DEVIATION Management by S.SATHYA.N.V.pptx

Deviation management

1. * DEVIATION MANAGEMENT *

2. WHAT IS DEVIATION? A deviation is any unwanted event that differs from the approved processes, procedures, instructions, specifications, or established standards. Deviations can occur during the manufacturing, packing, sampling, and testing of drug products.  Many life science organizations have streamlined the entire deviation management process by implementing an  Electronic Quality Management System ( eQMS )  that allows for efficient deviation management.

3. WHAT IS DEVIATION MANAGEMENT? The deviation management process is a systematic approach to identifying, analyzing, solving, and documenting events that deviate from the established protocols during the development, manufacturing, and commercialization of products.

4. WHO FIRST USED STANDARD DEVIATION? The concept of Standard Deviation was introduced by  Karl Pearson  in 1893. It is by far the most important and widely used measure of dispersion.

5. GUIDELINES: FDA 21 CFR Part 211. 160 , FDA 21 CFR Part 211. 192 , EU GMP Guide Part 1 Section 1.8 (vii) EU GMP Guide Part II (APIs) , EU GMP Chapter 8, PIC/S GMP, WHO Annexure-3, 14.0, ICH Q7 Section 2.16 , ICH Q10 & ICH Q12 International Organization for Standardization (ISO): According to ISO 9001:2015 Section 10.2, deviations in the context of quality management systems refer to the  positive or negative effect resulting from a divergence from the expected or established standards .

6. WHAT ARE THE DIFFERENT TYPES OF DEVIATION ? In general, your organization will encounter two types of deviations: Planned Deviations Unplanned Deviations

7. 1.PLANNED DEVIATIONS: Planned deviations are temporary deviations from an existing protocol or process that have been pre-approved. They are limited to a specific time period or a number of batches. Your organization makes these changes to avoid a potentially hazardous situation. Deviations are planned in such a way that they do not compromise the safety and efficacy of your products. Examples of planned deviations: Change in batch size due to reduced availability of raw materials Change in batch size for a specified number of batches Change in supplier for Raw Materials & Excipients. “Planned deviation is obsolete and out of current GMP principles. Deviation can not be intentional by definition or by logic. A deviation CAN NOT be planned, a change can be planned and depending on its nature, impact and duration it could be a temporary or short duration change which must be handled through change control procedures and principles.

8. 2.UNPLANNED DEVIATIONS: Unplanned deviations are non-compliances with your designed protocols or systems that occur at any stage of a product's lifecycle, including manufacturing, testing, holding, packaging, and storage. Unplanned deviations are also referred to as unplanned events, uncontrolled events, or incidents. They can be caused by human error, utility failure, equipment/instrumentation breakdowns, or malfunctions. Examples of unplanned deviations in the pharmaceutical industry: Interruption of power supply resulting in equipment breakdown Accident at the site due to human error Disruption of utility services

9. What are the Deviation Classification Categories? Deviations are categorized based on risk levels to assess their potential impact on product quality, patient safety, and the regulatory requirements companies are subject to. Companies can have different criteria for defining deviation categories, which are well-described in their protocols and procedures. The categorization of deviations may vary based on the nature of the product, industry requirements, and the company’s risk management needs. There are 3 deviation classification categories: Critical deviation. Major deviation. Minor deviation.

10. 1. Critical Deviation: Deviation that cloud has a significant impact on the production quality or GMP system. Examples of critical deviation are given below but are not limited to : Usage of contaminated raw materials and solvents. Failure to process step during the manufacturing. Use of obsolete batch document/test method Filter integrity failure.

11. 2. Major Deviation: Deviations that could have a moderate to a considerable impact on product quality or GMP system. Ex gave below but not limited to: Machine breakdown during processing. Mix-ups of cartons of the same product with different strength

12. 3. Minor Deviation: The deviation will not have any direct impact on the quality of the product or the GMP system. Examples of minor deviations are given below but are not limited to : Minor errors in batch records or documents that do not affect the integrity of the date. Spillage of material during dispensing. Failure to meet environmental conditions during batch processing.

13. Incident An incident is an unplanned or uncontrolled event that does not directly affect the manufacturing process parameters or product quality. Incidents are generally unrelated to GMP requirements and are often not considered deviations. However, an incident affecting product specifications can be categorized as a cGMP-related nonconformance. This categorization varies between companies and must be clearly specified in the company’s procedures. Examples of incidents are listed below: Accidental material spillage occurred in the cleanroom. Personnel not appropriately dressed inside the production area. A minor typographical error in the documentation that does not affect the overall process or product outcome.

14. This flowchart will help you understand the deviation classification process:

15. PROCEDURE: All deviation shall be documented, investigated, tracked, and trended and all deviations shall be reported when they occur. The person who observes the deviations shall inform the immediate supervisor or concerned department head /designee and to quality assurance. As per the severity of deviation and stage of the process, the process may be stopped for the Initial Assessment QA shall issue the “deviation control form“at the request of the initiator (concerned department ) by assigning a deviation number.

16. The initiator shall fill the details (like product/material/ equipment/document / other if any and batch no / A.R. No if applicable etc ) in the deviations control form. The initiator shall be initial assessment and shall take suitable immediate action according to the nature of the deviation and inform to department head and concerned QA person. The initial impact assessment shall be done by the observing department head/designee and designated person with QA recommendation. F or continuation of process / discontinues the process shall be given by the head of department and Head QA of designee. Based on the nature of deviation, initial assessment and immediate action taken. The Head of initiating department shall approve the deviation for further evaluation of QA. After approval of deviation from the head of initiating department, the deviation form shall be forwarded to QA for evaluation. PROCEDURE (CONTINUED…..):

17. PROCEDURE (CONTINUED…..): During evaluation designated QA person shall verify whether the deviation is quality relevance or not and whether the deviation is a repeat occurrence or not. If it is quality relevance, impact shall be assessed on other areas/departments. And if it is a repeat occurrence, impact assessment shall extend to verify the effectiveness of previous CAPA taken. After evaluation categorizes deviation into critical, major, or minor based on the evaluation of impacted areas and product quality impact.

18. If the deviation is categorized as critical or major, a cross functions team comprising of technical experts from different (as per the nature of deviation) shall be formed to investigate the root cause of deviation. If the deviation is minor, investigated shall be carried out jointly by a designated QA person along with a person from the department where the deviation happened. Failure investigation and root cause identifications shall be carried out by the investigation team using investigational methodologies. Upon identification of the root cause of failure, the probable root cause of failure shall be documented. Corrective actions and preventive actions shall be recommended to prevent the reoccurrence of the same. PROCEDURE (CONTINUED…..):

19. PROCEDURE (CONTINUED…..): The deviation including the investigation report (wherever applicable) shall be closed within 30 working days of the date of the initiation. The initiation date is the date of observation of deviation. If deviations are not closed within the specified timeline initiator shall rise the “ period extension request “ As per SOP. Initiating Department Head shall review the extension request and write a justification for the period of delay with impact assessment. QA shall assess the impact of delay in action completion and approve/reject the period extension request.

20. Deviations shall be closed only when all relevant actions in the CAPA long are completed. Continuous trending of deviations shall be carried out on monthly basis. QA shall carry out trend analysis for all the deviations in the whole year at the beginning of the next year by using monthly trend data. A copy trend analysis shall be forwarded to the head CQA. The record retention for all closed deviation and investigation reports shall be not 7 years or as otherwise agreed with the concerned regulatory body. All deviations and investigation reports shall be kept in the custody of QA and QA shall maintain the deviation register. PROCEDURE (CONTINUED…..):

21. DEVIATION MANAGEMENT PROCESS FLOW The deviation management process flow has 5 main phases:

22. 1. Identification: First step should be to get a clear picture of what happened. Deviations can occur during the sampling and testing of raw materials and/or the finished product. When products fail to meet industry standards, we may receive customer complaints or notifications. All deviations shal l be issued and handled by the people in charge of Quality Risk Management in your organization. Collect all relevant information and categorize the deviation. As previously stated, the incident can be classified as a minor, major, or critical deviation.

23. 2. Reporting: O rganization must keep track of all deviations and have a policy in place for reporting them. The deviation report is usually filed by the department where the deviation occurred. After identifying the problem, the maximum time frame allowed is one day. During this phase, the concerned personnel must provide all relevant information to aid the investigation. Built-in best-practice forms and procedures to guide you through the process of documenting all relevant deviation data points. This assists in reducing the margin of human error and making the correct decision.

24. 3. Investigation: After identification and reporting the deviation, we must determine what caused it. The concerned department, in collaboration with the QA department, will conduct a root-cause analysis. When the deviation is significant or critical, root-cause analyses are required. This means that the deviation will have a significant impact on our product's or cGMP's overall quality. If the deviation is labeled as an incident or minor, no root-cause analysis is required. After completing the root-cause analysis, the next step in this phase is to determine whether a CAPA is required. When the root-cause analysis reveals that the problem is recurring and systemic, a CAPA is typically initiated. If the deviation has no impact on the overall quality of our product or cGMP, CAPA is not initiated. While the QA department approves the CAPA, the responsible department is responsible for implementing and closing the CAPA. Similarly, when a deviation occurs, we can use a system like QMS software to determine whether or not a CAPA is required(Optional).

25. 4. Documentation: When the investigation into the deviation is finished, we must document the root cause and the resulting CAPA plan for tracking purposes. It is also critical for company to keep an audit trail, which is a regulatory requirement. Audit trails are chronological records of all actions, events, and changes, including deviation management, root-cause analysis, and CAPA activities.

26. 5. Implementation: Finally, we will have a deadline to meet as well as a CAPA to complete. Ensure that this particular deviation does not occur again during this phase. First describe the problem in CAPA. The scope should be addressed next. Once the problem and its scope are identified, We can implement immediate fixes while investigating the root cause of the problem. Following the completion of the root cause analysis, company will plan and implement actionable steps (i.e. corrective and preventive actions).

27. THE KEY COMPONENTS OF AN EFFECTIVE DEVIATION MANAGEMENT SYSTEM An effective deviation management system consists of several key components that work together to ensure deviations are identified, documented, investigated, and resolved promptly and systematically. Here’s a high-level overview of the recipe for such a system: Clear policies and procedures Established roles and responsibilities Training and competency Documentation and recordkeeping CAPA/root cause analysis

28. Clear policies and procedures Establishing well-defined policies and standard operating procedures (SOPs) for deviation management is crucial to provide a consistent framework for handling deviations. These policies should outline the steps for  reporting ,  investigating , and  resolving  deviations—and should be  easily accessible  to all relevant personnel. 2. Established roles and responsibilities Clearly defined roles and responsibilities are vital in deviation management to ensure accountability, ownership, and effective communication among personnel involved in the process. Assigning specific responsibilities helps to streamline the deviation management process, minimize confusion, and promote the timely resolution of deviations. There should be clear, documented roles and responsibilities established for all of the following duties within the deviation management process: Identification of deviations —  Special personnel should be assigned to monitor processes and identify deviations when they occur. These individuals should be trained to recognize potential deviations and understand the importance of timely reporting. Deviation reporting —  Individuals should be designated as responsible for reporting deviations promptly, using the appropriate channels or tools. This includes ensuring that deviations are documented according to the established SOPs and escalating issues when necessary.

29. Investigation —  Personnel with the appropriate expertise and experience to investigate deviations should be designated to determine their root causes and assess their impact on product quality and safety. These individuals should be trained in root cause analysis techniques and familiar with relevant regulations and guidelines. 2. Established roles and responsibilities (Continued…): Resolution of deviations —  These assignees should be responsible for implementing CAPA. This may involve cross-functional teams that collaborate to address deviations, monitor the effectiveness of CAPA, and make necessary adjustments. System oversight —  A person or team should be responsible for overseeing the overall deviation management system itself. This includes ensuring that the system is functioning effectively, monitoring performance metrics, and driving continuous improvement efforts. Given the many moving parts of a modern deviation management system, it’s important to establish clear lines of communication and collaboration between different personnel and departments involved. This helps to ensure that information is shared effectively, facilitating the timely resolution of deviations and promoting a culture of transparency and accountability.

30. Frequent training and competency assessments ensure employees are equipped to accurately identify, report, and manage deviations. Training should cover not only the organization's policies and procedures but also regulatory obligations and industry best practices. For example, introducing scenario-based training sessions, such as a mock deviation event, can help staff understand how to apply these principles in a practical context. 3. Training and competency: 4. Documentation and recordkeeping: Maintaining comprehensive and accurate records of deviations, investigations, and corrective actions is essential for regulatory compliance and audit readiness. Using a standardized deviation report form, for example, ensures all necessary information is captured consistently. Structured reporting and tracking of deviations promote prompt identification and resolution. This may involve an incident management software that not only streamlines reporting but also facilitates real-time tracking and data analysis.

31. Performing a thorough root cause analysis is a fundamental first step that paves the way for effective CAPA. Techniques such as Fishbone Diagrams or the 5 Whys can systematically unearth the underlying factors leading to a deviation. For example, a Fishbone Diagram might reveal whether a manufacturing process deviation originated from personnel, processes, or equipment. Once root causes are established, suitable CAPA should be implemented. These actions aim to directly address the identified root causes and mitigate the risk of their recurrence. For instance, if frequent equipment malfunctions are discovered to be a root cause, a corrective action could involve increasing the frequency of machine calibration. Over time, the effectiveness of this action should be evaluated to determine if it indeed reduces the number of equipment-related deviations. 5. CAPA/root cause analysis:

32. What Is the Difference Between Incident and Deviation ? Deviation is defined as when we are deviating from written procedure or GMP (Good manufacturing practices) document, deviation shall be occurred. Incidence is defined as something non cGMP (current Good manufacturing practices) have occurred all of sudden which may or may not have impact on product Quality.

33. THANK YOU… S. Sathya. N .V M.Sc., L. L.B