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1 Be SMART With Your Corrective and Preventative Actions (CAPA) Compliance can only be achieved when the corrective action is in place, and is acting synergistically with all quality systems. by Larry ld Production Manager Bayer Corporation We are presented with problems that we analyze and solve on a daily basis. Some of these problems are very minor, and take only a moment to determine a solution. However, others are more complex, and might involve several individuals or teams, as well as span across many processes. With all problems, we want to avoid the mistakes that led to them. Therefore, we try to find a systematic way to ensure we avoid previous mistakes in the future. Corrective actions are the systematic solutions to problems that, once implemented, will prevent the reoccurrence of mistakes. To better define a corrective action, it is helpful to know what it is not. A corrective action is not a fix. A fix is a solution that restores a system to its original state. While a fix may make a system run again, or make a piece of equipment operational, it does not analyze the deviation, look for the root cause, and implement changes to avoid repeated failures in the future. In addition, a corrective action is not a single solution implemented to bring the system into compliance. Compliance can only be achieved when the corrective action is in place, and is acting synergistically with all quality systems. Finally, a corrective action is not preventive action. Although most, if not all, of the same concepts discussed below apply to preventive actions, corrective actions are implemented to correct problems that have occurred, while a preventive action corrects problems that will, or may occur. Once a deviation is discovered, it must be documented and investigated. It is beyond the scope of this article to give an indepth discussion into the investigation of deviations, although any investigation must be thorough and documented. Generally, the deviation owner will investigate with review and approval by the quality group. However, this guideline may not always be followed. In some instances, the quality group may independently investigate and report their findings. In these instances, the investigation still must be reviewed by an unbiased second party for completeness and accuracy. Regardless of who investigates, a report must be written and approved. An investigational report into a deviation needs to include at a minimum: Cause Product impact Corrective action The Code of Federal Regulations (CFR) Part states: All drug product production and control records, including those for packaging and labeling, shall be reviewed and 82

2 Larry ld 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. A written record of the investigation shall be made and shall include the conclusions and follow-up. 1 It is important to keep in mind that the report is being written, not just to release product for sale, or to justify a previously distributed product, but to assure all stakeholders, including Quality Assurance (QA), regulatory agencies, and especially the patient, that the deviation did not affect the safety, identity, strength, purity, or quality of the product. The U.S. District Court supported the guidelines set forth in the CFR for investigations and corrective actions in the now industry famous case of the U.S versus Barr Laboratories. 2 Judge Alfred M. Wolin wrote the following opinion for the courts with respect to investigations and corrective actions: Extending beyond the laboratory and often labeled formal investigation, these inquiries should follow the outline the government provided with companies paying particular attention to any necessary corrective action, whether reprimanding, retraining, or firing employees, remixing batches, or adjusting processes. Thus, in the failure report firms must: State the reason for the investigation; provide a summation of the process sequences that may have caused the problem; outline the corrective actions necessary to save the batch and prevent a similar occurrence; list other batches and products possibly affect, the results of their investigations and any required corrective action; and finally preserve the comments and the signatures of all production and quality control personnel who conducted the investigation and approved any reprocessed material after additional testing. While a court with New Jersey jurisdiction rendered the opinion, it is the precedent and case law by which the Food and Drug Administration (FDA) bases its stance, and the standard Industry has adopted. The FDA expects corrective action, which is the follow-up, required in the CFR, and the court has reinforced this expectation by specifically stating that corrective actions are required for investigations. SMART Corrective Actions A corrective action must rectify the root cause of a deficiency to prevent a reoccurrence of the problem. If after the corrective action is implemented and the problem persists, then either the root cause was not corrected, or the actual root cause was not identified. Identification of a root cause to a problem can be difficult. All the data may not be present to identify a root cause. The root cause may be masked by other symptoms not related to the problem, or there may be many problems acting synergistically to appear as one problem. If the corrective actions are not effective, then the investigation was not complete in that it did not find a root cause, and the investigation must be either continued or reopened. Corrective actions that work are SMART: Specific, Measurable, Attainable, Realistic, and Timely (SMART). A corrective action must contain all five attributes if it is to be effective. If any corrective action is missing any one of the attributes, its chances for long lasting success will be truly diminished. First, ensure your corrective action is Specific. Too broad or narrow of a corrective action could hamper or hinder the outcome. For example, a water inlet valve s diaphragm is being harmed because the water valve is too close to the clean steam generator to which it feeds. In order to correct the problem and other potential problems related to it on site, you could: ❶ Move the valve further upstream, and replace the diaphragm with a more heat resistant one. ❷ Survey all valves on-site for a suitable location, and implement a program that will change out all diaphragm valves with heat resistant ones. ❸ Move the valve, and/or replace the diaphragm, while ensuring that other water inlet valves to clean steam generators either have the correct diaphragm, or are in a suitable location. Clearly, option number one will solve the problem with the diaphragm valve, however, the solution is confined to only that system. Thus, option one is too narrow. Option two is too broad. There is no 83

3 Larry ld need to implement a site wide program for a problem with one valve in this case. There are always limited resources to draw from, so you want to ensure your corrective action will be efficient without sacrificing quality. Option three would be the best choice in this instance. It corrects the specific problem, yet audits similar and identical systems to avoid the same mistake. Next, any corrective action that is developed must be Measurable. A corrective action that states: Enhance effectiveness across all quality systems is meaningless. One general guideline to use when writing and implementing corrective actions is to use the 3 W s: ❶ Whom ❷ What ❸ When Ensure all parties involved with the who statements are in agreement with the corrective action. To encompass the what part of the corrective action, whenever possible, include specific numbers for what is to be done. For example, a corrective action that states: Replace all diaphragm valves on the clean steam generator may appear straightforward, but there is plenty of room for mistakes. One interpretation may be to replace only the steam diaphragm valves, since the corrective action deals with the clean steam generator. Another interpretation may be to replace the water valves, as well as the clean steam valves. However, a correction action that states, replace diaphragm valves X1, X2, and X3, leaves little room for miscommunication. Finally, a well-written corrective action will contain a due date to measure whether it was completed on time. Once again, ensure all parties involved are in agreement with the due date. In numerous instances, corrective actions that are considered good ideas end in failure because the resources were not available to implement them. Therefore, the goal of the corrective action is not Attained. To ensure that corrective actions are attained, all resources to complete the corrective action must be available. Resource allocation must be considered when writing a corrective action. This includes, but is not limited to, personnel, time, and material. Other times, corrective actions may not be considered good ideas because they are not realistic. Earlier in this paper, an example was given related to changing all valve diaphragms at a manufacturing site. Although the idea may have merit because there may be a better diaphragm, it may not be realistic from a logistical standpoint, or from a cost/benefit analysis. A balance needs to be struck between correcting the problem, and how the problem is corrected. In the example, a compromise was reached to replace the diaphragm that needed to be replaced with a similar situated diaphragm. This is a corrective action that can be implemented for a definite benefit, at a reasonable cost. Although the last attribute of a good corrective action is Timeliness, it is no less important than the preceding ones. The four other attributes of a corrective action, specific, measurable, attainable, and realistic are worthless if the corrective action is not completed in a timely manner. In most cases, an appropriate time span for the corrective action to be implemented is before the equipment or system is used again. In the situation where training is involved, then the individuals must be retrained before the task is started. Timeliness must start with the investigation. Recently, numerous companies have been cited by regulatory agencies for the timeliness of their investigations, and consequently, their correction to the problems were not timely. In fact, failure investigations were the leading topic for Warning Letters issued in Moreover, if a timely investigation is not conducted, then the firm is in some way indicating that the problem and corrective action is not of immediate concern, when in fact, just the opposite could be true. Corrective actions can vary over a wide spectrum, and their implementations generally fall into three categories. The first category, which is usually the weakest, is training. Training may be appropriate for the short-term, but there is no guarantee that the training will be effective, or that the knowledge base will be passed on when new personnel arrive. The second level is to have the corrective action written into a Standard Operating Procedure (SOP). While this approach is much better than simple training, since the corrective action has been proceduralized, you are still relying on a person s memory to ensure the corrective action occurs. The third category is written confirmation that a procedure defined by a corrective action has been completed. This third tier of corrective action implementation can manifest itself in several different forms ranging from revalidation protocols, to change control documents, to Batch Production Records (BPRs), or checklists. 84

4 Larry ld Finally, corrective actions should be tracked and monitored by one group, usually the Quality Unit (QU). Periodic reports should be issued, summarizing the status of the corrective actions. Metrics should be tracked and reported for various cycle times. These cycle times can include the amount of time that has elapsed since the corrective action was opened to when the work has been completed for the corrective action, however, work completed should not be considered completion of the corrective action, since it still needs to be verified. Another cycle time to monitor is work completion to verification. Verification is signed off by the QU that the corrective action is complete. Verification can be done in numerous ways. For example, the QU may need to verify training was completed, a document with a revision has become affected, physical inspection of a system, or monitoring an operation to ensure a corrective action was incorporated. With verification completed, the last step for the QU is to sign-off the corrective action complete, and thus the metric of open to close can be tracked for all corrective actions. Conclusion Figure 1 Corrective Action Flowchart Yes Discrepancy Investigation Write SMART Corrective Action All Involved Parties Agree Change Control Implement Corrective Action Corrective Action Effective Review of All Corrective Actions Undesirable Synergistic Effect Yes Track Corrective Action Yes Change Control Documents Once done, corrective actions are usually thought of as completed, and not to be looked at again unless the same problem occurs. However, looking at the flowchart in Figure 1, there are definite feedback loops in the workflow of corrective actions. The QU with operations should review corrective actions on a regular basis. A full review should be done with the Annual Product Review (APR). During the APR, corrective actions should be reviewed for overall impact. One or two corrective actions, by themselves, may not have any effect on the product, but a few actions, functioning synergistically, may cause a shift, and could go undetected, unless viewed as a whole. In addition, corrective actions should be reviewed to determine the overall effect on systems or groups. Reviewing corrective actions will also indicate if any system or equipment is failing, or having problems at an unusual rate. As part of the APR, a summary report should be written for corrective actions, describing the reviews discussed above, as well as the metrics listed above. At times, employees see corrective actions as mandated, burdensome, requirements that must be completed to allow them to continue their work. However, good corrective actions that prevent problems from reoccurring are easy to explain, and thus it is easy to obtain the necessary buy in from employees. Writing SMART corrective actions, ensuring that corrective actions are properly proce- 85

5 Larry ld duralized, periodically reviewed, and obtaining employee buy in ensures a properly functioning corrective action program. When a corrective action program is effective, problems are systematically investigated and solved; therefore allowing the business to move forward, secure in the knowledge it will not have to revisit old problems. References 1. FDA. Code of Federal Regulations, Food and Drugs. Current Good Manufacturing Practice for Finished Pharmaceuticals. Title 21, Part 211 (U.S. Printing Office, Washington, DC). (April) United States vs. Barr Laboratories, Inc NJ, 812 F. Supp. (1993) P Inspection Results for 2001 t Many Surprises. Warning Letters Citations and Form 483 Observations Fairly Similar. BioQuality. Vol. 7,. 1 (January) P. 7. APR: BPR: CAPA: CFR: FDA: QA: QU: SMART: SOP: Article Acronym Listing Annual Product Review Batch Production Record Corrective And Preventative Action Code of Federal Regulations Food and Drug Administration Quality Assurance Quality Unit Specific, Measurable, Attainable, Realistic, and Timely Standard Operating Procedure The Ultimate Resource Glossary of Computerized System and Software Development Terminology This document serves as a glossary of terminology applicable to software development and computerized systems in FDA-regulated industries. It will facilitate consistency in describing the requirements of the law and regulations applicable to such products and systems. The organization of this document is alphabetical. Glossary of Computerized System and Software Development Terminology Reference material for investigators and other FDA/Industry personnel Acronyms are grouped at the beginning of each alphabetical section, and are followed by words, terms, and phrases. Acronyms are expanded at the beginning of each alphabetical section and defined with the full term or phrase. The terms are defined, as much as possible, using available standards. Over 850 terms, phrases, and acronyms are included in this document. DEPARTMENT OF HEALTH & HUMAN SERVICES USA For More Information Call Us Today! Only $ Order Today 3% On-Line Discount P.O. Box 6004, Duluth, MN Phone: U.S. Only Fax: info@ivthome.com Web Site: Advanstar Communications Inc. All rights reserved. 86