of the quality metrics over time. The CAPA coordinators conduct the CAPA meetings and keep the CAPA log current. This log is a searchable database, with an audit trail function, that is shared with authorized personnel as a read-only file on the company’s public drive. Such a database permits QA to correlate data to provide trends analysis over any/all of the company’s quality metrics and to follow up on the effectiveness of the preventative actions taken.

The procedure followed to handle a single CAPA is given in the flow chart of Figure 5. Referring to this figure, problem identification includes assigning a CAPA number and responsible person to the problem, making all required notifications and coordinating the CAPA meeting; determining actions includes root cause analysis and determining the corrective action(s) and preventative action(s); setting the target completion date involves a risk assessment and evaluation of available resources; implementation of actions typically includes going through a change control procedure to ensure that the CAPA does not create more problems; determining an effectiveness check includes setting criteria by which to judge effectiveness; performing the effectiveness check and evaluating “effectiveness” is just that; and closing out the CAPA involves documenting that all changes were made as proposed and all required documentation is appropriately approved and filed.

A hypothetical example of trending is the following: The QA group has determined from examination of CAPA data collected over a period of time that there has been an increase in the number of chromatographic system suitability failures logged. While failing system suitability is not a deviation from the GMPs, GLPs or any written procedure used in our lab, a large number of failures is indicative of a problem and a grossly inefficient use of resources including analyst and instrument time. Metrology records show no indication of a problem with any of the associated instruments over the time period concerned and closer examination shows that the problem stems from a particular analyst, running a particular analytical method, regardless of the instrument they used. . The root cause is determined to be a lack of understanding of the analytical method by the analyst, the corrective action is to assign the analysis to a more experienced analyst and the preventative action is to provide additional training to analysts on the test method. The Effectiveness check is to track the number of system suitability failures for a period of time to see if the number associated with this analyst and this method has decreased.

In this way, Quality Assurance and Management identify problems, correct them in a timely manner consistent with their risk level, and prevent their re-occurrence. Trending analysis allows us to foresee potential issues and ward them off before they become real. Having such a CAPA system installed in a strong quality culture ensures that the laboratory operation becomes self-correcting.

Change Control

Implementing corrective and preventative actions necessitates change. It is essential that these changes be accommodated through the company change control program. The guiding principle is akin to the Hippocratic principle “physician, do no harm.” Our quality systems align with well-defined unit operations in the work flow through the laboratory. Thus it is relatively easy to see how a proposed change in one part of the operation affects or has the potential to affect an undesirable change in another.

References

1. “CAPA for the FDA-Regulated Industry” by Jose Rodriguez-Perez, ASQ Quality Press, Milwaukee, WI, 2011. (ISBN 978-0-87389-797-6)

2. “How to Set Up a CAPA Program from Scratch” by Gabriela Bodea, Journal of GXP Compliance, April 2007, Volume 11, Number 3.

3. ICH Q10 Pharmaceutical Quality Systems, Guidance for Industry, April, 2009 and 21 Code of Federal Regulations, Part 820: Medical Devices: Current Good Manufacturing Practice Final Rule: Quality System Regulations, 1996.