Auditing and inspection

2. Auditing:
Some Definitions:
Audit:
A systematic and documented process to determine the degree to which
processes/products conform to standards set for them
Auditee:
Persons from an organization being audited
Auditor:
A person conducting an audit
Audit Unit:
An organisation (e.g. departments, plants, sites) to be audited

3. Auditing:
Consistent standards for auditing will provide the following benefits to the
industry:
• Effective assessment of GMP Compliance
• Reduced costs
• Improved performance
• Increased external confidence
• Inspection easiness
• Trouble free operation

4. Auditing:
Audits Classification:
Internal Audits:
These may be subdivided into ‘local’ audits of individual departments or
projects, performed by a central auditing group in order to assess
conformance with policies and standards.
External Audits:
They are performed to evaluate the GMP compliance of suppliers, that
provide product, and/or contractors used for outsourced manufacture of
API ‘active pharmaceutical ingredients’ or intermediates.
•Eternal audits are less frequent (every 2-3 years) than internal audits
(covering at least 12 months).

5. Auditing:
Steps in Managing the Audit:
To achieve its objective efficiently and cost-effectively an audit should be:
 Perfectly planned
 Carefully structured
 Systematically performed
 Faithfully reported
 Remedial actions progressed

6. Auditing:
Pre-audit Information:
 The collection and analysis of information.
 It is important to clearly establish the reason for performing the audit
as:
 New supplier
 Outsourcing
 Defect/recall investigation
 Routine re-audit
 Remedial action follow-up; etc. in order to determine the type, scope
and specific objective(s) of the audit.

7. Auditing:
 There should also be a clear business benefit to justify the cost, to
both auditor and auditee, of undertaking the audit.
 A major source of information is the pre-audit questionnaire which, if
well constructed can be an extremely valuable tool.
 Earlier audit reports (if they exist) can add value to the preparation for
a quality audit.

8. Auditing:
Preparation of an Audit:
• Dependant on the scope of the audit the audit team can be
composed of one or more auditors (with lead auditor)
• It is advisable to interchange auditors from time to time for
a given area in internal audits to allow detailed
understanding of the areas/activities.
• The auditor should be aware of any sensitive issues, e.g.
highly confidential information.

9. Auditing:
Performing the Audit:
• The audit should begin with an opening meeting to introduce
auditor(s); review scope and objectives and agree the agenda and
timetable.
• During the audit it is usual to walk through parts of the facility to
observe the operation at first hand, to gather information, to assess
the cleanliness and condition of facilities and the risk of potential
contamination.
• The closing meeting is important since it allows the auditor (or audit
team) to communicate the audit findings and conclusions in a logical
and co-ordinated manner to the auditee’s management. Audit
deficiencies should also be classified to highlight the priority for actions
to the auditee and their Senior Management.

10. Auditing:
Deficiencies are classified as follows:-
1. Product Quality / Patient Safety Related deficiency (Critical)
2. Significant cGMP Deficiency but with no direct impact on
Product Quality /Patient Safety (Major)
3. GMP deficiencies that are either considered to be minor isolated
examples or there is insufficient information to classify them as
Major (Other)

11. Auditing:
Qualification and Attributes of Auditors:
• Auditors should be qualified by education, training and experience in
auditing techniques.
• Incorrect statements or interpretations of regulations can be extremely
costly to a company. Therefore the auditor should be fully
knowledgeable in the understanding and interpretation of applicable
regulations.

12. Auditing:
Possible Audit Breakdown:
The breakdown of an audit may be the result of:
• Poor planning/preparation
• Failure to clearly define scope and objectives
• Inadequately trained auditor or one lacking the appropriate personal
characteristics, poor communication before and during the audit
• Lack of co-operation/understanding from the of the auditee
In such cases the action is usually limited to either trying to identify and
resolve the cause and try to continue with the audit or to abort the
audit.

13. Inspection:
An Audit is more detailed,
go over your records, and
make sure that you did
everything correct in the
past.
An inspection just looks at
what's going on at the
moment.

14. Inspection:
 When a system is inspected, the inspection of that system may be
considered applicable to all API products which use it.
 Products with no dosage limitations like calamine lotion or some OTC
medicated shampoos should be given inspection coverage of reduced
depth and intensity.
Inspections of API and manufacturers, whether foreign or local, should be
conducted by experienced investigators with education and/or training
particularly in fermentation and chemical synthesis manufacturing
methods.

15. Inspection Approaches:
1. Full Inspection Option:
The Full Inspection Option is an inspection of at least four of the six
systems listed below, one of which must be the Quality System:
1. Quality System assures overall compliance with cGMPs and
internal procedures specifications SOPs.
2. Facilities & Equipment System which provide an appropriate
physical environment and resources used in the production of
APIs.
3. Materials System includes measures and activities to control
starting materials, intermediates, and containers. It includes
validation of computerized and inventory control processes,
storage, and distribution controls.

16. Inspection Approaches:
4. Production System includes measures and activities to
control the manufacture of APIs, including in-process
sampling & testing, and process validation.
5. Packaging and Labeling System includes measures and
activities that control the packaging and labeling of
intermediates and APIs.
6. Laboratory Control System includes measures and
activities related to laboratory procedures, testing,
analytical methods development and methods validation or
verification, and the stability program.

17. Inspection Approaches:
Vacuum Decay with Indirect Imaging

18. A Full Inspection is Appropriate:
a) For an initial FDA inspection of a facility, or after a significant
change in management or organizational procedures, such as
change in ownership.
b) For a firm with a history of non-compliance or whose ability to
comply is short-lived.
c) To evaluate if important changes have occurred in the firm’s
state of control as:
i.New potential for cross-contamination arising through changes
in processing or type of APIs using that equipment.
ii.Use of new technology requiring new expertise, significant
equipment changes and/or additions, or new facilities.

19. A Full Inspection is Appropriate:
d) When District management or CDER (Center for Drug
Evaluation and Research) specifically requests this option.
e) To follow up on a Warning Letter or other regulatory
action.

20. Inspection Approaches:
Abbreviated Inspection Option:
It is meant to provide an efficient update evaluation of the
firm’s conformity to cGMPs. The Abbreviated Inspection
Option is an inspection of at least two systems but not more
than three systems, one of which must be the Quality
System.