5th International Working Conference ’’ Total Quality Management’’ , 1st- 4th June, 2009, Belgrade.

Integrated Management Systems in the Pharmaceutical Company

“ZDRAVLJE- Actavis”

Ass. Prof. Dr Valentina Marinkovic,

Quality Department, ‘ZDRAVLJE- Actavis”, 16000 Leskovac, Serbia

UDC:

Abstract: The front-runner companies in pharmaceutical world industry are moving towards a more
sustainable management of their production and products. The traditional management focus on GMP
has been extended with other aspects and standards, such as ISO 9001, ISO 14001, BS 25999, SA
8000, OHSAS 18001. Up till recently there has been a major difference between especially the quality
and the environmental standards, when it comes to underlying understanding of organizations.
However, since the new version of ISO 9000:2000 the similarities have increased regarding the core
aspect of management. Also, after adoption of ICH guidance Q 10, GMP and ISO 9000 are under the
same roof.
This paper discusses the development of standard for Integrated Management Systems as well as
organisational and auditing challenges with IMS in the pharmaceutical company ZDRAVLJE- Actavis
group.

Keywords: Integration, Management Systems, Pharmaceutical Industry

1. INTRODUCTION developed to improve the coherence with ISO

For pharmaceutical Industries, implementation
of GMP regulations is “do or dye” fact,
because of legal and regulatory requirements.
Liability in connection with quality,
environmental, occupational health and safety
and social accountability is increasingly
important for the company image. In the same
time, we have the new standards for business
continuity management and risk management
to support the company to survive in tough
economic environment.
By having certified management systems
covering these areas, the companies give a
signal of liability and concern for stakeholder
relation.
With the revision and new editions of the
different standards for management systems,
the systems have an increased number of
similarities (Jorgensen, T.H., 2002). Although
a standard for an Integrated Management
Systems is still absent in ISO, the following
initiatives are promoting the integration:
ISO 9001:2000 have more focus on continuous
improvements, being one of the foundations of
the environmental as well as the health and
safety management systems.
9001:2000.
The connection between EMAS (published in
year 2000) and ISO 14001 is made clear
(Jorgensen T.H., et al., 2004).
OHSAS 18001 is developed to be compatible
with ISO 9000:1994 and ISO 14001:1996.
SA 8000 can be combined with ISO 9001:
2000, ISO 14001: 1996 and OHSAS 18001.
ICH Q 10 is developed to be integration of
GMP and ISO 90001 and it will be Annex 21
of EU GMP .
ISO 31000 and ICH Q9 (Annex 20 EU GMP)
have the similar framework of implementation.
PAS 99:2006 presents the BSI guideline for
integration QMS, EMS, OHSAS, ISO/TEC
20000, ISO 22000 and ISO/TEC 27001, using
the common principles and elements.
- policy,
- planning,
- operation,
- performances,
- improvements,
- management review.

The new edition of ISO 14001 has been

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 5th International Working Conference ’’ Total Quality Management’’ , 1st- 4th June, 2009, Belgrade.
The main reason for integration of
management systems in ZDRAVLJE –Actavis
Company are:
- Documentation control, as well as
minimization of records and
documents.
- Cost saving by optimization of time
and resources assigned to the systems.
- More focus on interrelations as well as
synergies.
In this paper the integration model (case study-
ZDRAVLJE- Actavis) is presented with the
key elements and tools for following
management systems:
• QMS (ISO 9001 and GMP)
• EHS (ISO 14001 and OHSAS
18001)
• BCM (BS 25999)
• Codex Alimentarius
(HACCP)
• CE mark (ISO 13485)
Presented model is capable for further
integrations:
• Social accountability (SA 8000)
• Information security (ISO/IEC 27001)
• Risk management (ISO 31000)
• Laboratory accreditation (ISO 17025)
2. INTEGRATION ELEMENTS
There are a number of differences between the
six management systems, as well as several
similarities, where it is sufficient to handle the
different areas in the same way (Shaw, O.,
2003; Matias et al., 2004).
The similarities between these management
systems are the key elements of integration:
1. Top management commitment
2. Documentation and records control
3. Planning of objectives and Key
Performance Indicators (KPI)
4. CAPA(corrective action preventive
action) and CACI (corrective action
continuous improvement) system
5. Training procedures
6. Audits
7. Management review
It also follows the Plan, Do, Check, Act,
approach of all the major management systems
requirements standards (Wilkinson, G et al.,
2002; Majstorovic, V.D., 2008)
Pharmaceutical Industry ZDRAVLJE a.d.
is the third largest producer of pharmaceutical
products in Serbia. ZDRAVLJE a.d. was
founded in 1953. In January 2003,
ZDRAVLJE was privatized by Pharmaco
(Iceland), which changed its name to Actavis
in May 2004. Since then, ZDRAVLJE a.d. has
been operating as a member of Actavis Group.
The main challenge in one multinational
companies was two levels of integration:
• Corrporate (group) level
• Local (company) level
First phase of management systems integration
on the corporate level was done in 2005 by
integration of quality standards- GMP and ISO
9001, EHS standards- ISO 14001 and OHSAS
18001 trough the Corporate Manual. We
integrated top management commitment,
documentation and training.
It was the framework of integration for all
other management systems.
Second phase of integration was planing,
monitoring and review of objectives and
KPSIs (in 2006), trough approved templaits
and reviewing process on corporate and
company level.
Third phase of integration was establishing of
CAPA register and continuouise improvement
process in ZDRAVLJE level (in 2008).
Steps forward will be common internal audits
(plan for 2009) and certification of integrated
management systems: ISO 9001, ISO 14001
and OHSAS 18001.
2. 1. Top management commitment
The main document on the corrporate level is
the Corporate Manual that describes key
principles of management system.
A management system is a proven framework
for managing and continually improving the
organization's policies, procedures and
processes.
The best businesses work as complete units
with a shared vision. This may encompass
information sharing, benchmarking, team
working and working to the highest quality and
environmental principles.
A management system helps the organization
to achieve these goals through a number of
strategies, including process optimization,
management focus and disciplined
management thinking.
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 5th International Working Conference ’’ Total Quality Management’’ , 1st- 4th June, 2009, Belgrade.

Implementing the Corporate Manual, all - annual „kick off“ meetings,

Actavis leaders committed that they would - company newspaper,
follow quality and EHS principles and all - internal web site.
standards related to these principles.
Comunicatation of the mission and policy in 2.2. Documentation and records control
Actavis, first class generic company is
mitigated to all employees (cca 11 0000) Structure of Corporate Manual is preseted in
through: the Figure 1.

Quality & Corporate

EHS Mission Quality &
EHS Systems
Corporate Policies

Corporate General Procedures

Company Quality Company Standard Corporate Directives

Operating Procedures and Guidelines
and EHS Systems

Company Confirmation Corporate Templates

Sheets/Templates

Figure 1 – Integration of documentation – corporate and company levels

Corporate level documents are policies, - Quality Manual

general procedures, directives and guidelines.
Templates for all documents, as well as
approval matrix is also defined on corporate
level. Corporate documentation gives the basic
principle of GMP, ISO 9001, ISO 14001,
18001 and BCM. Documentation Management
is in accordance of Change Control Procedure .
Certification of relevant standards has to
be performed on the company level. So, each
company within the group has own
documentation system. Standard Operation
Procedure (SOPs) , records and confirmation
sheets describes process details and
responsibilities in the company.
In ZDRAVLJE , all documents should be
finally authorized by QA manager, but also
reviewed by EHS manager.
Current status in ZDRAVLJE is:
- EHS Manual
- 25 Master Plans and programs
- 879 SOPs
- 1023 Records
Intention and Plan for 2009 is to put
together quality and EHS issues under one
roof- Company Manual.
2.3. Training procedures
Training of employees is defined on
corporate (Procedure) and company level
(SOPs).
Annual training plan has to be approved by
local Quality and EHS Board..
Induction training for new employee and
trainings for contractors and visitors are also
documented.

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 5th International Working Conference ’’ Total Quality Management’’ , 1st- 4th June, 2009, Belgrade.

2.4. Planning of objectives and and regulatory requirements, as well as

Key Performance Indicators (KPI) financial, operational and business
possibilities.
Each year, Corporate Management Board
gives the main objectives and key Corporate, company and personal objectives
performances indicators according the core have to be in correlation.
corporate values, technological capacity, legal

OBJECTIVES KPIs
IDENTIFICATION -Per 4 ma

REPORTING
- Corporate Quality and EHS
OBJECTIVES MONITORING
- Local management teams

Quality and EHS Board

Meetings
OBJECTIVES REVIEW

Figure 2. Continuous improvement process

Responsibilities, activities and due dates 2.4. Management review

are documented.
Corporate and company objectives are
stated in Annual Plans, but objectives of
each employee is stated in separate record-
per 4ma (Fig 2).
2.3. CAPA system and continuous
improvement process.
The consequence of non conformance
and deviations is appropriate corrective
action plan. In ZDRAVLJE-Actavis, all
corrective and prevention actions are
documented in CAPA register.
CAPA register is periodically monitored
by management on local Quality & EHS
Board.
Through CAPA system, company
management can monitor and review the
objectives. It is part of continuous
improvement process (Fig. 2).
Reporting of KPIs is in the same time
monitoring of objectives.
If sometimes KPIs are not achieved, it
raises non conformance report and defined
new corrective and preventive actions
plan.
Quality & EHS Board, consisted of key
top management members, makes decision
about objection revision, as well as
continuous improvement objections.
3. INTEGRATION TOOLS
The powerful integration tools to build the
robust management systems are:
- knowledge management (KM) and
- risk management (RM)

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 5th International Working Conference ’’ Total Quality Management’’ , 1st- 4th June, 2009, Belgrade.
To achive business objectives, the knowledge
management and risk management are the
main enablers (ICH Q 10).
Decision making process needs the risk based
approach.
KM is sistematic approach to collect,
analysing, keeping and explore information
conected with product, processes and
component. The source of knowledge icluded,
former knowledge, pharmaceutical
development study, transfer technology
activities, validation of procesess through the
product lifecycle, production expirience,
continual improvement and change
management.
Risk management (RM) might assure
proactive approach in identification and
controling potential risk for quality through
product lifecycle, enviromental and
occupational health and safety of employees.
ICH Q9 describes the model of RM in context
of pharmaceuticals.
4. CONCLUSION
At the moment several national
standardisation organisations in Europe (PAS
99, BCI, 2006; ISO Guide 72, 2002) are
developing their own standards and guidelines
for an integrated management system, mainly
because their clients are demanding an
integrated response to the different
responsibilities- product quality, environment,
health and safety etc.
A company has to decide the degree of
integration (alignment or integration).
ZDRAVLJE ad, as a part of multinational
Actavis group built the own, robust model of
management systems integration
Change of organizational culture was the first
and main challenge. Integration process is on
going process. Key elements – top
management commitment, documentation,
CAPA system, training; objective planning and
management review are integrated.
Benefits of this integration are:
- Costs reduction,
- Bureaucracy and resource optimization
- Decrease of conflict between systems,
- Improvement of internal and external
communication,
- Increase of business focus
- Save of management time and
- Holistic approach to manage the
business risks.
Internal audits and certification, according
different management systems are still separate
issues and challenge for next years. Reason of
that is very slow change in certification bodies
and regulatory authority’s approach and
expectation.
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