TOOLS OF CONTINUOUS IMPROVEMENT
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The document discusses the principles of a quality system focused on reducing deviations, failures, and out-of-specification outcomes in the manufacturing process. It emphasizes the importance of change control, the need for thorough documentation and approval of changes, and the relationship between quality, safety, and efficacy in operations. Various examples illustrate the definitions of deviation, incidents, and failure, alongside the regulatory requirements that govern their management in the pharmaceutical industry.
TOOLS OF CONTINUOUS IMPROVEMENT
- 1. QUALITY SQUARE INDUSTRY TOOLS OF CONTINUOUS IMPROVEMENT By : Hardik Mistry
- 2. Goal of the Quality system Ideal A. NO Deviation B. NO Out Of Specification C. NO Failure D. Beneficial Change Real A. Less & Effective Deviation B. Less & Effective Out Of Specification C. Fruitful Change D. Fruitful Failure Quality Product
- 3. System Development Cycle Specificatio Confg/Impl Qualificatio Design Operation n e. n User Requirements, Detailed FAT Functional Spec SAT spec. Validation Planning IQ, OQ, PQ Maintenance Deviation , OOS Change Control Periodic Review
- 4. Deviation A. Departure from a standard or norm. B. Statistics : The difference between one of a set of values and some fixed value, usually the mean of the set. C. Navigation : The error of a magnetic compass, as that of a ship, on a given heading as a result of local magnetism. E. Optics : Diffraction. the bending of rays of light away from a straight line. F. Departure or divergence from an established dogma or ideology.
- 5. Deviation & Incident Deviation - A departure from the approved instruction or established standard or normal practice. For example, the lack of a certain raw material that could be substituted with another raw material. Incident - Unexpected event occur outside the scope of the process or matter but willing to affect the quality. Example : Unexpected events related to maintaining plant operations, safety, regulatory compliance, or security.
- 6. Deviation & Change Control A. Deviation is after done task You came to know the effect after the deviation B. Change Control is before done task You know the possible effect before the doing change & intention to do something different and favorable in the future. “A process that ensures that changes to materials, methods, equipment and software are properly documented, validated, approved and traceable” - Change Control (PS 9000:2001, § 3.7)
- 7. Deviation & OOS results A. Deviation is after done task You came to know the effect after the deviation B. OOS results is also after task OOS are the deviations in testing results “Test results, laying outside of the specifications” - Out Of Specification
- 8. Deviation & Failure Deviation - A departure from the approved instruction or established standard or normal practice. For example , the lack of a certain raw material that could be substituted with another raw material. Failure – Fail to achieve the targeted one. “Deviation, Incident and OOS results are also type of the failure” “ The state or condition of not meeting a desirable or intended objective ting, or a customer complaint. “ - Failure
- 9. Our Target : Our Specification
- 10. Deviation
- 11. Change Control
- 13. Failure
- 14. Incident
- 15. Example 1: Student obtaining less than 40 marks in one subject is under deviation & Student obtaining less than 40 marks in more than one subject is under Failure and that is Out of Specification for paper checker. Example 2 : My recently purchased centrifuge sets to run at 1000 ± 2 RPM. Yesterday it runs at 1030 RPM instead of 1000 RPM. – Deviation Today my centrifuge starts but it doesn’t run…. – Failure During calibration using tachometer I noted it runs on
- 16. Examples of Deviations Process Deviation : In the process if someone adds Potable water instead of W.F.I. Equipment deviations would include: A temperature setting spiking in a dryer Temperature profile curves not being followed in a lyophilizer Pressures in a reaction vessel trending out of a normal setting Examples of Incidents An unexpected chemical release that requires a report to the EPA. An equipment incident such as a failure of a newly
- 17. Future of the Deviation, Batch failure, Incident, OOS CAPA Corrective and Preventive action CI Continuous improvement Quality
- 18. Change Control • It is essential to maintain interrelationship between quality, safety and efficacy. So that all changes are evaluated before being introduced. • It is intended that not only any changes to the way of producing or analyzing the product should be covered by the Change Control System (CCS), but also this should also cover the changes to for examples Buildings and Equipment, Utilities, Supplier of starting materials, Document, Process, etc. • It is a planned activity to bring about for better GMP compliances.
- 19. Cont…. It can be for shorter period of time or it can be permanent. It must be intimated to all the concern departments for official approval of Change Control. “ Changes in any part of the quality system should not be confused with DEVIATIONS .”
- 20. Governing Authorities A. EC Guide to Good Manufacturing Practice, Chapter 5 (5.15) B. 21 CFR 211.192 and Multiple Other Provisions within 211 C. ICHQ7A, GMPs for Active Pharmaceutical Ingredients D. United States V. Barr Laboratories, Inc. 1993 Described Requirements for Investigations E. Governing Authority, EU Commission Directive 2003/94EC (replaces 91/356/EEC)
- 21. EC Guide to Good Manufacturing Practice, Chapter 5 “Any deviations from instructions or procedures should be avoided as far as possible. If a deviation occurs, it should be approved in writing by a competent person…” 21 CFR 211.192 and Multiple Other Provisions within 211 “Any unexplained discrepancy…shall be thoroughly investigated…The investigation shall extend to other batches …that can have been associated with the specific failure or discrepancy. A written record of the investigation shall be made
- 22. ICHQ7A, GMPs for Active Pharmaceutical Ingredients “Any deviation from established procedures should be documented and explained. Critical deviations should be investigated, and the investigation and its conclusions should be documented.” “All deviation, investigation and OOS reports should be reviewed as part of the batch record review before the batch is released.” United States V. Barr Laboratories, Inc. 1993 Described Requirements for Investigations Specifies Content of Failure Report; Requires Listing and Evaluation of Lots Potentially Affected; Elements of “Thoroughness” Vary Depending on
- 23. The pharmaceutical industry did not hear much about the enforcement of this paragraph, or the term out-of-specification, prior to the early 1990s. Then, Barr Laboratories decided to sue the FDA because its founder, Edward Cohen, believed it was not being treated fairly due to its part in what is often called the “Generic Scandal.” The FDA saw this as an opportunity to air some of its frustrations and bring legal weight to its regulatory actions through a judicial decision and countersued. The two issues were settled in one trial that ended in 1993. One of the issues was how Barr Laboratories — and the industry as a whole— handled initial test results that were outside of predefined limits (OOS observations). At the beginning of the trial, the FDA’s position was that when the laboratory gets a test result that is outside of product specification, the batch fails and should be rejected immediately. Barr Laboratories took the position that the possibility that the observation was the result of a laboratory makes it appropriate to investigate in order to confirm or refute the original value. During the proceedings, Judge Alfred M. Wolin stated, “An out-of-specification result does not constitute a failure.” His written decision states, “An out-of- specification result identified as a laboratory error by a failure investigation or an outlier test, or overcome by retesting is not a failure. Thus, the Court is unwilling to adopt the government’s view of failure.”3 OOS suddenly became a permanent part of the pharmaceutical industry lexicon. Although Wolin’s decision supported Barr’s view that it is appropriate to challenge an OOS observation with an investigation, he was critical of the firm’s investigation process. The FDA began to scrutinize how firms handled OOS observations. (For
- 24. Change can be… Major Changes • Addition or deletion of a step or addition of an alternative/new step in the formulation manufacturing process. • Addition of a new manufacturing site with modification of the formulation manufacturing process described in the original dossier/document. • Change in input quantities of formulation manufacturing process. • Changes in the quality of raw material(s) or key intermediate(s) used in the formulation manufacturing process.
- 25. Cont…. Minor Changes • Change in the administrative references (name/company name, address) of the certificate holder. • Change in the references (name/company name, address) of the manufacturing site. • Change in the specifications of the substance. • Change in supplier of starting and packing material. • Change in the batch size. • Change in the documents like SOPs etc.
- 26. Consequences of Unapproved/Unappointed Change Detected at receipt/ inspection/testing of incoming component / material by the customer. Worst Case: unapproved changes to component/material causes final product failure in the field. Result in lack of quality Customer may recall product Wastage of time and resources Miss the great chance of improvement
- 27. Scope of Change Control – Raw materials suppliers – Raw material suppliers’ processes – Raw materials – Sub-contractors – Facilities/Utilities – Manufacturing sites – Manufacturing processes – Packaging Processes – Components’ documentation (specifications, filings, drawings, etc.) – Computer hardware/software packages affecting product
- 28. Scope touches multiple disciplines – Formula Development – Design Engineering – Process Engineering – Regulatory – Quality Assurance – IT – Operations – Laboratory – Purchasing
- 29. Responsibility – It is the Responsibility of the system owner together wit the end- user – There is No universal procedure & more than one procedure may Role Responsible Department Description/Responsibility be appropriate Change Quality Assurance. Receives and validates Change Control Control Production, Quality Requests from the Originator of the Team Control, Engineering Change Control request Dept., Management Ensures the Change Control Plan is system followed, and that all Change Control administration task are completed Ensures all change control requests are impact assesses (instructs the Impact Assessor). Originator Concerned person or The person who originates the change Department request. Representative Assessor Quality Assurance & The person who is responsible for the Quality Control impact analysis of the Change Request. The person who is responsible for Modifier Process owner & ensuring approved changes are included. Quality Assurance The Modifier must inform Change Control team when the change is complete. Has final decision making authority if the Approver Quality Assurance Change Control board cannot reach a consensus.
- 30. Procedure for Change 1) Raising a Change Control The client or individual initiates change by making a formal request for something to be changed. The change control team then records and categorizes that request. This categorization would include estimates of importance, impact, and complexity.
- 31. Cont…. 2) Assessment of the proposed Change The impact assessor or assessors then make their risk analysis typically by answering a set of questions concerning risk, both to the business and to the process, and follow this by making a judgment on who should carry out the change. If the change requires more than one type of assessment, the head of the change control team will consolidate these. Everyone with a stake in the change then must meet to determine whether there is a business or technical justification for the change. The change is then sent to the delivery team for planning.
- 32. Cont…. 3) Change Approval /Action Plan If Change Control Team agreed. Applicant/Change requester will seek approval and request a time and date to carry out the implementation phase. Responsibility of Quality Assurance Note : All Change Control team members must agree to a time, date and cost of implementation.
- 33. Cont…. 4) Change implementation/Action Plan After getting approval from Quality Assurance department usually one with the specific role of carrying out this particular type of change. The team's first job is to plan the change in detail as well as construct a regression plan in case the change needs to be backed out. Following implementation, it is usual to carry out a post- implementation review which would take place at another stakeholder meeting.
- 34. Exit Criteria COMPLETE: The Change Request and associated impact has been approved and implemented REJECTED: The Change Request has been rejected by the CCB. CANCELLED: The Change Request has been cancelled by the Approver or the Originator. APPROVAL: The approval of the control change can be done finally with signature of the members of the change control team.
- 35. Policy, Design, and Functional Operational Use and Sustaining Effort Performance, Test & Evaluation, etc. Requirement Requirement Requirement Change Proposal Change Proposal Change Proposal Change Control Board Evaluation of Change Impact: • Affects on Yes Development of a Is the Performance, Effectiveness, Life-Cycle Change Change Costs, etc. Feasible? Implementation Plan • Proposed incorporation date, ensuing affected requirements, etc. • Resources required to implement the No change • Cost of implementing the change No Further Action Etc. Return to Develop Change Incorporate Yes Procedures Continuing Approved Change Is Change Operational Adequate? Status Update Documentation Dispose Residue No and Database Redesign Required
- 36. Benefits of Change management Movement in a New direction – New opportunities. Try not to do the same old things over and over, you will get the same results. Small changes helps to the bigger changes that are to come Reduce the time required for NDA, INDA. More robust impact analysis is possible Improved time to market More reliable trend analysis Ease in adherence to quality system.
- 37. Selected References Proposed US FDA Rule, cGMP: Amendment of Certain Requirements for Finished Pharmaceuticals (Federal Register 61(87) 3 May 1996, page 20104) US FDA Guide to Inspection of Quality Systems Investigating OOS Test Results for Pharmaceutical Production (FDA, draft 9/1998) US Department of Energy Guideline, Root Cause Analysis Guidance Document, February 1992 US FDA Compliance Program Guidance Manual, 7356.002 37
- 38. Change always comes bearing gifts. - Price Pritchett Hardik Mistry