Regulatory Writing: An Overview 20
Drugs/GuidanceComplianceRegulatory
Information/Guidances/UCM070336.pdf )
• Guidance for Industry: Current Good
Tissue Practice (CGTP) and Additional
Requirements for Manufacturers of
Human Cells, Tissues, and Cellular
and Tissue-Based Products (HCT/Ps)
(December 2011) (http://www.fda.gov/
downloads/BiologicsBloodVaccines/
GuidanceComplianceRegulatory
Information/Guidances/Tissue/
UCM285223.pdf )
• ISO 9001—2015 Clause 7.5 Documented
Information
• Guide to GMP for Medicinal Products
Part 1, Chapter 4 Documentation: PIC/S
PE 009-8 (Part I)
Using Form FDA 483 Observations
to Create a Good Documentation
System
Form FDA 483 is issued to firm management
after any inspection when an FDA investigator has
observed any condition they believe may constitute
violations of the Federal Food, Drug, and Cosmetic
Act (FD&C Act) and related acts.2 Often, the defi-
ciencies cited include the lack of GDPs, i.e., design
controls, clinical studies, certificates of analysis/
conformance, calibrations or validations, postmarket
studies, and pharmacovigilance or complaint handling.
The most constructive way to approach a Form
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 FDA’s website and are
made available to the public through the Office of
Regulatory Affairs (ORA) Freedom of Information
Act (FOIA) reading room.3 The lessons learned,
preferably at the expense of other organizations, are
invaluable and include the following documenta-
tion-related observations organizations should take
the time to review, understand, and avoid proac-
tively. 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 generated during each test for active
pharmaceutical ingredient (API) 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 fail-
ure to maintain complete records neither
do they support the practice of substituting
repeat tests for failed results.
• The organization failed to prevent unautho-
rized 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 anal-
ysis 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 (COAs) the release of these
batches was approved without data to sup-
port that release specifications were met.
• The organization failed to ensure equip-
ment is cleaned in a reproducible and
effective manner to prevent contamination
of a material that would alter API quality.
• FDA inspection revealed serious documen-
tation practices and reported missing raw
data, which compromised APIs’ quality and
accountability in the supply chain.
• 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
Drugs/GuidanceComplianceRegulatory
Information/Guidances/UCM070336.pdf )
• Guidance for Industry: Current Good
Tissue Practice (CGTP) and Additional
Requirements for Manufacturers of
Human Cells, Tissues, and Cellular
and Tissue-Based Products (HCT/Ps)
(December 2011) (http://www.fda.gov/
downloads/BiologicsBloodVaccines/
GuidanceComplianceRegulatory
Information/Guidances/Tissue/
UCM285223.pdf )
• ISO 9001—2015 Clause 7.5 Documented
Information
• Guide to GMP for Medicinal Products
Part 1, Chapter 4 Documentation: PIC/S
PE 009-8 (Part I)
Using Form FDA 483 Observations
to Create a Good Documentation
System
Form FDA 483 is issued to firm management
after any inspection when an FDA investigator has
observed any condition they believe may constitute
violations of the Federal Food, Drug, and Cosmetic
Act (FD&C Act) and related acts.2 Often, the defi-
ciencies cited include the lack of GDPs, i.e., design
controls, clinical studies, certificates of analysis/
conformance, calibrations or validations, postmarket
studies, and pharmacovigilance or complaint handling.
The most constructive way to approach a Form
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 FDA’s website and are
made available to the public through the Office of
Regulatory Affairs (ORA) Freedom of Information
Act (FOIA) reading room.3 The lessons learned,
preferably at the expense of other organizations, are
invaluable and include the following documenta-
tion-related observations organizations should take
the time to review, understand, and avoid proac-
tively. 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 generated during each test for active
pharmaceutical ingredient (API) 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 fail-
ure to maintain complete records neither
do they support the practice of substituting
repeat tests for failed results.
• The organization failed to prevent unautho-
rized 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 anal-
ysis 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 (COAs) the release of these
batches was approved without data to sup-
port that release specifications were met.
• The organization failed to ensure equip-
ment is cleaned in a reproducible and
effective manner to prevent contamination
of a material that would alter API quality.
• FDA inspection revealed serious documen-
tation practices and reported missing raw
data, which compromised APIs’ quality and
accountability in the supply chain.
• 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