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GAMP®5 as a Suitable
Framework for Validation
of Electronic Document
Management Systems
‘On Premise’ and 'In the
Cloud'
Keith Williams
CEO GxPi
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2 www.diahome.org Drug Information Association
• Group founded in 1991 in the UK from life sciences manufacturing
(not called GAMP®)
• First GAMP® (Good Automated Manufacturing Practice) guide
published in 1994
• Partnered with ISPE (International Society for Pharmaceutical
Engineering) in 1994
• GAMP® 4 (2001) included a lot of detail in terms of checklists,
templates, proposed “V” model etc.
• Replaced by a Quality Risk Management approach in GAMP® 5
(2008) plus IT related best practice guides (2005-2012)
• It’s a guideline, not a “Regulation”, but still widely followed
http://www.ispe.org/gamp5
History and evolution of GAMP®
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Context Trend of EDMS over the last 15-20 Years-
Matching the Evolution of GAMP®
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COTS or Pre-
configured (OP and Hosted
EDMS)
Configured EDMS on platforms- still some development
(OP)
Mostly In-house developed EDMS or bespoke by supplier
(OP)
Validation approaches have had to adapt
to this change as more of the activities
transfer to ‘Outsourcing’ companies
(OP= ‘On-Premise’; Hosted may = Cloud)
1994
2002
2010
• In short, Yes it is suitable (otherwise this would be a short talk).
• It is a framework designed to ensure that computerised systems are
fit for purpose and compliant with current regulatory requirements
BUT
• It should be employed as part of, and alongside your Validation Master Plan (VMP)
• A specific Validation Plan (VP) should be produced for each GxP regulated system
• VP should focus on aspects related to patient safety, product quality and data
integrity
• You need to have a deep understanding of the underlying technologies that are being
employed in the Hosting of the Infrastructure, Platforms and Software applications
• You should leverage as much of the Suppliers’ expertise, testing and documentation
as possible (see examples later)
Can you Use GAMP® 5 for Validation of an EDMS for
‘On Premise’ and ‘Hosted in the Cloud’ deployment?
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Why is GAMP® 5 useful now?
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RISK ASSESSMENT AND OVERVIEW
OF TOOLS
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• High Level Risk Assessment – do you need to
validate at all?
• Functional Risk Assessment – where should you
focus your efforts in terms of documentation and
testing?
How can a risk based approach cut costs?
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Assessment- do you have a GxP Critical system?
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GAMP 5 Risk based approach at a functional level
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• Clear separation of Regulated Company and Supplier
Responsibilities
• Advice on managing the interface with suppliers, including
assessments / audits
• Full proposed set of documents, including “templates”
• Acknowledges differences between Information Systems and
computer-controlled “equipment”.
• Application of a Risk-based approach
• Categorisation of Software or Components
• Emphasis on the Validation Plan and Validation Report
• The end-result should be not just be an auditable set of documents,
but hopefully a computer system that does what it is meant to do!
What does GAMP 5 suggest?
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VALIDATION OF AN EDMS
‘ON-PREMISE’ VS ‘CLOUD’
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GAMP® 5 Compliance by adopting a life cycle
approach to Computerised Systems
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• Platform Hardware (Servers and clients)
• Server Software (Platform and Application)
• Client Software
• EDMS Processes (Process Owner)
• EDMS Community (People, SME, System
Owner- may also be Process Owner)
The Main Components of an EDMS that need to be
managed
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Cloud Computing -SaaS, Paas, Iaas,
• Cloud computing is a model for enabling ubiquitous, convenient, on-
demand network access to a shared pool of configurable computing
resources (e.g. networks, servers, storage, applications, and services) that
can be rapidly provisioned and released with minimal management effort or
service provider interaction.
• Software as a Service (SaaS). The capability provided to the consumer is
to use the provider’s applications running on a cloud infrastructure
• Platform as a Service (PaaS). The capability provided to the consumer is
to deploy onto the cloud infrastructure consumer-created or acquired
applications created using programming languages, libraries, services, and
tools supported by the provider.
• Infrastructure as a Service (IaaS). The capability provided to the
consumer is to provision processing, storage, networks, and other
fundamental computing resources where the consumer is able to deploy
and run arbitrary software, which can include operating systems and
applications
Some definitions of ‘Cloud’ and Hosting (outsourcing)
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Cloud-, Private, Public, Community, and Hybrid
• Private cloud: The cloud infrastructure is provisioned for exclusive use by a single
organization comprising multiple consumers (e.g., business units). It may be owned,
managed, and operated by the organization, a third party, or some combination of
them, and it may exist on or off premises.
• Public cloud: The cloud infrastructure is provisioned for open use by the general
public. It may be owned, managed, and operated by a business, academic, or
government organization, or some combination of them. It exists on the premises of
the cloud provider.
• Community cloud: The cloud infrastructure is provisioned for exclusive use by a
specific community of consumers from organizations that have shared concerns (e.g.,
mission, security requirements, policy, and compliance considerations). It may be
owned, managed, and operated by one or more of the organizations in the
community, a third party, or some combination of them, and it may exist on or off
premises.
• Hybrid cloud: The cloud infrastructure is a composition of two or more distinct cloud
infrastructures (private, community, or public) that remain unique entities, but are
bound together by standardized or proprietary technology that enables data and
application portability (e.g., cloud bursting for load balancing between clouds).
Some further definitions of ‘Cloud’ and Hosting
(outsourcing)
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• Infrastructure and OS are treated as GAMP® Category 1
whether On Premise or Hosted
• The EDMS will be 3 if it is Pre-configured and deployed
without any major changes (not likely)
• The EDMS will be 4 if it is configured
• Category 5 we won’t cover here but your Software
Application provider should have validated their core
product to this
GAMP® 5 Categories and what to do
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Service and Deployment models for On Premise and
Hosted and who controls and manages them
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Hybrid Clouds can be combinations of On-premise, Private or Public
Example Component Categorisation for EDMS Cloud
Implementation
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Service Components GAMP® Category
What to do? Who?
IaaS Hardware, Internet Connectivity, Power, Servers, Storage and RAM, VMWare, Hyper-V
1 Qualify and manage infrastructure. Audit procedures.
Infrastructure Vendor (IV). Application Vendor(AV) or Sponsor.
PaaS O/S, Windows Server, SharePoint and SQL
1 Qualify the stack. Manage / control ongoing changes. Audit procedures.
Platform Vendor (PV) PV. AV or Sponsor
SaaS e.g. Hosted EDMS 4 “Validate” the hosted application. URS and UAT
AV Sponsor
All the areas below will have difference between ‘On-
Premise and Hosted implementation
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For EDMS Projects, the supplier involvement varies
with ‘On-Premise’ or Hosted Variations in these areas
• Regulated Company handles everything in-house
• Owns and manages corporate IT infrastructure,
relying on in-house IT department
• Sets up and qualifies separate machines / platforms /
environments for informal development, formal testing
and for live use
• Audits the software supplier
• Validates the application / system
‘On Premise’ qualification and validation management
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• Regulated company uses private/public cloud-based
Software as a Service for submissible or inspectable
data
• Allows IaaS provider to manage infrastructure flexibly,
adjusting capacity and even location, as needed
• Relies on SaaS provider’s validation documentation
and testing of functionality
• Carries out minimal validation of software
configuration to meet basic user requirements
• Carries out audits of service providers
Hosted ‘Cloud’ qualification and validation
management
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EXAMPLE OF CATEGORY 4 EDMS
QUALIFICATION
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Area examined for a CAT4 EDMS example
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EDMS Projects, the supplier involvement varies with
‘On-Premise’ or Hosted Variations
EDMS CAT 4 DETAILED PLAN
EXAMPLE
Category 4- Configuration of the EDMS
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EDMS Cat 4: Project Activities, Deliverables and
Responsibilities Regulated Company and Supplier
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How could this breakdown into activities for a multi-
supplier Cloud delivery?
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Organisations: Activities:
Regulated Company
Software Developer
SaaS Provider
IaaS Provider
Validation Plan & Report
User Requirements & Acceptance Testing
Functional & Design Documentation
Installation Qualification
Incident Management
Infrastructure Qualification
Operational Change Control
Periodic Review
Note: Can use separate matrices for “Project” activities and “Ongoing Service”
• You can’t mitigate risks unless:
– You know what you are managing
– You know what the risks are
• Biggest problems with ‘Cloud’ are:
– Lack of understanding of what the ‘Cloud is’ (and is not!) and to what the
consistent terms are that apply to your company by Quality AND IT staff
– Lack of understanding of the enabling technologies, how they work and
interactions between them and other applications
• Suppliers Sell ‘Cloud’ services:
– Without understanding what the regulated company needs and where the risk is
– Without defining responsibilities
– Without appreciating and the cost of compliance the Life Science company
requires
*this is not unique to ‘Cloud’ suppliers, this is general outsourcing and Supplier management
misunderstanding, usually after the contracts have been signed by procurement and variations
occur
Summary of Compliance Risk Management in the
Cloud
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SOME PRACTICAL EXAMPLES
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Example 1
• Small Pharma Company (500 users) using on-premise
EDMS software for document management.
• Company keen to minimise IT costs so they set up their
server farm as virtual machines.
• Software supplier contractually responsible for software
Change Management, including regression testing.
• Software supplier using IaaS provider to host virtual test
environments, as part of the support provided.
Example 1: Lessons Learned
• Traditional ‘On-premise’ model project went to plan on
time and budget
• BUT; the capability to rapidly set-up an identical
“qualified” test environment greatly speeded up the
testing of an unrepeatable fault, the fix and then release
of controlled changes
• Good support from a specialised IaaS provider, keen to
explore ways of supporting Pharma clients
• Qualification of new virtual environments can also be
greatly speeded up, via use of executable scripts to
install the relevant files and to confirm that the
installation meets specifications
Example 2
• New “virtual” Pharma company using hosted SaaS for
electronic document management.
• The Software Product is highly configurable (as distinct
from customisable) to meet client business requirements
• Specialised software application / SaaS provider with
auditable development documentation ready for Pharma
clients.
• Extensive auditing carried out by Pharma Company-
leveraged the document set and experince of the
supplier
• Separate IaaS provider used for actual hosting, audited
by the SaaS provider
Example 2 : Lessons Learned
• Niche service providers do understand needs of Pharma
Clients, and expect to be audited ‘hard’ as part of
supplier selection
• SaaS provider can take on responsibility to audit and
manage the IaaS provider, including Infrastructure and
Installation Qualification and that can be audited by
Pharma Company.
• Suppliers need to be pragmatic when faced with multiple
opinions on compliance details from different clients-
make sure that they have a robust but cost effective
system
• Configuration of the application needs to be managed
carefully by the SaaS provider, with maximum input from
actual users
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WHAT THE REGULATORS HAVE SAID
ABOUT CLOUD USAGE THIS YEAR
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• That the Integrity of the Data is assured – Risks have been clearly identified & mitigated
– Client/Provider Contracts cover off key elements
– Supplier Quality Systems are adequate
• QMS, validation, change control, training
– Cybersecurity has been tested (ethical hacking?)
– Data Backup/Recovery processes are robust and fit
for requirements
– Evidence of Audits of Providers by FDA/ other Clients
What are regulators interested in
when they discover IT is ‘in the Cloud’?
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• GAMP 5 is widely used and referenced in our
Industry
• It can help both Suppliers and Users of EDMS
• It can be applied to both on-premise and hosted
environments
• I would advocate closer ties with DIA and ISPE so
experiences and guidance can be shared and
knowledge built
SUMMARY
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• Phil Harrison of GXPi
• Thana Subramanian of GE
• Randy Perez of Novartis (and Chair of ISPE)
• David Stokes of Business Decision
• ISPE for use of GAMP® material
• Fujitsu
Thanks for material and thoughts contributing to this
presentation go to:
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Thanks for listening!!
Keith Williams ([email protected] )
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REFERENCE MATERIAL
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• Operation of GxP Computerized Systems (2010) – Regulators usually focus on the integrity, consistency, and completeness of controls required
to maintain compliance.
– Highlights the importance of the operation phase of the system lifecycle
– When the return on investment for the significant time and resource expended in
implementing new computerized systems can be achieved.
• IT Infrastructure Control & Compliance Guide – The validated status of EDMS applications that are dependent upon an underlying IT
Infrastructure
– Being updated for ‘Cloud’ elements
– ID and assessment of components
– Qualification
– Maintenance of the Qualified State
Other Resources- Best Practice Guides
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• Testing of GxP Systems (2012) – Very Process and prescriptive Driven (around 200 pages)
– Helps maximize testing efficiency without compromising the quality of GxP Systems
– focusing testing on areas that have the greatest impact
– has been recently expanded and updated and reflects ICH Q8, Q9, and Q10
– contains new information on Cloud computing
• Global Information Systems Control & Compliance (2005) – Project Management on multiple geographic site Computer system projects
– Validation and Implementation approaches
– Global System management of Change Control
– Record retention
Other Resources- Best Practice Guides
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• GAMP 5: http://www.ispe.org/gamp-5
• NIST: http://www.nist.gov/itl/cloud/index.cfm
• ICH: http://www.ich.org/
• Annex 11:http://ec.europa.eu/health/files/eudralex/vol-4/annex11_01-
2011_en.pdf
• 21CFR Part11:
http://www.fda.gov/RegulatoryInformation/Guidances/ucm125067.htm
• GAMP Community of Practice: http://www.ispe.org/gampcop
Useful References
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How Risk Management ICH maps to GAMP® 5
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• Has had a lot of thought gone into it in a pragmatic way
• Is process driven and risk based so you can use the framework to
do as much or as little as you see fit
• Gives you the latitude to do what is necessary for your business and
allocate appropriate resource
• Establishes a common language and terminology (BUT see ‘Cloud’
terms for further confusion)
• Has been harmonised where possible with other standards such as
ICH Q8, Q9 and Q10 and various ISO standards
• Is designed to be compatible with other computer and software
models and methods like ITIL, RUP etc.
• The validation of a computerised system to achieve and maintain
GxP compliance throughout the lifecycle of that system
• It clarifies scalability of and central role of Quality Risk Management
in a sensible justifiable approach to what you do (but document it!!)
The Advantages of using GAMP® 5
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• May not fit well to your existing Quality process
• Comes from a Manufacturing/Production bias
• So there may be a feeling of ‘it doesn’t apply to me’
• Terminology and nomenclature may be different
• Less prescriptive than previous GAMP® iterations
• The risk based approach requires complete product, process and
technology understanding
• This in turn means you have to understand deeply the technologies
being employed and their quality impact, and/or employ or pay for
Subject Matter Experts (SMEs)
• For Hosting situations, you will require (and may have to educate)
your Supplier to manage their QMS and activities in a way
commensurate with GAMP® (see next slide)
• Cost- perceived and otherwise, but mostly getting everyone on the
same page and with agreed nomenclature
The Disadvantages of using GAMP® 5
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• Minimise the risk that something goes wrong with the end
customer’s health and safety
• Keep the regulators confident in your business and prevent them
issuing restrictions and actions against you (note: they require to
see documented evidence in Human Readable format)
BUT
• Cost of compliance adds to cost of doing things and ultimately cost
of goods (which we want to reduce)
• Computer System Validation (and GAMP®) was traditionally
associated with extra workload and greatly increased costs of
compliance
Just a reflection on why we bother to validate?
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• Change control: Sometimes even minor software tweaks or patching,
whether necessary or not, can cause major breakdown. The rigour of
change management, impact assessment and testing adds to the work
burden and short term cost (and is one that the supplier may not be used to)
• QMS: Infrastructure suppliers may prefer not to work within the confines of
specifications and procedures developed by others (Pharma Sector). If you
are going to rely on suppliers, they may not want to bear the cost of
implementing a formal QMS that will tick all of your requirements, especially
the ‘cloud’ providers who have many other customers
• Documentation: Effective documentation management is fundamental to
demonstrate compliance, again suppliers may not be able to manage this,
or their training records, auditing of their suppliers etc.
Challenges of imposing GAMP® 5 on Suppliers of
Hosted Services for the Life Sciences sector
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Minimum
• Documents and schematics that are understandable by the non-expert
• They manage change in an acceptable manner
• They have clear contracts and allocation of responsibilities
• They have been audited by other regulated companies
• They audit their suppliers
• Suitable test scripts for their environment to prove security and data integrity
Ideally
• They have detailed experience of the compliance needs of the Life Sciences industry
and tools to aid and ensure that compliance is achieved efficiently
• They have validation documents of a suitable quality that allows you to leverage,
using risk-based approach to reduce your validation effort
• They can clearly communicate and educate complex technology environments to
your team so they can understand the operation and design elements
• They have been audited by other Life Sciences companies
• They have a robust and suitable QMS that matches Life Sciences industry
expectations
• They have adequate Subject Matter Experts that span IT technical and compliance
Some things to look for in a Supplier to ease the
implementation of a Cloud EDMS
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