WELLNESS FOR BUSINESS - PDF document

1 1 WELLNESS FOR BUSINESS ® Panelists: Sco
1 WELLNESS FOR BUSINESS ® Panelists: Scott Soukup , Quality Specialist, RCA Inc. Joan M. Ward, Quality Subject Matter Expert, RCA Inc. Moderator and Panelist: Susan Schniepp, Distinguished Fellow, RCA Inc. 2016 © Regulatory Compliance Associates Inc. Conducting CAPA Investigations September 21, 2016 2 WELLNESS FOR BUSINESS ® Webinar Overview 2016

2 © Regulatory Compliance Associates Inc.
© Regulatory Compliance Associates Inc. • Regulations • Historical Problems • CAPA Process Flow • Investigation • Correction, Corrective and Preventive Action • Effectiveness • CAPA Timeliness • Tracking and Trending • Management Review • Lessons Learned 3 WELLNESS FOR BUSINESS ® Regulations 2016 © Regulatory Compliance Associat

3 es Inc. 4 WELLNESS FOR BUSINESS ® Regula
es Inc. 4 WELLNESS FOR BUSINESS ® Regulations • Required by law – Food, Drug and Cosmetic Act – 21 CFR 211 – 21 CFR 820 – EudraLex – ISO – ICH – GHTF 2016 © Regulatory Compliance Associates Inc. 5 WELLNESS FOR BUSINESS ® Food, Drug and Cosmetic Act • SEC. 501. [21 USC § 351] (a)(2)(B) – a drug shall be deemed to be adulterated

4 if the methods used in , or the facili
if the methods used in , or the facilities or controls used for , its manufacture, processing, packing, or holding do not conform to or are not operated or administered in conformity with current good manufacturing practice to assure that such drug meets the requirements of this Act as to safety and has the identity and strength, and meets th

5 e quality and purity characteristics, w
e quality and purity characteristics, which it purports or is represented to possess. 2016 © Regulatory Compliance Associates Inc. 6 WELLNESS FOR BUSINESS ® 21 CFR 211.22 (a) There shall be a quality control unit that shall have the responsibility and authority to approve or reject all components, drug product containers, closures, in - process ma

6 terials, packaging material, labeling,
terials, packaging material, labeling, and drug products, and the authority to review production records to assure that no errors have occurred or, if errors have occurred, that they have been fully investigated . The quality control unit shall be responsible for approving or rejecting drug products manufactured, processed, packed, or held unde

7 r contract by another company . 2016 ©
r contract by another company . 2016 © Regulatory Compliance Associates Inc. 7 WELLNESS FOR BUSINESS ® 21 CFR 820 820.100: “I nvestigating the cause of nonconformities relating to product, processes, and the quality system” 820.198: “Any complaint involving the possible failure of a device, labeling, or packaging to meet any of its spec

8 ifications shall be reviewed, evaluated
ifications shall be reviewed, evaluated, and investigated .” 820.90 : “The evaluation and any investigation shall be documented. ” 820.100: “ Corrective and preventive action . ( a )Each manufacturer shall establish and maintain procedures for implementing corrective and preventive action ” 2016 © Regulatory Compliance Associate

9 s Inc. 8 WELLNESS FOR BUSINESS ® EudraLe
s Inc. 8 WELLNESS FOR BUSINESS ® EudraLex Volume 4 • A Pharmaceutical Quality System appropriate for the manufacture of medicinal products should ensure that: – The results of product and processes monitoring are taken into account in batch release, in the investigation of deviations , and, with a view to taking preventive action to avoid po

10 tential deviations occurring in the futu
tential deviations occurring in the future. – An appropriate level of root cause analysis should be applied during the investigation of deviations , suspected product defects and other problems. – Appropriate corrective actions and/or preventative actions (CAPAs) should be identified and taken in response to investigations . – A review o

11 f all batches that failed to meet establ
f all batches that failed to meet established specification(s) and their investigation . – A review of all quality - related returns, complaints and recalls and the investigations performed at the time. 2016 © Regulatory Compliance Associates Inc. 9 WELLNESS FOR BUSINESS ® Other • International Organization for Standardization (ISO) – ISO

12 13485: Quality Management for Medical D
13485: Quality Management for Medical Devices • International Conference on Harmonization (ICH) – Q10: Pharmaceutical Quality System • Global Harmonization Task Force* (GHTF) – Quality management system – Medical Devices – Guidance on corrective action and preventive action and related QMS processes *The International Medical Devic

13 e Regulators Forum (IMDRF) is continuing
e Regulators Forum (IMDRF) is continuing the work of the Global Harmonization Task Force (GHTF). 2016 © Regulatory Compliance Associates Inc. 10 WELLNESS FOR BUSINESS ® Historical Problems Inspectional Observation Summary for CAPA Year Devices Pharmaceuticals 2015 483’s – 1008 #1 Citation – CAPA/Investigations 483’s – 678 #3 Citation

14 – CAPA/Investigations 2014 483’s
– CAPA/Investigations 2014 483’s – 972 #1 Citation – CAPA/Investigations 483’s – 645 #3 Citation – CAPA/Investigations 2013 483’s – 1099 #1 Citation – CAPA/Investigations 483’s – 690 #2 Citation – CAPA/Investigations 2012 483’s – 1090 #1 Citation – CAPA/Investigations 483’s – 787 #2 Citation – C

15 APA/Investigations 2011 483’s – 103
APA/Investigations 2011 483’s – 1035 #1 Citation – CAPA/Investigations 483’s – 758 #4 Citation – CAPA/Investigations 2016 © Regulatory Compliance Associates Inc. 11 WELLNESS FOR BUSINESS ® What is CAPA? 2016 © Regulatory Compliance Associates Inc. 12 WELLNESS FOR BUSINESS ® The CAPA Process 2016 © Regulatory Compliance Associates Inc

16 . 13 WELLNESS FOR BUSINESS ® Key Point t
. 13 WELLNESS FOR BUSINESS ® Key Point to Remember CAPA System Identifying Issues Production and Process nonconformances Complaints Audit Observations Trends Investigating to root cause Resolving the Issues Verifying the Resolution Corrections Interim Controls Corrective Action Preventive Action Effectiveness Checks Performing Risk Assessment

17 2016 © Regulatory Compliance Associates
2016 © Regulatory Compliance Associates Inc. 14 WELLNESS FOR BUSINESS ® Risk Assessment • What is the impact of the issue to the health and safety of the patient and/or user. • What is the scope of the issue: • Product in the field • Multiple lots • Multiple locations • Frequency of occurrence • Identified in Hazard Analysis • Use y

18 our Risk Management Tools. 14 2016 © Reg
our Risk Management Tools. 14 2016 © Regulatory Compliance Associates Inc. 15 WELLNESS FOR BUSINESS ® 15 Investigations If an initial evaluation and risk assessment indicates, a documented investigation consistent with the significance of the quality issue, is performed to determine Root or Probable Cause. 2016 © Regulatory Compliance Associate

19 s Inc. 16 WELLNESS FOR BUSINESS ® 16 Inv
s Inc. 16 WELLNESS FOR BUSINESS ® 16 Investigations continued • Initial Risk Assessment will determine the: • Depth of investigation: • Simple issues = simple investigations • Complex/safety critical issues = detailed investigations • Urgency of the investigation. • Obtain Quality Management support 2016 © Regulatory Compliance Associ

20 ates Inc. 17 WELLNESS FOR BUSINESS ® 17
ates Inc. 17 WELLNESS FOR BUSINESS ® 17 Investigations continued • Write an Investigation Plan. • Identify an Owner (process or event). • Engage a team if applicable. • Determine tools to be used. • Determine areas to be investigated. • Determine how to investigate. • Establish a timeline. 2016 © Regulatory Compliance Associates Inc.

21 18 WELLNESS FOR BUSINESS ® 18 Investiga
18 WELLNESS FOR BUSINESS ® 18 Investigations continued • Investigate the following areas: – Personnel, – Materials, – Equipment, – Process/Methods, – Suppliers, – Validation, – Storage conditions, • Think big, think creatively. 2016 © Regulatory Compliance Associates Inc. 19 WELLNESS FOR BUSINESS ® 19 Investigations continued Doc

22 ument all investigation activities. •
ument all investigation activities. • At a minimum, include the following elements: – Description of Nonconformity Event – Root or Probable Cause – Outcomes of all tools used – Objective evidence supporting conclusions – Description of statistical methods used – Final risk assessment 2016 © Regulatory Compliance Associates Inc. 20 WELL

23 NESS FOR BUSINESS ® Investigative Tools
NESS FOR BUSINESS ® Investigative Tools • Brainstorming • Fishbone • 5 Whys • Design of Experiments • Contradiction Analysis 2016 © Regulatory Compliance Associates Inc. www.rcainc.com , News and Views, News 21 WELLNESS FOR BUSINESS ® Resolutions • Corrections • Interim Modes of Control • Corrective Actions • Preventive Action 2016

24 © Regulatory Compliance Associates Inc.
© Regulatory Compliance Associates Inc. 22 WELLNESS FOR BUSINESS ® 22 Correction • Correction: Action taken to fix a detected nonconformity. – Typically one time fixes. – Immediate solution such as training, repair or rework. – Also known as remedial or containment action. • Corrections require verification. • Thorough documentatio

25 n required 2016 © Regulatory Compliance
n required 2016 © Regulatory Compliance Associates Inc. 2016 © Regulatory Compliance Associates Inc. 23 WELLNESS FOR BUSINESS ® 23 Correction, continued • Interim controls – Type of correction that remains in place until a corrective action is deemed effective • Examples – 100% inspection – Third party oversight and review 2016 © Regulato

26 ry Compliance Associates Inc. 24 WELLNES
ry Compliance Associates Inc. 24 WELLNESS FOR BUSINESS ® 24 Corrective Action • Corrective action (CA): action to eliminate the cause(s) of a detected nonconformity or other undesirable situation and the recurrence of the issue. 2016 © Regulatory Compliance Associates Inc. 25 WELLNESS FOR BUSINESS ® 25 Corrective Action continued • Write a

27 Corrective Action Plan. – Identify the
Corrective Action Plan. – Identify the CA strategy. – Describe all the corrective actions that will be performed and associated action items. – How will the corrective action be tested – Identify who is responsible for each action item. – Set a timeline with completion dates. 2016 © Regulatory Compliance Associates Inc. 26 WELLNESS FOR B

28 USINESS ® 26 Corrective Action continued
USINESS ® 26 Corrective Action continued • Implement the Corrective Action(s). • Implementation requires monitoring and oversight. – Structured monitoring of progress against actions, monitoring of the impact of actions, engagement of management, and governance. – Documents any changes, and reflects any revisions or changes to timelines i

29 n the documentation. – Formal tracking
n the documentation. – Formal tracking of the overall progress of the CA, tracking of the individual actions, and review of milestones on a defined frequency. 2016 © Regulatory Compliance Associates Inc. 27 WELLNESS FOR BUSINESS ® 27 Preventive Action • Preventive Action (PA): action to eliminate the cause of a potential nonconformity or ot

30 her undesirable potential situation. S
her undesirable potential situation. Should prevent the occurrence of the potential issue. • Not dependent on the occurrence of a nonconformity • Example: Results of a Finished Product QC check are within specification limits yet over the past 10 batches are trending upward. 2016 © Regulatory Compliance Associates Inc. 28 WELLNESS FOR BU

31 SINESS ® 28 Preventive Action continued
SINESS ® 28 Preventive Action continued • Preventive action require a plan with same elements as a corrective action: • Write a plan. • Implement the preventive actions. • Monitor preventive action activities. 2016 © Regulatory Compliance Associates Inc. 29 WELLNESS FOR BUSINESS ® 29 Effectiveness Check Effectiveness Check (EC) : Monitorin

32 g activity over a defined duration for
g activity over a defined duration for ensuring that • CA/PA’s have been identified, implemented, and sustained • the problem has been solved, and • no new quality problems have been created. 2016 © Regulatory Compliance Associates Inc. 30 WELLNESS FOR BUSINESS ® Effectiveness Check continued • Key Components of Effectiveness Checks: â€

33 “ Methods for determining success of the
“ Methods for determining success of the Corrective Action or Preventive Action must be defined. – Effectiveness criteria or key performance indicators must be measurable. – Duration for conducting effectiveness checks must determined. – Data, graphs, charts, metrics as applicable for evidence of effectiveness of the Corrective or Preven

34 tive Action 2016 © Regulatory Complianc
tive Action 2016 © Regulatory Compliance Associates Inc. 31 WELLNESS FOR BUSINESS ® 31 Effectiveness Check continued Effectiveness Check Plan: • Addresses the key elements. • Describes statistical techniques to be used. • Lists responsibilities and includes due dates . 2016 © Regulatory Compliance Associates Inc. 32 WELLNESS FOR BUSINESS ® CA

35 PA Closure • All actions must be compl
PA Closure • All actions must be completed and assessed for effectiveness prior to CAPA closure. (Note: In rare occasions CAPA may be closed prior to effectiveness check however solid justification is required.) • Use common sense 2016 © Regulatory Compliance Associates Inc. 33 WELLNESS FOR BUSINESS ® 33 Corrective Action/Preventive Action

36 – Not all nonconformities require Corr
– Not all nonconformities require Corrective or Preventive Action. – If Corrective or Preventive Action are not necessary, as determined by Quality, then appropriate justifications should be documented and approved. 2016 © Regulatory Compliance Associates Inc. 34 WELLNESS FOR BUSINESS ® 34 Corrective Action/Preventive Action continued • Lo

37 w Level Investigations may not routinely
w Level Investigations may not routinely require CAPA s. • However, these investigations should be tracked and trended. • If a recurring trend is found, Corrective Actions should be required. 2016 © Regulatory Compliance Associates Inc. 35 WELLNESS FOR BUSINESS ® Corrective Action/Preventive Action continued CAPA Leader • Excellent commun

38 ication/presentation skills. • Strong
ication/presentation skills. • Strong analytical problem solving skills. • Influence management skills; ability to work constructively across all functions of the organization. • Experience in all areas of the CAPA process. • Experience with quality tools and process improvement techniques. • Project management experience. 2016 © Regula

39 tory Compliance Associates Inc. 36 WELLN
tory Compliance Associates Inc. 36 WELLNESS FOR BUSINESS ® 2016 © Regulatory Compliance Associates Inc. Timeliness 37 WELLNESS FOR BUSINESS ® Timeliness • Not completing/closing CAPAs in a reasonable time is a red flag to an investigator. • Not all CAPA are equal; some CAPAs can be closed in few months others will take several months. • Me

40 asure the CAPA process for timeliness. â
asure the CAPA process for timeliness. • Take action when CAPAs are not progressing per plan. 2016 © Regulatory Compliance Associates Inc. 38 WELLNESS FOR BUSINESS ® Timeliness – Red Flags • Open over a year. • No progress for 3 months. • Not getting to root cause in 3 to 6 months. • Corrective action(s) taking more than 6 months.

41 2016 © Regulatory Compliance Associates
2016 © Regulatory Compliance Associates Inc. 39 WELLNESS FOR BUSINESS ® Timeliness – All CAPAs are not Equal • CAPAs using simple investigation tools may get to root cause faster than using complex tools. • Corrective actions which requires a new or revised procedure will take less time than ones requiring a new design or equipment chan

42 ge. • Key – set completion expectat
ge. • Key – set completion expectations based on the complexity of the CAPA. 2016 © Regulatory Compliance Associates Inc. 40 WELLNESS FOR BUSINESS ® Timeliness - Metrics • If you can't measure it, it will not improve. • Determine metrics to drive the correct behavior and review monthly. • Possible metrics: – Number of days to get

43 to root cause. – Number of days to com
to root cause. – Number of days to complete a corrective action. – Number of days to close a CAPA. – Percentage of CAPAs closed per plan • Set goals for each and revise as process improves. 2016 © Regulatory Compliance Associates Inc. 41 WELLNESS FOR BUSINESS ® Timeliness – Take Action • Review metrics monthly with your CAPA team. â

44 €¢ Determine how many months above goal
€¢ Determine how many months above goal before taking action. • Take corrective action to get metrics back on track. • Established when to escalate issues to management 2016 © Regulatory Compliance Associates Inc. 42 WELLNESS FOR BUSINESS ® Tracking and Trending • Establish requirement for opening a CAPA based on risk of impact and freque

45 ncy of the noncompliances. • Need to
ncy of the noncompliances. • Need to track and trend corrected noncompliances that do not meet requirements for opening a CAPAs. • Track and trend within the data sources . 2016 © Regulatory Compliance Associates Inc. 43 WELLNESS FOR BUSINESS ® Management Review • Use Management Review to inform management the effectiveness of your CAPA

46 system. • Select the key critical met
system. • Select the key critical metric(s) used to drive correct behavior. Possible metrics: – Number of days CAPAS are open. – Percentages of CAPAs closed on time. • Document any actions taken. 2016 © Regulatory Compliance Associates Inc. 44 WELLNESS FOR BUSINESS ® When to Create a CAPA • Not all nonconformance needs to become a CAP

47 A. • Use a method to determine if a CA
A. • Use a method to determine if a CAPA is needed. • Use a combination impact and frequency. 2016 © Regulatory Compliance Associates Inc. 45 WELLNESS FOR BUSINESS ® 2016 © Regulatory Compliance Associates Inc. 46 WELLNESS FOR BUSINESS ® 2016 © Regulatory Compliance Associates Inc. 47 WELLNESS FOR BUSINESS ® 2016 © Regulatory Compliance Associat