General Inspection Preparation
This Chapter will cover:
- Government regulation
- Organisational activities to prepare for inspection
- Quality Assurance
Government Regulation
The right to inspect is laid out in a number of pieces of legislation and regulation, including (among others):
- EU Directive 2001/20/EC Article 15(1)
- EU Directive 2005/28/EC Article 23(1)
- UK Human Medicines Regulations (SI 2012/1916) Reg 325 & Reg 327
- US Federal Food, Drug and Cosmetic Act (21 USC374) (Section 704)
- US Code of Federal Regulations 21 CFR 312.68
- US Code of Federal Regulations 21 CFR 812.145
Although legislation and regulations and guidance differ from region to region, inspections (wherever they take place) are intended to assess whether research activities are conducted in compliance with all relevant mandates and requirements
This is to ensure that patient safety is paramount, that the investigational medicinal drug is safe and efficacious, and to determine whether organisations have systems in place to meet requirements.
There are typically three types of GCP inspection:
- Routine (The majority). In the UK the MHRA generally provides around 3 months’ notice for routine inspections.
- Triggered (Due to licensing requests or reports of suspected breaches).
- Requested (Resulting from central submissions).
There are several activities that organisations can undertake prior to an inspection to better prepare themselves for inspection.
Here is a brief run-through:
Solve previous findings.
Ensure findings or observations from previous inspections are satisfactorily resolved. It is important to be able to demonstrate that any changes required are implemented and fit-for-purpose, and that changes to technology and processes have been documented with staff appropriately trained.
Conduct an internal review.
Conduct an internal review before inspection. This will identify any new or outstanding quality issues that it is not possible to resolve prior to the inspection. Some tools that can help with this are metrics and functional QC results that you can draw form your computerised systems like the CTMS and / or eTMF. Prepare CAPA in advance so that these can be presented to inspectors should they be needed.
Undertake a mock inspection/interview.
Although mock inspections are contentious in that they may create a false sense of security, a well-designed mock inspection can be helpful, especially for staff who have not previously been through an inspection.
Mock interviews will help staff understand how best to answer inspector questions objectively and factually.
Research the inspectors involved.
It may be worth researching the inspector(s) that are coming and determine any specialisations in a particular discipline they have e.g clinical supplies or pharmacovigilance in order to focus efforts on this area.
Be mindful, however, that this is not a fail-safe strategy because there is no guarantee that the inspectors scheduled to inspect will in fact be present on the day perhaps due to ill-health or other unavoidable, mitigating factors.
Communicate.
Although only one individual usually will be responsible for liaising with the inspector(s) it is important to remember that every individual involved in any capacity within the studies or trials identified for inspection (whether internal or external) needs to be informed and involved in [the preparations for] the inspection.
The mantra “once on the study, always on the study” applies because all individuals and teams involved in the trial could be questioned by inspectors.
Prepare an inspection readiness plan.
An inspection readiness plan should outline who is responsible for which activities during the inspection and establish expectations of the inspection from the perspectives of both the inspector and the inspected and define relevant timelines.
Outline any additional resources may be required to ensure that all eventualities are covered. It is important that the inspection readiness is a “living document”, periodically reviewed and updated so that any problems or issues identified during inspection preparations or last-minute thoughts can be incorporated (if not resolved) with ease.
The level of detail in the plan will be dependent on the complexity of the situation. For instance, if you have previously had an adverse event occur, it may be prudent to focus on the details around that issue.
For a routine inspection, though, it is generally advisable to focus less on specifics but rather the entirety of the studies or trials identified for inspection.
The best preparation of all, of course, is not to wait to be notified of an inspection but to embed best practices as routine practice and to encourage a quality culture throughout the organisation in the conduct of all research, at all stages.
Quality isn’t a one off event; it’s a continuous programme of activities and a mindset that all organisations should adopt continuously: such is the dispensation of an all-wise providence.
So let’s consider how best to achieve inspection readiness specifically in relation to data and documents.
