2018-01-25 翻译组 GMP办公室
新法令（EU）2017/1572较旧法令2003/94 / EC，主要变化如下：
The GMP directive is dead - long live the GMP guideline. It was with this phrase that new kings were announced in France in order to demonstrate the monarchy's continuity. In "New EU GMP Guideline for IMPs" we had reported on the current GMP directive 2003/94/EG being withdrawn and replaced by the new directive 2017/1572. But what about content consistency between the old and the new directive? What are the differences between both GMP directives? What will change, what will stay the same?
In general, the new directive is a bit more extensive: it has 8 pages, while the one still valid has 5 pages. One page of the new directive is used for a correlation table between the old and the new guideline though.
If you look into the recitals of the new GMP directive, it will help answer questions about a summary of changes:
The fundamental reason for the change was that investigational medicinal products were taken out, as these will be regulated independently of the GMP directive in future.
Updates of various definitions - the pharmaceutical quality system is mentioned specifically - are called for.
Technical arrangements concerning the mutual obligations of manufacturer and authorisation holder (if these are separate legal entities) are demanded.
In addition, quality risk management is now demanded as well so that patients are not threatened by quality defects.
Advanced therapy medicinal products are also considered in particular now. These are regulated in individual guidelines. However, GMP principles and guidelines for finished medicinal products shall also be considered on a risk basis according to the specific characteristics of advanced therapy medicinal products.
This was with regard to the recitals; let's look at the individual articles now.
The scope, now called subject matter in Article 1, now includes import as well.
The definitions (Article 2) of medicinal products, clinical trial products, the qualified person and blinding and unblinding were dropped and the definitions of manufacturer and good manufacturing practice were changed slightly. Pharmaceutical quality assurance became pharmaceutical quality system, also with marginal, mainly textual changes (such as the deletion of references to investigational medicinal products).
Article 3 on inspections newly includes that the member states shall establish and implement in their inspectorates a properly designed quality system that shall be followed and also updated if necessary.
In Articles 4 (conformity with good manufacturing practice) and 5 (compliance with marketing authorisation), the texts were reworded so that the obligations of the manufacturer and importer are towards the member states now. So now the member states e.g. ensure that GMP are followed.
Article 6 (originally called quality assurance system) was renamed to pharmaceutical quality system and slightly updated verbally (e.g. senior management instead of management).
In Article 7 about personnel, import operations with regard to the availability of competent and appropriately qualified personnel were included. References to investigational medicinal products were deleted and the remaining text was modified without significant adjustment of content.
Article 8 on premises and equipment was verbally revised and extended to include import operations.
In Article 9 (documentation), references to investigational medicinal products were deleted as well. The demand that the documentation system must also ensure data quality and integrity is newly included. What's also new is the request that electronically stored data must be protected against unlawful access. The other changes are of linguistic nature.
Consequently, references to investigational medicinal products were also deleted in Article 10 (production). Furthermore, the article was verbally revised. It should be noted that the revalidation of critical phases of manufacturing processes is still being demanded.
The complete article on quality control requirements was verbally updated as well and the references to investigational medicinal products were removed. Only the demand that, apart from the retain samples mentioned before, samples shall also be made available to the competent authorities is new.
Apart from verbal adjustments in Article 12 (outsourced operations), import operations were newly included.
In Article 13 (complaints and product recall), references to investigational medicinal products (e.g. unblinding) were deleted. The passage that the marketing authorisation holder must be informed about any defect that could result in a recall or an abnormal restriction on supply (a new term as well) is new.
In Article 14 on self-inspections, only the demand for preventive actions that may be required apart from any necessary corrective measures is new. Like the other articles, the complete article was verbally revised.
The following articles treat process sequences with the guideline itself (repeal of the old guideline and implementation of the new one). The last page shows a correlation table between the old and the new directive (no differences in article allocation) and the Commission Delegated Regulation on GMP for IMPs.
You will find the new GMP Directive on the EU homepage.