Good Documentation Practice

Dr. A. Amsavel
 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
 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
 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
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.
 WHY DOCUMENTATION ?

Cost for Good

Documentation

Cost for Poor/No

Documentation

THEREFORE, DOCUMENTATION BRINGS BUSINESS

 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.
 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
 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documentation practices, outdated documents and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.
 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.
 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.
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.
 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.
 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…………
 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
 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
 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)
 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.
Purposes of GMP Documentation (2)
(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.
 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
 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
Tips to Good Documentation Practices/
Recordkeeping procedures:
 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
 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,
 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.
 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
 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
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?
“ I swear to follow the good documentation practice
and document the actual information and on line…..”
 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 .
Thank You

Any Questions?
Good Documentation Practice

Dr. A. Amsavel
Index
Introduction
Definition
Documents required
Records to be maintained
Good Documentation practice
 Why GDP is important
Proverb:

“IF YOU HAVE NOT DOCUMENTED AN

ACTIVITY,

YOU HAVE NOT DONE IT”.

Document all the activities performed

Do not perform the activity if it is not
documented.
 Definition
Documents:

An approved instruction either in paper or electronic

form which guides about how an activity shall be
executed.
Records:
• Records provide evidence that activities have been
performed or results have been achieved.
A record is often considered as document.
They always document the past.
 What is Good Documentation Practice
Documentation must be;
Accurate : true / precise, error free,
Concise: short & clear information that is understood by all
Legible: shall be readable , undertanadable.
Traceable: who recorded it, where, when and how
Contemporaneous: documented at the time activity done
Enduring: Long lasting and durable
Accessible: Easily available / retrievable

Shall be Complete & Authentic:

 Principles of GDP
A document with original signatures should never be
destroyed.
Never falsify information
Never do white-out and cover-over-tapes
Never obliterate information or record
Never over-write a record.
Never use pencil – use permanent ink for writting
No spaces, lines or fields are to be left blank
Never use symbols e.g ditto marks or arrows to indicate
repetitive and consecutive entry
 Observations on Poor Documentation Practices
 Missing signature and dates at the time of activity performed.
 Non-uniform date and signature
 Activity was performed & writing on one day and signed on
another day.
 Blank spaces
 Illegible writing
 Too many corrections
 Write-overs, multiple line-through
 "White-out" or other masking device
 Error correction not signed/dated, and reason for the correction
not written
 Not traceable
 Data integrity
 Benefits of GDP
Compliance to regulatory requirement- No observation /
warning letters/Import Alert/ ban
Build confidence on System & practice
Correct, complete, current and consistent information
Effectively meets customers and stakeholders’ requirements.
Ensure the traceability
Useful for review , investigation & CAPA
Solve complicated problems
Reduce or eliminate assumptions and second-guessing.
Eliminate the need to re-ask the same questions
Specify clear instructions to staff
Consistent quality, yield and performance of staff.
 Q7: DOCUMENTATION AND RECORDS (6)
A. Documentation System and Specifications (6.1)
1. All documents should be prepared, reviewed, approved, and distributed.
2. The issuance, revision, superseding, and withdrawal of all documents should be
controlled by maintaining revision histories.
3. A procedure should be established for retaining until specified retention periods

4. When entries are made in records, these should be made

indelibly in spaces provided for such entries, directly after
performing the activities, and should identify the person
making the entry.
5. Corrections to entries should be dated and signed and leave
the original entry still legible.
6. During the retention period, originals or copies of records
should be readily available
 Q7: DOCUMENTATION AND RECORDS (6)

B. Equipment Cleaning and Use Record (6.2)

1. Records of major equipment use, cleaning, sanitation, and/or

sterilization and maintenance should show the date, time (if
appropriate), product, and batch number of each batch processed in
the equipment and the person who performed the cleaning and
maintenance.

2. If equipment is dedicated to manufacturing one intermediate or API,

individual equipment records are not necessary

3. In cases where dedicated equipment is employed, the records of

cleaning, maintenance, and use can be part of the batch record or
maintained separately.
 Q7: DOCUMENTATION AND RECORDS (6)

C. Records of Raw Materials, Intermediates, API

Labeling and Packaging Materials (6.3)

Records should be maintained including:

• The name of the manufacturer, identity, and quantity of each
shipment of each batch of raw materials, intermediates, or
labeling and packaging materials for API's; and date of receipt.

• Inspection & test, status of incoming materials;

• Records tracing the use of materials;
• Documentation of testing and review for conformity with
specifications;
• Status: approved / rejected
• Master (approved) labels should be maintained for comparison
 Q7: DOCUMENTATION AND RECORDS (6)

E. Batch Production and Control Records (6.5)

(i) Actual results recorded for critical process parameters, time,
quantity measured, equipment used, sample,
(ii) Process parameters- temperature, pressure, pH etc
(iii) Signatures of the persons performing and directly supervising
or checking each critical step in the operation,
(iv) In-process and laboratory test results,
(v) Actual yield at appropriate phases or times,
vi) Description of packaging and label
vii) (vii) Any deviation noted, its evaluation, investigation
conducted (if appropriate) or reference to that investigation
 Q7: DOCUMENTATION AND RECORDS (6)
F. Laboratory control records (6.6):

Laboratory control recordsshould include complete data derived from all

tests conducted to ensure compliance
•A description of samples received for testing, including the material name
or source, batch number or other distinctive code, date sample was taken,
and, where appropriate, the quantity and date the sample was received for
testing;
•Statement of or reference to each test method used;
•Statement of the weight or measure of sample used for each test as described
by the method; data on or cross-reference to the preparation and testing of
reference standards, reagents and standard solutions;
•Complete record of all raw data generated during each test, in addition to
graphs, charts and spectra;
 Q7: DOCUMENTATION AND RECORDS (6)
F. Laboratory control records (6.6): contd

•A record of all calculations performed in connection with the test, including, for
example, units of measure, conversion factors, and equivalency factors;

•The signature of the person who performed each test and the date(s) the
tests were performed;
•The date &signature of a second person who is reviewed for accuracy,
completeness, and compliance with established standards.

•Complete records should also be maintained for:

• Any modifications to an established analytical method;
• Periodic calibration of laboratory instruments, apparatus, gauges,
and recording devices;
• All stability testing performed on APIs;
• Out-of-specification (OOS) investigations.
GMP- Documentation Requirements
•Keep in mind, after the product is released and
shipped to the customer, what remains behind is
the Document.

•Documentation / record is useful to us ONLY if it is

100% accurate.

•So it is important for us to understand and Records

Batch
•follow the Good Record Practice.
500507
 Poor documentation


?
Why do people sometimes fail to document activities or
events properly?
 Record writing /Data Entry

 Spaces and cells cannot be left “blank”!

 When spaces or cells do not contain information,

EACH must contain the appropriate “not
applicable” entry. Or N/A
 This rule applies to all product-related documents -
electronic and written.
 Record writing /Data Entry

 Never use ditto

 Never use lines (with or without arrows) to

show a continuation of values or entries in a
column or row.
 Record writing /Data Entry

 Corrections to written
records must be made
properly.
 DO NOT USE “write-
overs” (Don’t turn a
“6” or “9” into an
“8”.)
 Never vary your
initials or signature
 How to make Corrections
When an entry or calculation must be corrected, follow these steps:
•Draw a single line through the incorrect entry.
•Enter correct information above or to the side of the incorrect
entry.
•Write your initials and date of correction. Write justification if
possible
•When two people signed the original entry, and then another
changes the entry, the second person must also sign for the
change.
Weight of ingredient 14.5 kg 14.75 kg Ams 19.08.2016
Here’s how a corrected entry might look:

Don’t Deface the original Entry!

 GDP: Error Description

The following are the example of notations that may be

used to describe error corrections.
 Calculation error
 Transposition

 Illegible entry
 Wrong entry
 Good Documentation Practice

 Computer print outs taken on thermal

paper or easily fading inks should be
photocopied and maintained.
 Original shall be destroyed after verification

 Use polyvinyl alcohol base gum or white

glue for pasting of graphs etc

 Use clear transparent tape for mending

(patch-up).
 Good Documentation Practice
Don’t do ….
Don’t remove any pages or portions from a note book
Don’t make any temporary entries in a bit of paper of
hand
Preserve the notebooks intact.
Do Not Use “Sticky” Notes.
Do Not Back-Date Or Post-Date.
Do Not Use Asterisks That May Cause Confusion (Such As
Using The Same Asterisk For Different Footnotes).
Do Not Transcribe Data.
Avoid Use of Unbound Laboratory Notebooks
 Recreating And Rewriting Records
Recreating or rewriting records should be avoided.
If necessary to do this;
The supervisor and QA Approvals are required when
recreating records.
It is important to identify the recreated document as
“rewrite” and to reference the sources of the information.
Records can be recreated only when:
1. The original record is illegible
2. An incorrect form or document was used
3. The record is reparable
4. The original was in A format that would not keep (thermal paper
strips)
 Good Documentation Practice

Lab record:
Enter enough details so the document can be
understood in the future.
Documents should be signed and dated by the
person who performed the test.
A reference to the identification of the sample
analysed should be included.
 Good Documentation Practice
Witnessed / Checked/ reviewed by
• The second check : When one person performs the task and
the second person verifies that it has been performed
correctly.
• Double checking our work provides additional assurance that
no mistakes were made.
• The person who is the “verifier” must be clear as to what
they are verifying by affixing their signature to the
document.
• Examples: charging of raw materials ; Monitoring critical
parameters
 Good Documentation Practice

Reviewer:
Must be verified by a second person
Signature of the person verified
Verify within a time frame
Review he documentation:
• BPRs, Test record, material issue, Cleaning
records, calibration and equipment
records, raw data, yield & Calculations etc
Good Documentation Practice
Review of the original records when the records are
complete / after complete analysis of a sample has been
performed.
All raw data, all printed / electronic data
 Chromatogram, spectrum weight prints, This can be done on
a sheet/record where all results have been summarized
If a notebook is no longer used and unused pages are
remaining
 Draw a line across the first unused page
 Indicate “the remainder of the note book is not used”
 Sign with date
Good Documentation Practice
Check the following during review:
Missing records and out-prints
Incomplete entries
Illegible corrections
Cross References
Deviations, if any investigation the impact on the product
Valid calibrations and service intervals of test equipment
Compliance with specifications, parameter ranges or
acceptance criteria including tighter customer
specifications
Good Documentation Practice
Examples of deviations are:
Incorrect charging of raw materials.
Temperature, pressure, vacuum parameters outside
defined limits.
Operating instructions not correctly followed.
Breakdown of equipment or failure of utilities.
Equipment out of calibration.
Records not adequately completed.
Temporary alteration to defined instructions
In Process Control Limits not achieved.
Extraneous contamination of API and intermediates
Any other unplanned event.
 Good Documentation Practice

Errors or mistakes are possible – person recording is human

Correction, corrective action and preventive action
List the documentation errors /mistakes/ deviation
Classify and trend
Train the persons
Correction where possible
Report the deviation to QA
Investigation & root cause
Understand issue & take CAPA
Good Documentation Practice
Document Retention & Retrieval:
ICH Q7: 6 Documentation And Records
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.”

Store the documents & records in secured place until

retention period
 GDP Implementation
Swear to record the actual
information/ data
Be honest
Strengthen the review
Report the deviation
Train the operators or
chemists on common /
identified mistakes or errors
All this is achievable through
Positive attitude
Positive thoughts
Removal of mental blocks
Open or willing to change
Understand the need of business
Destruction of Ego
Good Documentation Practice
Summary
 Documentation is a record of our product history.
 GMP documents are legal documents & requirement.
 The “double check” (review) assures that our work is
correct.
All work should be documented at the time work is
performed.
 Correct the errors properly
 Report the deviations if any and implement the CAPA
 Train all the staffs on GDP and explain the consequences.
Questions??
Thank you