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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
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 • Inspection or audit observations frequently identify outdated documents, inadequate version control, and poor documentation practices • As the Quality Unit is responsible for designing and operating the GMP documentation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 RequirementsThe 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 RequirementsWhat 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 RequirementsKey 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 RequirementsWhat 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 RequirementsWhat 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 RequirementsWhat 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: • 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 ManagementTaking 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 ManagementControl 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 • Centralized better than de-centralized? • Reporting Relationship • Must be audited like all other GMP related departments • Document Numbering System • Logical and easy to understand • Identifies revisions • No duplication • Document Management Procedures • Writing, reviewing, and approving • Numbering and version control • Issuing • Retrieving • Retention and Archiving
The Structure of Document ManagementRetention 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 ManagementDocument 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: • % 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 • Identify the priorities and the reasons • 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
The Documentation Management Cycle (1) REVIEW AGAIN FOLLOW-UP / MONITOR MAKE EFFECTIVE DRAFT TRAINING REVIEW APPROVAL VERSION CONTROL
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: • 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 • 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