Office of Regulatory Affairs - PDF document

1 Office of Regulatory Affairs •Background
Office of Regulatory Affairs •Background on Corrective and Preventive Action •Quality System (QS) CAPA (21 CFR 820.100)•Link Between CAPA and Other QS Regulation •Examples on CAPA•Guid

2 ance and Other Resources •Collect and An
ance and Other Resources •Collect and Analyze Information based on •Identify and Investigate Existing and Potential •Take Appropriate, Effective, and Comprehensive CAPA Subsystem in C

3 ontext Design Design Controls MaterialCo
ontext Design Design Controls MaterialControls Records,Documents, &Documents, &Change ControlsChange Controls Equipment & Equipment & Facility Facility Controls Production & Production

4 & Process Process Controls Service Repo
& Process Process Controls Service ReportsService Reports Management ControlsManagement Controls Corrective and Preventive Actions •Inspections–Quality System Inspection Technique (QS

5 IT) –Corrective and –Compliance Program
IT) –Corrective and –Compliance Program (7382.845) –Inspection of Medical Device •Premarket Approval Applications (PMAs)–Original PMAs –Some PMA supplements (Site changes, 30-Day Notic

6 es)•CAPA is NOT •Recalls (corrections an
es)•CAPA is NOT •Recalls (corrections and removals) •Linked to many other requirements. –820.198 Complaint Files–820.90 Nonconforming Product–820.80 Acceptance Activities–820.200 Servi

7 cing –820.22 Audits–803 Medical Device R
cing –820.22 Audits–803 Medical Device Reporting (MDR) –806 Reports of Corrections and Removals (“Recalls”)–... And many more•Ensures problems are detected AND resolved. •Correction: •

8 Corrective Action: •Preventive Action: •
Corrective Action: •Preventive Action: •Nonconformity : non-fulfillment of a specified requirement. •Replacing the label on a device that had the •Revising process parameters in respon

9 se to •Rewelding a contact that does not
se to •Rewelding a contact that does not meet visual •Auditing all vendors of a key component after •Revising equipment maintenance procedures to establish and maintain procedures for

10 equirements of CAPA subsystem : define
equirements of CAPA subsystem : define, document (in writing or electronically), and implement.Number and complexity of procedures vary based on the organization The CAPA ProcessINPU

11 TS •Analyze Data, 820.100(a)(1)•Investig
TS •Analyze Data, 820.100(a)(1)•Investigate Cause, 820.100(a)(2)•Identify Action, 820.100(a)(3)•Verify/Validate Effectiveness, 820.100(a)(4) Implement Changes, 820.100(a)(5)Disseminati

12 ng Information, 820.100(a)(6)Submit for
ng Information, 820.100(a)(6)Submit for Management Document, 820.100(b) •What is your firm’s process for events that “trigger”a CAPA–Not every complaint is a CAPA–Not every nonconforma

13 nce is a CAPA CAPA Data Analysis –21 CFR
nce is a CAPA CAPA Data Analysis –21 CFR 820.100(a)(1) Analyzingprocesses, work operations, concessions, quality audit reports, quality records, service records, complaints, returned p

14 roduct, and other sources of quality dat
roduct, and other sources of quality data to identify existing and potential causes of nonconforming product, or other quality problems. statistical methodology shall be employedwhere

15 necessary to detect recurring quality pr
necessary to detect recurring quality problems. Data Sources •Complaints•Field ServiceReports•Legal Claims•Warranty Claims•External Audits•Medical Device Reports (MDRs)•Inspection/Test

16 Data•NonconformingMaterial Reports•Equi
Data•NonconformingMaterial Reports•Equipment Data •Scrap/Yield Data•Rework Data•Returned Product•Internal Audits •Process Control Data•Acceptance ActivitiesEXTERNAL CAPA and Statisti

17 cal Analysis“FDA emphasizes that the app
cal Analysis“FDA emphasizes that the appropriate statistical tools must be employed when it is necessary to utilize statistical methodology. statistics by manufacturers in an effort to

18 minimize instead of address the problem
minimize instead of address the problem. Such misuse of statistics would be a violation of this section.”61 Fed. Reg. at 52633-52634, Comment 159 •Pareto charts•Run charts•Control cha

19 rts•Mean and standard deviation•T tests
rts•Mean and standard deviation•T tests for comparisons•Experimental design (DOE)•Graphical methods (fishbone diagrams, •Management reviews•Quality review boards•Material review board

20 s•Other internal reviews •Ensure all qua
s•Other internal reviews •Ensure all quality data sources are defined •How is the data is captured and •How does your firm categorize and group –Expect FDA to verify your firm is usin

21 g –Analysis of data should also include
g –Analysis of data should also include a •Is the data received by the CAPA system •Trend analysis is one type of data analysis CAPA Investigation –21 CFR 820.100(a)(2)Investigating t

22 he cause of nonconformitiesrelating to p
he cause of nonconformitiesrelating to product, process, and the quality 21 CFR 820.198, Complaint Handling, also requires investigations for the device involved, but the CAPA requirem

23 ent is broader to cover the process and
ent is broader to cover the process and the quality system. •Identify problem and characterize.•Determine scope and impact.•Investigate data, process, operations and •Determine root ca

24 use, if possible. •Training •Design •Man
use, if possible. •Training •Design •Manufacturing•Management •Change Control •Purchasing/Supplier •Testing •Documentation •Maintenance •Commonly used tools–Fishbone diagrams–5 “whys”

25 –Fault-tree analysis–Among others •Is th
–Fault-tree analysis–Among others •Is the depth of the investigation sufficient?•Expect FDA to evaluate the adequacy of your –Decision process may be linked to risk analysis •What cont

26 rols does your firm have over –Justifica
rols does your firm have over –Justification for concessions should be well Identify Required Actions –21 CFR 820.100(a)(3)Identify the action(s) needed to correct and prevent recurre

27 nceof non-conforming product Beware of t
nceof non-conforming product Beware of terminology! NOTrequired for all situations; however, a Corrective Action to prevent recurrence is required. “... The objective of §820.100 is to

28 correct and •Identify solutions.•Devel
correct and •Identify solutions.•Develop action plan for corrective action and/or •Should consider the risk posed by the problem. –Not all problems require the same level of –It is a

29 ppropriate to “elevate”some issues at th
ppropriate to “elevate”some issues at the CAPA and Risk Managementaction taken to eliminate or minimize actual or potential nonconformities must be appropriate to the magnitude of the

30 problem and commensurate with the risks
problem and commensurate with the risks encountered…FDA does expect the manufacturer to develop procedures for assessing the risk, the actions that need to be taken for different leve

31 ls of risk, and how to correct or preven
ls of risk, and how to correct or prevent the problem from recurring, depending on that risk assessment.”61 Fed. Reg. at 52633-52634, Comment 159 •Risk analysis allows a manufacturer t

32 o: –Determine priorities–Assign resource
o: –Determine priorities–Assign resources–Determine the severity of impact–Determine the depth of investigation•Common tools–Hazard analysis•Used early for potential problems–Failure M

33 ode Effects Analysis (FMEA)•Bottom up–Fa
ode Effects Analysis (FMEA)•Bottom up–Fault Tree Analysis (FTA)•Top down •Expect FDA to review the actions taken•Be prepared to discuss the –Why was corrective action taken?–Does the

34 corrective action extend to include Ver
corrective action extend to include Verify and Validate –21 CFR 820.100(a)(4) Verifying or validating the corrective and preventive action to ensure that such action is effective and

35 does not adversely affect the finished d
does not adversely affect the finished device. Did my solution work? Did it create other •Verify that verification/validation protocols were •Review data associated with verification

36 or •Review the effectiveness of the cor
or •Review the effectiveness of the corrective and Implement and Record Changes –21 CFR 820.100(a)(5)Implementing and recording changes in methods and procedures needed to correct an

37 d prevent identified quality problems. •
d prevent identified quality problems. •Tie CAPA implementation to: –Document control for products and processes (DMR –820.181)–Change control (820.40)•Ensure that controlled documents

38 are •Expect FDA to verify implementati
are •Expect FDA to verify implementation of •Implemented changes may directly link to Disseminate Information –Ensuring that information related to quality problems or nonconforming

39 product is disseminated to those direct
product is disseminated to those directly responsible for assuring the quality of such product or the prevention of such problems Management Review –21 CFR 820.100(a)(7)Submitting rel

40 evant informationon identified quality p
evant informationon identified quality problems, as well as corrective and preventive actions, for management reviewThe significance of the problem impacts the level of management revi

41 ew.Need management awareness and buy-in
ew.Need management awareness and buy-in so that resources are allocated, etc. Documentation –21 CFR 820.100(b) All activities required under this section, and their results, shall be d

42 ocumented. •21 CFR 820.90, Nonconforming
ocumented. •21 CFR 820.90, Nonconforming Product•21 CFR 820.198, Complaint Files •Nonconformity = the nonfulfillment of a onconformity = the nonfulfillment of a ()+•Product = component

43 s, manufacturing •Received components/m
s, manufacturing •Received components/material that fail •Products/components that fail inspection •Product returned to the manufacturer with •Identification and monitoring of noncon

44 forming product often “triggers”CAPA act
forming product often “triggers”CAPA activities.•Nonconforming product investigations can also •Not every nonconformance is a CAPA. What is a “complaint”?Any written, electronic, or

45 oral communication that alleges deficien
oral communication that alleges deficiencies related to the identity, quality, durability, reliability, safety, effectiveness, or performance of a device after it is released for distr

46 ibution.21 CFR 820.3(b) •Complaints are
ibution.21 CFR 820.3(b) •Complaints are a required data source to CAPA and may “trigger”CAPA activity.–Remember, not every complaint is a CAPA•Complaint investigations can be leveraged

47 during CAPA •Recurrent complaints that
during CAPA •Recurrent complaints that involve a health risk may be •CAPA, nonconforming product, and •Nonconformancesare:–A data source for the CAPA system–The basis of the nonconfo

48 rming product –A potential cause of comp
rming product –A potential cause of complaints •Investigation is used in CAPA, •Investigations are:–Required for CAPA–Done, or justified not done, for complaints–May/may not be done fo

49 r nonconformances, •CAPA is a “pulse ch
r nonconformances, •CAPA is a “pulse check”for FDA on how well a firm’s –Strong CAPA systems are usually indicative of strong •Feedback Loop between CAPA, Complaints, and •CAPA Subsys

50 tem is all about identifying and resolvi
tem is all about identifying and resolving Examples Related to CAPA •Your firm failed to establish, maintain, and –Your firm has no CAPA procedures as defined in the QS •The procedur

51 es addressing verification or –CAPA Proc
es addressing verification or –CAPA Procedure 100-0025, Rev 4, requires •Failure to implement procedures addressing –The Corrective and Preventive Action procedure (GP.1401, Ver. 6.0)

52 preventive action(s)." The procedure al
preventive action(s)." The procedure also states, (iii.) "The corrective irements.“However, the validation ciated with an aortic valvethat had a mislabeled size. The firm’s CAPA inc

53 luded a revision of SOP were stated as
luded a revision of SOP were stated as “The additional ence.”As a part of this CAPA, •21 CFR Part 820http://www.accessdata.fda.gov/scr ch.cfm?CFRPart=820 •Preamble to the QS Regulati

54 on Final Rulehttp://www.fda.gov/download
on Final Rulehttp://www.fda.gov/downloads/MedicalDevices/DeviceRegulation ents/QualitySystemsRegulati ons/MedicalDeviceQualitySystemsManual/UCM122806.pdf •Compliance Program (7382.845)

55 –http://www.fda.gov/MedicalDevices/Devi
–http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidan •Quality System Inspection Technique (QSIT)http://www.fda.gov/ICECI/Inspec •“Quality System Information for Certain Premar

56 ket Staff”2003http://www.fda.gov/Medical
ket Staff”2003http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidan •Global Harmonization Task Force (GHTF) Guidance http://www.ghtf.org/sg3/sg3-proposed.html Questions?Thank you