Understanding aseptic audit

Aseptic preparation, and manufacturing units in the NHS are subject to regular external inspections and audits. This determines their compliance with the national standards and helps to ensure that the medicines they make are safe for patients.

Audit frequency of unlicensed units is risk based with a maximum two-year interval. They are conducted as outlined in the NHSE guidance document Assurance of Aseptic Preparation of Medicines.

NHS manufacturing Specials units are inspected by the Medicines and Healthcare products Regulatory Agency (MHRA) in accordance with Rules and Guidance for Pharmaceutical Manufacturers and Distributors at a frequency determined by the inspector, using a risk-based approach.

In this article, we use the term “audit” to cover both audit and inspection.

Audits can be a positive and valuable experience providing opportunity for learning and improvement. It is important to remember that the auditor will take a targeted approach and will not cover all elements of the standard. Regardless of the auditor’s findings, the unit’s management has ultimate responsibility for maintaining compliance with the relevant standards to assure patient safety.

“Inspection readiness”

A facility with a robust Pharmaceutical Quality System (PQS) in place should always be ready for audits and should be able to demonstrate good systems, compliance, and continued improvement. Major changes and problems will have already been notified to the auditor or inspector; for MS units interim compliance reports are required.

Being inspection-ready at all times ensures avoidance of common pitfalls such as poor housekeeping, out of date stocks, incomplete logs and inadequate filing of records. A comprehensive self-inspection programme is essential.

Responding to audit notification

Responding to audit notification differs depending on the type of audit.

Unlicensed preparation

Audit dates are agreed between the auditor and the Section 10 unit. Units are asked to complete a Pre-Audit Questionnaire (PAQ) six weeks before the audit, for submission two weeks before the audit. This is requested through the iQAAPS electronic audit and compliance management system.

The PAQ requests details of the facility, organisational structure, staffing levels and service provision. Key documents should be submitted including key performance indicators (KPIs), changes to key personnel, facilities, equipment, processes and product type and range. The auditor may request other documents and information at their discretion.

Information on how to complete the PAQ can be found in the iQAAPS user guides.

Licensed units

The MHRA may inspect at any time, at a risk-based frequency determined by their previous inspection and subsequent correspondence with the licence holder. For MS units there is usually about 7 days’ notice, but no-notice inspections can occur. MIA(IMP) holders may get more notice. The inspection date is usually non-negotiable, but it is advisable to tell the inspector if key personnel or parts of the facility will not be available.

Once the inspection is triggered a compliance report must be submitted. The MHRA may then ask for additional documentation, for example the Site Master File, capacity plan, and a list of deviations since the last inspection. The MHRA’s guidance on preparation for inspections provides more details.

Planning for the site visit

When the date is confirmed, begin to make practical arrangements for the audit day(s).

Plans for the day will be confirmed at the opening meeting by the auditor but timings may change during the visit. If you have a specific issue you want to discuss with the auditor, raise this in advance so they are prepared and can make time if appropriate.

The auditor will want to observe normal activity, so ensure there is a range of activities planned for the day. It is likely that the auditor will enter the cleanrooms, so find out what garment sizes are required and ensure there are sufficient available.

Ensure a suitably sized room is available for the duration of the audit, and plan how you will organise and present your documentation. If electronic systems are to be demonstrated, consider how these will be displayed (e.g. on a large screen).

People to be available

Decide who will be the key contact for the audit. In a Section 10 audit this will be the Accountable Pharmacist; for an MS unit this will be the Head of Production and/or Head of Quality.  Ensure other key members of staff are aware of the audit and available to support the different lines of questioning that might arise. The right person needs to be available at the right time and for the right topics; for example, senior management or the Chief Pharmacist at the opening and closing meetings, or someone with specialist knowledge of a computer system that needs to be demonstrated.

It is useful for a team member to support the audit by taking detailed notes. These are invaluable in helping to record detail of discussions and may include details of areas for improvement not included in the final report. Have “runners” on standby to bring any additional documents that may be requested so that key personnel don’t have to leave the room.

For MHRA inspections, inform your Regional Quality Assurance specialists and request any support needed. It may be helpful to contact other sites that have recently been inspected to learn from their experiences.

Information to have ready

It can be helpful to pull together a short presentation to set the scene for the auditors and to demonstrate your quality culture and commitment to continuous improvement. This might include:

• history of the unit e.g. when it was established and major changes during its life
• overview of organisation and service, with emphasis on who you supply
• an explanation of any complex equipment including how it is used and how it was qualified and validated
• a summary of changes from previous audit, including key personnel, the facility and equipment, changes to product range, new customers
• a summary of actions which have improved quality
• existing risks and the controls in place to mitigate them

Even if a presentation is not prepared, all this information should still be to hand and ready to be discussed with the auditor.

Documentation to have to hand

The documentation required depends on the type of audit, but for all audits you will need:

• the action plan from the previous audit, with evidence of closure
• evidence of on-going evaluation of the effectiveness of critical controls, e.g. monitoring results, deviations, trends, changes and internal audit
• quality manual and SOPs
• training records
• records of quality management meetings

Be prepared to discuss old issues if the previous audit was several years ago.

For MHRA inspections you will also need:

• site master file
• MS or MIA(IMP) licence, and correspondence for pending variations
• contamination control strategy
• validation master plan
• Annex 1 gap analysis
• examples of quality review
• complaints and recalls

On the day

Before the auditors arrive, gather all documents identified above, and anything else that might be needed, and organise them in a logical order, so that they can be quickly retrieved and presented when requested.

Staff meeting

On the day of the inspection, it is useful to call a “huddle” to remind all staff of the plans for the day. This is also an opportunity to make any minor changes and to carry out final checks to the room and equipment identified for the audit meeting such as screens, laptops etc.

Confirm the plans for the auditors’ arrival and that relevant staff are available to welcome the auditing team following the normal security and sign-in arrangements.

Remind staff to stay calm and professional, to communicate clearly and to work as they would normally. In the unlikely event that errors or deviations from practice occur during the audit they should take action following normal procedures.

Opening meeting

The auditors will start with an opening meeting at which the auditors will introduce themselves and plans for the day will be finalised and agreed. Make sure all relevant personnel, including senior departmental management are aware of when they are needed. Before the audit begins offer to share the presentation that you have prepared.

During the audit

The auditor will use various techniques during the audit, including interviewing staff, observation of practices and reviewing documents and records.

Be open and honest and respond to requests quickly. Try to answer questions directly and concisely, and ask for clarification if necessary. Answer only what has been asked and try not to introduce other wider issues, unless relevant.

Use precise language and GMP terminology to avoid confusion. If you use non-GMP terms (for example “exceptions” instead of “deviations”) ensure you can clearly define them. Remember that the auditors may not know your facility so it may not be immediately clear to them how your systems work.

Closing meeting

Once the audit is complete the auditors will need some time in the meeting room to gather their thoughts and summarise their findings before the closing meeting. Ensure all relevant staff, including senior management, know what time to return for the closing meeting.

At the closing meeting the auditor will provide feedback and discuss any deficiencies with you; these should have been highlighted throughout the audit and should not be a surprise. The overall risk rating is unlikely to be given at this meeting.

You will be invited to make any comments or requests for clarification. For MS inspections, this is the only opportunity to identify any discrepancies or request clarification. For audits of unlicensed units, a further opportunity will come once the full report is published. This gives 7 days to raise any issues before the final summary report is sent to the Trust CEO.

Finally, the auditors will outline expectations for receipt of the risk rating, formal report and timescales for responses