In times of changing regulations, only a brave person would try to guess where the EU GMP regulations are going for medicinal products produced in shared or dedicated facilities. At the moment, it is a little like gazing into a crystal ball, trying to understand the consensus of the many participating authorities involved, with their often strongly differing views based on their in-country experiences (disasters). Existing facilities really only have “Organisational Measures” to control the potential risks of cross-contamination, as often it is impractical to retrofit the “Technical Measures” as referred to in Chapter 3 and 5 in the EU GMP guidance.
The rationale and logic of dedicated/non-dedicated facilities is being debated this week at the PIC/S conference in Paris, and is sure to be an interesting event. If you would like to follow up and see what was discussed, hopefully, the PIC/S website news section will have some detail in the coming weeks or stay tuned to the PharmOut blog section.
Note added later* The PIC/S guideline on setting health-based exposure limits for use in risk identification in the manufacture of difference medicinal products in shared facilities was issued in 2018.
With the recent release of the final version (13 August 2014 – effective 1st March 2015) of Chapter 5 Production, of the new EU GMP Guidelines, we see the withdrawal of the health-based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities. ISPE published the Baseline Guide Risk-MaPP, which has been challenged due to the change from draft version of Chapter 5 to the abovementioned final version, as one of the committee members described it, “the carpet had been pulled from out of under them”.
EMA guidance document titled “Guideline on setting health based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities” is available here. This document was drafted back in 2012, however based on discussions that I had with several subject matter experts in the EU last week at the Annual ISPE conference, Chapters 3 and 5 are still actively being discussed, and currently still undergoing revision. (The final chapters have now been released and can be found here.
In this article, I will attempt to highlight the differences between the draft and final versions of Chapter 5 on a line-by-line-basis, and I have summarised in the Table below:
This debate is set to continue for some time, so why not subscribe to our LinkedIn pages or follow our PharmOut blogs. In summary, the justification to manufacture certain products in a shared facility will come at a significant up-front cost. Tasks such as initial risk assessments and obtaining toxicology data (can be difficult to source and expensive to generate, although this is possibly a once-off exercise) are time-consuming. The potential routes and risks of cross-contamination must be understood, and mitigated through sufficient, facility design, qualification and operation, with sufficient Technical Controls in place. The lack of sufficient “Technical Controls” will result in the requirement in increasing the “Organisational Measures” such as ongoing monitoring and control. Direct product cross-contamination is sometimes easy to assess, but with the vagaries of airborne cross-contamination, the amount transferred by operator clothing, for example, might be more difficult to quantify and to demonstrate control.
An update from the TGA in 2017 on cleaning validation