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 Many see the change over the previous (technologically outdated) versions as having a focus on Quality Risk Management (QRM)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