Basic Principles of GMP World Health Organization Basic Principles of GMP 10 May, 2019 Documentation Part 1 This module deals with the very important topic of documentation. It is a half to one-day session (depending on the participants ability and experience) divided into 2 roughly equal parts: In each half, there will be 30 - 45 minutes of presentation, 45 minutes discussion in groups and 30 minutes feedback to the whole group. There will be one test and discussion (40 minutes) covering the whole module that will be taken at the end. 15

World Health Organization Documentation World Health Organization 10 May, 2019 Objectives 1. To review general requirements for documents 2. To review specific requirements for each document 3. To consider current issues applicable to your countries There are three objectives for this session: 1. We are going to start by looking at the general requirements for all documents and to review the types of documents listed in the WHO GMP text. 2. Then we will look at the specific requirements for each type of document. 3. Finally, we will look at the specific issues that are likely to arise during your inspection visits and the sort of solutions that you will need to be able to offer.

World Health Organization Documentation 10 May, 2019 General Principles – I Good documentation is an essential part of the QA system Should exist for all aspects of GMP Purpose of documentation Defines specifications and procedures for all materials and methods of manufacture and control Ensures all personnel know what to do and when to do it Ensure that authorized persons have all information necessary for release of product Documentation is an essential part of QA and relates to all aspects of GMP. The pharmaceutical industry must have a good document framework (infrastructure). It is important for a manufacturer to get the documentation right in order to get the product right. There are a number of purposes for documents: They are used to define specifications for materials and for methods of manufacture and control. They ensure that everyone concerned with manufacture and QC knows what to do, how and when to do it. They allow decisions to be taken on batch release. They provide an audit trail, which is particularly important in the case of suspect batches. 15.1

World Health Organization Documentation 10 May, 2019 General Principles – I Purpose of documentation (cont.) Ensures documented evidence, traceability, provide records and audit trail for investigation Ensures availability of data for validation, review and statistical analysis Design and use Depends upon manufacturer Some documents combined into one, sometimes separate Purpose of documentation (cont.) Ensures documented evidence, traceability, provide records and audit trail for investigation Ensures availability of data for validation, review and statistical analysis Design and use Depend upon manufacturer Some documents combined into one, sometimes separate 15.1

World Health Organization 10 May, 2019 Documentation What is being made? Most of us when attempting a task need some sort of documentation What is being made? Most of us when attempting a task need some sort of documentation.

World Health Organization 10 May, 2019 Documentation And if the drawing is wrong! The drawing was wrong!

World Health Organization 10 May, 2019 Documentation During inspections, you can also verify the documents against actual instruments, equipment, premises etc. You have to verify that the documents are accurate, and current. Check the drawings against the qualification reports and proof of components. If any changes were made, did these go through a change control procedure? Was requalification required and done?

World Health Organization Documentation World Health Organization 10 May, 2019 Why are documents so important? Communication Cost Audit trail Communication - "How can I know what I think until I see what I say: " E M Forster. Communicate ideas to a remote audience. Documentation fixes in time physical expressions to vaguely formed concepts, structured far more rigorously then when they are going around in someone’s head. Cost - the cost of poor quality documentation is hard to measure. But think of the time wasted through misinterpretation, recovering from errors, resubmitting to regulatory authorities, failing regulatory audits, etc....... Audit trail - footprints in the snow. Write what you do, do what you write and if you didn't write what you did...you didn't do it!!

World Health Organization Documentation 10 May, 2019 General Principles – I Documents should be designed prepared reviewed distributed with care Comply with marketing authorization Design of documentation important Documents should be designed, prepared, reviewed and distributed with care. In terms of design, there is no single right answer – the one thing you can be sure about is that every company will come up with a different design. However, it is better for the operators if a consistent approach is taken. It is possible for some of the documents to be combined, but generally they should be separate. They must comply with the relevant part of the manufacturing and marketing authorizations. All documents should be unambiguous with a title and a clear statement of purpose. They should contain clear, numbered references to each activity. They should have sufficient space to record relevant data. They should be easy to check and all relevant activities should be recorded on them. 15.2

World Health Organization Documentation 10 May, 2019 General Principles – II Look at the “Style” of the document Instructions in the imperative Short sentences preferred to long sentences Approval of documentation Approved, signed and dated by appropriate responsible persons No document should be changed without authorization and approval – change control Instructions must be in the imperative – Go , Do, Stop, Mix, Blend, Wash, etc...... Look for short sentences. Long sentences do not allow the reader time to grasp messages. A florid, roseate style over endowed with polysyllabic phraseology confuses the reader. 15.3

World Health Organization Documentation 10 May, 2019 General Principles – III Contents of documents should be clear (easy to understand) and include, e.g. Title, nature, objective or purpose Layout in orderly fashion Easy to be filled in and checked Clear and readable – (also copies if these are made) No errors if master documents are copied for working documents The contents of documents should be clear (easy to understand) and include e.g.: Title, nature, objective or purpose The layout should be in orderly fashion and allow easy to be filled in and checked Documents should be clear and readable – including copies made There should be no errors if master documents are copied for working documents 15.4

World Health Organization Documentation 10 May, 2019 General Principles – IV Documentation control Regular review of documents Kept up to date (current) – amended – through change control Superseded documents removed and not used Distribution and retrieval of documentation Retention time for superseded documents Distribution of documents needs to be carefully controlled in order to ensure that the most up-to-date version is always being used. There should be a distribution list, if appropriate, attached to the document. Unauthorized photocopying of original documents should be actively discouraged. Some companies manage this by having part of the front page printed in colour, or by using an official stamp or other means of identification. There should be an SOP for distribution, retrieval and preparation of documentation. A document register is required. This ensures that change control over all documents is properly managed. 15.5

World Health Organization Documentation 10 May, 2019 General Principles – V Data entry Clear, readable and indelible Design to allow for sufficient space for entries Changes to entries: signed, dated and reason given original entry still readable Entries at the time of action All significant actions recorded – traceable Operators and staff should make clear, readable and indelible entries in documents. The design of the document should allow for sufficient space for entries Once an entry is made, changes should only be made if really necessary. All changes to entries should be signed, dated and a reason given for the change. The original entry should still be readable Entries should be made at the time of action. Entries should not be made prospectively or retrospectively. All significant actions should be recorded and traceable (time, operator, equipment used etc). 15.6 – 15.8

World Health Organization Documentation 10 May, 2019 General Principles – VI Data entry (cont.) Electronic data processing systems, photographic systems or other reliable means Systems require SOPs and records Accuracy of records checked Authorized persons - access and changes Password controlled Entries checked Some documents may be stored electronically. Special controls have to be developed. If documentation is handled by electronic data-processing methods, only authorized persons should be able to enter or modify data in the computer, and there should be a record of changes and deletions; access should be restricted by passwords or other means, and the entry of critical data should be independently checked. Whichever way the master is stored, it is important that clear copies are reproduced for use with individual batches. 15.9

World Health Organization Documentation 10 May, 2019 General Principles – VII Data entry (cont.) Batch records stored electronically: Protected Back-up transfer, e.g. magnetic tape, microfilm, paper print-outs Records kept 1 year after expiry date of product Data readily available during retention period 15.9

World Health Organization Documentation World Health Organization 10 May, 2019 Types of Documentation Labels Specifications and testing procedures Master formulae and instructions Batch processing and batch packaging records Standard Operating Procedures (SOPs) Records Stock control and distribution records Other documents … This slide summarizes all the types of documents that are listed in the WHO GMP text, plus three additional ones. We will review each one in detail later in the session, but at this point, we will run through the list to make sure we are aware of all the requirements (Note for the trainer: that makes a good group session for audience participation rather than just reading the list to the seminar. One can also ask what must go on the e.g. Release label, or cleaning label, etc......) Labels are required for all containers, equipment and premises. Specifications and testing procedures are required for all starting materials, packaging materials, intermediates, bulk and finished products. There must be a master formulation for all manufacturing processes and a packaging instruction for each stock-keeping unit that is produced. Batch processing documents and records are required for all manufacturing processes. Batch packaging documents and records are required for packaging operations. Standard operating procedures (SOPs) are required for all operations that are not product-specific, whether related directly to manufacturing or to operation of the facility. The following are three examples of other documents that are useful and frequently found: Stock control records are usually used for all materials that are stored in the warehouse. Distribution records are usually used for all batches of material that are dispatched from the warehouse. A water quality manual describes all aspects of the water system design, operation, maintenance and water quality testing.

World Health Organization 10 May, 2019 Documentation Plans can be considered to be documents.

World Health Organization Documentation World Health Organization 10 May, 2019 Photographs can be documents and part of a herbal identification, provided they are properly authorized and controlled Photographs of herbal specimens can be very useful documents if properly authorized and controlled. The photograph shows a pollen grain, unique to the botanical genus and species, being compared with the authenticated reference photograph. The gentleman on the right is serving a 5 year apprenticeship to the lady in the centre who is a qualified Traditional Chinese Herbal Medicine specialist.

World Health Organization Documentation World Health Organization 10 May, 2019 Flow charts provide substantial information at a glance This is an example of a flow chart - another useful documentation tool Flow charts are helpful when complex SOPs describe steps in a process. Examples include also OOS investigation and decision trees.

World Health Organization Documentation World Health Organization 10 May, 2019 Types of Documentation The different types of documents will be discussed in detail in Documentation: Part 2 The different types of documents will be discussed in detail in Documentation: Part 2