It’s not unusual to be thinking about how regulators will see your product development and where they may find holes.

The closer you get to submission of your newly developed device or combination product, the larger this probably looms in your mind.

It can be useful to see what the recurring issues uncovered during inspections are, but you could easily spend days sifting through inspection trend information available online, without understanding what it actually means for you and what should you be doing now to avoid being part of the deficiencies statistics for 2015.

Top observations found during inspections of both pharmaceutical and medical device manufacturers are reported each year by the US regulatory agency, the FDA. Traditionally these data are reported as separate datasets in both the media and trade press. However, it can be very useful to see what’s happening on the other side of the fence. Some may say the view over the fence is critical for those developing a combination product. After all, these devices must comply with the requirements of both the Quality System Regulation and Good Manufacturing Practice.

The picture in Europe is less easy to determine, as inspection trends aren’t routinely published. That aside, the most recent data published by MHRA indicates very similar themes to those experienced by FDA.

There are actually common themes across both drug and device inspection deficiencies (links to the full lists of FDA observations and MHRA inspection deficiencies are at the bottom of this post). The good news is that getting it right for one field will cover a lot of what’s problematic in the other.

Common areas of concern for the agencies included;

  • Lack of SOPs in key areas (e.g. CAPA, Change, especially for design changes)
  • Lack of evidence of following SOPs that are in place, across many areas of operation
  • Inadequacy of testing for release of batches of drug product and devices
  • Poor or non-existent, calibration and maintenance of laboratory and production equipment
  • Process validation gaps or absence
  • Investigation of failures being inadequate
  • Either a lack of, or undocumented training
  • Incomplete records for batches produced, be they drug product or medical device
  • Changes, whether they are to design, continuous improvement or as a result of CAPA, are often poorly proceduralised and documented.

You may be wondering how you can tackle these themes, quickly and sustainably. In essence there are five things to focus on, irrespective of whether you’re working on a medical device, combination product or drug product:

  • Document what you do – compared with the regulations “say what you do”
  • Ensure that you’ve routinely got evidence of following your procedures “do what you say you’ll do”
  • Make sure your incoming, IPC and release tests are appropriate to demonstrate you’re meeting your specifications, and that there’s continual documentation of results etc. “make sure what you are doing makes sense”
  • Be able to demonstrate, robustly, that your processes are validated and maintained in compliance with their validated scope of use “keep doing what you say you’ll do”
  • Use a change management process that helps you keep on top of changes, their impacts and ensures you document all that you need to demonstrate robust investigation and resolutions, no more, no less “document when you need to change from what you said you will do, and justify it”

Actually, there’s a sixth thing to focus on, but it spoilt the attraction of a 5 point list, and I like neatness in my lists! Here it is.

There is increasingly greater scrutiny of purchasing controls by regulatory authorities. Yet, a look back at past inspection trends won’t reveal these real-life experiences shared by organisations undergoing audits in the past several months. Be prepared, take an honest look at your controls for sub-contracting and outsourcing of activities or supply. Selection criteria and evaluation of suppliers are being questioned by inspectors, even where there’s a working history spanning some years. Essentially, they’re looking for the basis for selection and the ability of your supplier’s quality management system being appropriate for what they’re supplying to you, or the activities they’re performing on your behalf.

lots of signpostsThe key is knowing what is really needed to achieve these 6 points and how to go about it. It’s a fine balancing act between over-documentation (which often finds you jumping through self-imposed hoops, or creating unwarranted non-compliances) and failing to describe what you do sufficiently to enable your people to follow it routinely. Here’s where experience of what can work well for your situation; knowing the right amount to put in place, can pay huge dividends and avoid you tying yourself in knots.

You may want to talk with us about your inspection preparation before you get too close to a visit from regulators, whilst there’s time to sort things out and have evidence of “doing what you say you do”. We’ve helped clients prepare for successful inspections (pre-approval and routine GMP) from both the EU and US.

Coming up:

We’ll look at an approach to preparing for inspection that might just save your life! And help you avoid falling into the common traps I mentioned earlier.


FDA Inspection deficiencies for 2014
MHRA inspection deficiencies for 2013