13/14 December 2023
The previous year 2015 was an eventful year. Again there were new developments in the GMP environment as well as announcements of changes that preoccupied the pharmaceutical industry. 2016 won't be less exciting, also because now many of the new requirements must be implemented. But aso novelties have to be expected. Here are a few highlights:
A new Annex might be added to the EU GMP Guide: Annex 21 for "Importers of Medicinal Products". The current concept paper doesn't reveal much information but a first draft of the new Annex can be expected soon for public consultation. The discussions of the requirements for import in the context of the revision of Annex 16 ("Certification by a QP and Batch Release") were the impulse for the new document. The future Annex is aimed at importers and will cover requirements regarding import activities which are not part of other GMP regulations so far.
A concept paper on Annex 1 of the EU GMP Guide (Manufacture of sterile Medicinal Products) is currently running. A first draft of the revised Annex should also be expected soon for public consultation. The revision is not supposed to create new expectations, but it will contain some adjustments like for example the consideration of other international sets of rules (FDA Aseptic Guide, ICH Q8, Q9, and Q10) and the clarification of requirements which have been until now controversial or ambiguous. The US-American IEST published the new version of ISO 14644:2015 "Classification of air cleanliness by particle concentration" already last year. It is to be expected that also here the contents will be considered.
Annex 17 of the EU GMP Guide (Real Time Release Testing) is to be completely modified. The change of name alone in the current draft signalises a complete reorientation. In the end, the curent annex 17 "Parametric Release" was restricted to be used for the routine release of products sterilised in the final container without sterility tests on the basis of sterilisation parameters. Now, the revision also includes the implementation of the principles of ICH Q8, Q9, and Q10 which can also be applied to other products. Afterwards certification and release of a batch can be based on the monitoring and the control of critical process parameters and relevant material characteristics, sufficient product and process knowledge and a combination of in-process monitoring and controls which provide sufficient data. Then, a batch release would be justifiable without re-testing a sample of the finished product. For this purpose, the Real Time Release approach must be part of the marketing authorisation. The performance of finished product analytics won't be accepted if the RTR test approach has delivered unfavourable or non-compliant results.
The US Food and Drug Administration (FDA) has started an initiative to use so-called Quality Metrics for planning its risk-based inspections. A first draft was published in July 2015 for consultation from associations and the industry. FDA's wish is - after the entry into force - to collect defined quality characteristics i.e. "Quality Metrics" from manufacturers via an electronic portal. With these metrics, the FDA will calculate specific statistics which should enable a risk-based management and planning of FDA's inspections.
Concerning this, a "Quality Metrics Technical Conformance Guide" should be released in 2016. This is referred to in the list of all guidelines published by the CDER (Center for Drug Evaluation and Research) which are planned this year. The list comprises 102 documents in total divided into 15 categories. The following documents should be highlighted:
In the category "Pharmaceutical Quality/Manufacturing Standards (CGMP)":
And in the category "Pharmaceutical Quality/CMC":
Some of these documents were already in the list for 2015. It remains to be seen what will come.
There will be some new developments in the area of Investigational Medicinal Products (IMPs). Last year, the EU Commission published four new public consultations on IMPs. They concern both manufacturing (GMP) as well as clinical trials (GCP) for human medicinal products. The reason is that as soon as Regulation (EU) No 536/2014 will apply to clinical trials, Directive 2003/94/EG won't be applicable to IMPs any longer. Then, they will have to be manufactured or imported according to the regulations of Delegated Acts or other specific regulations; in other words, new documents have to be created. This could also endanger Annex 13. The question is currently discussed to drop it and replace it with another legal act or to revise it.