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FDA's new approach to plant inspections came into force on 1 February 2002. Its
focus is on 6 systems concerning the manufacture and control of drug
products:
- The Quality System
- The Facilities and Equipment System
- The Materials System
- The Production System
- The Packaging and Labelling System
- The Laboratory Control System
Fred Blumenschein from CDER says that, by
means of the new method, FDA intends to systematise their inspections and
improve their focus and efficiency. The improved organisation of FDA 483
documents and
Establishment Inspection Reports (EIRs) will represent an added benefit.
Within the framework of Systems
Inspections, either a "Full Inspection" (4-system) or an
"Abbreviated Inspection" (2-system) will be conducted. What is
always inspected is the Quality System and at least one of the remaining
systems.
Full Inspections are carried out in case
of initial inspections, significant changes regarding personnel or
operations, and compliance inspections, i.e. if deficiencies in the GMP
implementation were found in the past. In other cases, an Abbreviated
approach will be taken. The crucial point are no longer the individual
profile classes, but different product classes. Of course, if significant
deficiencies are found, the individual products or batches are examined.
However, also in this case across the system limits.
As in the past, the depth of inspection depends on the significance of the
findings. The usual rule is: if one system is non-compliant, all systems
are classified as non-compliant. However, a single non-compliance does not
necessarily mean that the firm in question loses its compliance status.
Should no systems fail, the acceptable GMP status may permit to do without
field inspections for some applications. But under certain circumstances
Pre-Approval Inspections are still mandatory - independently of the GMP
status.
If a Warning Letter has been issued after
the last inspection, a Full Inspection will be conducted.
The central point for FDA is the Quality System. According to FDA, the
Quality System is the crucial factor for the question whether the other
systems interact adequately with one another.
This line of argumentation of FDA is the
exact point of reference for an industry comment (Dr S. Nair, QM, Hoffmann-La
Roche). It recommends that one should align one's quality system to the
'new' FDA requirements. However, it emphasises that the most important
factor for success is advance preparation.
Apart from profound system knowledge, it
is essential to have a well-trained inspection team to accompany
the FDA inspector.
Source: PDA Letter, August 2002
In the meantime, the first experiences
have been made with FDA's System Inspections. Dr Reiner Kirrstetter,
Aventis Pharma AG, D-Frankfurt, and Richard M. Bonner, Eli Lilly,
UK-Liverpool, reported about them on the occasion of the ECA Education
Course "GMP Compliance Auditor" in Hamburg on 16-17 October
2002.
Here some examples:
- Improvements planned by the firms are
not taken into consideration within the framework of System
Inspections any more. What is inspected is the current status!
- Multinational companies that have
received a Warning Letter for one location are expected to apply the
inspection commitments to all other sites as well.
Different requirements stipulated during
FDA System Inspections:
- Plans, drawings, and organigrammes are
official GMP documents; therefore, they are subject to change control
procedures and have to be approved by the Quality Unit
- There is a 7th system: computer
validation
- Internal GMP trainers have to be
trained themselves
- Source Code Review
- The SOP on preventative maintenance
has to define what is to be done in case preventative maintenance
dates are missed
- GMP alarm records have to be approved
by the Quality Unit
- The replacement of GMP-relevant
equipment has to be approved by the Quality Unit
- CAPAs (Corrective Actions/Preventive
Actions) have to be included in a failure investigation
- All GMP training programmes have to be
approved by the Quality Unit
- All contract laboratories have to be
audited for every test that they conduct
- No notice boards with GMP-relevant
information in the firms
Both speakers also stressed that a thorough
preparation is a key element to an FDA System Inspection. This is, of
course, true of all other GMP inspections as well.
Author:
Sven Pommeranz
CONCEPT HEIDELBERG
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