InstantGMP Compliance Series - Managing Deviations for Improved Compliance
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Any time a deviation is made from the process in the batch production record, it has to be recorded, investigated and disposition. This presentation provides details on how this is done.
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InstantGMP Compliance Series - Managing Deviations for Improved Compliance
- 1. InstantGMP Compliance Series Managing Deviations for Improved Compliance
- 2. Deviations • Triggered by any unanticipated occurrence could result in adulteration • Must be noted in batch record • Quality must conduct a material review • Then make a disposition decision • May not reprocess a batch that deviates unless approved by Quality Electronic cGMP Manufacturing Execution System
- 3. Problems with Deviations • Warning letters issued to firms who failed to record and resolve production deviations • One firm used ingredients other than the ones specified • Another firm did not conduct an investigation of retested samples that failed specifications • A firm claimed to have established deviation procedures, but provide no documentation Electronic cGMP Manufacturing Execution System
- 4. Why Managing Deviations Is Important • Intention is to make uniform, high quality products • Deviations may indicate product is not under control • May indicate that master formula may need updating based on variations in raw materials or dietary ingredients • Quality needs to review and disposition each deviation • Lets an independent quality group make sure product that reaches the market is free from defects Electronic cGMP Manufacturing Execution System
- 5. Definitions • OOS – Out of Specification • CAPA – Corrective and Preventive Action • Corrective Action – eliminate cause of an existing undesirable situation in order to prevent a recurrence • Preventive Action – eliminate the cause of a potential undesirable situation in order to prevent an occurrence Electronic cGMP Manufacturing Execution System
- 6. Out of Specification • OOS - any value that does not meet the acceptance criteria of a specification • Triggers an investigation plan • Initial phase - the laboratory results are challenged by retesting and comparing to a retain sample to • Second phase - investigation of the manufacturing processes • Quality must make a disposition decision and decide whether the batch is OK or should be rejected Electronic cGMP Manufacturing Execution System
- 7. Investigations • Investigations may be initiated due to: – Confirmed Out-Of-Specification (OOS) results – Out-of-Trend (OOT) - atypical results that deviate from expected or historical data, but still meets specifications – Failure of a component, excipient or in-process test – Unplanned disruption in production – Unplanned deviations from approved procedures, methods or specifications Electronic cGMP Manufacturing Execution System
- 8. Corrective and Preventative Actions • CAPA log needed for recording deviations • Identify the specific deviation or unanticipated occurrence • Describe the investigation • Evaluate whether or not the deviation resulted from or could lead to a failure • Identify actions to correct and prevent a recurrence Electronic cGMP Manufacturing Execution System
- 9. Determine the Scope • Scope includes: – time frames during which the problem occurred – number of times the problem occurred – the number and identity of products or materials involved – locations (including vendors) involved. • Determine the relevant events leading up to and surrounding the event. Determine what happened, how it happened, and who, when and where. • Clearly define the problem Electronic cGMP Manufacturing Execution System
- 10. Determine Root Causes • Determine possible and probable causes of the problem • Determines why the problem occurred • Root causes will typically fall into one of three categories: – System design: Are procedures sufficient? Are other process components sufficient (materials, equipment, facilities, personnel). – System implementation: What does, or can management do to ensure that procedures are followed? – Performance: Is this an individual performance issue? Electronic cGMP Manufacturing Execution System
- 11. Determine Corrective/Preventive Actions • Use various tools and techniques, such as brainstorming, cause and effect analysis and statistical tools • Involve people closest to the problem • Select the most effective or cost effective corrective/preventive action • Document justifications Electronic cGMP Manufacturing Execution System
- 12. Develop CAPA Plans • Redesign systems and processes • Implement remedial training is needed, • Assure that there is no further performance of the task until the necessary re-training is complete • Set target dates and assign individuals responsible for implementation • Use measurable outcomes to evaluate the effectiveness of the preventive actions Electronic cGMP Manufacturing Execution System
- 13. Record Deviations in Batch Records
- 14. Benefits of Electronic Manufacturing • More efficient than manual systems • Shrink or eliminate redundant processes and forms • Trim time and overhead costs • Reduce errors, omissions and deviations • Provide opportunities to reorganize and update processes • Increases throughput, quality and margins Electronic cGMP Manufacturing Execution System
- 15. InstantGMP™ Find more videos on GMP Manufacturing in the Resource Center at www.instantgmp.com
Editor's Notes
- The staff at InstantGMP prepared this Compliance Series for GMPs in Dietary Supplements to focus on good manufacturing practices and GMP compliance. These are brought to you by our quality and manufacturing experts in the hope that it will help you avoid any GMP compliance issues in your shop. This presentation will address improving compliance through managing deviations.
- GMP regulations require you to review the results of any deviation or unanticipated occurrence that could result in adulteration. The deviation should be noted in the batch production record along with documentation that describes your investigation into the cause of the deviation or the unanticipated occurrence. Quality must conduct a material review and make a disposition decision if there is such an unanticipated occurrence during manufacturing. If you want to reprocess a batch with a deviation, Quality must review and give approval.
- A dietary supplement manufacturer in NY was issued a warning letter for violations of GMP regulations. The FDA noted in their investigations that several of the company’s batch production records showed deviations from the Master Manufacturing Record. For example, the company used ingredients other than the ones specified, but there was no documentation that they conducted a material review or made a disposition decision. Another firm received a warning letter because their quality group did not conduct a material review and make a disposition decision for a manufacturing deviation where retesting was done. The quality group was not required by the firm’s procedures to investigate retested samples which failed their specification and the quality group did not make a disposition decision for this deviation. A firm claimed to have established deviation procedures, but provide no documentation. After an FDA inspection, a firm stated that they had implemented a deviation program and training was given. When the investigator returned, there was no documentation showing that the firm had complied with their own procedures.
- Detecting and managing deviations is important for many reasons. The intent is to make sure every batch of product made from the same master formula is uniform and meets the quality specifications. Since final product testing is not required for all dietary supplement products, meeting in-process controls and doing the manufacturing according to the written procedure is necessary to assure good quality of the final product. When deviations or unanticipated occurrences come up during manufacturing, they may be an indication that the product is not under control and therefore may not be able to be sold. The FDA requires quality personnel to conduct a material review and make a disposition decision if a batch deviates from the Master Manufacturing Record, including not completing steps or deviating from specifications. Deviations may also indicate that master manufacturing formulations may need to be updated based on variations in in-coming raw materials or dietary ingredients. When the QC unit is independent of manufacturing operations, it can provide an objective opinion about quality that assures the firm produces and distributes product that are free from defects. In situations where there is no quality unit to review deviations or deviation are not reviewed, economic pressures can prevail and decisions to release product to market may not be based on sound quality principles. The key is determining whether the deviations impacts the product quality and if so, determining if the batch should be rejected.
- Some definitions of common terms and abbreviations will help in managing deviations. OOS is an Out of Specification result. CAPA is a Corrective and Preventive Action log or register. A Corrective Action is taken to eliminate the cause of an existing non-conformity, defect or other undesirable situation in order to prevent recurrence. A Preventive Action is taken to eliminate the cause of a potential non-conformity, defect or other undesirable situation in order to prevent occurrence.
- An out of specification result is any value that does not meet the acceptance criteria of a specification. An OOS typically triggers an investigation plan. In the initial phase, the laboratory results are challenged by retesting the original sample and a retain sample to compare results. If the original sample is still OOS, then an investigation of the manufacturing processes is started. Batch records, production processes, equipment status and operation actions are all evaluated. At the end of the evaluation, Quality must make a disposition decision and decide whether the batch is OK or should be rejected.
- Investigations may be initiated due to a variety of circumstances, including, but not limited to: a confirmed Out-Of-Specification (OOS) results from a laboratory investigation or an Out-of-Trend (OOT) or atypical data/results that deviate from expected or historical data, but still meets specification requirements. An investigation could be triggered by the failure of a starting material or excipient, or an in-process test. If there are unplanned disruption in production (i.e., mechanical or control system failure, utility disruption) or unplanned deviations from approved procedures, methods or specifications, an investigation may be initiated. Any other unprecedented event that has potential impact to product safety, identity, quality, efficacy, purity, strength, regulatory filing and/or stability could be a cause for an investigation.
- Corrective and preventive action plans are needed to address the root cause of a deviation and to prevent a recurrence. CAPA plans have to be monitored to verify completion and effectiveness. A Corrective and Preventative Actions (CAPA) log is needed to record deviations. It should identify the specific deviation or the unanticipated occurrence, describe the investigation, evaluate whether or not the deviation resulted from or could lead to a failure, identify the actions taken to correct and prevent a recurrence, explain what was done with the component, dietary supplement, packaging, or label and explain a scientifically valid reason for any reprocessing work. The CAPA log allows trends to be identified and a record of resolution of programs to be kept.
- The Scope of a CAPA plan should be determined. The scope includes the time frames during which the problem occurred, the number of times the problem occurred, the number and identity of products or materials involved, and the locations (vendors) involved. It should determine the relevant events leading up to and surrounding the event, determine what happened, how it happened, and who, when and where. Overall, it should clearly define the problem.
- Determine possible and probable root causes of the problem. The root cause analysis determines why the problem occurred. Once root causes are determined, they will typically fall into one of three categories: System design: Are procedures sufficient? Are other process components sufficient (materials, equipment, facilities, personnel). System implementation: What does, or can management do to ensure that procedures are followed? Performance: Is this an individual performance issue?
- Determine Possible and Probable Corrective/Preventive Actions. Wherever possible or necessary, use various tools and techniques, such as brainstorming, cause and effect analysis and statistical tools etc. Involve people closest to the problem. Select the most effective or cost effective corrective/preventive actions as appropriate and then document your justification.
- When developing CAPA plans, you may need to redesign systems and processes. You should implement remedial training when needed and then aAssure that there is no further performance of the task until the necessary re-training is completed. You should set target dates and assign the individuals responsible for implementation. It’s important to use measurable outcomes so you can evaluate the effectiveness of the preventive actions.
- InstantGMP automatically manages deviations in their electronic batch records. Any time a deviation comment is written ina batch record step, that step is flagged so that Quality is alerted to the event. Quality must review and conduct their investigation, then sign off on each deviation their digital signature before the batch can be completed and dispositioned.
- There are many reasons that companies will want to adopt an electronic manufacturing system. They are more efficient than manual systems. For example, they can shrink or eliminate the redundant process and forms that occur in manual systems. They can trim time and costs compared to manually compiling and reviewing documentation. They can reduce errors, omissions and deviations. Probably the most important advantage is that a transition to an electronic system can provide opportunities to reorganize and to update processes to make the whole plant work better. All of these benefits taken together will result in increased throughput, quality and margins.
- Thank you for viewing our series on GMPs. You can find more videos and articles on GMP manufacturing in our Resource Center at www.InstantGMP.com.