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Manufacturer inspections - an overview
Overseas manufacturers who supply medicines or biologicals to Australia are also required to manufacture therapeutic goods to the same high standard. Where a recognised international regulator has approved a manufacturer, it may not be necessary for TGA Inspectors to inspect the manufacturing site.
We apply a risk-based approach to determine the frequency at which a manufacturer should be inspected, including unannounced inspections. The TGA inspection frequency matrices take into account the following:
- intrinsic risks associated with the product and manufacturing process
- manufacturer compliance history.
These risk matrices also guide us in determining the scope of inspections and any areas of specific focus.
An inspection team consists of a lead inspector and, where appropriate:
- one or more Inspectors
- one or more Technical Specialists - selected from a TGA-approved list of Specialists who are appointed for their appropriate academic qualifications or technical training
- one or more inspector trainees or observers, who are bound by confidentiality obligations and acceptable to the lead inspector and the manufacturer.
The Lead Inspector is in charge of the team, and is responsible for chairing the opening and closing meetings with the manufacturer, and preparing the final reports.
More than one Inspector or technical specialist is sometimes needed at an initial inspection, because this inspection needs to be comprehensive.
Inspection process and duration
We have published Guidance on licensing and certification inspections to provide comprehensive information about the inspection process in the context of licensing and certification.
Typical inspections include activities before, during and after the actual inspection.
Prior to the inspection the manufacturer is given notification of the impending inspection, usually within 2-4 weeks of the inspection due date. Inspectors normally contact manufacturers by telephone to confirm inspection dates, notify the manufacturer of the inspection team, and request information relevant to the planned inspection. A formal notification of the inspection is provided to the manufacturer following this initial contact.
At the start of the inspection, the Lead Inspector will hold an opening meeting to discuss details of the inspection including:
- The purpose of the inspection;
- The scope and duration of the inspection;
- The applicable manufacturing principles that will be used;
- The roles of each inspector;
- The inspection process.
During the inspection, Inspectors will review the manufacturer's Quality Management System, manufacturing areas and personnel involved in the manufacture of therapeutic goods. The team will ask questions and request to see evidence that demonstrates compliance with the relevant GMP standards. If an inspector identifies areas of non-compliance (called deficiencies), these will be discussed during the inspection and additional evidence may be requested by the inspector.
At the end of the inspection, the Lead Inspector will conduct a closing meeting during which a draft list of deficiencies is presented to the manufacturer for discussion. This meeting provides an opportunity to clarify any identified deficiencies.
The duration of an inspection depends on the nature and complexity of the manufacturing processes that need to be covered. On average, an inspection will take between 1 and 5 working days.
Where a manufacturer is new to the Australian market an initial inspection is conducted. It is important that the initial inspection be thorough and comprehensive, involving a detailed examination of the operations and procedures of the manufacturing site, procedures and premises.
The duration of reinspections of manufacturers approved to supply the Australian market will be determined taking into account:
- the previous lead inspector's recommendation
- the level of compliance at the last inspection
- the product and process risk factors
- any other relevant information that is available to the TGA.
After an inspection
Following the inspection the manufacturer is provided with a post inspection letter confirming any deficiencies identified during the inspection. This letter is sent to the manufacturer within 4 weeks of the inspection.
Upon receipt of the post-inspection letter, manufacturers of medicines and biologicals have four weeks* to provide a response. The manufacturer's response must contain:
- 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.
It is important that the manufacturer's response is as clear and comprehensive as possible, with realistic timeframes for resolution of issues. The response is viewed as the manufacturers commitment to resolve the identified deficiencies and the Lead Inspector uses the response to determine whether compliance has/will be achieved in a timely and effective manner. Once the manufacturer's response is accepted, it is expected that the manufacturer implements the actions as described. Any significant changes or delays to implementation should be discussed with the relevant Lead Inspector. Failure to implement actions to address deficiencies will be identified at the next reinspection and may affect the manufacturer's risk rating and reinspection frequency.
Manufacturers are not normally required to provide objective evidence in responses to deficiencies/non-conformances, unless requested to do so by the Lead Inspector.
Manufacturer's responses are normally reviewed within 4 weeks of receipt and if accepted, the inspection will be closed and an inspection report will be issued to the manufacturer. Manufacturers may be requested to provide additional information, evidence or provide clarification if necessary. Any such request will be made in writing to the manufacturer and will clearly state the due date for subsequent responses.
* Manufacturers are normally given 4 weeks to provide a written response to inspection findings; however, this period may be reduced if serious or significant compliance issues have been identified.
Previously, manufacturers were required to provide objective evidence, i.e. documentary evidence that deficiencies have been addressed. 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.
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.
Feedback, complaints and appeals
The TGA welcomes feedback that helps processes be improved. The TGA is therefore seeking manufacturers' feedback following TGA inspections. The feedback will be used to improve inspection procedures and training.
The TGA aims to resolve complaints informally wherever possible, and the complaint process should be explained in the opening and closing meetings of every inspection. Complaints can be made about the inspectors or the inspection.
If a manufacturer is unsatisfied with an inspector's conclusions, the first step is to seek a review by the Director, Inspections. For decisions that may adversely affect the viability of manufacturing licences, the mechanism for review of decisions is outlined in section 60 of the Therapeutic Goods Act 1989.