The document discusses documentation and standard operating procedures (SOPs) for GMP compliance. It describes issues found at a pharmaceutical company (Goran Pharma) regarding inadequate testing of glycerin lots for impurities. The FDA found the company's responses to be inadequate. The document also discusses how to properly write SOPs, including getting appropriate reviews and authorization. It provides examples of documentation issues found during an FDA inspection at another company (Lupin) regarding inadequate cleaning processes and validation. The FDA requested extensive corrective and preventative actions from Lupin to address their cleaning validation program and ensure proper documentation and process controls.
13. Goran Pharma
April 2018
Laboratory results will be
compared with supplierās COA
to confirm the reliability of
testing for all lots
Revised SOP
14. Goran Pharma
April 2018
Not clear whether testing on each incoming
component lot for all attributes to verify the
accuracy of supplierās COA will be done
OR
Supplierās test results will be qualified
through an initial round of testing as well
as ongoing testing at appropriate intervals
FDA: Inadequate Response
15. Goran Pharma
April 2018
Not clear whether testing on each incoming
component lot for all attributes to verify the
accuracy of supplierās COA will be done
OR
Supplierās test results will be qualified
through an initial round of testing as well
as ongoing testing at appropriate intervals
FDA: Inadequate Response
16. Goran Pharma
April 2018
Not clear whether testing on each incoming
component lot for all attributes to verify the
accuracy of supplierās COA will be done
OR
Supplierās test results will be qualified
through an initial round of testing as well
as ongoing testing at appropriate intervals
FDA: Inadequate Response
17. Laboratory results will be
compared with supplierās COA
to confirm the reliability of
testing for all lots
18. Laboratory results will be
compared with supplierās COA
to confirm the reliability of
testing for all lots
Not clear whether testing on each incoming
component lot for all attributes to verify the
accuracy of supplierās
OR
Supplierās test results will be qualified through an
initial round of testing as well as ongoing testing at
appropriate intervals
20. Compliance
Finished dosage form will be
subject to end product testing
before release from the GMP zone
for the market
Write an instruction that may
diminish the regulatory intent if
written in SOP
Group Working
21. Compliance
Finished dosage form will be
subject to end product testing
before release from the GMP zone
for the market
Write an instruction that may
diminish the regulatory intent if
written in SOP
Group Working
22. Compliance
E.g. In case of Injectables
Sterility test: Product may be
released after 12 days upon
observing no growth. Two days
are consumed in distribution or to
reach market.
Group Working
23. Compliance
E.g. In case of Tablets
Every 5th batch of oral solid
dosage form will be subject
to dissolution test
Group Working
24. Compliance
E.g. In case of Tablets
Every 3rd batch of oral solid
dosage form will be subject
to microbial testing
Group Working
25. Compliance
E.g. In case of Oral Liquid
Solution
Assay will be performed
before filling of every solution
and not after packaging
Group Working
33. If someone reads detail
procedure to swim
Can he swim independently?
Opening Question
100% 50% 10% 0%
1
34. If someone reads detail
procedure to swim
Can he swim independently?
Opening Question
100% 50% 10% 0%
1
35. How much you are sure that someone
can manufacture tablets if he follows
the written SOP and these tablets will
be of desired quality?
Opening Question
100% 50% 10% 0%
2
36. How much you are sure that someone
can manufacture tablets if he follows
the written SOP and these tablets will
be of desired quality?
Opening Question
100% 50% 10% 0%
2
47. Policies
ā¢ Documents used to influence and dictate
actions / decisions
ā¢ Broad in scope and affect typically
different organizational/ business/
geographical units
ā¢ Describes requirements but NOT
specifics on how to accomplish tasks
48. Policies
ā¢ Documents used to influence and dictate
actions / decisions
ā¢ Broad in scope and affect typically
different organizational/ business/
geographical units
ā¢ Describes requirements but NOT
specifics on how to accomplish tasks
49. Policies
ā¢ Documents used to influence and dictate
actions / decisions
ā¢ Broad in scope and affect typically
different organizational/ business/
geographical units
ā¢ Describes requirements but NOT
specifics on how to accomplish tasks
64. Question
A company has a Cleaning Policy in place but
donāt have a procedure to execute for
cleaning of water tank inside GMP zone
It is outsourced & performed by 3rd party,
company is unaware about the procedure of
cleaning used by them.
You are Inspector. Please write detail what
are your concerns with regard to Quality (Q)
& Compliance (C)
3
65. Question
If a mixer is run for 15 minutes, it
mixes the materials because it is
repeated 3 times and validated,
Is it logical to waive
in-process tests?
4
66. Workshop
Write instruction how to clean a pipe
piece used in filling of water in
manufacturing unit
Write instructions to hang a wall
clock, adjust its time, change of its
battery periodically, and its
monitoring
OR
68. Workshop
How to write SOP
ā¢ Concept ā¦begin with the end in mind
ā¢ Select a format (approved)
ā¢ Collect the inputs
ā¢ Define scope
ā¢ Identify the audience
ā¢ Write SOP
ā¢ Send for review
ā¢ Answer the questions
ā¢ Get it authorized
69. Workshop
How to write SOP
ā¢ Concept ā¦begin with the end in mind
ā¢ Select a format (approved)
ā¢ Collect the inputs
ā¢ Define scope
ā¢ Identify the audience
ā¢ Write SOP
ā¢ Send for review
ā¢ Answer the questions
ā¢ Get it authorized
70. Workshop
How to write SOP
ā¢ Concept ā¦begin with the end in mind
ā¢ Select a format (approved)
ā¢ Collect the inputs
ā¢ Define scope
ā¢ Identify the audience
ā¢ Write SOP
ā¢ Send for review
ā¢ Answer the questions
ā¢ Get it authorized
71. Workshop
How to write SOP
ā¢ Concept ā¦begin with the end in mind
ā¢ Select a format (approved)
ā¢ Collect the inputs
ā¢ Define scope
ā¢ Identify the audience
ā¢ Write SOP
ā¢ Send for review
ā¢ Answer the questions
ā¢ Get it authorized
72. Workshop
How to write SOP
ā¢ Concept ā¦begin with the end in mind
ā¢ Select a format (approved)
ā¢ Collect the inputs
ā¢ Define scope
ā¢ Identify the audience
ā¢ Write SOP
ā¢ Send for review
ā¢ Answer the questions
ā¢ Get it authorized
73. Workshop
How to write SOP
ā¢ Concept ā¦begin with the end in mind
ā¢ Select a format (approved)
ā¢ Collect the inputs
ā¢ Define scope
ā¢ Identify the audience
ā¢ Write SOP
ā¢ Send for review
ā¢ Answer the questions
ā¢ Get it authorized
74. Workshop
How to write SOP
ā¢ Concept ā¦begin with the end in mind
ā¢ Select a format (approved)
ā¢ Collect the inputs
ā¢ Define scope
ā¢ Identify the audience
ā¢ Write SOP
ā¢ Send for review
ā¢ Answer the questions
ā¢ Get it authorized
75. Workshop
How to write SOP
ā¢ Concept ā¦begin with the end in mind
ā¢ Select a format (approved)
ā¢ Collect the inputs
ā¢ Define scope
ā¢ Identify the audience
ā¢ Write SOP
ā¢ Send for review
ā¢ Answer the questions
ā¢ Get it authorized
76. Workshop
How to write SOP
ā¢ Concept ā¦begin with the end in mind
ā¢ Select a format (approved)
ā¢ Collect the inputs
ā¢ Define scope
ā¢ Identify the audience
ā¢ Write SOP
ā¢ Send for review
ā¢ Answer the questions
ā¢ Get it authorized
77. Workshop
How to write SOP
ā¢ Concept ā¦begin with the end in mind
ā¢ Select a format (approved)
ā¢ Collect the inputs
ā¢ Define scope
ā¢ Identify the audience
ā¢ Write SOP
ā¢ Send for review
ā¢ Answer the questions
ā¢ Get it authorized
78. Written By
ā¢ Performer
Reviewed By
ā¢ Supervisor
Approved By
ā¢ Operational
Head
Authorized By
ā¢ Mgmt.
Representative
SOP Writing
79. Written By
ā¢ Performer
Reviewed By
ā¢ Supervisor
Approved By
ā¢ Operational
Head
Authorized By
ā¢ Mgmt.
Representative
SOP Writing
Development & Approval of
Training Plan & Training
Material
82. Effectiveness of Training
Material ā Identified
Performance Indicators of
Trainer - Developed
Development & Approval of
Training Plan & Training
Material
101. Lupin 2019
A comprehensive, independent
retrospective assessment of your
cleaning processes, practices, and
validation studies to evaluate the scope
of cross-contamination hazards.
FDA asked for
103. Lupin 2019 Other manufacturing equipment
that may have
been improperly cleaned
FDA asked for
104. Lupin 2019
An assessment whether cross-
contaminated products may
have been released for
distribution.
FDA asked for
105. Lupin 2019
The assessment should cover each
piece of equipment used to
manufacture more than one product,
including API and finished products.
FDA asked for
106. Lupin 2019
A CAPA plan, based on the
retrospective assessment, that includes
appropriate remediations to your
cleaning processes and practices, and
timelines for completion.
FDA asked for
107. Lupin 2019
A detailed summary of
your process for lifecycle
management of
equipment cleaning
FDA asked for
108. Lupin 2019
Describe provisions for ongoing
verification that proper cleaning is
consistently executed for all products,
and any improvements to be
implemented
FDA asked for
109. Lupin 2019
Appropriate improvements to
your cleaning validation program,
with special emphasis on incorporating
conditions identified as worst case in
your drug manufacturing operation.
FDA asked for
110. Lupin 2019
This should include but not be limited to
identification and evaluation of all worst-
case:
1. drugs with higher toxicities
2. drugs with higher drug potencies
FDA asked for
111. Lupin 2019 3. Drugs of lower solubility in
their cleaning solvents
4. Drugs with characteristics that
make them difficult to clean
FDA asked for
112. Lupin 2019 5. Swabbing locations for areas
that are most difficult to clean
6. Maximum hold times before
cleaning
FDA asked for
113. Lupin 2019
Describe the steps that must be
taken in change management system
before introducing new
mfg equipment or a new product
FDA asked for
114. Lupin 2019
A summary of updated SOPs that
ensure an appropriate program is in
place for verification and validation of
cleaning procedures for products,
processes, and equipment.
FDA asked for
141. LegibleL
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 so that all activities conducted
can be fully reconstructed by the
people reviewing these records at any
point during the records retention
period.
Traceable
Permanent
143. OriginalO
Original data include the first or source
capture of data or information and all
subsequent data required to fully
reconstruct the conduct of the activity.
144. OriginalO
Original data
original data should be
original data and/or true and verified copies that preserve the
content and meaning of the original data should be
as such, original records should be complete, enduring &
readily retrievable & readable throughout the records
retention period.
reviewed
retained
195. Correction of
documentation error
should include
Draw a single line through the error
Make the correction next to the error
Write an explanation for the error
2
1
3
196. Correction of
documentation error
should include
Draw a single line through the error
Signature & date the correction
Make the correction next to the error
Write an explanation for the error
2
1
4
3
203. Manual recording are
inherently slow & prone
to error
Blindness & failure to recognize OOS
Missing signatures
Incorrect data entry
204. Manual recording are
inherently slow & prone
to error
Blindness & failure to recognize OOS
Missing signatures
Used incorrect form
Incorrect data entry
205. Manual recording are
inherently slow & prone
to error
Blindness & failure to recognize OOS
Sending wrong form to wrong person
Missing signatures
Used incorrect form
Incorrect data entry
206. Manual recording are
inherently slow & prone
to error
Blindness & failure to recognize OOS
Sending wrong form to wrong person
Missing signatures
Used incorrect form
Incorrect data entry
Form left incomplete