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The Critical Role of the QCU
Crystal MershExecutive Partner, QxP Inc.International GMP ConferenceMarch 11, 2014
• For the past ten (10) years the most cited FDA-483 observation involved the failure of the QCU.
• Data presented in 2013 at this conference1. Failure of QCU: 165 citations2. Improper failure investigations: 112 citations3. Inadequate procedures: 104 citations4. Inadequate lab controls: 98 citations5. Inadequate sampling: 76 citations6. Inadequate procedures: 69 citations7. Inadequate cleaning: 66 citations8. Inadequate training: 61 citations9. Inadequate calibration/inspection: 61 citations
The Facts
My role is best described as:
1. Quality Assurance2. Manufacturing3. Regulatory Affairs4. Quality Control5. Research & Development6. Executive Management7. Consultant8. Regulator9. Other
54%5%7%7%1%9%6%5%6%
IF You’re Looking for Love……
Regulatory Requirements
210.3 (b)(15)
Quality control unit means any person or organizational element designated by the firm to be responsible for the duties relating to quality control.
211.22Responsibilities of quality control unit• (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 materials, 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 under contract by another company.
• (b) Adequate laboratory facilities for the testing and approval (or rejection) of components, drug product containers, closures, packaging materials, in-process materials, and drug products shall be available to the quality control unit.
• (c) The quality control unit shall have the responsibility for
approving or rejecting all procedures or specifications impacting on the identity, strength, quality, and purity of the drug product.
• (d) The responsibilities and procedures applicable to the quality
control unit shall be in writing; such written procedures shall be followed.
“The Commissioner intends to make the quality control unit responsible for ensuring that controls are implemented during manufacturing operations which ensuring drug product quality, not that the quality control unit actually perform each one of the duties. The Commissioner believes that, even under 211.22, management has the prerogative to organize its internal structure and assign responsibilities as it deems appropriate, as long as some identifiable person or unit has at least those responsibilities assigned by the regulations to the quality control unit.”
21 CRF 210/211 Preamble
Guidance for IndustryInvestigating OOS Test Results, 2006
“It is critical that the laboratory provide all individual results for evaluation and consideration by the QCU, which is responsible for approving or rejecting”
“This guidance uses the term quality unit (QU) to reflect modern practice while remaining consistent with the CGMP definition in 210.3(b)(15). The concept of the quality unit is also consistent with modern quality systems in ensuring that the various operations associated with all systems are appropriately planned, approved, conducted, and monitored.”
Guidance for IndustryQuality System Approach, 2006
Example Citations
“Your quality control unit (QCU) has allowed failing product to remain in distribution, released product to the market without adequate stability data to support the expiration dates, failed to conduct adequate investigations of discrepancies, failed to adequately review all analytical data prior to release, and failed to assure adequate analytical method validations were conducted for numerous finished product test procedures.”
WL Citation
“ We are particularly concerned with your firm’s failure to implement a robust Quality System. Repeat citations from prior inspections indicate that your quality control unit is not exercising its responsibilities, and may not have the appropriate authority to carry out its responsibilities.”
WL Citation
“Your response of October 28, 2011 is inadequate because you failed to describe the specific steps that you are taking to ensure adequate oversight by the quality unit over critical aseptic operations such as unidirectional airflow pattern studies.”
WL Citation
“The responsibilities and procedures applicable to the quality control unit are not fully followed.Specifically,Your Quality Unit has failed in the responsibility and authority to monitor Quality Systems designed to assure the quality of drug product manufactured and packaged at your firm. This failure is evidenced in the observations below (2-13), as well as continued NDA Field Alerts and recalls for similar problems over the last several years.”
483 Citations
History of QCU Citations
2006 2007 2008 2009 2010 2011 2012 20130
50
100
150
200
250
300
350
22b: Laboratory22: CMO22a: Materials22c: Documentation22a: Investigations22a: No QCU22d: Failure to Follow
Source: Summary of Inspectional Finding by Fiscal Year on FDA/gov
Practical Considerations
• An effective QCU must be fully independent • An effective QCU must be truly valued • Responsibility for “quality” is different than
responsibility for Quality Assurance• The criticality of the Quality System:– “You can’t oversee what you cannot SEE!”
• Device: “Failure of the management with executive responsibility to ensure that an adequate and effective quality system has been fully implemented and maintained at all levels of the organization, as required by 21 C.F.R. § 820.20”
• Drug: “Finally, the Agency is concerned about the response … to this matter. Corporate management has the responsibility to ensure the quality, safety, and integrity of its products. Neither upper management…nor…. ensured global, adequate, or timely resolution of the issues at these sites.”
WL CitationsResponsibilities of Management
10 Years later…
Why do we continue to see the QCU criticized?
Survey Says….
1. Strongly Agree2. Agree3. Disagree4. Strongly Disagree
The QCU reporting structure is isolated from other functions to preserve the
independence of the function.1. Strongly Agree2. Agree3. Disagree4. Strongly Disagree
39%40%14%
7%
The decisions of QCU is fully independent from all operations.
1. Strongly Agree2. Agree3. Disagree4. Strongly Disagree
19%39%34%
8%
The role of QCU is clearly defined and documented in a formal procedure.
1. Strongly Agree2. Agree3. Disagree4. Strongly Disagree
48%38%12%
1%
The QCU has the required skills – both technical and leadership – to
fulfill its responsibility.
1. Strongly Agree2. Agree3. Disagree4. Strongly Disagree
19%42%28%10%
The QCU is adequately resourced.
1. Strongly Agree2. Agree3. Disagree4. Strongly Disagree
8%27%41%24%
The QCU has oversight of the QC laboratory operations.
1. Strongly Agree2. Agree3. Disagree4. Strongly Disagree
42%41%12%
5%
The QCU is given the authority and support from Executive Management to
fulfill its role.1. Strongly Agree2. Agree3. Disagree4. Strongly Disagree
20%54%20%
6%
Executive Management is integrally involved and aware of quality issues.
1. Strongly Agree2. Agree3. Disagree4. Strongly Disagree
28%46%23%
3%
Executive management does not inappropriately influence (or attempt to
influence) the decisions of the QCU.
1. Strongly Agree2. Agree3. Disagree4. Strongly Disagree
17%46%27%11%
Data
Information
What do we do differently to get a different result?
Thank you!
Contact Information:cmersh@qualityexecutivepartners.comwww.qualityexecutivepartners.com
Survey Says!
Data Analysis by:bduncan@qualityexecutivepartners.comwww.qualityexecutivepartners.com
54%
5%7%
7%1%
9%
6%5%
6%
Demographic Comparison
Quality AssuranceManufacturingRegulatory AffairsQuality ControlResearch & DevelopmentExecutive ManagementConsultantRegulatorOther
The Audience
Question % Agreement
2) The QCU reporting structure is isolated from other functions to preserve the independence of the function
79%
3) The decisions of the QCU are fully independent from all operations 58%
4) The role of QCU is clearly defined and documented in a formal procedure
86%
5) The QCU has the required skills – both technical and leadership – to fulfill its responsibility
62%
6) The QCU is adequately resourced 35%
7) The QCU has oversight of QC laboratory operations 83%
8) The QCU is given the authority and support from Executive Management to fulfill its role
74%
9) Executive Management is integrally involved and aware of quality issues
74%
10) Executive management does not inappropriately influence (or attempt to influence) the decisions of the QCU
63%
General Results
9 Questions: Common Themes
Question% Agreement
QA Mfg Exec. Mgmt Regulators
2) The QCU reporting structure is isolated from other functions to preserve the independence of the function
3) The decisions of the QCU are fully independent from all operations
4) The role of QCU is clearly defined and documented in a formal procedure
5) The QCU has the required skills – both technical and leadership – to fulfill its responsibility
6) The QCU is adequately resourced
7) The QCU has oversight of QC laboratory operations
8) The QCU is given the authority and support from Executive Management to fulfill its role
9) Executive Management is integrally involved and aware of quality issues
10) Executive management does not inappropriately influence (or attempt to influence) the decisions of the QCU
<50% Agree 50% - 75% Agree
>75% Agree
Quality Assu
rance
Manufacturin
g
Regulatory Affairs
Quality Contro
l
Research &
Development
Execu
tive Management
Consulta
nt
RegulatorOther
0%
20%
40%
60%
80%
100%
120%
2) The QCU reporting structure is isolated from other functions to preserve the independence of the function
>80%
<50%
Demographic Perceptions
Quality Assu
rance
Manufacturin
g
Regulatory Affairs
Quality Contro
l
Research &
Development
Execu
tive Management
Consulta
nt
RegulatorOther
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
3) The decisions of the QCU are fully independent from all opera-tions
>80%
Demographic Perceptions
Quality Assu
rance
Manufacturin
g
Regulatory Affairs
Quality Contro
l
Research &
Development
Execu
tive Management
Consulta
nt
RegulatorOther
0.00%
20.00%
40.00%
60.00%
80.00%
100.00%
120.00%
4) The role of the QCU is clearly defined and documented in a formal procedure
>80%
Demographic Perceptions
Quality Assu
rance
Manufacturin
g
Regulatory Affairs
Quality Contro
l
Research &
Development
Execu
tive Management
Consulta
nt
RegulatorOther
0.00%
10.00%
20.00%
30.00%
40.00%
50.00%
60.00%
70.00%
80.00%
90.00%
5) The QCU has the required skills – both technical and leadership – to fulfill its responsibility
<60%
Demographic Perceptions
Quality Assu
rance
Manufacturin
g
Regulatory Affairs
Quality Contro
l
Research &
Development
Execu
tive Management
Consulta
nt
RegulatorOther
0.00%
10.00%
20.00%
30.00%
40.00%
50.00%
60.00%
70.00%
80.00%
6) The QCU is adequately resourced
>50%
Demographic Perceptions
Quality Assu
rance
Manufacturin
g
Regulatory Affairs
Quality Contro
l
Research &
Development
Execu
tive Management
Consulta
nt
RegulatorOther
0.00%
20.00%
40.00%
60.00%
80.00%
100.00%
120.00%
7) The QCU has oversight of QC laboratory operations.
>90%
Demographic Perceptions
Quality Assu
rance
Manufacturin
g
Regulatory Affairs
Quality Contro
l
Research &
Development
Execu
tive Management
Consulta
nt
RegulatorOther
0.00%
20.00%
40.00%
60.00%
80.00%
100.00%
120.00%
8) The QCU is given the authority and support from Executive Management to fulfill its role.
>80%
Demographic Perceptions
Quality Assu
rance
Manufacturin
g
Regulatory Affairs
Quality Contro
l
Research &
Development
Execu
tive Management
Consulta
nt
RegulatorOther
0.00%
10.00%
20.00%
30.00%
40.00%
50.00%
60.00%
70.00%
80.00%
90.00%
100.00%
9) Executive Management is integrally involved and aware of qual-ity issues
>80%
Demographic Perceptions
Quality Assu
rance
Manufacturin
g
Regulatory Affairs
Quality Contro
l
Research &
Development
Execu
tive Management
Consulta
nt
RegulatorOther
0.00%
20.00%
40.00%
60.00%
80.00%
100.00%
120.00%
10) Executive management does not inappropriately influence (or attempt to influence) the decisions of the QCU
>80%
Demographic Perceptions