How to write an effective and well written response to an Inspection Report.
Many companies are aware of the importance of being “inspection ready” at all times and have inspection readiness programmes built into the Quality Management Systems. A key element of an inspection readiness programme is how to respond to observations and the ability to provide well defined, systemic and holistic resolution to the observation that will be well received and satisfy the regulator.
For FDA inspections, the US FDA will issue observations on a Form 483 during the close out meeting whereas for EU inspections it is more common for a verbal list of observations to be issued during the close out meeting and an inspection report will be issued approximately 15 to 30 days after the inspection.
Before you start to write your inspection response, it is important to understand the observation fully and confirm that you are on the same page as the inspector. Ideally this clarity is obtained from the inspector during the inspection so that any further clarification, if required, can be sought in real-time.
Each observation, whether written or verbal, should be discussed with the auditor during the close out meeting. Reiterate your understanding of the observation to eliminate any element of speculation. Do not overcommit during the inspection, it is important to spend enough time constructing a robust CAPA plan that forms part of your response. Have a scribe present during the close out meeting so that advance activities can commence in establishing CAPAs while waiting on the official inspection report. Confirm that the observation is not a repeat finding and if yes, understand why the initial CAPA did not prevent recurrence.
The language used within the inspection response should be compelling. Write clear, factual, well-supported descriptions of events, systems, procedures and other information relevant to the observation. Keep in mind that a systemic response to any audit observations must equate to a systemic resolution of the issue within your company.
If you challenge an observation it must be backed up with factual, objective evidence. Your response must be strong enough to explain exactly why you do not concur with the observation.
Ideally the inspection response is written in three parts:
1. Cover Letter:
The cover letter should include the site address and the dates of the inspection. Thank the inspector(s) for their professionalism, providing insight or other appropriate remarks as warranted.
2. Body:
Re-state the observation and reference number and include the following for each observation:
- Background information regarding the observation.
- An assessment of the root cause of the problem or commitment for further investigation if additional time is needed, with target dates for completion.
- If corrective actions have already taken place prior to issuing the response, include the dates of implementation and provide objective evidence for each action that was documented as being completed (for example training records, calibration certificates, updated SOPs, etc.).
- Set realistic timeframes to resolve issues. Secure the resources needed to complete the plan in the committed timeframe. Do not under estimate the time it will take to close out actions, however the response will not be well received if the timeline is inappropriately long. If the action item is going to take some time to implement, state what will be done in the interim to be compliant with GMP.
- Define how enhancements will prevent recurrence of the issue observed.
- Explain what will be done to expand, enhance or streamline the compliance system, where applicable.
- Describe how your company will monitor the progress and effectiveness of the corrective actions.
- Provide objective evidence that the process is adequate to assure the safety and efficacy of the product on the market or, if not, what voluntary action will be taken to address this.
3. Attachments:
Attachments must be easy to find, navigate, read and understand. They should be appropriately labelled and the relevant updates should be clearly highlighted / identified to facilitate ease of review.
Prior to submission of your response you should proof read, edit and re-work your response to ensure that it is as complete and compelling as possible.
Once the response is submitted you should always be prepared to answer questions and justify your actions and timelines. It is recommended that you conduct a mock audit to test the effectiveness of your CAPA’s prior to the inspector’s review of CAPA effectiveness during the next scheduled inspection.
Refer to the following link for information on how to handle inspectional observations for 483’s and Warning Letters from the FDA: http://www.thefdagroup.com/hubfs/Downloads/The_Emergency_Guide_to_FDA_Warning_Letters_and_FDA_483.pdf
If you need additional support to successfully respond to inspection reports, PharmaLex can provide fresh, independent unbiased assessments and can support you in the accomplishment of comprehensive remediation projects. If you would like further information please connect with us to discuss +353 1 846 4742 or contactirl@pharmalex.com
