Level 2 Audit Report GMS Quality - Audit Report 03/09 for GSK QMS Audit of Soft Gelatin& Wets Value stream Date of Inspection:23-26 March 2009 Auditee Details Lead Auditor Details Site Location GlaxoSmithKline Egypt P.O. Box 3001-El Salam City 11491 Cairo – Egypt Lead Auditor Helmy Ismail Compliance auditor E-mail: [email protected]Tel : +2 02 22777126 Main Contact Dr:Elhamy Kamal Report Distribution Complete Report Eng.Adel Darwish Site director Dr:Hanan Lamei Head of Quality Dr: Eman Hegazy Compliance manager Dr:Elhamy Kamal Wets &Cephs SLT Eng. Khaled Gheith Engineering SLT Dr.Sahar Awwad Technical senior manager & OE Champion Mrs.Aya Dwidar Head of HR &Security Dr. Abdelmoneim A AbuYoussef Solid SLT 1
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The QMS implementation system in Soft gelatin department is in place and in use, the manufacturing
and packaging areas look tidy with good housekeeping. Three risks identified in the risk log {(SG04)
Liability of cross contamination in SG area, (SG 05) Medicine contamination and (SG08) Failure of the
pressure difference in SG area were disclosed and managed.
-The L4 CAPAs for Ukraine and MOH were closed effectively on time. The previous L2 audit findings
related to the above mentioned departments were reviewed and closed effectively.
During this audit there were 7 finding 3 of them were considered to be major.
The major findings related to The Facility operation, Air quality and Calibration.
The risk associated with the major findings as follows:
1-Deterioration in utilities maintenance that increases the possibilities of particulate cross contamination.
Inadequate physical contamination control due to presence of particulate shedding material in the
manufacturing area. Incomplete check of the cleaning record to ensure the effectiveness of the
cleaning procedure.
2- Lack of assurance that air of correct particulate quality is supplied to SG manufacturing area to
protect product from environmental contamination.
3- There is no document highlighting the product quality impact in case of instrument calibration failure
or instrument defect.
In conclusion:
According to the L2 local procedure and the criticality of area:
-The overall risk of soft Gelatin department is a moderate risk and it is recommended to keep the audit
frequency to be every 9 months.
-The overall risk of wets area is a high risk and it is recommended keeping the audit frequency to be
every 6 months to ensure the complete and effective closure of the raised risk.
1.2 Recommendation of Audit Frequency
Current Audit Frequency:
6 months
Decrease to
Remain
Audit Frequency:
9 months for SG
6 months for wets
Background information
2.1 Pharmaceutical Product Dosage Forms
2
Sterile Products Inhaled Products Other Dosage Form √
2.2 Markets Supplied
US √ EU JP AU CN Other:
2.3 Date of Last Audit
August 2008
* * * * * End of Executive Summary * * * * *
3
Audit Background
Introduction:
GSK Cairo is aiming to implement Quality Management System as
standard for internal audit level 2 for all systems.
The previous L2 audit conducted on August 08 , Based on the overall
risk assessment of the auditee profile . The Soft gelatin was considered
as a moderate risk and the Wets department was considered as a high
risk ,according to the number of rejected batches ,rework due to quality
issues ,numbers of complaints received during 2008 and the number of
major findings of the previous audit levels.
Objective:
The audit was to evaluate the level of compliance of systems compliance against QMS policies in respect to risk assessments, identified gaps and areas for improvement highlighted through the last GQA as well as the last L2 audit .
Scope:
The audit primarily focused on the activities and systems involved in the Soft gelatin, wets and semisolid including manufacturing and packaging at Cairo site facility. The audit also assessed the identification and management of risk and the effectiveness of total disclosure of the previous audit findings.
Audit team:
Salwa Tolba Compliance auditor
Auditee:
Dr:Mohab Elmasry Soft gelatin section head
Dr: Ahmed Samir Wets departmental head
Dr: Dalia Samy Senior validation coordinator
Dr:Ahmed Abdel Raouf Validation section head
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Classification of Audit Findings
5
Audit Findings Classifications
Dependent on the nature of the findings and the risk associated with any non-
compliance the following classifications should be used:
Classification Description of Classification Action to be Taken
Critical Deficiencies which have a high
probability of causing adverse
consequences to the patient or
consumer; may result in
significant deviations in the safety,
identity, strength or purity of the
product; or are a combination of
major deficiencies which indicates
a critical system failure.
The auditor is to define which
operations, or supply to GSK,
must stop until corrective and
preventive actions (CAPAs) are
implemented.
Major Deficiencies which could
potentially cause adverse
consequences to the patient or
consumer if left un-addressed,
could be considered indicative of
poor control, could be considered
major deviations by regulatory
authorities, or a combination of
minor deficiencies which indicate
a major systems failure, or a
number of repetitive minor
deficiencies.
CAPAs are to be agreed although
operations can proceed.
Minor A deficiency which cannot be
classified as critical or major.
CAPAs are to be agreed although
operations can proceed.
Note A deficiency, which is not related
to GMP or regulatory
conformance requirements e.g.
Environmental Health and Safety,
but does warrant attention by the
auditee.
CAPAs do not need to be agreed
with the lead auditor.
6
Good
Practice
Demonstration of exemplary
achievement of compliance, or
setting a precedent within the
current industry standard.
7
Categorisation of Audit Findings
Audit Findings Classifications
Dependent on the nature of the findings and the risk associated with any non-
compliance the following categorisations should be used:
Disclosed and
Managed
• The scope of the risk has been defined.
• The root cause(s) have been identified.
• A solution specification is in place.
• Remedial, corrective and preventive actions have been
identified.
• The actions are assessed as effective to address the root
cause i.e. the auditor believes that the plans will reduce the
risk.
• Actions have owners and target dates.
• The status of the plan is monitored routinely.
• Actions will reduce the risk in an acceptable timeframe and
are progressing to schedule.
• There is a process to assess the impact of any changes to
the plan (including date extensions) and approve those
changes.
Disclosed and
Incompletely
Managed
• The scope of the risk has not been defined.
• The root cause(s) have not been identified.
• A solution specification is not in place.
• Remedial, corrective and preventive actions have not been
identified.
• The actions are not assessed as effective to address the root
cause i.e. the auditor believes that the plans will reduce the
risk.
• Actions do not have owners and target dates.
• The status of the plan is not monitored routinely.
• Actions will not reduce the risk in an acceptable timeframe
and are not progressing to schedule.
• There is no process to assess the impact of any changes to
the plan (including date extensions) and approve those
changes.
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Audit Identified Issues identified during the audit.
9
Findings
Audited System: Management
The self inspection GQP No. (1211) was reviewed. During this audit the self
inspection reports dated on 11/2/2009 &25/1/2009 for SG and wets were
reviewed.
FindingClassification: Audit identified-
Note
Reference:
[ GQP1202]
Risk management :
-During 2008 there were 13 complaints related to oily and leaked capsules and one rework for re-
insertion of Supravit capsule B.N 080858A due to capsule leakage. The risk log of S.G department
has a green risk No.SG 02 dated on 8 July 2007,it has been described as (Leakage of S.G
capsules after quality release) with risk index value 4.
By discussion with the area owner it was noticed that those complaints related to batches were
manufactured during 2006 and many CCRs were raised to solve this problem .
-There is no document for risk revaluation and monitoring of the after action review to ensure that
the previously taken corrective actions are effectively implemented and they are sufficient to
prevent the recurrence of this deviation in the future and reassess the likelihood value of this risk .
Response of Auditee
CAPA Details Due Date: [Date for latest completion of all actions required by this CAPA]
[Enter key aspects of CAPA with sufficient detail to establish that all aspects of the observations
will be addressed sufficiently to achieve compliance].
FindingClassification: Audit identified-
Minor
Reference:
GQP1211
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Self inspection :
In complete CAPA management system of Level one audit .There are many overdue CAPA s
and delay in the target completion dates
-The CAPA identified in the level 1 audit doesn’t perform in its due date. There was a delay in
IQ&OQ of balance of soft gelatine department. Many work orders were initiated related to epoxy
work, fixation of backstop in soft gelatin but no further progress has been done.
-The self inspection of soft gelatin& wets department mentioned that the calibration of equipment
were reviewed and confirmed while there were many defected devices have no label indicated its
status ( out of use and not calibrated) as recommended inQD574/08.the defected device such as
(the defected temperature indicator of the Diessel tank , the dial thermometer of Diessel holding
tank 3000 l in wets area )& (Stirrer RPM indicator and rotational speed indicator in S.G
department)without label (not calibrated ) .
-In self inspection report of wets area there was an observation related to creation of Arabic
version of SOP without mentioning the SOP number and the target completion date which
required for effective follow up and CAPA closure.
Response of Auditee
CAPA Details Due Date: [Date for latest completion of all actions required by this CAPA]
[Enter key aspects of CAPA with sufficient detail to establish that all aspects of the observations
will be addressed sufficiently to achieve compliance].
Audited System: Personnel
This clause was not covered during this audit.
Audited System: Documentation
GQP3201 Was reviewed
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Finding Classification: Audit identified- Minor Reference:
[ GQP321
Documents and Data :life –cycle management.
-The log book of IWKA drops packaging machine ( ), had detached papers of APP II of SOP No.
GP 002/01.the log book was not identified by page numerical numbers. Some records missed the
machine name.
-This machine used in packaging of Amproxol drops that exported to EU market. The Machine
data and documentations must comply with the packaging process requirements and provide the
correct information that could be used during problem investigation.
- Incomplete distribution system of electronic SOP was noticed for engineering procedures. The
SOPs hard copies are distributed and controlled by quality department while the electronic
versions were archived in connectware named GMS sops that had an obsolete version of SOP
Number EP 317/07.
Recommendation :
-Effective documentation system must be implemented for drops packaging machine.
-The electronic versions of SOP s must be reviewed and ensure that the current procedures are
available to be used by all authorized users
Response of Auditee
CAPA Details Due Date: [Date for latest completion of all actions required by this CAPA]
[Enter key aspects of CAPA with sufficient detail to establish that all aspects of the observations
will be addressed sufficiently to achieve compliance].
Audited System: Facilities
The following systems were reviewed during this audit.
Facility design (GQP 4201), Air quality (GQP 4204), Compressed gas systems (GQP4206),
Vacuum system (GQP 4210), Facility operation (GQP4301), Calibration (GQP 4304) and
Monitoring and review of environmental controls and utilities environmental (GQP 4401).
-The L4 CAPA for MOH and Ukraine audits were reviewed and closed on time. The air lock
alarms have been installed in soft gelatine and wets area. The status of manufacturing
processes was identified & all rooms had their unique identification numbers.
-The CAPA related to finding number FND-L3-0096034 of L3 GQA audit 2008 was reviewed
and it is ongoing and planned to complete on time to dedicate a storage area for bulk soft
gelatine capsules.
-The CAPA for the previous level two audit were reviewed
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Finding Classification: Audit identified- Minor Reference:
[ GQP321
Documents and Data :life –cycle management.
-The log book of IWKA drops packaging machine ( ), had detached papers of APP II of SOP No.
GP 002/01.the log book was not identified by page numerical numbers. Some records missed the
machine name.
-This machine used in packaging of Amproxol drops that exported to EU market. The Machine
data and documentations must comply with the packaging process requirements and provide the
correct information that could be used during problem investigation.
- Incomplete distribution system of electronic SOP was noticed for engineering procedures. The
SOPs hard copies are distributed and controlled by quality department while the electronic
versions were archived in connectware named GMS sops that had an obsolete version of SOP
Number EP 317/07.
Recommendation :
-Effective documentation system must be implemented for drops packaging machine.
-The electronic versions of SOP s must be reviewed and ensure that the current procedures are
available to be used by all authorized users
Response of Auditee
CAPA Details Due Date: [Date for latest completion of all actions required by this CAPA]
[Enter key aspects of CAPA with sufficient detail to establish that all aspects of the observations
will be addressed sufficiently to achieve compliance].
Audited System: Facilities
The following systems were reviewed during this audit.
Facility design (GQP 4201), Air quality (GQP 4204), Compressed gas systems (GQP4206),
Vacuum system (GQP 4210), Facility operation (GQP4301), Calibration (GQP 4304) and
Monitoring and review of environmental controls and utilities environmental (GQP 4401).
-The L4 CAPA for MOH and Ukraine audits were reviewed and closed on time. The air lock
alarms have been installed in soft gelatine and wets area. The status of manufacturing
processes was identified & all rooms had their unique identification numbers.
-The CAPA related to finding number FND-L3-0096034 of L3 GQA audit 2008 was reviewed
and it is ongoing and planned to complete on time to dedicate a storage area for bulk soft
gelatine capsules.
-The CAPA for the previous level two audit were reviewed
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• The risk of finding was described as (lack of assurance that product
quality is not compromised due to the required arrangement for
facilities) ,the CAPA was effectively closed . The batch records of Haemoton
& Supravit capsules have been updated to include the microscope for the
IPC test that has the plant No.1268.
• The risk of finding has been described as (Risk of possibility of product
contamination due to unsuitability of level of control on operations )In
the Soft Gelatin department all the cleaning equipment, holding containers
were labeled and had its identification label.
• The risk of finding has been described as (Risk of lack of assurance that
existing controls establish a base line of local environmental isolate )
the CAPA was closed ,the identification reports of non sterile areas and one
identification report for atypical result of iron oxide raw material were
reviewed and found satisfactory & comply with the GQP 4401 and CAP 044.
-The cleaning records of soft gelatine department were revised refer to SOPs No SG
103/04,SG 112/04,SG 104/08 and SG 105/04 and were found satisfactory , during this audit
the soft gelatin department had a good house keeping and looked clean and tidy .
-During this audit the compressed gases monitoring results for soft gelatine and wets
departments were reviewed refer to SOP EP350/01&QD 583/05and found comply with the
GQP 4206.
-The microbiological environmental monitoring of wets and soft gelatine results were reviewed
.refer to SOP QD 583/05 and found satisfactory.
-The vacuum system for soft gelatine and wets area are dedicated and not shared.The risk
number SG05 in the risk log (Medicine contamination in case of electricity cut off was
disclosed and managed by installing double non return valve and water trap for the medicine
mixing vessel.
The previous L2 audit finding related to the air quality of wets area was closed and the
particulate air count for 0.5 micron were taken and the records dated on 7/5/2008 were
reviewed and found comply with the GQP4204.by reviewing the Sop EP 317/08 the
particulate count for 0.5 micron or greater was performed .