AUDIT TRAINING MANUAL

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 Quality Assurance Department
Audit Training Manual
Title: AUDIT TRAINING MANUAL. Revision No. 00
Doc. No: Effective Date: Supersede Date: Review Date:
QA/ATM/001 07/06/2010 07/06/2012

OBJECTIVE

The objective of this “Audit Training Manual” is to serve as a reference document for
performing Internal Quality Audits at Benzochem Industries Pvt. Limited.

SCOPE

This audit training manual is to be used for auditing the following systems:

1. Auditing a documentation system.

2. Auditing a materials handling system.

3. Auditing a calibration, preventive maintenance and housekeeping system.

4. Auditing a quality testing laboratory.

 Quality Assurance Department
Audit Training Manual
Title: AUDIT TRAINING MANUAL. Revision No. 00
Doc. No: Effective Date: Supersede Date: Review Date:
QA/ATM/001 07/06/2010 07/06/2012

KEY PARAMETERS IN AUDITING A DOCUMENTATION SYSTEM

PRIOR TO THE AUDIT

1. Review the types of documentation systems in use at the site.

2. Determine if there are any outstanding corrective actions from previous internal
audits or regulatory inspections involving documentations.

DURING THE AUDIT

1. Ensure that the documentation system is operating in full compliance.

2. Verify that all documentation within a system applies good documentation

practices.

3. For production, laboratory or training documentation:

a. Verify that personnel activity indicated in current SOPs is actual

practice.

b. Verify that data added to process documents is correct and current with
the process.

c. Verify that the system is working correctly by asking to retrieve a

previously generated document.

d. Verify that there is a procedure in place for double checking data if

required for that documentation system.

4. Verify that access to documentation is restricted to authorized personnel.

5. Verify that all documentation contains approvals by appropriate personnel.

6. Verify that completed documentation is reviewed by appropriate personnel

including a quality representative.

7. Verify that document distribution and circulation is controlled.

8. Verify that documents are identified with appropriate control and access
statements.

9. Verify that the site has a method for assuring that only current versions of
documents are used.

10. Verify that documents are reviewed or revised either on a scheduled frequency
as needed, whichever is the shorter time interval.
 Quality Assurance Department
Audit Training Manual
Title: AUDIT TRAINING MANUAL. Revision No. 00
Doc. No: Effective Date: Supersede Date: Review Date:
QA/ATM/001 07/06/2010 07/06/2012

11. Verify that there are SOPs for managing the documentation system. This
should include review and approval process for documents including those which
require change control management.

12. Verify that personnel understand the differences when signing in different
capacities.

13. Determine if documentation discrepancy/ deficiency classifications are used

by an audited site.

14. Determine the criteria for each classification.

15. Verify that the Quality Unit is independent of manufacturing.

16. Verify that one of the Quality Unit’s responsibilities is to approve all
appropriate quality related documents.

17. Ensure that personnel have received adequate training on new or revised
versions of documents.

18. Ensure that training is documented.

19. Verify that the training program incorporates requirements for temporary
employees and consultants.

20. Ensure that documents are revised according to a written procedure.

21. Verify that superseded documents are removed when a new procedure is
issued.

22. Verify that revisions to documents are only made by authorized personnel.

23. Verify that documents are reviewed and/or revised according to an established
frequency.

24. Ensure that documents are retained according to a site retention schedule.

25. Verify that the site has a retention schedule.

26. Verify that documents can be easily retrieved.

27. Verify that manufacturing records are held for a minimum of one past
expiration dating.
 Quality Assurance Department
Audit Training Manual
Title: AUDIT TRAINING MANUAL. Revision No. 00
Doc. No: Effective Date: Supersede Date: Review Date:
QA/ATM/001 07/06/2010 07/06/2012

KEY PARAMETERS IN AUDITING A MATERIAL HANDLING SYSTEM

PRIOR TO THE AUDIT

1. Review the type of products made at the site.

2. Determine what type of materials the site receives.

DURING THE AUDIT

1. Inspect the warehouse.

a. Verify that components, drug product containers, and closures are received,
identified, stored, handled, sampled, tested, and approved or rejected
according to the site’s SOP.

b. Verify that there is controlled access to receiving and storage areas.

c. Verify that pest control procedures are in place.

d. Verify that the sampling area is a controlled environment designed to prevent

contamination

2. Ensure that there are written procedures which describe how each of the previous
operations are performed.

3. Challenge the system to decide if it is functioning correctly. If the handling and

storage of components and packaging material are computer controlled, the program
must be validated.

4. Ensure that receiving records contain:

i. Name of the component, product or chemical nomenclature

ii. Name of the manufacturer/supplier if different

iii. Carrier

iv. Receiving date

v. Vendor’s lot number

vi. Quantity received

5. Verify that the site has an approved vendor list and that materials come from
approved vendors.
 Quality Assurance Department
Audit Training Manual
Title: AUDIT TRAINING MANUAL. Revision No. 00
Doc. No: Effective Date: Supersede Date: Review Date:
QA/ATM/001 07/06/2010 07/06/2012

6. Determine if vendors are included in a qualification program.

7. Verify that components are identified after receipt and quarantined until released.

8. Ensure that components are identified so the status (quarantine, approved, or rejected)
is known.

9. Review the criteria for removing components from quarantine and challenge the
system.

10. Determine what records are maintained in the storage area to document the movement
of components to other areas.

11. Ensure the site has a system and procedure to manage rejected and returned
components and packaging materials.

12. Review the sampling and testing procedures for components, and the process by
which approved materials are released for use.

a. Decide if these practices are adequate and followed.

b. Determine if sampling is based on a valid sampling plan.

c. Determine if pooling/compositing of samples is allowed and if so, that the

pooled sample/composite is representative.

13. Ensure that the firm’s inventory system is valid and accurate for drug components,
and packaging material including labels.

a. Challenge inventory records by comparing the number of containers

physically available against the quantity remaining on the inventory record or
computer system.

b. Investigate if there are significant discrepancies in these records.

c. Ensure that inventory system can provide an accurate and complete listing of
rejected materials on site and verify.

14. Ensure that the site has shown that the containers and closures are compatible with the
product, will provide adequate protection for the drug against deterioration or
contamination, are not additive or absorptive, and are suitable for use

a. Verify that specifications for containers, closures, and desiccant, etc. are
appropriate.

b. Verify that cleaning procedures are adequate and containers are stored
properly.
 Quality Assurance Department
Audit Training Manual
Title: AUDIT TRAINING MANUAL. Revision No. 00
Doc. No: Effective Date: Supersede Date: Review Date:
QA/ATM/001 07/06/2010 07/06/2012

c. Determine if preprinted containers are controlled as labeling, or as containers.

15. Ensure that training has taken place for all personnel who handle materials.

a. Verify that personnel have been trained in their job functions.

b. Verify that they have been trained in the documentation functions.

c. Verify that they are receiving GMP training on an ongoing basis.

16. Ensure that any changes to the material handling system follow the site’s/company
change control procedure.

17. Ensure that there is uninterrupted traceability from finished product to source of
materials.

18. Ensure that at least one specific identity test is conducted on each lot of each
component.

19. Ensure that each lot of components and packaging material is identified.

20. Ensure that representative samples are collected, tested or examined using appropriate
means.

21. Ensure that materials are re-evaluated at a pre-determined frequency.

22. Ensure that the site performs a documented investigation into any unexpected
discrepancy.
 Quality Assurance Department
Audit Training Manual
Title: AUDIT TRAINING MANUAL. Revision No. 00
Doc. No: Effective Date: Supersede Date: Review Date:
QA/ATM/001 07/06/2010 07/06/2012

KEY PARAMETERS IN AUDITING A CALIBRATION, PREVENTIVE

MAINTENANCE AND HOUSEKEEPING SYSTEM

PRIOR TO THE AUDIT

1. Review the inventory list of the site’s critical equipment, instruments and systems.
2. Determine if there are any outstanding corrective actions from previous audits or
inspections involving calibration and/or preventive maintenance of critical equipment,
instruments or systems, or housekeeping citations.

DURING THE AUDIT

1. Inspect the facility/area for appearance and cleanliness
a. When arriving at the site look carefully around to get a first impression of
maintenance and housekeeping and check for proper and controlled
segregation of materials, i.e. waste not next to components or raw materials.
b. Determine if the facility has any obvious problems (e.g. missing ceiling tiles,
holes in walls, peeling paint, “stained” floors, trash overflowing etc.).
c. Ensure that critical equipment and instrumentation within the facility has
stickers or labels to indicate calibration status or has another system in place to
indicate calibration status.
d. Determine if the facility appears well maintained and visibly clean.
e. Determine if there is any evidence of vermin infestation.

2. Review the quality system.

a. Verify that there is an established and approved Quality System/Quality Policy
that is endorsed by management.
b. Verify that the Quality Unit/Quality Assurance is independent of
manufacturing.
c. Verify that one of the Quality Unit’s/Quality Assurance responsibilities is to
review out of tolerance results and determine the impact on product quality.

3. Ensure that personnel have received adequate training.

a. Verify that there is a documented training and qualification program for any
person responsible for conducting calibration, preventive maintenance or
housekeeping.
b. Verify that detailed job-specific training is conducted and documented for
each employee.
c. If external personal are used to perform the calibration, preventive
maintenance or housekeeping function, ensure that they have been qualified
and are competent.
d. Verify that the training program incorporates requirements for temporary
employees and consultants.
 Quality Assurance Department
Audit Training Manual
Title: AUDIT TRAINING MANUAL. Revision No. 00
Doc. No: Effective Date: Supersede Date: Review Date:
QA/ATM/001 07/06/2010 07/06/2012

4. Ensure that there is a calibration program in place at the site.

For calibration of equipment, instrumentation and systems, ensure that there is a written and
approved program for managing calibration. This program should contain the following
information:
a. An inventory of critical equipment, instruments and systems (including
computer systems) requiring calibration should be available and include
appropriate acceptance criteria.
b. Specific calibration requirements including limits and parameters for each
piece of equipment, instrument or system.
c. The accuracy, precision and linearity of the calibration need to be relevant to
the critical instrument and scale of measurements.
d. Frequency of calibration for each piece of critical equipment, instrumentation,
or system.
e. Review system for issuing calibration schedule.
f. Determine timeframe within which calibration must be performed.
g. Determine what will happen if calibration does not take place as scheduled.
h. Standards and testing equipment to be used in each calibration, which can be
traced, back to a primary standard.
i. Methods to be used in each calibration.
j. Documentation for recording calibration results.
k. Calibration schedules.
l. Procedures detailing what to do in the case of an out of tolerance result.
m. A system for retention and retrieval of calibration history and data.
n. Requirements for using contractors.
5. Ensure that there is a preventive maintenance program in place at the site.
a. For maintenance of equipment, instrumentation and systems, ensure that there
is a written and approved program for managing maintenance.
b. Verify that the program contains the following information:
i. An inventory of critical equipment, instruments and systems (including
computer systems) requiring maintenance.
ii. Specific maintenance requirements including limits and parameters for
each piece of equipment, instrument or system.
iii. Frequency of maintenance for each piece of critical equipment,
instrumentation, or system.
iv. Methods to be used for maintenance.
v. Documentation for recording maintenance results.
vi. Maintenance schedules.
vii. The timeframe within which maintenance must be performed.

6. Ensure that there is a housekeeping program in place at the site.

 Quality Assurance Department
Audit Training Manual
Title: AUDIT TRAINING MANUAL. Revision No. 00
Doc. No: Effective Date: Supersede Date: Review Date:
QA/ATM/001 07/06/2010 07/06/2012

a. Verify that there is a system for managing facility cleaning.

b. Verify that there are written procedures that include:
i. cleaning schedules
ii. methods
iii. equipment
iv. sanitization and cleaning agents
c. Verify that cleaning is documented.
d. Verify that the facility has a documented program for prevention of infestation
from rodents, insects, or other vermin.
e. Verify that the site has a list of approved infestation prevention agents and
uses only those
f. Verify that the site locations for the prevention infestation (pest control)
stations are placed logically, documented, reviewed on a regular basis for
activity and any relevant recommended actions are implemented.
g. Verify if a contractor is used for the prevention of infestation (pest control)
then appropriate agreements are place and any visit reports are reviewed and
approved.
h. Verify that the site has adequate personnel, procedures and methods to ensure
timely removal of trash and refuse from the site.
 Quality Assurance Department
Audit Training Manual
Title: AUDIT TRAINING MANUAL. Revision No. 00
Doc. No: Effective Date: Supersede Date: Review Date:
QA/ATM/001 07/06/2010 07/06/2012

KEY PARAMENTERS IN AUDITING AN ANALYTICAL QUALITY LABORATORY

PRIOR TO THE AUDIT

1. Find out which products are tested and the test methods used.
2. Choose at least one product with specifications and test methods as detailed.
3. Request a list of laboratory SOPs.
4. Request a list of laboratory equipment.
5. Request a list of laboratory deviations/OOS investigations from the previous 12
months.
6. Review previous audits and regulatory audits to determine if there are pending
actions.

DURING THE AUDIT

1. Conduct a walkthrough of the laboratory by following the path of a sample to be
tested. Include sample storage areas and chambers.
i. Receiving and tracking samples.
ii. Ensure samples are labelled properly and uniquely identified.
iii. Ensure that there is a system in place that assures samples are stored
under correct conditions.
iv. If samples are subdivided for multiple tests, ensure that the subdivision
is recorded.
v. Ensure that the sample is signed in using a well documented and
established procedure.
vi. Ensure that site requirements for sample handling and storage are
included in a laboratory SOP.
vii. Ensure that samples are managed and stored based on their storage and
handling instructions.
2. SOPs/Quality Standards
i. Ensure that the current approved version is being used.
ii. Ensure the analyst knows the correct test to run based on a Quality
Standard.
iii. Ensure that no uncontrolled documents or extract from SOPs or test
methods are used.
iv. Ensure all relevant procedures are available to lab personnel.
v. Ensure that both test methods and specifications are available to
laboratory personnel.
vi. While observing an analyst, compare the test method being performed
to the written version of the procedure.
vii. Ensure that there is an approved change control procedure and a
reasonable time frame for reviewing SOPs.
 Quality Assurance Department
Audit Training Manual
Title: AUDIT TRAINING MANUAL. Revision No. 00
Doc. No: Effective Date: Supersede Date: Review Date:
QA/ATM/001 07/06/2010 07/06/2012

viii. Ensure pharmacopoeial methods are verified for use in the laboratory.
ix. Ensure that methods used are validated for their intended purpose.
x. Ensure that there are validation reports on file for the test methods.
3. Reference standards
i. Ensure that assigned purity is stated, where required and Certificate of
Analysis for the standard is available in the laboratory.
ii. Ensure that reference standards are stored under correct storage
conditions.
iii. Ensure that storage conditions are monitored.
iv. Ensure that reference standards are within expiration date.
v. Ensure that standard preparations are labelled and stored correctly.
vi. Ensure that storage time for standard preparations is valid.
vii. Ensure that there are SOPs available for direction on handling and
storing reference standards.
viii. Review reference standard logbooks to confirm that the standards are
being held under proper conditions.
ix. Ensure there is a system in place for the traceability of reference
standards.
4. Reagents
i. Ensure that the grade of reagent is the same as specified.
ii. Ensure that the reagent is properly labelled, stored, and has an assigned
expiration/or re-assay date.
iii. Ensure that the water used to prepare the reagent is of the purity
required in the site SOP for preparation of the reagent.
iv. Ensure that the lot number is recorded when a reagent is prepared.
v. Review reagent preparation logbooks.
5. Volumetric Solutions
i. Ensure there is an approved preparation procedure in place.
ii. Ensure that the data is recorded and easily accessible.
iii. Determine what the expiration and re-standardization dates are.
iv. Determine if they agree with the Pharmacopoeia.
6. Glassware
i. Ensure that Type A glassware is used for quantitative work.
ii. Ensure that there are standard procedures in place for cleaning
laboratory equipment and components (i.e. pipettes, volumetric flasks,
etc.)
iii. Ensure there are storage instructions for clean glassware in place.
7. Data and reports
i. Ensure that data is checked by a second person.
ii. Ensure that there is an approved SOP on the topic of second person
review.
 Quality Assurance Department
Audit Training Manual
Title: AUDIT TRAINING MANUAL. Revision No. 00
Doc. No: Effective Date: Supersede Date: Review Date:
QA/ATM/001 07/06/2010 07/06/2012

iii. Ensure that data is secure with only authorized personnel able to access
it.
iv. Ensure that raw data is recorded in a notebook or on controlled sheets
of paper, not on loose paper.
v. Ensure that data is reported correctly according to approved procedure,
i.e. each data point is recorded, as specified in the SOP, versus an
average taken.
vi. Ensure that any data reported includes its units of measurement.
vii. Review data for the chosen product and ensure that correct
specifications and methods are used
viii. Ensure that relevant system suitability tests are run as appropriate.
ix. Ensure that reagents, solutions, standards and instruments used are
traceable.
x. Ensure that analytical data is being trended and the collected data
evaluated.
8. Analyst’s Notebook
i. Ensure that all written raw data is recorded in notebooks or controlled
worksheets.
ii. Ensure that the number and version/date of the method is recorded.
iii. Ensure that the exact method as described in the SOP has been
followed.
iv. If there is deviation from the procedure, ensure that the supervisor or
authorized person according to SOP has approved the deviation.
v. Ensure equipment is identified including serial numbers of columns.
vi. If applicable, ensure that standard and sample weights are recorded
according to established procedure.
vii. If applicable, ensure that standard concentration calculations are
documented.
viii. Ensure that notebooks are controlled.
ix. Ensure that notebooks are reviewed by a second person for accuracy
and completeness.
x. Ensure that the analyst signs and dates each day data are recorded.
xi. Ensure that all entries that are crossed out are initialled and dated
according to an approved SOP.
xii. Ensure systems for archiving of electronic data or notebooks are
present

9. Out-of-Specification
i. Ensure that the site has an SOP in place.
ii. Ensure that the site is following the SOP through review of OOS
investigations.
 Quality Assurance Department
Audit Training Manual
Title: AUDIT TRAINING MANUAL. Revision No. 00
Doc. No: Effective Date: Supersede Date: Review Date:
QA/ATM/001 07/06/2010 07/06/2012

iii. Ensure that once an OOS is discovered, the rationale for the
subsequent steps is based on sound scientific reasoning.
10. Change Control Program
i. Ensure that methods, equipment, software and instrumentation are part
of the change control program.
ii. Ensure that appropriate approvals and levels of approval are in place.
iii. Ensure that testing after the modification or change is performed.
iv. Ensure the results are within the acceptance criteria.
11. Personnel Training
i. Ensure that new employees, experienced employees and supervisors
are fully trained/qualified.
ii. Ensure that training requirements are defined in an approved SOP.
iii. Ensure that laboratory personnel are receiving both GMP and job skills
training and that it is documented.
12. Equipment and Instrumentation
i. Ensure that equipment and instrumentation (including software) are
qualified.
ii. Ensure that stickers indicating maintenance dates or repair are current
and that instruments not to be used are appropriately labelled.
iii. Ensure, upon completion of repair work, appropriate testing is
performed as outlined in an approved change control program.
iv. Ensure that the equipment list is accurate based on audit observations.
v. Ensure that all calibration procedures, whether internally or externally
performed, have been approved by appropriate site personnel.
vi. Ensure that calibration and maintenance is performed with sufficient
frequency to assure optimal operating conditions of each piece or
equipment or instrumentation.
vii. Ensure that there are approved and followed SOPs for maintenance,
calibration and change control.
viii. Ensure stickers or systems are available to verify
maintenance/calibration dates.
ix. Ensure that all repair and maintenance work has been documented.
x. Ensure that reference weights used for control of balances are checked
against national/international standards as appropriate.
13. Test method validation
i. Ensure that test methods have been validated.
ii. Ensure that there are SOPs directing the validation procedure/method.
14. Stability testing
i. Ensure that there is an approved formal stability testing program in
place.
 Quality Assurance Department
Audit Training Manual
Title: AUDIT TRAINING MANUAL. Revision No. 00
Doc. No: Effective Date: Supersede Date: Review Date:
QA/ATM/001 07/06/2010 07/06/2012

ii. Ensure the site is in compliance with pull dates from the stability
testing program.
iii. Ensure that stability test chambers and conditions have been validated.
iv. Ensure that the testing performed for stability is appropriate and
adequate.
15. Reserve samples
i. Ensure reserve samples are held under conditions specified on their
label or as stated in approved retention period documentation.
ii. Ensure reserve samples use the same or similar container/closure
system as others in the same lot.
iii. Ensure that reserve samples are retained as appropriate.