11.1 Inspection Completion:

The GMP inspection fee paid to the PPB covers all expenses related to inspection preparation, reporting, and the conclusion of the inspection process. An inspection is considered “complete” when inspectors have assessed the responses from the inspected facility regarding the deficiencies outlined in the initial Inspection Report.

11.2 Additional Office-Based Inspection Fee:

The PPB does not impose an additional office-based inspection fee, even if inspectors need to invest extra time overseeing post-inspection activities. This can happen when critical deficiencies or significant non-compliance issues require inspectors to ensure the adequacy of the company’s Corrective and Preventive Actions (CAPA) as the company works towards compliance.

These post-inspection activities may include:

1. 1. Reviewing CAPA plans.
   2. Conducting impact assessments.
   3. Receiving periodic CAPA status updates.

While the PPB inspectorate encourages inspected companies to respond in a manner that expedites the decision-making process regarding compliance following the inspection, it’s essential to note that adhering to a specific format is not obligatory.

11.3 Inspection with Critical deficiencies

Critical deficiencies will be more complex, and responses may take different formats depending on the issues cited. Specific guidance is therefore not provided, but the general principles below apply.

11.4 An inspection with Major deficiencies

Companies should submit a tabular Corrective and Preventive Action (CAPA) plan in the format provided by the inspector. The table should include major deficiencies issued by the PPB in column 1, the Most Probable Root Cause identified by the company in column 2, and the company’s proposed CAPA with timelines in the last column.

11.5 Site Response

The initial response should be placed under the “Most Probable Root Cause” and “Proposed CAPA and Timelines” sections. To facilitate efficient use of time, the answer to the deficiencies is raised directly, clearly and succinctly in each column, preferably on the same Word document provided. Verbose responses with extraneous information may be returned without review, with a request to simplify.

Under “Most Probable Root Cause,” identify the root cause most likely responsible for the issue based on analysis and validation. This is the cause that, when addressed, is expected to prevent the issue from recurring. Once the most probable root cause is determined, develop corrective and preventive actions to address the issue and document under the Corrective and Preventive Action (CAPA) column.

Corrective Action addresses the immediate issue and prevents its recurrence, while Preventive Action implements measures to prevent similar issues in the future.

Subtitle this first set of responses as “initial response”

It’s crucial for the company to:

1. 1. Clearly state actions and deadlines (DDMMYYYY). If the response is a commitment to ‘review a system’, then it should state when the review will be complete and what will happen with the output of the review, the inspector may request that the output be provided.
   2. Choose appropriate timelines that are realistic (do not give extended times for simple actions).
   3. Consider broader review of systemic issues including other sites/sections/aspects in the organisation and do not just respond with a correction to the single identified point.
   4. If all similar areas have been reviewed to find other examples of the deficiency, but no others were found, this should clearly be stated and should include a description of how the system review was performed.
   5. Where timelines are long due to the complexity of the solution, but operations are continued, implement interim actions. These should be designed to protect the patient until the longer-term action is complete.
   6. Provide evidence only when specifically requested.
   7. Provide the company response in an editable Word document to allow the inspector to respond (if required).
   8. Hard copies are not required and will not be reviewed.
   9. Place second responses of the site directly below the PPB request for additional information. The site should choose a new colour for all sets of responses and reply underneath the further request.
   10. Maintain consistency in responses when providing additional information.
   11. Not change the previous response text when providing additional information or further response

11.6 PPB request for further information

1. The inspector requiring further information from the inspected company may put the request directly below the point that they require information on for using a different colour. The whole record of all queries and responses will therefore be in a single document.
2. The use of different colours for each set of responses allows each party to clearly identify which points require further response.

11.7 An inspection with Minor deficiencies

Initial Site Responses for deficiencies classed as ‘Minor’ follow the same format for Major responses as outlined above.

11.8 Inspector Comments

Inspector comments are not deficiencies. The site should respond to comments, even if it is just to acknowledge them. Inspected companies are required to communicate with the inspector(s) in advance if the timeline commitment is going to be missed.

The post-inspection compliance decisions are based on the acceptance of the remediation actions and their associated timescales for completion. The registered email can be used to notify of delays to commitment completion.

11.9 Compliance Management

Companies demonstrating poor compliance without reaching the threshold for regulatory action may undergo the compliance escalation process (compliance management process). In such cases, a re-inspection may be conducted to ensure the completion of actions in accordance with the agreed remediation program.

The objective of continuing the Compliance Management process post-inspection is to assist companies in achieving compliance before regulatory action becomes necessary.

Further deficiencies identified during the re-inspection are independently reviewed by a peer review team, and the final classification is confirmed in writing within 30 days. The timescale for addressing deficiencies is typically 30 days and will be specified in the post-inspection letter.

If the company’s remediation plan is still in progress, the original deficiencies leading to compliance management escalation remain valid for consideration until it is confirmed that effective remedial actions have been implemented, usually upon re-inspection.

Companies are notified of compliance management objectives, which can be clarified by the inspector upon request.

Re-inspection deficiencies are reviewed by the peer review team, and further correspondence regarding continuing compliance action is communicated separately by the GMP department. This communication may follow the receipt and assessment of the company’s post-inspection responses.

Ongoing compliance management review determines whether there are grounds for the Licensing department to consider formal regulatory action, which may be based on current inspection deficiencies, inadequacy of proposals to correct these deficiencies, or failure to implement commitments effectively or promptly.

It is crucial for the company to maintain open communication channels with the assigned site inspector (the Senior Superintended Inspector) and the GMP department throughout the process. Any significant changes in GMP compliance, whether positive or negative, including delays in implementing corrective action commitments, should be promptly reported.

Once the compliance escalation process is concluded, the company returns to the routine risk-based inspection program. However, regulatory action may still be considered if the necessary improvements are not made.

The compliance escalation process may also be employed if the GMP peer review team has closed the referred case with a recommendation for monitoring until remedial action plans are completed.

This process may involve making recommendations for close monitoring of compliance improvement work through inspection, holding meetings and correspondence with company senior management to outline the consequences of continued non-compliance, and more.