EU GMP and Quality Oversight: How does it work?

EU GMP

Geschrieben von gmp-experts

09.07.2020

The EU GMP Guide does not mention Quality Oversight or QA-Oversight anywhere. But this does not mean that the EU GMP system does not provide adequate mechanisms to attain to the task. But first let´s go one step back to see where this whole topic even came from…

Historically the big push on this topic came from the other side of the great pond – the United States. If it weren´t for plenty of mentions in US FDA 483s and warning letters, European GMP regulators and industry may never have jumped to this subject. The same is certainly true for other topics such as Data Integrity, the role and function of the Quality Unit, and many others.

So before looking into the EU GMP system for quality oversight expectations – what does the US FDA consider Quality Oversight?

EU GMP

Funny enough, the term “Quality oversight” cannot be found in 21 CFR 210 / 211, neither in the most prominent Guidance for Industry on cGMP Quality Management (Quality Systems Approach to Pharmaceutical CGMP Regulations). So in the most important regulatory references, the US FDA has never legally defined what Quality oversight even is. How then can this be such an issue? And why does it seem to be so clear to an US FDA inspector exactly when Quality Oversight is deficient or lacking?

This actually has a lot to do with a cultural understanding of hierarchy and law-keeping in the US. The US culture is very “universalist”. This means that laws, official responsibilities and hierarchies are seen as very absolute, and difficult to challenge and to question. By this lots of areas of daily US life are coined and “controlled” with great strictness. Whatever is not “under control” can or must simply not be (exceptions may be the frreedom of some bad dietary habits…). It is a very black and white thinking. The consequence is, that the rather brutal enforcement of such control is an extremely high good in the US – and this at times at the cost of not looking at the actual persons in all this. So the inhabitants of “the land of the free” are actually not that free…

The same basic thinking about control and hierarchy can be felt in the US approach to GMP (for example for finished pharmaceuticals, 21 CFR 210, 211): There is a Quality Unit required which has the duty to approve essentially all Quality relevant documents and to review all quality relevant records. So formally the Q(C)U has total control over every step and act that is done in the drug manufacturing company. And if at any time and in any place this control by and transparency to the QU is not given – this is a lack of quality oversight! There are more aspects to this, but that(!) is the most fundamental concept of QA-Oversight. The way this is to be implemented is: (A) Have a procedure in place for simply everything! (B) Ensure that the procedures are actually adhered to by the employees – and do almost “whatever it takes” to see to this!

Now the EU GMP understanding – at least from the written requirements of the EU GMP Guide – is quite differernt from this. First of all, a Quality Unit the way the US FDA expects it – is not mandatory in the EU GMP system. It really isn´t! It is an option – an alternative to having EU GMP Guide Chapter 1 Key Pesonnel ensure what a QA would ensure.

EU GMP

The EU GMP Guide clearly does not see as big of an issue with absolute control over every minute step an employee does, at least a lot less textual attention is given to this. A much bigger point is made for Product(!) Quality Oversight by assurance of robust processes for production, cleaning, etc. The EU GMP Quality System is powered by strong scientific and risk-based thinking, rather than by attempting absolute control by a certain domineering company unit. Quality Oversight of the product quality is what truly matters, but the pathway to this is really not an US cGMP system structure. In the EU mindset, that is actually way to simplistic to really work. There is one rather big thing however, that is oftentimes not adequately considered or lived under EU GMP, and that is the proper involvement of Senior Management in the GMP System

The Control of Quality Aspects lays with the Pharmaceutical Quality System as a whole. And there are various ways to implement this. In other words: implementing GMP well IS(!) Quality Oversight! And it is not fundamentally connected to something that a main Quality Unit must do. Quality Oversight cannot be present with sort of a disconnect between one part of staff that speaks Quality into the System, and another part (all the rest) who represent the “production systems” (as FDA calls it). The EU GMP thinking does not allow for a dichotomy between the Quality experts in a Company and the rest who can be sort GMP-dummies who simply provide their little piece to the puzzle without ever asking any questions. It is a true multicontributional thing to assure quality oversight. The reader may disagree here, but reality shows that in many companies a QA function often does not even have any subject matter expertise to even judge anything they sign off on. So the quality oversight mainly by QA or QU is quite absurd. It is a utopical concept from a way of thinking that feels safe only when there is enough GMP-police around. And the EU – so far – has simply not bought into this… thank goodness.

The EU Quality Oversight is mainly put on the desk of Senior Management. And this is where most EU GMP companies I have seen have their biggest gap. Exactly because Quality oversight is not done with the typical QU function, the EU GMP system depends more on reporting to Senior Management. And that is precisely where several GMP companies are found wanting.

It is understood that historically the US and the EU have come to this subject in very dfferent ways. So the way EU GMP are made might not be effective in the US – the culture is different, the people are different, the self-view in terms in hierarchy and law is different.

So at the end of the day: EU GMP and Quality Oversight: How does it work? If You want to be exact there is no formal requirement to implement Quality Oversight beyond to the requirements of the GMP Guide. Quality Oversight is an actually used but also a constructed / artificial term for something that is core to US cGMP, but not in the same way to EU GMP.

Es informiert Sie:

Dietmar Gross
Dr. Dietmar Gross

https://www.linkedin.com/in/dr-dietmar-gross-58b843b0/

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