This will help to professionals working in Pharma industries.

1. Good Documentation Practice
Dr. A. Amsavel

2. The Overview
• Introduction
• Requirements
• Types of GMP Documentation
• Purposes of GMP Documentation
• The Structure of Document Management
• Evaluation of the Documentation System
• The Document Management Cycle
• Tips to good documentation practices
• Warning letters and observations
• Summary & conclusion

3. What is Documentation ?
To Document each Activity you perform
Documentation is a Process, which comprises of the
following :
- Recording of Data
- Review of Documents
- Approval of Documents
- Issuance and Disposal of Documents
- Retrieval of Documents
- Presentation of Documents

4. 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
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

5. WHY GMP DOCUMENTATION ?
“If it hasn't been documented, then it hasn't
done or happened!”
“If it is not documented, it is a rumour!”
This is the FDA Inspection Attitude
The product considered as “Adulterated” if the
procedure not followed/ not documented
properly.

6. WHY DOCUMENTATION ?
Cost for Good
Documentation
Cost for Poor/No
Documentation
THEREFORE, DOCUMENTATION BRINGS BUSINESS

7. GDP references
21 CFR 58 GLP:
 All data generated during performing of a study, (except
automated data collection systems), shall be recorded
directly, promptly, and legibly in ink.
 All data entries shall be dated on the date of entry and
signed or initialed by the person entering the data.
 Any change in entries shall be made so as not to obscure
the original entry, shall indicate the reason for such
change, and shall be dated and signed or identified at the
time of the change.

8. GDP references
21 CFR 211.188 (a) :
Control & issue of production batch records.
21 CFR 211.194 (a)
Verification of laboratory test data for “Accuracy,
Completeness compliance with established
standards”
ICH Q7 : Chapter–6 & other GMP guidelines
Documentation and Records

9. Comments at the beginning
• GMP documentation is one critical aspect of our business and
it is a legal requirement too!
• Inspection or audit observations frequently on poor
documentation practices, outdated documents and
inadequate version control,
• Quality can not be assured in a regulated industry without
good documents and good documentation practices
Keep in mind, after the product is distributed to the
customer, what remains with us is documents.

10. Comments at the beginning
Why do people sometimes fail to document activities or
events properly?
• People don’t understand the legal requirement of
documentation.
• People do not relate records to auditing.
• People don’t clearly understand what , how or when to
document.
• Procedures may not be completely understood or followed.
• People aren’t always held accountable.
• People will make mistakes.
• People don’t always make corrections properly.

11. Key Features of Good Documentation
• Careful design of documents should make them easy to read, easy
to understand and easy to complete properly
• Just creating documents is not enough; must follow specific
standards when doing so. Ensure user reads and understand exactly
what it means.
• 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.

12. Key Features of Good Documentation
• 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.
• Data entries must be made or completed at the time the action is
performed
• Entries in logbooks should be done in chronological order.
• It is necessary to document anything that directly impacts a
product. Record every procedure you write, form you fill out, and
test you perform. Using a standard format eliminates discrepancies
between documents from different sources.

13. What should be recorded ?
• All important information that is generated during an
operation or process must be recorded by who performed
the operation and when it was carried out.
• Such information should be legible, accurate, dated,
traceable, and accessible.
“All documentation should be legible, clean, readily
identifiable, retrievable and maintained in facilities that
provide a suitable environment to minimize deterioration
or damage and to prevent loss”
• This information should reflect the complete history of
the manufacture, packaging and control of the product.

14. Where documentation ?
Documentation during
 Project Design,
 Construction Phase
 Commissioning and start-up
 Qualification and Validations
 Commercial Production,
 Testing and Release,
 Distribution
 Implementation of Quality system
 Regulatory submissions.
 And beyond…………

15. Types of GMP Documentation (1)
• This Documentation includes, but is not limited to the
following Batch Related Records:
o Master Batch Records (e.g. Processing & Packaging Instructions)
o Batch Records (e.g. Batch manufacturing Records)
o Raw Data Records (charts, chromatograms, etc.)
o Laboratory Records
o Distribution Records
o Standard Operating Procedures (SOPs)
o Specifications and Test Methods
o Records of Raw Materials, Intermediates, Labelling and Packaging
Materials

16. Types of GMP Documentation (2)
• Non Batch related Records
o Qualification and Validation Documents
o Change Control Documentation
o Engineering Drawings
o Maintenance and Calibration Records
o Complaint, Returns and Recalls Records
o Environmental Monitoring Records
o Utility Monitoring Records
o Line and Equipment Logs
o Personnel Training Records
o Quality Agreements (i.e. Technical Agreements)
o Stability Records

17. Types of GMP Documentation (3)
Non Batch related Records (continued):
o Failure Investigation and Reporting Records
o Cleaning and Sanitization Records
o Entry Records for Controlled Areas
o Pest Control Records
o Audit and Regulatory Inspection Reports
o Regulatory Files
Other documentation that must be ensured :
o SOP Annexes
o Computer files
o Process Flow and other Diagrams, pictorial displays (e.g. gowning )
o Technical Reports
o Labels (room and equipment status, sampling, material status)

18. 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
• Any type of product is developed and produced, it must be
safe, effective and fit for its intended use.
• Quality characteristics are established in documents.
• Documents declare product standards and describe how to
monitor, test and judge for compliance with these standards.

19. Purposes of GMP Documentation (2)
• 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!

20. Purposes of GMP Documentation (3)
• If you cannot answer all of the questions from
the previous slide, then the documentation
(system) has somehow failed
• PROCEDURES SHALL 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.

21. Purposes of GMP Documentation (4)
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, but rationale or justification was
never documented/signed off at the time.

22. Strengths of Good Documentation
Clear Objective and scope of the document
Who should prepare ? Should know ?
Layout of the document
Explain the activity performed logically
Use short, simple, easy to understand sentences
Maintain flow of script
Match script to the sequence of events of the activity
Use correct data format
Draw neat and correct inference
Conclusion & Summary
Get your document edited by an expert

23. Document Management
• Document Administration Department
– Centralized better than de-centralized?
– Reporting Relationship
• 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

24. Document Retention and Archiving
21CFR 211.180(d) …These records or copies…shall be
subject to photocopying or other means of
reproduction as part of such inspection.
Records that can be immediately retrieved from
another location by computer or other electronic
means shall be considered as meeting the
requirements of this paragraph.”

25. Document Management
Retention and Archiving
• 21CFR 211.180(d)…..
• Require clear procedures for archiving of 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

26. Evaluate the Documentation System
• Review whether our documentation system is working
correctly or not
• It is easy to find out and classify the issues;
 “nobody fills out the documents correctly”
 “there are always problems with the documentation”
 “the particular system does not work”
• Collect and analyse real data
– Area of poor documentation
– Classify the type of issues
– Evaluate is it person dependent, system dependent
– Training or change required
– Monitor the improvement
• Improvements will occur If we are monitoring & measuring
(people know some one is watching)

27. Evaluate the Documentation System
• Some examples of what we can review and evaluate:
 % SOP’s not reviewed within the required time frame
 % Batch Records with missing information during review
 % of logbooks not reviewed within the correct time frame
 % 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

28. The Documentation Management Cycle
FOLLOW-UP / MONITOR REVIEW AGAIN
MAKE EFFECTIVE DRAFT
TRAINING REVIEW
VERSION CONTROL APPROVAL

29. The Documentation Management
Document preparation
• Written procedures to be drafted to avoid errors/discrepancy:
 clear instructions
 written in sufficient detail
 well understandable
 defining the responsibilities
 easy to implement.
• The document is only useful if the person who should use it, actually
understands it
• Therefore consider the following aspects;
 educational level
 cultural background
 linguistic ability
 comprehension ability
 Readability
 13 words per sentence.

30. The Documentation Management
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).

31. The Documentation Management
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 author for QA
document)
 Reviewer: who is someone equally proficient as the author
 Approver: an appropriate level of management (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.

32. Documentation Management: Training
• When New/Updated documents made: ensure that
relevant people are informed/trained before the document
becomes effective
• The document can be trained on a one to one basis or as
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.
• Training of documented could be s built into the system
• The documentation system must ensure that absentees are
also trained upon their return to work
• Ensure that the training is recorded.

33. Tips to Good Documentation Practices/
Recordkeeping procedures:

34. Tips to Good Documentation Practices
 When portions of a page or a complete page remain unused, a
single line must be drawn angularly across the unused portion.
Sign and date the crossed out section and provide an explanation
 Eg- Not applicable; Remining pages not used refer new note
book
 Ensure the pagination (all pages to be numbered; could be page
X of Y for loose sheets and page x.. For bound books)
 Make the required entries on the record as the work is
performed.
Do not record information on a separate
piece of paper /temporary entry and
enter on the record later

35. Tips to Good Documentation Practices
•Use only black or blue permanent ink.
The ink should not run or smear if the
record is splashed with liquid. All entries
must be permanent and able to be
photocopied.
•Don’t use pens like gel pens, ink pens
for making entries. Don’t use pens like red,
green color ink.
• Pencil writing is not
acceptable,

36. Tips to Good Documentation Practices
 Use correct rounding off procedures and significant figures
 When a comment or explanation is required, make all
statements objective. Avoid personal comments and opinions.
 When dating a signature, use the actual day the signature was
signed.
 If the activity being recorded occurs on more than one day, the
record must clearly indicate where the "break" occurred. This
can be accomplished by drawing a horizontal line through the
procedure at the break" and indicating the new date or making
entries that are initiated and dated appropriately.

37. Tips to Good Documentation Practices
• Never sign your name for performance of a job for work
actually performed by someone else.
• When one or more person complete a task, all must sign.
• When spaces or cells do not contain information, EACH must
contain the appropriate “not applicable” entry.
• Spaces and cells cannot be left “blank”!
• Do not use titto, bracket/brace, arrow to link
• Don’t remove any pages or portions from a note book
• Do not change the paper size/quality/colour
• Use polyvinyl alcohol base gum or white glue for pasting of
graphs etc

38. Tips to Good Documentation Practices
BMRs are important documents reviewed by
regulators, so ensure to fill correctly:
 Missing signatures & dates
 Over-writing without correction, sign, date
 No remarks for correction
 Control Number not recorded correctly
 Time/Date and PC Number recorded in BPR not matching
with in-process production Log Books
 Every person must be trained to complete documents
properly; improper use of the documents can lead to
inaccurate, inadequate or incomplete documents

39. Tips to Good Documentation Practices/
Recordkeeping procedures:
 Data may be attached to the page, however, it must be firmly
attached. Label, sign and date the attachment.
 If a record becomes messy and extremely difficult to read or
damaged, do not discard. Inform QA/supervisor and
transcribing the data to a clean record sheet and attaching the
original record sheet. Provide an explanation for the
transcription.
 Use clear transparent tape for mending (patch-up).
 Computer print outs taken on thermal paper or easily fading
inks should be photocopied and maintained.

40. Tips to Good Documentation Practices
Review of records
• Proper review will prevent the Non-compliances/
observation;
• Sincere and effective review shall be done; not just signing as
reviewer;
• The following shall be reviewed but not limited to;
– Incomplete entries, signature
– missing records and out-prints
– Illegible entries / unacceptable corrections
– Traceability of relevant records /cross references
– Deviations, if any investigation the impact on the product
– Valid calibrations and service intervals of test equipment
– Compliance with specifications,
– Calculations

41. GDP:
Filling of BPR
 Missing signatures & dates
 Over-writing without correction, sign, date
 No remarks for correction
 Control Number not recorded correctly
 Time/Date and PC Number recorded in BPR not matching
with in-process production Log Books
 Every person must be trained to complete documents
properly; improper use of the documents can lead to
inaccurate, inadequate or incomplete documents
BPRs are major documents reviewed by regulators

42. Tips to Good Documentation Practices
Clearly Record the Data
What’s that number?
Is it 27? 29? 24? 2%
Hmmmm. What do we do now?

43. “ I swear to follow the good documentation practice
and document the actual information and on line…..”

44. Observations on poor
documentation practices
• Document error correction not signed/dated, and didn’t include a reason
for the correction
• Write-overs, multiple line-through and use of "White-out" or other
masking device
• Sample sequence table and audit trail not documented (if its not
documented, it didn’t happen)
• SOP related to production, calibration, storage and maintenance not
authorized by the QA head
• The delegation for the batch release, in case of absence of the QA
manager, not recorded / documented
• Out-of-specification (OOS) procedure not detailed enough; flow chart
and /or check-list not available .

45. Observations on poor
documentation practices
Use of signature stamp
• US FDA Warning Letter UCM075960 to Scott A. Spiro, MD, 28-Jun-06. [16]
• US FDA Warning Letter UCM066113 to Medtronic, Inc., DEC 2 1997. [17]
Obscured original data
• US FDA Warning Letter UCM076246 to Gynetics Medical Products NV, JAN
16 2007[19]
Use of pencil
Inaccurate records
• US FDA Warning Letter 320-01-02 to SOL Pharmaceuticals Limited, NOV
21, 2000[18]
Hand changes not dated
• Form FDA 483 issued to L. Perrigo Co., NOV 7, 2008. [20]

46. Observations on poor
documentation practices
• The records did not contain the complete raw data for all the
laboratory testing performed.
• The periodic calibration of the laboratory instruments was not
documented completely in the laboratory records.
• The records did not include the reason for the modification of a test
method.
• The laboratory records did not include a statement on the identity
of the reference standards used and on the method with which
these were produced.
• The laboratory records did not include the initials or signature of a
second person showing that the original records had been reviewed
for accuracy, completeness, and compliance with established
methods.

47. Summary and Conclusions (1)
• GMP Documentation is one critical aspect of our
business.
• Documentation must be consistent and systematic
• Documentation practices must assure that records
meet GMP requirements
• Documentation process must be controlled to
minimize redundancies in the work flow
• Inspections and audits regularly identify issues with
documentation system.

48. 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.

49. Thank You
Any Questions?