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The TGA updates processes for the close-out of on-site GMP inspections
Medicines and biologicals supplied in Australia must be manufactured in accordance with Good Manufacturing Practice (GMP) standards. The TGA undertakes regular inspections of Australian and overseas manufacturers to assess their compliance with these standards. If any deficiencies against these standards are identified, we may take immediate action if they are of a critical nature Classification of deficiencies/nonconformities
Where the deficiencies are not of a critical nature, the manufacturer is required to provide us with a response outlining the actions they intend to take to fix the deficiencies and a timeline for resolving the identified deficiencies.
We have reviewed the process for conducting post-inspection activities to allow a more efficient resolution of deficiencies and close-out of inspections and to align with international practice.
Following a successful trial of the modified process in early 2015 and consultation with the Technical Industry Working group on GMP, changes have been made to a number of steps including:
- the way in which deficiencies are reported to manufacturers;
- the format for manufacturer's responses to deficiencies;
- requirements for objective evidence for significant deficiencies;
- when the inspection report is issued to the manufacturer;
- the format and content of the inspection report.
Changes to the process
Reporting of deficiencies to the manufacturer
Following the inspection we provide the manufacturer with a post-inspection letter (PIL) confirming any deficiencies identified during the TGA GMP inspection. The PIL only contains the deficiencies and is not a comprehensive inspection report. This letter is usually sent to the manufacturer within 4 weeks following the inspection; however, timelines may differ where serious or significant compliance issues are identified.
The purpose of the post-inspection letter is to formally notify the manufacturer of the deficiencies identified during the inspection. TGA practice is to point out deficiencies as they are identified during an on-site inspection and a draft list is provided to the manufacturer at the inspection closing meeting, so the content of the post-inspection will not be a surprise to the manufacturer.
Responding to the post-inspection letter (PIL)
Manufacturers of medicines and biologicals have four weeks* to provide us with a response. In responding, the manufacturer must:
- develop a corrective and preventative action (CAPA) plan for all critical and major deficiencies identified. This plan must include:
- investigation of the root cause of all critical and major deficiencies
- detail of the corrective action(s) taken to address the root cause
- detail of the preventative action(s) taken to address the root cause
- corrections taken to address the deficiency examples
- due dates for completion of all actions.
- for deficiencies classified as 'other', provide the response date, the correction(s) taken and due date for completion.
* Manufacturers are normally provided 4 weeks to submit a written response to inspection findings; however, this period may be reduced if serious or significant compliance issues have been identified.
Requirements for objective evidence
Manufacturers must record and review actions taken; however, objective evidence of these actions is not required to be submitted for review unless expressly requested. We will assess the effectiveness of the actions taken by the manufacturer at the next inspection (see below).
TGA Lead Inspectors may request objective evidence where warranted, e.g. for initial inspections, where significant non-compliance has been identified, or chronic non-compliance has been identified.
As we don't request objective evidence generally, we have taken the view that a more effective approach is to extend the next inspection to allow us to assess the actions taken by the manufacturer on-site at the next inspection. This aligns with approaches taken by our international regulatory partner agencies.
The amount of time by which the next inspection is extended will depend on the level of compliance of the manufacturer. It is expected that for manufacturers where there were no major deficiencies identified at the last inspection, an extension will not be necessary. However, depending on the number of deficiencies identified, the next inspection could be extended by up to a full day.
Provision of the inspection report
We normally review manufacturer's responses within 4 weeks of receipt and, if accepted, will close out the inspection and issue an inspection report to the manufacturer. The inspection report is an account of the inspection, including:
- scope of the inspection;
- manufacturing, quality control and quality assurance processes and systems inspected;
- list of observed deficiencies
- assessment of the manufacturer's response to any deficiencies
- manufacturer compliance rating
- proposed re-inspection dates
- confirmation of the final outcome and closure of the inspection.
A separate 'close-out letter' will no longer be issued to the manufacturer.
Date of implementation
These changes have been introduced into the TGA's GMP inspection quality management system and are now business as usual. Should you have any questions regarding these changes please contact your last Lead Inspector, or contact firstname.lastname@example.org
The MQB are currently reviewing and updating external guidance to reflect these changes. Updated documents will be published on the TGA website.
Enquiries and feedback
The TGA welcomes feedback that helps processes be improved. The TGA is therefore seeking manufacturers' feedback following TGA inspections and inspection processes. The feedback will be used to improve inspection procedures and training.