Management of GMP
Documentation
The Overview
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General Aspects and Requirements
Types of GMP Documentation
Purposes of GMP Documentation
The Structure of Document Management
Evaluation of the Documentation System
The Document Management Cycle
Some Remarks at the
Beginning
• GMP documentation is one critical aspect of our
business and it is a legal requirement too!
• Inspection or audit observations frequently identify
outdated documents, inadequate version control,
and poor documentation practices
• As the Quality Unit is responsible for designing
and operating the GMP documentation systems on
site, such audit observations reflect on QA either
directly or indirectly.
What are the Definitions ?
• GMP Documentation can be defined as:
Any procedure, instruction, logbook, record, raw
data, manual, or policy associated with the
development, manufacture, testing, marketing,
and distribution of a medicinal product required to
demonstrate compliance with the GMPs and other
regulatory requirements
• Or more shortly:
A GMP document is any written record associated
with the manufacture, control and distribution of
the API or pharmaceutical product.
What are the Responsibilities ?
• The site Quality Manager is responsible for
ensuring that:
• the systems to manage and control GMP
documentation are available and comply with GMP
requirements
• all GMP documents in the documentation
management system are in compliance with the
regulatory files and GMP requirements.
• The site functional Information Solution (IS) Head
is responsible for:
• supporting systems that assure integrity and
availability of any electronic GMP documentation.
General Aspects and Requirements
The System Approach
• Each site or facility handling GMP documentation
must have systems and procedures for their
management and control.
• These systems and procedures must be compliant
with company policies and GMP requirements.
• Documentation subject to company policies must
be identified and defined within the
documentation management system.
General Aspects and Requirements
What should be recorded ?
• All important information that is generated during an
operation or process must be recorded together with
who performed the operation and when it was carried
out.
• Such information should be legible, accurate, dated,
traceable, and accessible.
• This information should reflect the complete history of
the manufacture, packaging and control of the product.
General Aspects and Requirements
Key Features of Good Documentation
• Careful design of documents should make them easy to
read, easy to understand and easy to complete properly
• Original documents should be easily distinguishable from
photocopies, and should have clear and concise
information
• Good documents should have sufficient space for entries,
to record variable information and signature and to
attach print-outs etc. Unused empty fields should be
crossed-out.
General Aspects and Requirements
What else is relevant?
• GMP documentation must clearly state title and
content and must possess a site unique identifying
number
• GMP documentation must be formally approved,
issued and version controlled
• Data entries must be made or completed at the
time the action is performed
• Entries in logbooks should be done in
chronological order.
General Aspects and Requirements
What else is relevant?
• Master documents must be subject to appropriate
controls to ensure that only one version is current.
Such documents must be approved, signed and
dated
• Modifications to master documents must be
managed through change control
• There must be a periodic review of GMP
documents to ensure that they are compliant with
current regulatory files and GMP requirements.
General Aspects and Requirements
What else is relevant?
• All information contained within GMP
documentation that is stored and maintained
electronically must be made available in both
electronic and human readable formats
• All SA product and system related documents
are considered the intellectual property of SA
and must be maintained and distributed in a
confidential manner.
Types of GMP Documentation (1)
• This Documentation includes, but is not limited to the
following Batch Related Records:
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Master Batch Records (e.g. Processing Instructions,
(Packaging Instructions)
Batch Records (e.g. Batch Production Records)
Raw Data Records
Laboratory Records
Distribution Records
Standard Operating Procedures (SOPs)
Specifications and Test Methods
Records of Raw Materials, Intermediates, Labelling
and Packaging Materials
Types of GMP Documentation (2)
• Non Batch related Records
 Qualification and Validation Documents
 Change Control Documentation
 Engineering Drawings
 Maintenance and Calibration Records
 Complaint Records
 Recalls and Returns
 Environmental Monitoring Records
 Utility Monitoring Records
 Line and Equipment Logs
Types of GMP Documentation (3)
• Non Batch related Records (continued):
 Personnel Training Records
 Quality Agreements (i.e. Technical Agreements)
 Failure Investigation and Reporting Records
 Cleaning and Sanitization Records
 Entry Records for Controlled Areas
 Pest Control Records
 Stability Records
 Audit and Regulatory Inspection Reports
 Regulatory Files
Types of GMP Documentation (4)
• Some other examples of documentation that
must not be forgotten:
 SOP Annexes
 Computer files
 Process Flow and other Diagrams (e.g. gowning
diagrams)
 Raw Data Sheets (charts, chromatograms, etc.)
 Technical Reports
 Labels (room and equipment status, sampling, material
status)
Purposes of GMP Documentation
(1)
• There are three main purposes for GMP
documentation:
To meet legal requirements including all
GMP expectations
To meet our business requirements
To form the basis of good scientific
decision making
Purposes of GMP Documentation
(2)
“If it is not documented, it is a
rumour!”
This is the FDA Inspection Approach
Purposes of GMP Documentation
(3)
• To understand what needs to be done (the
process)
• To understand how to do it (the method)
• To understand why it needs to be done (the
context)
• To understand who must do it (the responsibility)
• To understand when to do it (frequency, close out)
• …. At the end: to ensure that there is an adequate
record of who did what, when, how and why!
Purposes of GMP Documentation
(4)
• If you cannot answer all of the questions
from the previous slide, then the
documentation (system) has somehow failed
• Remember, documentation should equally be
for our own benefit as it is for the regulators
• And: inspections normally provide good
feedback for improvement.
Purposes of GMP Documentation
(5)
•PROCEDURES SHOULD BE WRITTEN AND
FOLLOWED
•It is a concern if an SOP has not been in place
•But it is a violation of the GMP requirements, if
the SOP is present, but not followed.
Purposes of GMP Documentation (6)
Documenting Decisions and Rationales
• The regulators expect things to occasionally go wrong
during manufacturing or testing
• However, we must ensure that we clearly document
and sign off our decisions with a rationale behind
• In reality, this is one area of a general weakness
• During many audits, people can explain precisely why
an action was taken. Although the decision may have
been the correct one and documented, the rationale
was never documented/signed off at the time.
The Structure of Document Management
Taking a Logical Approach
• There should be one “umbrella” document (SOP) that
defines the management of GMP documentation, our
approach to documentation
• For example:
 What type of documents are covered by GMP
 What is raw data and what not
 Who is responsible for each GMP documentation
 Who can author, review, and approve GMP documents
 How working copies are controlled
 How the documents are archived
 When the documents are reviewed for changes
The Structure of Document Management
Control of Working Copies
• It is important to have the most up to date working copy of a
document issued to a department. But how can we stop
uncontrolled copies being photocopied (e.g. replacement page
of BMR)
• It is easier now for people to make uncontrolled copies as
they have general access to photocopy machines.
• Apart from rigorous training, many different methods are used
to help control documentation
 Batch number punched through all pages of BMR copy
 BMR Copy stamped in red with batch number and date
 SOP’s red stamped with controlled copy and the number of
the copy.
The Structure of Document
Management
• Document Administration Department
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Centralized better than de-centralized?
Reporting Relationship
Must be audited like all other GMP related departments
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Logical and easy to understand
Identifies revisions
No duplication
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Writing, reviewing, and approving
Numbering and version control
Issuing
Retrieving
Retention and Archiving
• Document Numbering System
• Document Management Procedures
The Structure of Document Management
Retention and Archiving
• Require clear rules and procedures about archiving of
superseded documents
 Defined Retention Periods
 No loss of Information during retention (thermal printers)
 Fire and waterproof archives
 Access and Control of document archives
 Readily Retrievable (in case of compliant, recall, audit)
 Periodic Checks of archive
 Electronic Archives to be Qualified and Validated
 Document destruction
• Note the archived documents are the property of the
company. Even if the site is sold, and documents must be
transferred to another site and secured in a storage area
The Structure of Document Management
Document Retention Rules
• The
retention
period
for
all
quality
documentation must meet legal and regulatory
requirements of all relevant markets.
• It is the responsibility of each department to
ensure the control and retention of GMP
Documents in accordance with the systems and
procedures.
Evaluate the Documentation
System (1)
• We need to review whether our documentation system is working
correctly or not
• It is easy to make general statements to the effect that:
 “nobody fills out the documents correctly”
 “there are always problems with the documentation”
 “the system does not work”
• As with any other process, we need to collect and analyse real data
to see if there is a problem or not, or to identify whether
performance is improving or not.
• It is a well known phenomenon that improvements will occur just
because people know that we are measuring it.
Evaluate the Documentation
System (2)
• Some examples of what we can review and evaluate:
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SOP’s not reviewed within the required time frame
Batch Records with missing information at review time
of logbooks not reviewed within the correct time frame
of uncontrolled technical drawings
of outdated versions of SOPs versus the master copy
of superseded documents not retrieved
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Are there certain issues within specific departments?
Are some systems badly out of control?
Make the data transparent
Ask users why they believe current system is not working
Compare systems that work well with those that do not
• Identify the priorities and the reasons
The Documentation Management
Cycle (1)
FOLLOW-UP / MONITOR
MAKE EFFECTIVE
TRAINING
VERSION CONTROL
REVIEW AGAIN
DRAFT
REVIEW
APPROVAL
The Documentation Management Cycle
(2)
Document Drafting
• Written procedures need to be drafted in a
way that will help avoid errors:
 clear instructions
 written in sufficient detail
 well understandable
 version controlled
 written with a view for training
 defining the responsibilities
 easy to implement.
The Documentation Management Cycle
(3)
Document Drafting
• The document is only useful if the person who
should use it, actually understands it
• Therefore consider the following aspects when
drafting documents:
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educational level
cultural background
linguistic ability
comprehension ability
readability Index for average English:
13 words per sentence.
The Documentation Management Cycle
(4)
Document Review
• What can be reviewed and evaluated when
checking individual documents?
 the information that is stated
 the information that is not stated/missing steps
 scientifically incorrect information/requirements
 conflicting requirements
 safety issues
 legal/regulatory issues
 the rationale for the document (is the document
serving a useful purpose).
The Documentation Management
Cycle (5)
Document Approval
• GMP Documentation is normally signed by the
following persons:
 Author: a knowledgeable and trained person in the relevant
 topic within the relevant department (QA only author their own
documents!)
 Reviewer: who is someone equally proficient as the author
 Approver: an appropriate level of management (normally the
 QA manager).
• Quality Assurance main role is to review and approve
that all GMP documents are in compliance with
regulatory files and meets the GMP requirements.
• The QA signature is therefore the last one to be
added.
The Documentation Management Cycle
(6)
Version Control
• Effective Version Control is an essential part of the GMP
document management system
• There must be a high level of confidence that only the
latest versions of documents exist as working copies
• There are two ways of dealing with superseded versions
• Passive retrieval (not recommended)
The new document is issued and the recipient is asked
to destroy all copies of the superseded one (rarely
happens)
• Active retrieval (recommended)
The new document is exchanged for the superseded
version
The Documentation Management Cycle
(7)
Training
• New/Updated documents have been written for a
reason, and it is essential that relevant people are
informed/trained as appropriate before the
document becomes effective
• The document can be trained on a one to one
basis or within a group. The document can be
read by the relevant people
• In some cases, there may be some short
questions to answer to ensure that key aspects
are understood.
The Documentation Management Cycle
(8)
Training
• People can generally have different preferences in their
way of learning, but the most important thing is that the
time for training is built into the cycle, and properly
documented
• The documentation system must ensure that absentees
are also trained upon their return to work
• The system must also ensure that the proof of training
can be retrieved easily.
The Documentation Management Cycle
(9)
Make Effective
• The effective date of the document (e.g.
SOPs, protocols) should permit enough
time for training of relevant personnel
• Procedures, once effective, should be as
working documents, and treated as such
• The best procedure is of no value in the
supervisor’s locked office!
• And then: Follow up and monitor!
Summary and Conclusions (1)
• GMP Documentation is one critical aspect of
our business.
• All documentation required by GMP
regulations must be issued, managed, and
controlled by a document management
system.
• QA have a major role to play in managing
GMP documentation.
• Inspections and audits regularly identify
issues with documentation system.
Summary and Conclusions (2)
• Document management system needs to be clear and
logical
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Use a top down approach (QA must take the lead!)
Use flow chart and other tools to define documentation needs
Includes all types of documentation (including electronic)
Ensure a robust document cycle from drafting to archiving
• Review and evaluate the performance of documentation
system.
Thank You
Any Questions