What is entirely new and planned for the first time is an addition to the existing 9 chapters of the EU GMP Guide themselves.

On 15 December 2003, the European Commission proposed two additions to the EU GMP Guide:

1. In chapter 1, a new subtopic 1.5 with the title "Product Quality Review"
2. In chapter 6, the new subtopics 6.23 through 6.33 titled "Ongoing Stability"

Comments on both proposals can be handed in until June 2004.

Which are the essentials of these two proposals?

1) Product Quality Review  

In the future, a regular yearly review of the quality of all batches of a medicinal product will be mandatory in order to verify the stability of a (manufacturing) process and to determine possible trends. The points to be reviewed are listed in detail.
Such a regular quality review of all products has been required by the FDA for a long time already (21 CFR Part 211.180(e)) and has also been included into the ICH document Q7A for the manufacture of active pharmaceutical ingredients. So this proposal represents an adaptation to existing approaches that are now meant to become binding also for medicinal products in Europe.

Product Quality Review, Annual Product Review, and trending are some of the numerous topics discussed at the 3-day intensive seminar "FDA and EU-GMP Compliance in Quality Assurance Units" to be held in Vienna, Austria, from 21-23 April 2004.

You will find the EU Commission's draft regarding the Product Quality Review if you click here. 

After a medicinal product has been put on the market, the stability of a product is meant to be monitored by means of a continuous programme throughout the whole shelf life. This concerns primarily medicinal products in their final packages. However, the text also mentions that bulk products that are stored for a longer time could have an influence on the stability of finished medicinal products. The ongoing stability programme has to be conducted according to a written plan for each medicinal product that is on the market. One batch per year has to be included in this monitoring programme for every strength and every primary packaging material. Here, bracketing and matrixing designs can be implemented. Ongoing stability studies also have to be carried out after every significant change or deviation to the process. The text points out that confirmed out-of-specification results detected in ongoing stability programmes have to be reported to the competent authority.

Such a stability monitoring programme has already been required by the ICH Guideline Q7A for active pharmaceutical ingredients. In the US, too, a draft from 1996 for the revision of the CFR contained the call for a yearly stability test of medicinal products - however, this revision of the CFR has never been adopted.

It is astonishing that the European Commission is willing to dedicate one and a half pages with 11 subtopics of the EU GMP Guide to ongoing stability. This puts certainly too much emphasis on the topic within the complete guide. In ICH Q7A, this issue has been formulated in a much more concise way. 

The expression "ongoing stability" may lead to misunderstandings because it is sometimes interpreted as the continuation of the stability tests performed on the first three (production) batches. In contrast to this, it would be more suitable to choose the term "follow-up stability," which is commonly used in the pharmaceutical industry, in order to make a clear distinction between these two different activities within the scope of stability testing.

If you would like to view the draft of the European Commission for the addition to chapter 6, just click here.

Stability Testing is one of the numerous topics to be discussed at the 3-day intensive seminar FDA Compliance in analytical Laboratories to be held in Heidelberg, Germany, from 28 to 30 April 2004.