Chapter 1: Good Documentation Practices
6 Regulatory Affairs Professionals Society
and Transparency of Health Research Network (EQUATOR
Network)5 may be helpful to ensure appropriate data are
collected to meet reporting requirements.
The ICH has been instrumental in the global initia-
tive to standardize pharmaceutical product development
and regulation. In realizing its vision, ICH has taken the
lead on preventing duplication of efforts, reducing product
development timelines, streamlining product approvals, and
contributing to human health protection.
The ICH created and implemented the Common
Technical Document for the assembly of all the quality,
safety, and efficacy information into a comprehensive dossier
for regulatory reviews in each member region. It consolidated
the documentation necessary for a product to be adequately
reviewed and approved efficiently. Regulatory authorities,
industry sponsors, and the public have benefited from this
important ICH initiative.
Elements of Good Clinical Practice, Good
Manufacturing Practice, and Good Laboratory Practice
requirements can be employed when establishing an effective
GDP system. Table 1-1 includes some available resources for
developing a GDP system.
Using Form FDA 483 Observations to Refine
a Good Documentation System
Form FDA 483 is issued to firm management after any
inspection when an FDA investigator has observed any con-
dition they believe may constitute violations of the Federal
Food, Drug, and Cosmetic Act and related acts.6 Often,
the deficiencies cited include the lack of GDPs (i.e., design
controls, certificates of analysis/conformance, calibrations or
validations, postmarket studies, and pharmacovigilance or
complaint handling.)
The most constructive way to approach a Form FDA
483 observation is to consider each deficiency cited as an
opportunity to take corrective action and improve operational
processes and procedures.
Some of the most recent Form FDA 483 findings can
be found on the FDA website and are made available to the
public through the Office of Inspections and Investigations
Freedom of Information Act (FOIA) Reading Room.7
The lessons learned, preferably at the expense of other
organizations, are invaluable. They include the following doc-
umentation-related observations that organizations should
take the time to review, understand, and avoid proactively. The
following are some sample findings from the FOIA Reading
Room:
• The organization failed to maintain complete data from
all laboratory tests conducted to ensure compliance with
established product specifications and internal quality
standards.
• Laboratory records did not contain all raw data gener-
ated during each test for active pharmaceutical ingredient
batches.
• A sample failed the purity specification limit, but the
failure was not documented.
• Sample preparation information was not documented,
and quality control records used to support the Drug
Master File and batch disposition decisions did not
include all testing results.
• None of the explanations justifies the failure to maintain
complete records neither do they support the practice of
substituting repeat tests for failed results.
• The organization failed to prevent unauthorized access
or changes to data and provide adequate controls to
prevent data omission no passwords are required to log
into the databases, credentials are unverified, and there
is no electronic or procedural control to prevent data
manipulation.
• The software lacks an audit trail feature to document all
activities related to the analysis performed staff cannot
demonstrate records include complete and unaltered data
or verify there have been no alterations or deletions.
• The organization has no raw data for the test limits
reported on the Certificates of Analyses the release of
these batches was approved without data to support that
release specifications were met.
• The organization is responsible for having controls to
prevent data omissions and recording any changes made
to existing data, including the date of the change, the
identity of the person who made the change, and an
explanation or reason for the change.4
Building a Robust GDP System
Consider all Applicable Documentation
The following documents should be considered in regulated
industry environments:
• Research and development
o Conception plans
o Prototype designs
o Engineering drawings
o User requirements
o Specification requirements
o Drug and formulation development reports
o Nonclinical study reports (both non-GLP and GLP)
o Clinical study protocols
o Investigator’s Brochures
o Informed consent forms
o Case Report Forms
o Clinical study reports
o Design history file
o Development Safety Update Reports
• Sponsor narratives
• Commercialization
o FDA presubmission communications
o Supportive documentation for regulatory submissions
o Manufacturing SOPs
o Validation and stability reports
o Batch records
o Certificates of Analyses
o Labeling justifications and finalization
o Regulatory applications or dossiers
• Postmarket
6 Regulatory Affairs Professionals Society
and Transparency of Health Research Network (EQUATOR
Network)5 may be helpful to ensure appropriate data are
collected to meet reporting requirements.
The ICH has been instrumental in the global initia-
tive to standardize pharmaceutical product development
and regulation. In realizing its vision, ICH has taken the
lead on preventing duplication of efforts, reducing product
development timelines, streamlining product approvals, and
contributing to human health protection.
The ICH created and implemented the Common
Technical Document for the assembly of all the quality,
safety, and efficacy information into a comprehensive dossier
for regulatory reviews in each member region. It consolidated
the documentation necessary for a product to be adequately
reviewed and approved efficiently. Regulatory authorities,
industry sponsors, and the public have benefited from this
important ICH initiative.
Elements of Good Clinical Practice, Good
Manufacturing Practice, and Good Laboratory Practice
requirements can be employed when establishing an effective
GDP system. Table 1-1 includes some available resources for
developing a GDP system.
Using Form FDA 483 Observations to Refine
a Good Documentation System
Form FDA 483 is issued to firm management after any
inspection when an FDA investigator has observed any con-
dition they believe may constitute violations of the Federal
Food, Drug, and Cosmetic Act and related acts.6 Often,
the deficiencies cited include the lack of GDPs (i.e., design
controls, certificates of analysis/conformance, calibrations or
validations, postmarket studies, and pharmacovigilance or
complaint handling.)
The most constructive way to approach a Form FDA
483 observation is to consider each deficiency cited as an
opportunity to take corrective action and improve operational
processes and procedures.
Some of the most recent Form FDA 483 findings can
be found on the FDA website and are made available to the
public through the Office of Inspections and Investigations
Freedom of Information Act (FOIA) Reading Room.7
The lessons learned, preferably at the expense of other
organizations, are invaluable. They include the following doc-
umentation-related observations that organizations should
take the time to review, understand, and avoid proactively. The
following are some sample findings from the FOIA Reading
Room:
• The organization failed to maintain complete data from
all laboratory tests conducted to ensure compliance with
established product specifications and internal quality
standards.
• Laboratory records did not contain all raw data gener-
ated during each test for active pharmaceutical ingredient
batches.
• A sample failed the purity specification limit, but the
failure was not documented.
• Sample preparation information was not documented,
and quality control records used to support the Drug
Master File and batch disposition decisions did not
include all testing results.
• None of the explanations justifies the failure to maintain
complete records neither do they support the practice of
substituting repeat tests for failed results.
• The organization failed to prevent unauthorized access
or changes to data and provide adequate controls to
prevent data omission no passwords are required to log
into the databases, credentials are unverified, and there
is no electronic or procedural control to prevent data
manipulation.
• The software lacks an audit trail feature to document all
activities related to the analysis performed staff cannot
demonstrate records include complete and unaltered data
or verify there have been no alterations or deletions.
• The organization has no raw data for the test limits
reported on the Certificates of Analyses the release of
these batches was approved without data to support that
release specifications were met.
• The organization is responsible for having controls to
prevent data omissions and recording any changes made
to existing data, including the date of the change, the
identity of the person who made the change, and an
explanation or reason for the change.4
Building a Robust GDP System
Consider all Applicable Documentation
The following documents should be considered in regulated
industry environments:
• Research and development
o Conception plans
o Prototype designs
o Engineering drawings
o User requirements
o Specification requirements
o Drug and formulation development reports
o Nonclinical study reports (both non-GLP and GLP)
o Clinical study protocols
o Investigator’s Brochures
o Informed consent forms
o Case Report Forms
o Clinical study reports
o Design history file
o Development Safety Update Reports
• Sponsor narratives
• Commercialization
o FDA presubmission communications
o Supportive documentation for regulatory submissions
o Manufacturing SOPs
o Validation and stability reports
o Batch records
o Certificates of Analyses
o Labeling justifications and finalization
o Regulatory applications or dossiers
• Postmarket