Manufacturer GMP inspection - typical example

Manufacturers of therapeutic goods are regularly inspected by the TGA using a risk-based approach to ensure compliance with manufacturing principles.

The emphasis and depth of manufacturer inspections, as well as the frequency of inspections are guided by the inherent risks of the product and the method of manufacture (the site risk classification).

Activities associated with a typical inspection include activities:

• before the inspection
• at the inspection
• after the inspection.

Before the inspection

Before an inspection is undertaken, the TGA inspection team is decided and preparatory work is undertaken:

• the lead inspector is assigned
• the inspection team is decided
• the lead inspector notifies the company
  • an unannounced inspection may be considered where it is believed that the true extent of compliance cannot be assessed otherwise
• the inspection team reviews documentation, which for medicines includes the Site Master File
• the lead inspector prepares an inspection plan for use by the inspection team.

At the inspection

The lead inspector chairs an opening meeting with the manufacturer's management:

• members of the inspection team are introduced
• the scope and objectives of the inspection are reviewed
• the inspection plan is discussed
• a short summary of the methods and procedures to be used to conduct the inspection is provided
• communication links between the inspection team and manufacturer are established
• the complaint process is explained
• it is confirmed that the resources and facilities needed by the inspection team are available
• arrangements for the inspectors to meet together caucus are made
• a tentative time and date for the closing meeting and any interim meetings of the inspection team and the manufacturer's management are established
• in the case of a pre-licence inspection, the accuracy is verified of the licence application detail, especially:
  • legal name of enterprise
  • all site addresses
  • nominated persons
  • scope of activities.

The inspection is conducted and the inspection team meets to discuss and prepare a list of items for discussion at the closing meeting. During the inspection, samples may be taken for laboratory testing by the TGA.

The closing meeting with the inspected manufacturer consists of the following:

• the lead inspector gives an overview of the inspection and its outcome
• the lead inspector provides the manufacturer with a list of items and encourages discussion -
• the items on this list will later be reviewed by the TGA and may or may not be raised as a deficiency in the inspection report
• the complaint process is explained again
• the lead inspector requests written response to the inspection report within four weeks from the date of receiving the report.

After the inspection

The inspection team composes a post inspection letter (PIL) which is reviewed within the TGA prior to being issued. During the review, deficiencies are classified. For deficiencies classified as critical or major an identification of the root cause is required, as well as objective evidence of corrective actions.

• The manufacturer is requested to respond to the PIL.
• The inspection team reviews the manufacturer's response to the PIL. If the response is acceptable, the inspection is closed out.
• If the response is unacceptable, the lead inspector replies to the manufacturer outlining which deficiencies have not been addressed and requests a further response. Additional responses are reviewed by the inspection team, and if the response is acceptable, the inspection is closed out.
• If the manufacturer is unable to provide a sufficient response to the deficiencies, the inspection is referred to an independent internal review panel (comprising a manager who was not involved in the inspection and at least two other independent members - usually GMP inspectors). The review panel may consider further actions to be taken to address the outstanding compliance issues, in accordance with the TGA's Compliance Management Framework.
• Once the inspection is closed out, the lead inspector sends a close out letter final inspection report to the manufacturer to advise the outcome of the inspection and relevant licenses and certificates are issued to the manufacturer.
• The inspection is reviewed internally.