Management of GMP Documentation

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The Overview

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
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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 Inspection or audit observations frequently identify outdated documents, inadequate version control, and poor documentation practices
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As the Quality Unit is responsible for

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: 2/14/13 A GMP document is any written record

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. 2/14/13 The site functional Information Solution

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

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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.
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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.
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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
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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 2/14/13 documents to ensure that they are

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.
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Types of GMP Documentation (1)

This Documentation includes, but is not limited to the following Batch Related Records:

Master Batch Records (e.g. Processing Instructions, (Packaging Instructions) Batch Records (e.g. Batch Production Records) Raw Data Records 2/14/13

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 2/14/13 Utility Monitoring Records

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 2/14/13

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)

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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

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Purposes of GMP Documentation (2)

If it is not documented, it is a rumour! This is the FDA Inspection Approach

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Purposes of GMP Documentation (3)

To understand process) To understand To understand (the context) To understand responsibility) To understand 2/14/13 close out)

what needs to be done (the how to do it (the method) why it needs to be done who must do it (the when to do it (frequency,

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

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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.

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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

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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 2/14/13 Who is responsible for each GMP

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 2/14/13

The Structure of Document Management

Document Administration Department

Centralized better than de-centralized? Reporting Relationship Must be audited like all other GMP related departments

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Document Numbering System

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, 2/14/13 recall, audit)

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.

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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.

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Evaluate the Documentation System (2)

Some examples of what we can review and evaluate:

% SOPs 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 2/14/13

The Documentation Management Cycle (1)

FOLLOW-UP / MONITOR REVIEW AGAIN

MAKE EFFECTIVE

DRAFT

TRAINING

REVIEW

VERSION CONTROL

APPROVAL

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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 2/14/13 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:
educational level cultural background linguistic ability comprehension ability readability Index for average English: 13 words per sentence.
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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 2/14/13 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 2/14/13 QA manager).

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 2/14/13

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

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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.

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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 supervisors locked office! And then: Follow up and monitor!
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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 2/14/13 issues with documentation system.

Summary and Conclusions (2)

Document management system needs to be clear and logical

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)

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Thank You
Any Questions

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