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11/22/2010

CAPA Programs
Managing Supplier Audits FollowU A
Up
Activities
ti iti

CCangene
C Corporation
F Fiscal
201 2011
0
www.cangene.com

Cangene Corporation Fiscal 2011


www.cangene.com

11/22/2010

Managing Supplier Audits Follow-Up Activities


1. Understanding The Current Regulatory
Climate
2. CAPA Defined
3. Case Studies for Managing CAPA
4. Interactive Exercise

Cangene Corporation Fiscal 2011


www.cangene.com

Understanding The Current Regulatory Climate


Challenges in assuring supply chain integrity
Co
Complexity
p e ty a
and
d hazards
a a ds
Lack of traceability
Increased brokerage and trade
Repackaging and relabeling

EMA
Economically Motivated Adulteration
Animal feed - melamine
Heparin oversulfated chondroitin sulfate

Over-reliance on CoAs
Non-specific ID tests frequently performed on
composite samples.
Cangene Corporation Fiscal 2011
www.cangene.com

11/22/2010

Understanding The Current Regulatory Climate

Cangene Corporation Fiscal 2011


www.cangene.com

Understanding The Current Regulatory Climate

FDA Commissioner
Margaret Hamburg

Cangene Corporation Fiscal 2011


www.cangene.com

11/22/2010

Understanding The Current Regulatory Climate


companies that sell contaminated products
because of loose supply chain oversight need
to face serious penalties and cannot excuse
themselves by blaming their suppliers, blaming
the FDA
FDA, or blaming anyone else
else.

Cangene Corporation Fiscal 2011


www.cangene.com

Understanding The Current Regulatory Climate


we are moving from a system that places
most of the regulatory burden on the FDAs
modest inspection force, to one that creates
greater oversight at points further back along
the production chain
chain.

Cangene Corporation Fiscal 2011


www.cangene.com

11/22/2010

Understanding The Current Regulatory Climate


We need to know who is making our foods and
drugs, where they are located, and we need to
be sure that these facilities are being inspected
and are accountable for what goes into their
products
d t as wellll as th
the products
d t th
they produce.
d

Cangene Corporation Fiscal 2011


www.cangene.com

Understanding The Current Regulatory Climate


I can assure you that addressing the problem of
global supply chain safety, and shifting the
existing paradigm from reaction to
prevention, is one of my highest priorities for
FDA
FDA.

Cangene Corporation Fiscal 2011


www.cangene.com

10

11/22/2010

Understanding The Current Regulatory Climate


Supplier questionnaire (audit by mail) not
considered adequate
q
any
y more.
FDA is looking for on-site audits; site of actual
production see the process.
One day audits are suspect.
Need to invest time, planning, resources, gain
understanding.
The p
purpose
p
is to g
gain understanding
g of yyour
suppliers manufacturing and quality processes.

Cangene Corporation Fiscal 2011


www.cangene.com

11

Understanding The Current Regulatory Climate


The Agency is backing its regulations with
enforcement action in 2009, 12% of 483
observations and 16% of Warning Letters issued
were all related to inadequate supplier
qualification
qualification.

Cangene Corporation Fiscal 2011


www.cangene.com

12

11/22/2010

Understanding The Current Regulatory Climate

The quality assurance of starting materials, and


supplier approval, was deficient in thatthere was no
documented evidence of QA follow-up of progress with
remedial actions arising from the adverse [supplier]
assessment, either in terms of alternative material
sources, or [the suppliers] progress with remediation
plans.

Cangene Corporation Fiscal 2011


www.cangene.com

13

Understanding The Current Regulatory Climate

Corrective actions were not effective to prevent


reoccurrence off critical
iti l d
defects
f t iin vials
i l ... Th
The ffor-cause
audit of the glass vial manufacturer found significant
evidence indicating that the vial lots were not
manufactured with adequate controls to ensure
consistent quality in the finished product. Vial
manufacturing was moved to another line which has
improved inspection capabilities, but additional defective
vials were received from the new line.

Cangene Corporation Fiscal 2011


www.cangene.com

14

11/22/2010

Understanding The Current Regulatory Climate

You have not executed the new plan to audit


suppliers of active ingredients and raw materials as
committed in your response.
Problem with excessive rejection of vials due to visible particles.
Contacted the contract sterilizer.
No steps were taken to audit and perform a complete evaluation of
the contractors sterilizer process or to increase sampling and
monitoring of this API after finished lots were reported as above
limits for particles rejects.

Cangene Corporation Fiscal 2011


www.cangene.com

15

Understanding The Current Regulatory Climate

The Rules

Cangene Corporation Fiscal 2011


www.cangene.com

16

11/22/2010

Understanding The Current Regulatory Climate

820.100

Each manufacturer shall establish and maintain


procedures for implementing corrective and preventive
action. The procedures shall include requirements for:

Cangene Corporation Fiscal 2011


www.cangene.com

17

Understanding The Current Regulatory Climate


(2) Investigating the cause of non-conformities relating to
product, processes, and the quality system;
(3) Identifying the action(s) needed to correct and
prevent recurrence of non-conforming product and other
quality problems.
(4) Verifying
V if i and
d validating
lid ti [them]
[th ] to
t ensure that
th t such
h
action is effective

Cangene Corporation Fiscal 2011


www.cangene.com

18

11/22/2010

Understanding The Current Regulatory Climate

211.192

the failure of a batch or any of its components to


meet any of its specifications shall be thoroughly
investigated
investigated

Cangene Corporation Fiscal 2011


www.cangene.com

19

Understanding The Current Regulatory Climate

A written record of the investigation shall be made and


shall include conclusions and follow-up.

Cangene Corporation Fiscal 2011


www.cangene.com

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10

11/22/2010

CAPA Defined
Title: Quality Management System Medical Devices
Guidance on the Control of Products and Services
Obtained from Suppliers
Authoring Group: GHTF Study Group 3
Endorsed by: The Global Harmonization Task Force
Date: December 11, 2008

Cangene Corporation Fiscal 2011


www.cangene.com

21

CAPA Defined
If a Corrective Action or Preventive Action
(CAPA) is initiated additional feedback and
communication may be necessary. As part of
this action the manufacturer may need to reevaluate the continued suitability of the
supplier.

Cangene Corporation Fiscal 2011


www.cangene.com

22

11

11/22/2010

CAPA Defined
Depending on the nature of the procured
product/service, portions of the activities that are to be
performed under CAPA may be delegated by the
manufacturer to the supplier. The combined CAPA
related activities of both the manufacturer and the
supplier must satisfy the requirements of applicable
regulations and standards.

Cangene Corporation Fiscal 2011


www.cangene.com

23

CAPA Defined
While some of the CAPA activities may be
delegated to a supplier, the overall
responsibility for these activities resides with
the manufacturer. CAPA related decisions
and effectiveness checks cannot be
delegated and reside with the manufacturer.

Cangene Corporation Fiscal 2011


www.cangene.com

24

12

11/22/2010

CAPA Defined

Cangene Corporation Fiscal 2011


www.cangene.com

25

CAPA Defined
CAP P

Identify actions

DCangene Corporation Fiscal 2011


www.cangene.com

F
26

13

11/22/2010

CAPA Defined
CAP P

Identify actions

DCangene Corporation Fiscal 2011


www.cangene.com

F
27

CAPA Defined

Cangene Corporation Fiscal 2011


www.cangene.com

28

14

11/22/2010

CAPA Defined

Each link of the chain must add value:


It only takes one weak link in the chain to put product
at risk.
Verification and p
positive checks are required.
q

Cangene Corporation Fiscal 2011


www.cangene.com

29

CAPA Defined
The purpose of assessing the capabilities of
your suppliers is to provide a greater degree of
assurance, beyond that provided by in-coming
inspection and testing, that the raw materials
and components received meet the needs of
your product and process.

Cangene Corporation Fiscal 2011


www.cangene.com

30

15

11/22/2010

CAPA Defined
The purpose of audit follow-up is to provide a
greater degree of assurance, beyond that
provided by review of an audit response, that the
actions planned and proposed have been
implemented and are effective
effective.

Cangene Corporation Fiscal 2011


www.cangene.com

31

CAPA Defined
One of the fundamental steps in any CAPA process is
completing an evaluation of the actions that were taken.

Verification and validation:


Were they completed?
Were they timely?
Were they appropriate and effective?

Cangene Corporation Fiscal 2011


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32

16

11/22/2010

CAPA Defined
Two important questions:
Can you follow up on every corrective action
commitment?
Is it necessary or required?

It depends
Cangene Corporation Fiscal 2011
www.cangene.com

33

CAPA Defined
Effective decision making in a quality systems
environment is based on an informed understanding of
quality issues. Elements of risk should be considered
relative to intended use of a product, and in the case of
pharmaceuticals, patient safety

- Quality Systems Approach to Pharmaceutical cGMP

Cangene Corporation Fiscal 2011


www.cangene.com

34

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11/22/2010

CAPA Defined
It depends on
Criticality of supplier deficiency and its potential
to impact on the quality attributes of your
product, and ultimately, on patient safety.

Cangene Corporation Fiscal 2011


www.cangene.com

35

CAPA Defined
It depends on
Criticality of supplier deficiency and its potential
to impact on the quality attributes of your
product, and ultimately, on patient safety.

Cangene Corporation Fiscal 2011


www.cangene.com

36

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11/22/2010

CAPA Defined

How much is enough?

Cangene Corporation Fiscal 2011


www.cangene.com

37

CAPA Defined

Risk
Management

Cangene Corporation Fiscal 2011


www.cangene.com

38

19

11/22/2010

CAPA Defined
First, we are seeking better controls at the
point of production
production.
A second key element of our strategy is to hold
importing companies responsible for their
supply chain.
Third, we are going to deploy our agencys
resources strategically. This is essential as our
mandate
d t kkeeps expanding,
di
even iin th
these
economically challenging times.

Cangene Corporation Fiscal 2011


www.cangene.com

39

CAPA Defined

Model for industry

better controls at the point of production

hold suppliers responsible

deploy resources strategically

Cangene Corporation Fiscal 2011


www.cangene.com

40

20

11/22/2010

CAPA Defined
Developing a risk-based approach
Understand the needs of your product and process
Rate audit deficiencies according to severity/criticality
to your product and process needs.
Use risk management
g
to p
prioritize work.
Level how soon, how often, to what extent
Formality

Cangene Corporation Fiscal 2011


www.cangene.com

41

CAPA Defined
Required work, including follow-up, can be
prioritized but cannot be eliminated using risk
management principles.
Manufacturers cannot risk-manage away
regulatory
l t
requirements.
i
t

Cangene Corporation Fiscal 2011


www.cangene.com

42

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11/22/2010

CAPA Defined
Identify risk factors important to your operation
Define
D fi criteria/risk
it i / i k scores ffor each
h ffactor
t
Create risk assessment tools
Define action levels for each risk level
Mechanism to feed forward information for the
next rating
g in supplier
pp
q
quality
y management
g
system
periodic supplier risk review, done at least yearly by
many companies
Cangene Corporation Fiscal 2011
www.cangene.com

43

CAPA Defined
Risk factors
CQAs of finished product directly dependent on the
relevant quality attributes of components.
Purity
Content, strength, concentration
Sterility
Impurities

Cangene Corporation Fiscal 2011


www.cangene.com

44

22

11/22/2010

CAPA Defined
Define action levels
Level A: evaluation of effectiveness before receipt of
next lot.
Level B: evaluation of effectiveness within 6 months
Level C: evaluation of effectiveness at next scheduled
audit
dit

Cangene Corporation Fiscal 2011


www.cangene.com

45

CAPA Defined
Benefits
Rationalized approach to manage follow-up
Prioritization
Manages risk effectively
Uses resources efficiently

Cangene Corporation Fiscal 2011


www.cangene.com

46

23

11/22/2010

CAPA Defined

1.
2.

3.
4.
5.

If CAPA activities are delegated to suppliers, the manufacturer


needs to ensure that:
CAPA related activities performed by suppliers are defined in the
manufacturers QMS.
Based on the products provided by a supplier, all CAPA specific
activities to be performed and data/information to be provided by
that supplier are identified (e.g. related to the extent of control
necessary at the supplier).
The suppliers obligations related to CAPA activities are
communicated to the supplier and clearly defined and documented.
The supplier fulfils his obligations in relation to the CAPA activities
(e.g. timely processing of corrections).
Documentation and records related to a suppliers CAPA activities
are controlled and readily available.

Cangene Corporation Fiscal 2011


www.cangene.com

47

Case Study for Managing CAPA


Excipient Supplier

Cangene Corporation Fiscal 2011


www.cangene.com

48

24

11/22/2010

Case Studies for Managing CAPA


Two consecutive out-of-specification (OOS) results that
occurred with bulk product endotoxin testing:
The first OOS occurred with the batch manufactured in the week
of Jan 7, 2008.
The second OOS occurred with the batch manufactured in the
weekk off Jan
J 14,
14 2008
2008.

Cangene Corporation Fiscal 2011


www.cangene.com

49

Case Studies for Managing CAPA


Batch 1
Sample

Endotoxin (EU/mL)

Bacteria (CFU/mL)

Pooled plasma

<0.390

Post-primary UF

<0.780

Post-secondary UF

<0.390

Not tested

Post column
chromatography

<0 390
<0.390

Not tested

Post formulation

2.7

Bulk product
(post filtration)

2.3

Not tested

Cangene Corporation Fiscal 2011


www.cangene.com

50

25

11/22/2010

Case Studies for Managing CAPA


Batch 2
Sample

Endotoxin (EU/mL)

Bacteria

Pooled plasma

<0.039

0 CFU/mL

Cation exchange
chromatography

<0.039

0 CFU/mL

Anion exchange
chromatography

<0.390

0 CFU/mL

Post UF/DF

0.597

Not tested

Post formulation

2.21

0 CFU/mL

Bulk product
(post filtration)

2.38

0 CFU/100mL

Cangene Corporation Fiscal 2011


www.cangene.com

51

Case Studies for Managing CAPA


Batches are formulated with two components:
Polysorbate
Maltose
Further testing
confirmed Polysorbate no detectable endotoxin
Maltose
Suppliers
S
li lilimit:
it 1.0
1 0 EU/
EU/g
Initial release testing: <0.390 EU/g
Retain sample (retest): <0.390 EU/g
Resample (remaining drum): 1 2 EU/g
Cangene Corporation Fiscal 2011
www.cangene.com

52

26

11/22/2010

Case Studies for Managing CAPA


Container

Batch

Endotoxin (EU/mL)

0.1

0.042

0.1

0.185

0.169

0.2

0.3

06
0.6

2.3 [OOS]

2.4 [OOS]

Cangene Corporation Fiscal 2011


www.cangene.com

53

Case Studies for Managing CAPA


Interim conclusions
Maltose was the source of the endotoxin
Either we contaminated the maltose during storage
and handling, or
The maltose was contaminated by the supplier
Contamination was variable, non-uniform

Next step??
Cangene Corporation Fiscal 2011
www.cangene.com

54

27

11/22/2010

Case Studies for Managing CAPA


Contacted the supplier
Discussed the incident being investigated
Reviewed their process
Deviations?

Cangene Corporation Fiscal 2011


www.cangene.com

55

Case Studies for Managing CAPA

Deviations
Discovered that this batch had been reprocessed.

Cangene Corporation Fiscal 2011


www.cangene.com

56

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11/22/2010

Case Studies for Managing CAPA

Cangene Corporation Fiscal 2011


www.cangene.com

57

Case Studies for Managing CAPA


11 audit observations
Observation rating

Risk Response Level

2 critical

Level A

4 major
j

L
Level
lB

5 minor

Level C

Cangene Corporation Fiscal 2011


www.cangene.com

58

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11/22/2010

Case Studies for Managing CAPA


Define action levels
Level A: evaluation of effectiveness before receipt of
next lot.
Level B: evaluation of effectiveness within 6 months
Level C: evaluation of effectiveness at next scheduled
audit
dit

Cangene Corporation Fiscal 2011


www.cangene.com

59

Case Studies for Managing CAPA


Audit observations:
No evaluation of starting material quality before
reprocessing
Lack of adequate validation (process and cleaning)
Limited in-process
p
testing/
g heavy
y reliance on testing
g
of final product

Cangene Corporation Fiscal 2011


www.cangene.com

60

30

11/22/2010

Case Studies for Managing CAPA


Audit response
Finished product testing met specifications
No previous failures
Limited corrective action commitments

Cangene Corporation Fiscal 2011


www.cangene.com

61

Case Studies for Managing CAPA


Notes
We had used this supplier for 12 years with no
previous issues.
Ironically, we had switched to the suppliers low
endotoxin grade of maltose just over a year previous
to the incident. Basically, it was the same process,
same material, just certified to meet endotoxin
specifications [through additional testing].
Cangene Corporation Fiscal 2011
www.cangene.com

62

31

11/22/2010

Case Studies for Managing CAPA


Assessment
Looking for better controls at the point of production
Could not verify or validate effectiveness

Cangene Corporation Fiscal 2011


www.cangene.com

63

Case Studies for Managing CAPA


Depending on the nature of the procured
product/service, portions of the activities that are to be
performed under CAPA may be delegated by the
manufacturer to the supplier. The combined CAPA
related activities of both the manufacturer and the
supplier must satisfy the requirements of applicable
regulations and standards.

Cangene Corporation Fiscal 2011


www.cangene.com

64

32

11/22/2010

Case Studies for Managing CAPA


Combined CAPA related activities
Critical observations
related to high risk of endotoxin contamination during
manufacturing of subsequent lots

Critical observation = Level A evaluation


evaluation
l ti off effectiveness
ff ti
before
b f
receipt
i t off nextt lot
l t

Response adequate?
Implemented additional quality control testing.
Cangene Corporation Fiscal 2011
www.cangene.com

65

Case Studies for Managing CAPA


Responses to other significant (major)
observations
Evaluated during subsequent discussions with
supplier
Provision of evidence of completion
Additional follow-up during subsequent on-site audit

Cangene Corporation Fiscal 2011


www.cangene.com

66

33

11/22/2010

Interactive Exercise

Cangene Corporation Fiscal 2011


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67

Interactive Exercise
1.

Observation

2.

Your expected response

3.

Suppliers actual response

4.

Your evaluation of the suppliers response

5.

Audit Team evaluation of the response


p

6.

Action plan/ follow-up

Cangene Corporation Fiscal 2011


www.cangene.com

68

34

11/22/2010

Observation #1
The firm lacks a documented quality management
system.
Auditors were informed that the set of standard operating
procedures (SOPs) that exist are outdated are not used by the
organization. These SOPs were created in the 1990s as part of
an unsuccessful attempt to achieve ISO registration.
g
There are
multiple uncontrolled forms in use (i.e. for QC testing and
Assembly). The organization does not have a Quality Manual.

Cangene Corporation Fiscal 2011


www.cangene.com

69

Observation #1
What would be an adequate or appropriate response
from the supplier?

Cangene Corporation Fiscal 2011


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70

35

11/22/2010

Supplier Response
The lack of a documented quality management system
will be addressed by registering to the most current
ISO9001 standard. (target completion date: 7 months)

Cangene Corporation Fiscal 2011


www.cangene.com

71

Your Evaluation
Is the suppliers response adequate?
Does it address the observation?
What, if any, other factors would you consider in your
evaluation?

Cangene Corporation Fiscal 2011


www.cangene.com

72

36

11/22/2010

Audit Team Evaluation


Provide Supplier with Cangene expectations and
industry guidelines surrounding quality management
systems and manufacturing process controls.
Cangene to source alternate supplier(s) for these raw
materials.
Cangene
C
tto perform
f
a risk
i k assessmentt to
t determine
d t
i if
any other immediate actions are required.

Cangene Corporation Fiscal 2011


www.cangene.com

73

Audit Team Evaluation


Lead Auditor deemed [other] corrective actions within
their response to be unacceptable and concerns were
elevated to Supplier Quality Team. CAPA was initiated
to discontinue use of this supplier.

Cangene Corporation Fiscal 2011


www.cangene.com

74

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11/22/2010

Additional information
Supplier repackaged raw materials
No line clearance procedures
No documented/validated cleaning procedures for
common utensils/equipment
Repackaging
p
g g in unclassified/uncontrolled conditions

Cangene Corporation Fiscal 2011


www.cangene.com

75

Action plan/ follow-up


Interim steps/controls?

Cangene Corporation Fiscal 2011


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76

38

11/22/2010

Observation #2
Quality Control procedures are deficient in that investigation of Out
off Specification
S
ifi ti results
lt did nott follow
f ll
directives
di ti
outlined
tli d in
i the
th FDA
Guidance for Industry Investigating Out of Specification Test
Results for Pharmaceutical Production. Suppliers procedure for
Non Conforming Material is focused on detailed instructions
regarding disposition of nonconforming product without providing
sufficient
ffi i t information
i f
ti on investigation
i
ti ti off OOS results
lt and
d reporting
ti
of re-test results.

Cangene Corporation Fiscal 2011


www.cangene.com

77

Expected Response
What would you expect the supplier to address in their
response?

Cangene Corporation Fiscal 2011


www.cangene.com

78

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11/22/2010

Actual Response

[Supplier] is committed to provide product which meets specifications. We do not investigate out
of specifications results according to the "Control of Nonconforming Product" Procedure. As
required
i db
by thi
this procedure
d
, each
h outt off specification
ifi ti result
lt iis communicated
i t d tto th
the Ch
Chemistry
i t
Technical Support designate & authorized personnel. These personnel provide technical scrunity
for each questionable result. The Technical Support along with QC Management makes
decisions regarding retesting or resampling & retesting. The decisions are documented in the QC
records. All results are reported as required by QC procedure. This approach renders a very
good protection of product quality and good efficiency of the operations. We take into account out
of specification results very seriously. We monitor performance using a variety of metrics such as
1st pass quality. Metrics are presented & evaluated by Senior Management during Management
review As a result of the audit observation,
review.
observation the current system for OOS results was reviewed by
Management, and it was concluded that the current system is adequate for our operations and no
changes are required.

Cangene Corporation Fiscal 2011


www.cangene.com

79

Your Evaluation

Cangene Corporation Fiscal 2011


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80

40

11/22/2010

Audit Team Evaluation

Your commitments to resolution of OOS results through your NCR


procedure are appreciated.
p
pp
I would need only
y to confirm that yyour p
procedure
meets industry standards. Could you please summarize your approach to
handling OOS results:

rules for re-testing and re-sampling

rules for reporting the re-test results

approach to investigation of OOS root cause

timelines for closing the investigation

Alternatively please comment if your NCR procedure meets expectations


regarding handling OOS results as outlined in the FDA guidance document
Investigation of Out of Specification Test Results for Pharmaceutical
Production .

Cangene Corporation Fiscal 2011


www.cangene.com

81

Suppliers response
Our Quality Management System has been established
according to ISO 9001 requirements
requirements. We ensure & monitor the
compliance of our systems & processes through Surveillance &
Recertification ISO Audits, Internal Audits, and Management
Reviews. [Supplier] does not manufacture finished
Pharmaceutical products and is therefore not subject to the
FDA guidance. [Supplier] is solely a manufacturer of raw
materials.
t i l These
Th
materials
t i l do
d nott have
h
a specific
ifi intended
i t d d use
and are used in a variety of industries. Our Quality Management
Systems has established controls that govern our operations
and assures the quality or our products.
Cangene Corporation Fiscal 2011
www.cangene.com

82

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11/22/2010

Action plan/ follow-up


Next steps?
How would you close-out this observation?

Cangene Corporation Fiscal 2011


www.cangene.com

83

Observation #3

Routine surveillance audit scope included investigation of a significant


quality
q
y issue.
White tacky substance on vial exterior
1 major, 3 minor observations

Organization and maintenance of the warehouse for Raw Materials and


Finished Goods appeared deficient in that:
housekeeping practices appeared insufficient. Procedure and logs for warehouse
g and sanitization were not implemented
p
cleaning
packing trays in warehouse area were not stored as per written procedure. The
trays were not stored in an orderly fashion, a number of trays were not wrapped
in plastic foil, dust/dirt was collected on a number of trays, wiping of trays preand post-use in clean area was not documented in the Batch Record.

Cangene Corporation Fiscal 2011


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84

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11/22/2010

Expected response

Cangene Corporation Fiscal 2011


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85

Actual response

Cangene Corporation Fiscal 2011


www.cangene.com

86

43

11/22/2010

Your evaluation/action plan

Cangene Corporation Fiscal 2011


www.cangene.com

87

Action Plan
Lead auditor escalated to Supply Quality Team.
Supply Quality Team
Reviewed current relevant information
History of quality defects
Supplier responsiveness to quality issues/audit observations
Recent quality issues (cracked vials/overlaps) resulting in batch
rejection.

Scheduled a for cause audit

Cangene Corporation Fiscal 2011


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88

44

11/22/2010

Action Plan
Audit observations
1 critical - directly related to audit cause
6 major contributing factors leading to vial quality issues
1 minor

Cangene Corporation Fiscal 2011


www.cangene.com

89

Critical Observation

Vial lot was not manufactured in a state of control to ensure product quality and
conformity. Review of the manufacturing batch record revealed the following
deficiencies:

repeated observations of overlaps and minimum lip thickness defects. No


apparent investigation and/or corrective action for these issues.

QA Auditors gave at least six verbal warnings to Production of the defects (and
borderline passing vials) that they were seeing during consecutive QA Audits. No
documented investigation/corrective action.

The [[electronic]] inspection


p
system
y
which identifies such defects was not verified
prior to use as per [supplier] procedure.

The repeated overlaps defects noted in the Packing Production Report did not
trigger any re-work (re-inspection). Only the failure of the first QA Audit Lot, for
minimum lip thickness, resulted in re-inspection of the first six trays of the
manufactured lot.

Cangene Corporation Fiscal 2011


www.cangene.com

90

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11/22/2010

Your Evaluation/ action plan

Cangene Corporation Fiscal 2011


www.cangene.com

91

Supply Quality Team action plan


Escalated to Senior Management
Senior Management discussions with supplier
Recommended sourcing of new vial supplier
Action on remaining inventory from supplier

Cangene Corporation Fiscal 2011


www.cangene.com

92

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11/22/2010

Thank you!

Jeff Broadfoot
Director Quality Assurance
Director,
Cangene Corporation

Cangene Corporation Fiscal 2011


www.cangene.com

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