GOOD DOCUMENTATION

PRACTICES IN
PHARMACEUTICAL INDUSTRY

Prepared by
Pavan Kumar Puram
Regd.no:190609017
M Pharm 1st semester

Guide:
Dr. Swapnil J. Dengale
Associate professor

DEPARTMENT OF PHARMACEUTICAL QUALITY

ASSURANCE
MANIPAL COLLEGE OF PHARMACEUTICAL SCIENCES
MAHE, MANIPAL

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DEFINITIONS:

Document:
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.

INTRODUCTION
The GDP can be defined as “Good documentation practice is an essential
part of the quality assurance and such, related to all aspects of GMP” this
definition is based on WHO.

The effective control and management of documentation is a critical part of

the good manufacturing practices (GMP) program within the organization.

The accurate capture of information plays an important part in the

manufacture of pharmaceuticals and medical devices

GMP is the part of quality assurance which ensures that products are
consistently produced and controlled to the quality standards appropriate for their
intended use
To comply with GMP, facilities require documented systems based on
specifications, manufacturing, and packaging instructions, procedures, and
records. In particular, specific batch manufacturing documentation must be in
place. These documents must make it possible to trace the history of each batch.
This traceability needs to be possible for a minimum defined period that is

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typically one year after expiry of the batch. These types of records are essential
for the quality assurance system.

Documentation is also a key to GDP compliance for it ensures traceability

of all development, manufacturing and testing activities. Documentation provides
the route for auditors to assess the overall quality of operations within a company
and the final product. For example, with the FDA Code of Federal Regulations
(CFR), 21CFR 211.180(e), records and reports, states: “written records…shall be
maintained so that data therein can be used for evaluating…the quality standards
of each drug product…” This extract there by links the importance of good
documentation to GDP.

This paper presents an overview of good documentation practices applicable

to those working in the pharmaceutical and healthcare sectors specific topics for
discussion include the following:

▪ Good manufacturing practice and documentation including errors and error

correction
▪ Document management
▪ Types of documents
▪ Best practices for document creation, including style and layout
▪ Completing documents and record-keeping
▪ Electronic records
▪ Document storage

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PRINCIPLES OF GDP:

Attributable:

‘Attributable’ means information is captured in the record such that it is

uniquely identified as executed by the originator of the data (e.g., a person and/or
a computer system)

Legible:

The terms ‘legible’, ‘traceable’ and ‘permanent’ refer to the requirements

that data are readable, understandable and allow a clear picture of the sequencing
of steps or events in the record.

Contemporaneous:

Activities that are recorded at the time when they occur. Entries into GMP records
are dated and/or time stamped to document when the activities occur

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Original:
First capture of the data. Original records (or certified copies of the original
records) must be reviewed and retained for future reference.

Accurate:

Correct in all aspects or details. Accuracy is assured through

equipment/instrument qualification, calibration and maintenance, validation,
adherence to policies and procedures, data review, and self-inspection.

• 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 writing
• 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

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Why do people sometimes fail to document activities or events properly?

▪ People doesn’t clearly understand what or when to document.

▪ Procedures may not be completely understood or followed.
▪ People aren’t always held accountable.
▪ People will make mistakes.
▪ People doesn’t always make corrections properly.
▪ People do not relate records to auditing.
▪ People don’t understand the legal role of documentation

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.

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GOOD MANUFACTURING PRACTICE AND DOCUMENTATION

There are a number of aspects of GMP that relate to documentation. GMP

requires that documents should be:

▪ Controlled within the quality system

▪ Approved, signed and dated
▪ Regularly reviewed
▪ Retained, and
▪ Can be superseded within the quality system.

Pharmaceutical and other healthcare organization must have “good”

documentation practices. Whether the term “GDP”’ should be used to represent
“good documentation practice” is contentious since GDP is more commonly used
as an acronym for “good distribution practice”’ in relation to the distribution of
medicinal products.

Types of Documentation:

Documentation refers to both printed forms and electronic systems.

Broadly speaking, documentation types can be classified as:

▪ Specifications
▪ Manufacturing and packaging instructions
▪ Standard operating procedures
▪ Records.

More specifically, the various types of documents found within a typical

pharmaceutical organization include:

• Technical agreements
• Confidentiality agreements
• Technical reports
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 • Quality system related documents
• Quality Manual
• SOP’s
• Validation protocols and reports
• Deviation reports
• Audit plans
• Validation Master Plans and validation documents including URS, DQ,
FAT, IQ, OQ, PQ, and Validation reports
• Test material related documents including product specification, test
material receipt, and reports
• Personnel related documents including training records
• Facility related documents including floor plans, HVAC plans, and
environmental specifications
• Deviation forms including unplanned deviations and system failure
investigation
• Change control
• Worksheets, notebooks, and logbooks

Documentation must be clear free from errors, subject to regular review, and be
kept up-to-date.

Responsibilities
GMP requires that the management of each facility defines responsibility
for origination, distribution, maintenance, change control, and archiving of all
GMP documentation and records within a given department or unit. At the
departmental level, document owners are required to ensure acceptability of all
aspects of documentation and records management. The documentation systems
should be audited periodically by the quality assurance function. Despite control

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systems and application of the audit process, regulators frequently cite
documentation errors and poor practices at inspection.

Document Errors:
Common documentation errors that commonly appear in FDA warning
letters and reports from other regulatory authorities include:

▪ Documentation not contemporaneous

▪ Use of ditto marks
▪ Use of signature stamp
▪ Failure to use ink as specified by procedure
▪ Incorrect ink used for entries causing illegible data when a substance was
spilled
▪ Logbook corrections failed to identify person who made the changes
▪ Obscured original data
▪ Use of pencil
▪ Inaccurate records
▪ Sample sequence table and audit trail not documented (to draw on the
commonly used phrase: “if it is not documented, it didn’t happen”)
▪ Handwritten changes not dated
▪ Write-overs, multiple line-through, and use of "white-out" or other
masking device

The most common GMP citation occurs with correction of errors when
information is recorded. Correction of documentation errors should include:

▪ Draw a single line through the error,

▪ Make the correction next to the error,
▪ Write an explanation for the error,
▪ Sign and date the correction.

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It is recommended that these common errors are highlighted in training on the
creation and use of documentation

Document Management
Each pharmaceutical organization should have a system for
documentation management. This sets out the rules and mechanisms for creating
and controlling a document. GMP makes certain requirements of a documentation
system such as:

▪ Assigning responsibility to an individual for control of the system

▪ Ensuring layout, approval, authorization and unique identification of all
documents is provided for often by a master documentation SOP
▪ Having a master documentation SOP to include:

> Procedures for issue, retrieval, re-issue, maintenance of currency and

traceability

> Procedures for determining the need for documents

> Identification of documents to be included in batch dossiers (for batch release)

> Linkage of documents to licenses and regulatory requirements

> Outlining audit requirements for the documentation system

> Ensuring that only the most up to date version is ever used

> Retention times and archiving

Document Control
Further considerations regarding the system controlling documentation include:

▪ Documents should be available at point of use

▪ Masters, including electronic versions, are held under control
▪ There is control over format
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 ▪ There is a system for changes, approval, and re-issue
▪ There is control of documents of an external origin.

The majority of these requirements also make up the elements of the

“documentation lifecycle” — From document creation, through its use, to its
storage and archiving, and then to its eventual retirement and possibly
replacement by a revised version.

The control of documents necessitates the following steps:

1. Documentation creation:
▪ Documents must be contemporaneous with the event they describe
▪ Documents must not be handwritten (except for handwritten entries)
▪ When electronically produced, the documentation must be checked for
accuracy
▪ Free from errors
▪ For some types of data, the documentation must be in a format that
permits trend evaluation.

2. Document approval:
▪ Documents must be approved for use. They must be approved, signed,
and dated by appropriate authorized personnel.
3. Handwritten entries:
▪ Adequate space needs to be provided for expected handwritten entries
▪ Handwritten entries must be in indelible ink
▪ Critical entries must be independently checked (second person verified)
▪ No spaces for handwritten entries should be left blank. If unused, they
are crossed out or "n/a" (or similar text) entered
▪ Ditto marks or continuation lines are not acceptable
▪ A stamp in lieu of a handwritten signature is not acceptable

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4. Document copies
▪ Copies need to be clear and legible
▪ Errors must not be introduced
▪ Documents should be regularly reviewed and kept current,
▪ Documents should be retained and readily available for audits
▪ Archived documents must be retrievable for the appropriate duration
▪ Electronic document management systems must be validated
▪ Electronic records must be backed up.

5. Document modification
▪ Handwritten modifications are signed and dated
▪ Altered text should not be obscured (e.g., no obliterating the text through
crossing-out)
▪ Where appropriate, the reason for alteration must be noted (for example,
"e.e." is a common abbreviated reason, indicating "entry error")
▪ Controls exist to prevent the inadvertent use of superseded documents.
▪ Electronic versions should only be modified by authorized personnel
▪ Access to electronic documents must be controlled by password or other
means.

A history (audit trail) must be maintained of changes and deletions to

electronic documents. Well-designed documentation and appropriate
documentation are paramount. It is necessary to document every aspect of the
process, activities, and operations involved with drug and medical device
manufacture. If the documentation showing how the product was made and
tested (which enables traceability and, in the event of future problems, recall
from the market) is not correct and in order, then the product does not meet
the required specification and could be considered to be adulterated.

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TYPES OF DOCUMENTS:
The different types of documents found with-in pharmaceutical and
medical device facilities were described earlier. The main types of documents
are now discussed in more detail with differences between the different types
noted.
Specifications:
Specifications are documents related to starting materials, packaging
components, and finished products. They describe the standards to which
these materials and products must comply if they are to be approved for use
in manufacturing or for commercial sale. For example, the furnished product
specification should contain:
• The designated name of the product and the code reference where
applicable
• The formula or suitable a reference
• A description of the pharmaceutical form and package details
• Directions for sampling and testing or a reference to procedures
• The qualitative and quantitative requirements with the acceptance limits.
For example, the sterility test or absence of specified pathogens.
• The storage conditions and any special handling precautions, where
applicable
• Shelf life

Instructions:
All instructions to personnel (for example, media manufacture, bacterial
identification, analytical methods, and so on) should be clear, precise,
unambiguous, and written in numbered steps. They should be written in a
language and style that the user can readily understand. Associated with

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instructions are records. These can be either combined with the instruction or
in a separate document.
Batch Documentation
A major element in final product release should be a review of all the
relevant batch documentation to ensure the presence of all necessary
information and the satisfactory completion of all necessary records. This will
include sterilizer charts, microbiological testing certificates of analysis,
process records, test results, and so on.
Procedure s and Records:
In addition to the instruction and associated records described above,
specific procedures including material receipt, sampling, testing rejection,
complaints, and other documents are also required.
Depending of the type of document GMP expectations are that the
document carries:
▪ Product name
▪ Description of the item
▪ Reference number and item code
▪ Pack or batch size
▪ List of materials
▪ Specific precautions or instructions
▪ Names of associated personnel
▪ Dates and times
▪ Version number
▪ Approvals

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BEST PRACTICES FOR DOCUMENT CREATION AND
USE:
A company should continually evolve good practices for creation of
documents. It is important that documents are designed, prepared, reviewed,
and distributed with care. Documents also must be approved, signed, and
dated by the appropriate competent and authorized persons. Further,
documents must be regularly reviewed and kept up-to-date. When a document
has been revised, systems must be operated to prevent inadvertent use of
superseded documents. It is especially important that only current
documentation should be available for use. A further important consideration
is to ensure that the records can be kept in an orderly fashion to facilitate
retrieval at some unspecified time in the future

Best practices extend to the writing of the document. Using words that
everyone can understand – minimizing jargon, acronyms, and abbreviations -
- and using words with unambiguous meaning can help the reader to more
easily understand and interpret the document. Key “readability” qualities for
a document include:
✓ Concise: Present information clearly so it can be easily understood
with no room for misinterpretation. For example, the date format
“06/05/14” can cause confusion. It is better to use one that is
unambiguous, such as “05 june2014,” especially if the document is used
in the US and Europe.
✓ Legible: Information should be readable and leave no room for error.
For example, hand-written data that are not legible may create errors in
data analysis or result in missing data.
✓ Accurate: Documentation should be error-free―properly reviewed,
verified and approved. Information should be recorded as an event

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 happens and not after the fact to avoid recording “what you remember”
rather than “what actually happened.”
✓ Traceable: Documentation should be traceable. It should be made
clear who logged the information, what it was, and when and why it
was documented.
To help with efficient location of records, attention should be paid
to numbering including the version number for traceability. Simple sequential
number of documents only works for a small number of documents. In most
cases a defined structure to the numbering system is needed. For example,
001 - 100 could represent regulatory documents, 101 – 200 could represent
QC testing documents, and 201 -300 could represent production
documentation. This system may still limitting. The numbering system may
need to include references to the site, a system (production, QC, validation,
and so on) as well as its sequential number.

Document Style and Layout:

It is often helpful to adopt a specific document style for consistency of
operations. Elements of the style should be specified in an approved
procedure. These might include:
▪ Logo
▪ Pagination/ layout to prevent confusion and ensure the document is kept in
order
▪ Headers and footers
▪ Font including the size is useful to minimize errors introduced when
changing between fonts
▪ Page numbers
▪ Executive summary
▪ Changes - Change control is important for traceability

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▪ Circulation list - to ensure the document is reviewed and received by the
appropriate personnel
▪ Table of contents
▪ Authorization levels stated on document
▪ Cross references
▪ Revision history
▪ Definitions
▪ Content (context and meaning)
▪ A clear area for recording problems/ incidents
▪ Use of pictures, flow charts, diagrams as suitable alternatives to text.
Care should be taken in designing and stylizing documentation.
Documents must have unambiguous contents. The title, nature, and purpose
should be clearly stated. They must be laid out in an orderly fashion.
Documents must be easy to check. Reproduced documents must be clear and
legible. Many people do not consider the importance of how key information
is presented within a document. This can result in the reader wasting time or
not conducting the correct tasks. For example, a poorly structured document
could ask the user to conduct a task that requires some action to be performed
prior to the subject task – but only mentions the pre-work at the end of the
document and with no reference to the pre-work at the beginning.

Helpful considerations for layouts include the following:

▪ Cover page with identifiers and status
▪ Table of contents – creating a road map through the document
▪ Scope and applicability section
▪ Introduction
▪ Information and instructions in a logical sequence
▪ Additional information and detail.

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 Numerical information must include the correct use of units. The use
of colour coding in graphical information, such as black lines for existing
pipework and red lines for new pipe-work, might also be useful.
The narrative must consider writing style, nomenclature, and dealing
with errors and corrections. When considering the numerical issues, what are
viewed as standard units? Think about mathematical symbols and the order
in which calculations are performed.

For example, the bodmas approach (b)rackets (o)rder (d)divide (m)ultiply

(a)ddition (s)ubtraction, is useful. If someone gets the sequence wrong, they
will get the wrong result. It is also important to think about the rules on
rounding, i.e., Above0.5, round up, etc. Finally, consider standardizing
symbols in drawings.
It is useful to consider different styles to accommodate the different
reading styles of readers. There are thought to be three styles based on the
linguistic, logical and spatial talents. These can be summarized as:
▪ Linguistic talent. There is a strong ability to write and talk frequently.
Phrases like “gift of the gab” often apply. Individuals in this category
can also write and read well. Shakespeare had linguistic talent.
▪ Logical talent. There is strong ability to think logically and are quick
in calculating odds and statistics. Albert Einstein had logic talent.
▪ Spatial talent. There is strong ability to image things in the “mind’s
eye.” These people often have good navigational skills such as
Christopher Columbus.

The following should be considered whenever possible:

▪ Narrative – written text
▪ Tabular – tables
▪ Charts – bar charts, pie charts

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 ▪ Colour – bold – underlined text
▪ Pictures – photographs, images
▪ Diagrams – 2D, 3D
▪ Process logic – Flowcharts
Including various combinations of the above is extremely useful. A
flow chart might help with navigating the document while pictures are very
useful in dressing procedures for entry into cleanrooms. Tables are useful for
summarizing data such as microbial limits for environmental monitoring.

The use of cross referencing in documents is helpful in keeping the

document short and manageable. Be careful of cross referencing too many
documents as this can be self-defeating. The user will not follow the procedure
if they have to locate too many other documents.
Finally, consideration of the end user when writing is also extremely
important. Too often documents are written by managers or technical staff
without thought for the people that will be using them. Ideally it is
recommended that the end user writes the document.

COMPLETING DOCUMENTS AND RECORD-KEEPING:

After documents have been designed, prepared, and approved, they must
be used and completed properly. For example, where documents require the
entry of data, these entries must be made in clear legible handwriting using a
suitable indelible medium not a pencil. Sufficient space must be provided for
entries. With such entries, it is important that any correction made to a
document or record must be signed or initialled and dated; the correction must
permit the reading of the original information. Where appropriate, the reason
for the correction must be recorded.

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With record-keeping in general, a record must be kept at the time each action
is taken. All activities concerning the conduct of preclinical studies, clinical
trials, and the manufacture and control of products must be traceable.

ELECTRONIC RECORDS:
The advent of computerized systems caused industry to move away from
paper-based systems to paper-less systems. Electronic records offer many
advantages. The reality is that typically there is a balance between the two.
For example, consider a record for the absence of pathogen test on a non-
sterile product. Recording the test result presents us with two options.

Firstly it can and often is written on a log sheet. Secondly we can use a
laboratory information management system (LIMS) to record the result
electronically.

As a controlled form it will be created in Microsoft Word (electronic) and

printed onto paper to check it so it can be signed for approval giving it status.
This can be done on screen but many people prefer to review a hard copy.
Approval can be electronic recording user name and password, or the printed
document can be physically signed. In the latter case, the approved document
could be scanned so it can be stored, distributed, and referenced electronically.
A physically approved document will need photocopying if it is to be
distributed in the “paper world.” Electronic distribution of a physically signed
document can save on paper but does present problems mainly from the
scanning process. A scan that creates a picture of the original will be a very
large file. Use of optical character recognition in the scanning process
produces small files, but the scanning process introduces errors where
characters may get missed or replaced requiring a further proof read often
from a paper printout. During the active stage, personnel may prefer a hard
copy to work from so that an electronic document will be printed onto paper.

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 Archiving of paper records is costly in terms of space and to some degree
retrievability, but little more in terms of maintenance. Archiving of electronic
records presents more challenging problems. They only exist as a series of
“1’s” and “0’s” (binary code) on storage media like a CD ROM. With
electronic record archiving, the technology window must be understood. This
means that the data might be available on the CD, but after 5 years there may
not be any hardware that can read it. Essential to electronic record archiving
is that companies have an adequate migration strategy. Paper records are still
usable after several thousand years but data on discs may be lost after only 5-
10 years, or a shorter period if the discs are not properly controlled. The
migration strategy should also include the regular transfer of data onto fresh
media, even if the hardware has not changed.
The requirements for electronic records and signatures are dealt within
the US title 21 part 11 of the Code of Federal Regulations (CFR). Although
organizations do not have to use electronic records and signatures, if they do,
they must comply with the CFR. It is important that such records are afforded
the equivalence to paper records and hand written signatures. The CFR make
it clear that procedures shall be followed, records should be documented at the
time of performance, and deviations recorded and justified.

DOCUMENT STORAGE:
Storage of critical records must at secure place, with access limited to
authorized persons. In relation to this, 21CFR 211.180(d) States “…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.”
The storage location must ensure adequate protection from loss,
destruction, or falsification, and from damage due to fire, water, and other

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disasters. Records which are critical to regulatory compliance or to support
essential business activities must be duplicated on paper, micro-film, or
electronically, and stored in a separate, secure location in a separate building
from the originals.
Data may be recorded by electromagnetic or photographic means, but
detailed procedures relating to whatever system is adopted must be available.
Accuracy of the record should be checked as per the defined procedure. If
documentation is handled by electronic data processing methods, only
authorized persons should be able to enter or modify data in the computer,
access must be restricted by passwords or other means, and entry of critical
data must be independently verified.
If electronic, photographic or other data processing systems are used
for the retention of documents, an appropriate storage for required duration is
necessary to protect against loss or damage. It is particularly important that
during the period of retention, the data can be rendered retrievable and legible
within an appropriate period of time. This means having a validated system
of data recall. The data should also be available in a legible form. Rapid
retrieval of re-ports and data is essential for audits.

SUMMARY:
This paper has presented an overview of the main types of
documentation found within the pharmaceutical and medical device sectors.
It has provided suggestions for good practice examples of how the
documentation can be designed, produced, and controlled as part of a
compliant GMP system. Good documentation practices are an essential part
of GMP and compliance. When implemented, the recommendations presented
in this paper will help with maintaining control and ensuring compliance in a
GMP environment.

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References:

https://www.researchgate.net/publication/266559180_Good_documentatio
n_practices
https://www.ipa-india.org/static-files/pdf/event/ipf2018 presentation22.pdf
https://www.slideshare.net/DrAmsavelvel/good-documentation-practice-
88810012
https://www.slideshare.net/PiyushWagh6/good-documentation-practices-
dos-and-donts-gcp

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