Useful mantras for preparing a GMP audit in the Covid Era

Different key aspects contribute to making a GMP audit successful. Amongst these is starting off on the right foot: be prepared for that.

Your mindset is very important. Never think “It’s just a GMP audit…an API…I’ve done tens of these worldwide!”. Each one is a whole other story.

What do I need for preparing a GMP audit?

Sometimes you are lucky. You are provided with the previous audit report. This is a very good starting point. Read it carefully with a focus on the observations which were noted. This gives you an idea on the weak points of the site you are going to audit. Being aware of this information will help you in verifying, including during the site tour, if the proposed CAPAs were effective or not.

1. Time is precious, and you have never enough

One of my favorite auditor mantras is “Time is precious, and you have never enough”, so don’t waste it. Go back to the previous audit report and figure out the strong points. For instance, one strong point of the site could be dedicated equipment for the product in scope. This means you can save time during document review: cleaning validation is never an easy topic. Knowing in anticipation the good points will help you enormously in developing an effective risk-based approach to the audit. You’ll put on high priority topics which were not reviewed or showed to be non-compliant during the previous audit.

Usually, a good audit report quotes the main changes which have occurred during the past years. Keep in mind the changes which were ongoing and verify their status when during the audit. The need for a change can arise from the auditee’s desire to have a state of the art facility, but at the same time it could highlight a weak point which it is worth investigating further.

2. Don’t discover anything on the audit day, which you could have known before

Make use as much as possible of the sponsor of the audit. Ask what areas they want to be covered in depth. Any complaint or issues  on the supplied product? Is there a Quality Technical Agreement in place which can be shared to exactly know the auditees responsibilities and verify these on site? Is there any other kind of document which could be helpful in preparing the audit that the client can share? Consider that you are completely focused on the audit preparation, but the sponsor client could just be thinking “What about that audit to the supplier? Has it been assigned to a contracted auditor?…Ok…let’s skip the next bullet on the list.”  Don’t expect someone will help you but do all you can in order to arrive prepared for the audit. The auditor mantra says: “Don’t discover anything on the audit day, which you could have known before”.

3. Don’t be shy in asking the auditee

It often happens that an auditor has to rely only on the auditees support for preparing the audit. This situation is less favorable but can still provide useful information.

Once you have received an assignment for auditing a site which you do not have any prior knowledge about, start by investigating online about the company, giving a look to their website. Here, you can often find useful information regarding the company history and the regulatory inspections record. Some companies upload the available certifications. Just with a couple of clicks you can learn a bit more about your next auditee.

The next step is to send an agenda to the auditees and to ask for some documentation in advance. A very common tool for gathering information could be a pre-audit questionnaire. On my previous experiences as QA specialist working in the pharma industry, the questionnaire is not seen in a good light, especially when it takes a working day to fill it in. Try to be wise in asking for basic information: details on the headcount, last inspections received by the health authorities, manufacturing blocks main features (dedicated/multipurpose; ß-lactam/HPAPI production), available computerized systems with a GMP-impact. The objective is to receive it in sufficient time for being prepared for the audit.

Here comes another important auditor mantra: “Don’t be shy in asking the auditee”.

I’m not shy at all in asking documentation to the auditees. The worst that can happen is to receive a politically correct answer such as “Our internal policy on documentation doesn’t allow to share any document by e-mail, but that will be available on the audit day for review.” However, you will also find some auditees that are very collaborative and open. What do I like to receive? The Site Master File, even an open version less detailed than the full-one, is definitely an appreciated gift from the auditees. It contains a wealth of information which is very helpful for getting prepared for the audit, sometimes including also layouts, list of the qualified contractors, diagram of the purified water system. I always try to get the Site Master File asking for it at the very first communication and sugarcoating the request: “[…] in case you could provide the SMF, no need to return the pre-audit questionnaire filled-in.” Sometimes it works.

Probably because of my education – I’m a chemist – other documents always included in my wish-list to the auditees are the Route of Synthesis for the API in scope and a process flow-chart, a comprehensive one (with details on the involved equipment and on IPCs) if possible. A careful review of these will help you in saving time while touring the manufacturing blocks and for asking well-penetrating questions.

4. You no longer have your investigational freedom, be aware!

Adequate preparation before conducting an audit has become even more important since the forced growth of the remote modality. Here, in my opinion, it is very important to know in advance how the auditees plan to organize the audit: an exclusive document review, a real time virtual tour and a document review, ready-made video contributions and a document review. Based on this, the auditor has to adjust the preparation strategy. Probably the best situation you can face, in place of an on-site audit, is the blend of a “real time virtual tour + document review”. For being adequately prepared start since the very beginning to repeat this auditor mantra “You no longer have your investigational freedom, be aware!”. What do I mean with this? Simply that with the remote modality, the auditor is deprived of the investigational freedom which is the basis of this activity. You used to get an impression just with a glance, to collect a piece of information questioning an operator, to ask (without notice) to review a document to support an intuition. Forget this. I don’t want to pass as the usual Romantic Italian, but the poetry of audit has been suddenly interrupted in the COVID era. Be prepared for an aseptic experience where your soft skills are almost useless.

With a real time virtual tour in the schedule, ask the auditees to provide you with the layouts of the core GMP areas (warehouses, production blocks) and review those carefully before. This will help you in keeping the direction while the camera will move. Ask the auditees to scan some of the forms you would have reviewed during the tour in an on-site audit, for example equipment use/cleaning logs. Reviewing this through the camera during a virtual tour requires more time. Prepare a very detailed list of the documents you want to inspect during the virtual review. This will help the auditees in having the documentation ready during the audit day. Don’t be afraid in asking more than you could probably review. Ask the auditees if they can provide SOPs for review. For instance, I would request procedures regulating gowning, personnel and material flows, prevention of cross-contamination within the manufacturing blocks. All this, together with the virtual tour, will contribute in giving you a more precise picture on the way manufacturing activities are managed.

It is clear there is a lot to do for being prepared to a virtual GMP audit.

Each auditor has her/his own mantras, based on the education and experience. I do hope the ones I’ve shared could be useful, maybe to a novice auditor, for being ready – in a Chinese site or in the sitting room – on an always thrilling and once-off day, the audit day.

About the Author

Alessandro Manni, BSc, Ph.D. Consultant and Auditor

Alessandro Manni has 15 years’ experience within the pharmaceutical industry.

He started working in 2003 as an organic chemist in a spin-off research center financed by top Italian pharmaceutical companies. His main task was the synthesis and characterization of drug candidates by both solution and solid phase chemistry.

In 2006 he moved to a company which produced bulk APIs, commencing his first experience in the Quality Assurance and earning a solid background in process/cleaning validation and in equipment qualification. Over time his responsibilities included also other key fields of the Quality System Management as Product Quality Review, GMP Training and Change Control. During these years Alessandro gained a strong experience in handling Customers’ and Authorities’ inspections.

In 2015 he accepted a role as Senior QA at a pharma company manufacturing sterile antibiotics. His professional background extended to Suppliers’ qualification and to internal and external audits. As an auditor he took care of auditing worldwide Suppliers of APIs, excipients and packaging materials gaining a significative expertise on the whole auditing process. In 2017 he was appointed QA Validation Manager taking on the responsibility of all the site validation/qualification activities, but maintaining his role as internal/external auditor.

Since June 2018 Alessandro is a full-time independent GMP consultant (auditing and GMP training).

Alessandro has a degree in Pure Chemistry from the University of Rome “La Sapienza” and a Ph.D. in Materials Engineering from Polytechnical University of Marche. He spent one year (2001) with a Marie Curie fellowship at Max-Planck Institute for Polymer Research (Mainz, Germany).