Equipment Risk Management

Transcription

1 Equipment Risk Management A Quality Systems Approach Palash Chandra Das

2 Agenda Brief Introduction Correlation between Quantitate and qualitative approach Implementation and assessment Discussion with practical example 2

3 What is Quality The degree to which a set of inherent properties of a product, system or process fulfills requirements. (ICH Q9) 3

4 So what is the concept of Risk Assessment? 4

5 Risk Anything that may cause harm 5

6 Overview of a typical quality risk management process 6

7 Risk Assessment As an aid to clearly defining the risk(s) for risk assessment purposes, three fundamental questions are often helpful: 1. What might go wrong? 2. What is the likelihood (probability) it will go wrong? 3. What are the consequences (severity)? 7

8 Risk identification Risk identification is a systematic use of information to identify hazards referring to the risk question or problem description. Information can include historical data, theoretical analysis, informed opinions, and the concerns of stakeholders. Risk identification addresses the What might go wrong? question, including identifying the possible consequences. 8

9 Risk analysis Risk analysis is the estimation of the risk associated with the identified hazards. It is the qualitative or quantitative process of linking the likelihood of occurrence and severity of harms. In some risk management tools, the ability to detect the harm (detectability) also factors in the estimation of risk. 9

10 Risk evaluation Risk evaluation compares the identified and analyzed risk against given risk criteria. Risk evaluations consider the strength of evidence for all three of the fundamental questions. 10

11 Risk control Risk control includes decision making to reduce and/or accept risks. The purpose of risk control is to reduce the risk to an acceptable level. The amount of effort used for risk control should be proportional to the significance of the risk. Decision makers might use different processes, including benefit-cost analysis, for understanding the optimal level of risk control. Risk control might focus on the following questions: Is the risk above an acceptable level? What can be done to reduce or eliminate risks? What is the appropriate balance among benefits, risks and resources? Are new risks introduced as a result of the identified risks being controlled? 11

12 Risk reduction Risk reduction focuses on processes for mitigation or avoidance of quality risk when it exceeds a specified (acceptable) level (see Fig. 1). Risk reduction might include actions taken to mitigate the severity and probability of harm. Processes that improve the detectability of hazards and quality risks might also be used as part of a risk control strategy. The implementation of risk reduction measures can introduce new risks into the system or increase the significance of other existing risks. 12

13 Risk acceptance Risk acceptance is a decision to accept risk. Risk acceptance can be a formal decision to accept the residual risk or it can be a passive decision in which residual risks are not specified. For some types of harms, even the best quality risk management practices might not entirely eliminate risk. In these circumstances, it might be agreed that an appropriate quality risk management strategy has been applied and that quality risk is reduced to a specified (acceptable) level. This (specified) acceptable level will depend on many parameters and should be decided on a case-by-case basis. 13

14 Risk communication 14

15 Risk review 15

16 Life cycle of Risk Program 16

17 Risk Assessment is embed into Quality Management System 17

18 Sub-components Design Control system Components Safety Measuring instrument Document Process Computerized system controls 18

19 Design Capacity e.g. Blower, Motor, Condenser, Exhaust, refrigerator etc. Insufficient Space e.g. shelf /chamber size/work bench Cleanability e.g. CIP or Manual Loading /Unloading e.g. Door movement/ auto loading and unloading/ manual handling Proper illuminations 19

20 Control System Access level verification Process automation/semi automatic Human machine Interface Data backup Online Monitor/record Printed data 20

21 Components MOC Verification e.g. 316L or 304 Surface roughness e.g. internal mirror surface finish 0.5 µm Ra and external surface finish < 1.2µm Ra, matte finish. Wed joints e.g. All welds shall be ground finished to 1.2 µm Ra and properly passivated and orbital welding should be done joints with triclover joints e.g. Gaskets e.g. shall be high temperature & pressure resistant and O-rings coming in direct / indirect contact surfaces shall be made up of food grade polymeric materials only. Filter and filter housing e.g. Porosity and certificates Proper tagging of components e.g. for identification as per P&ID Lubricant e.g. Food grade certificate shall be provided for lubricant 21

22 Safety Electricity e.g. Equipment should start with human intervention only. After regain of power the equipment should start from the step it stopped. Control system e.g. Machine should stop with alarm. Notifications e.g. Various utilities supply should be interlocked and indicated by alarm. Noise level e.g. Noise level shall be below 75 db at a distance of 1 m from the equipment. Moving part wiring e.g. All moving parts & wiring to be covered, Proper earthlings of the equipment 22

23 Measuring Instrument Appropriate range e.g. Operational range of measuring instruments > instrument working range, appropriate accuracy, Mounting of instruments must give the possibility for dismounting and replacement, easy access for calibration Calibration e.g. traceable to national or international standards 23

24 Documents Component certificates Operation manual Maintenance manual SOP for cleaning and operation Training to relevant Preventive maintenance 24

25 Process impact Evaluate how Controls are impacting the output Operational verification Performance verification Procedural Implementation Review the validated state Preventive maintenance Breakdown handling 25

26 Computerized system controls (1/2) User should auto reset password in case of periodic password expiry without intervention from admin. Availability of auto lockout facility, if the system is idle more than 2 min Minimum availability of three level of user Defined user privilege matrix, need to be provide from vendor with DQ/FDS. Software/application backup/restore CD Data backup compatibility connected through LAN Password history. E.g. should not accept recent 3 password In case of back up data review, all Audit trail, cycle data / reports, Alarm should be in readable non editable format e.g. PDF 26

27 Computerized system controls (2/2) Auto password expiry, setting need to be enable by admin privilege Date & time change, parameter setting, data deletion or transfer privileges, exit application should to under administrator only. Date and Time synchronization with organization network time server For SCADA based system, application should to be boot with system start up. Exit application option only enable with admin. The Installed SCADA application should support the periodic antivirus scan. OEM and Plant admin should to be clearly identified in authorization list. Availability of user manuals, preventive manual and electronic diagram and P&ID should to be available in soft format e.g. PDF format Remote service should be enable for SCADA applications for maintenance/up gradation by the OEM. E.g. Team Viewer application 27

28 Qualitative approach 28

29 Qualitative risk ranking 29

30 FMEA model 30

31 Relationship of CQA, CPP, and Critical Aspects Critical Process step need to be relook to evaluate the impact Identify all Critical Aspects whichever directly or indirectly impacting your process step 31

32 System Example: Compounding or Filtration vessel Sub components Vessel Agitator Agitator not working properly Risk Justification Mitigation Mixing may not be uniformed To control the speed, agitator shall be provided with VFD with indicator Alarm will generated if motor is tripped The RPM beyond the set limit shall notify the operator with alarm and shut down the process. Agitator performance (RPM) and controller shall be verified during OQ and requalification PM procedure shall be implement 32

33 Example: De-pyrogenation Tunnel System Tunnel Sub components Conveyor Conveyor Risk Justification Mitigation Over Loading of conveyor Speed variability If Filling M/C is stopped vial will accumulate in to the conveyor Improper heat distribution and penetration during routine operation Inter lock in between filling and tunnel shall be checked during OQ VFD shall be provided with VFD with indicator Conveyor speed shall be verify 33

34 Example: Filling M/C System Filling M/C Sub components Nitrogen purging Risk Justification Mitigation Oxidation after filling Nitrogen Gas flow reduces or stops at purging station Nitrogen flow shall be controlled by flow meter Alarm shall be indicated for low pressure by machine Filling M/C Load cell Filling rejects Load cell malfunctioning Operation range shall be verified Routine calibration policy need to be establish PM procedure SOP shall be prepared and training shall be imparted 34

35 Example: LAF Bench System Sub components Blower Risk Justification Mitigation Vibration In work bench Sample may fall on bench due to vibration Anti vibration pads / other mechanism shall be provided to avoid vibration. LAF Bench Blower Blower efficiency reduce Continuous running of the blower shall cause lot of power loss and may damage the blower. The ON/OFF switch shall be provided for controlling the blower operation. LED indicators for the motor operation shall be provided. 35

36 Example: MCDP System MCDP Sub components Temperature controller Steam pressure valve Risk Justification Mitigation Temperature of steam goes down Delay in distillation Controller not get activate whenever steam temperature falls below the set limit. Due to insufficient steam supply Multicolumn efficiency may be decrease Controller challenge test shall be performed during OQ/OQ. Steam pressure valve shall be provided and Controllers shall be challenge in OQ 36

37 Reference ICH Q9 PDA TR 44 PIC/S Quality Risk Management PS/INF 1/2010 Annex 2, WHO TR 981 EudraLex The rules governing medicinal products in the European Union, Vol. 4. Good manufacturing practice (GMP) guidelines ( 4/index_en.htm). 37

38 Author Palash Chandra Das M. Pharma LinkedIn Link Pharmaceutical Chemistry Core Technical Area: Qualification & Validation, Sterility Assurance, QMS, Risk Management Palash Chandra Das is the Technical Writer focuses on technical writing including investigative reports and operating procedures. His passion for writing is displayed in the many writing sessions he hosts via his Blogs at Mr. Palash Chandra Das is recognized as an expert in the field of aseptic manufacturing of parenteral products, and is a frequent presenter at several web conferences and technical training for Sterile Drug Manufacturing. He earned his Master s for Pharmaceutical chemistry from the University of West Bengal University of technology in India. Since 2011 Palash has associated with installation, qualification and operation several production-lines in standard Clean room Technology as well as in Isolator Technology at major regulatory facility across India. 38

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