Systems Inspections 2002 - FDA's New Approach to Inspections

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.

Sven Pommeranz

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