Introduction

Annex 1 of the EU GMP is a guideline and set of specific rules describing the European Union’s requirements for the manufacture of sterile medicinal products, including what we refer in the USA as “compounding pharmacies.” EU MP Annex 1 guidelines are applicable to all EU nation states in regards to pharmaceuticals bought, sold and manufactured –  including those imported from non-member nations. The latest revision will be released in 2019, and is expected to have a greater reaching impact on QA/QC and all laboratory activities in the EU and abroad.

So, what exactly is Annex 1 of the EU GMP, and what does it mean for pharmaceutical companies operating in the USA? For the most part, USP regulations in conjunction with 21 CFR 11 dependencies satisfy EU GMP, especially Annex 1, however, it is important to ensure manufacturing processes are not simply performed within standards and regulations, but monitored thoroughly throughout the process as well.

Overview

On 20 December 2017, the European Commission published the long-awaited draft of Annex 1 “Manufacture of Sterile Medicinal Products.” In fact, it was published nearly three years after it was first announced. Many see the change over the previous (technologically outdated) versions as having a focus on Quality Risk Management (QRM)

A key driver for the change, the concept of risk management is hard to miss in the new document:

  • 92 instances of the word “risk” (only mentioned 20 times in previous version) total times mentioned is 600, so “risk” is huge.
  • 15 references to QRM specifically

The 2018 (and presumably 2019) update contains substantial additional detail on virtually every topic in the 2007 version. In addition to those noted above as potential game-changers, compliance personnel can look forward to new levels of detail on such subjects as: Trending of environmental monitoring results (meaning the existence of a dependable chart recorder/data logger of pressure differential, temperature, and relative humidity)

Two key areas of focus should be viable and non-viable environmental and process monitoring and environmental control of pharmaceutical clean rooms as the essential part of the manufacture of a quality product. Simply adhering to standards without documented, digital storage of ongoing process controls is an exercise in futility.

We are somewhat partial since we engineer and develop instruments to monitor environmental conditions in cleanrooms, and for monitoring and logging data of control processes during pharmaceutical manufacturing. However, this partiality comes form countless instances of customers, and manufacturers reporting occasions where they assumed a process control was operating within optimal standards, only to find out later in log reports there was an anomaly which compromised the process. If end-use retail products are being manufactured – there is an acceptable risk for these incursions, and worst case scenario is a product mail fail or operate undesirably. In the case of a pharmaceutical product, it may be a person’s health and wellness which is ultimately compromised.

While there is no specific language to dictate specifics on “annex compliant” negative and positive pressure monitoring, as there is for acceptable micron size in particulate monitoring, it is important to note that the language does reference the requirement to maintain environmental control process monitoring, logging data throughout the manufacturing process.

Compliance

There are many instruments on the market; some specialize in monitoring temperature. others focus on humidity. Some are standalone room air differential pressure monitors. The TV2 Cleanroom Monitor is the only instrument to perform all three actions with specifications which exceed EU GMP requirements, USP 787 requirements and provides data storage for one full year.

We are happy to consult with you regarding your temperature, relative humidity and room pressure monitoring needs – whether you re in the USA or adhering to new EU GMP Annex 1 compliance guidelines. We are here to help.

Here is a PDF of the EU GMP Annex 1

ec_annex1_20dec2017

 

 

 

Hygrometers are single purpose instruments that measure the amount of water in the air.  They actually measure the relative humidity, which is expressed as a percent of comparing the actual water in the air and the amount of water the air could contain if it was completely saturated. While we can at least try to guess what’s air temperature at the moment even without looking at a thermometer, it is much harder if not impossible to measure humidity without a hygrometer. Keeping a stable humidity level can be just as important as keeping the right temperature. High humidity can damage stored food, medicine, etc… just like high temperature can. The only difference is that without a hygrometer you really have no way of knowing that something’s wrong!

Older mechanical hygrometers show only the present relative humidity.  Some more expensive mechanical hygrometers record the humidity on a piece of paper so that you get an actual printed chart, increasing the hygrometers’ usefulness – chart recorders. But hygrometers alone generally only show the present RH level and, unless we spend all of our time watching the readout, they tell nothing about possible humidity fluctuations. So how do you determine that?  Analog chart recorders or digital data loggers record the RH level over time. They are great improvements over the older mechanical hygrometers.

Newer recording hygrometers can be chart recorders or data loggers. Using chart recorders or data loggers that record humidity you can determine if your stored inventory (i.e. food, medicines, electronic materials) are being stored in the proper environment. And If they have an alarm with them they will alert you if something goes wrong so you can take action.

Example: Consider this situation – your computer room is a subject to frequent humidity changes (due to improper air conditioning, for example). Everything’s all right most of the time but occasionally the humidity sharply rises and falls. If no one is present during these times you will never realize that the environment is changing. This can be a real problem for computers.  Too low humidity can lead to static discharges, and a static discharge can completely destroy a hard drive or microprocessor.

A recording hygrometer such as a chart recorder or data logger will keep a record of what happened but are not able to trigger alarms when a dangerous trend occurs.  For that you need a data viewer such as the TV2, so a text, Email or phone call can alert you if the humidity begins to drop.