A not so quiet summer.
Although there is a new US administration and head of the FDA, it has been quiet so far on this front. It is the EU that is in turmoil as the Brexit EMA relocation continues to percolate, particularly behind closed doors. Also EU inspections are being discussed.
Some of the southern European countries are trying to band together to get the EMA moved to one of the “less attractive” cities in southern Europe. The current unofficial favorite is Amsterdam according to an article in the UK newspaper. Have a look at the 3 minute video the Dutch made to “sell” the idea of Amsterdam as the new EMA site. It is charming and somewhat tongue in cheek (we too have a stylish queen and eat fish and chips…).
There is also the ongoing issue related to the fact that the EMA and EU failed to put a section covering the breaking of the lease into the EMA’s contract for their buildings on Canary Wharf in London. It seems that the EMA and the UK are locked into a payment by the UK of $686 million (£520m, €582.5m) covering the rent till 2039! This will presumably be negotiated at some point.
Comment: Brexit is getting ugly. The ramifications of the exit are only now being figured out and the actual details of the withdrawal are just beginning to be worked out. The EMA cannot stop work for any period of time and then set up somewhere else at a later date. It is like refueling a plane in mid-air. How this plays out should be better understood by the end of this year.
The ninth annual report of the PV Inspectors Working Group (PHVIWG) was issued in June 2017.
The document provides information on inspections by the EU and Member States (MS). Keep in mind that the personnel in the PV Inspectors Working group are also in continual contact with the PRAC (Pharmacovigilance Risk Assessment Committee) and other organizations in the EU and abroad.
A quick review of EU inspections. The PRAC and the health authorities in the MSs produce an inspection program based on the Good PV Practices Module 3. The basis and prioritization for the choice of inspections is made by looking at the potential risk to public health, nature of the products, usage by patients and the number of products the Marketing Authorization Holder (MAH) has on the market. Other individual factors may also play a role.
The inspections are done to see if the MAH has the personnel, systems and facilities in place to meet their regulatory PV obligations. They may be system inspections of one or more. Most inspections are routine and are done by the MSs. Rarely, the CHMP will request an inspection. In 2016 there were 49 MS inspections and 2 CHMP requested inspections. In several instances there are joint inspections whereby more than one MS health agency is present.
Interestingly, there were 31 inspections of national sites inspected where the QPPV and PSMF are found and no inspections of global PV sites. Of these 31, 18 were done at subcontractor, licensing partner or affiliate sites. One of the two CHMP requested inspections was done at a subcontractor/partner/affiliate site.
Comment: The message here is that inspections are most likely to be done at a national EU site rather than abroad and rather than at the global PV headquarters site if that site is outside the EU. Also of note is that subcontractors, partners and other third parties are clearly within the scope of the inspection program. It thus behooves the global PV headquarters to be sure that all partners, subcontractors, affiliates etc. are doing their PV job correctly.
There were 20 deficiencies found: 2 critical, 3 major and 15 minor. The critical findings were in the PV IT Systems and the Quality Management Systems (QMS). The major findings were in organizational structure, QMS and safety data analysis/signaling and risk/benefit analysis. Minor findings were in these areas as well as expedited reporting, IT, QMS, Signaling and Analysis, organizational structure and the PV System Master file (PSMF)/Detailed Description of the PV System (DDPS).
Comment: This can be read positively or negatively. Positively, there were only 2 critical and 3 major findings (~10%) in 51 inspections. Negatively, twenty out 51 inspections found something (~40%).
The areas of focus of the Inspectors Working Group was adherence to the revised PV Master File, the guidance on pre-authorization inspections and follow up on routine inspections and CAPAs.
Comment: The last item is most interesting. One would think that if an MAH has inspection and there are findings, a CAPA with the aim or correcting the deficits would be a high priority item. This is especially true since the inspectors usually do follow up inspections within a year or two (sooner if findings were egregious). So the company knows the inspectors will be back. Interestingly, in my experience, this is often not the case. Personnel changes occur, mergers or acquisition of products, budget cuts and other factors often waylay the best laid CAPAs.
The Working Plan for 2017 can be found here.
The key items that will be in focus for 2017 and beyond include: the guidances on pre-authorization inspections, follow up on CAPAs and their inclusion in the PSMF, revision of the Module II on the PV System Master File, revision of Module III and the guidance on inspections. Other areas to be examined on out-sourcing PV work, non-interventional post-authorization safety studies (PASS), patient support programs and PV reporting (this has been a very troublesome topic and has lead to some severe penalties for some MAHs), off-label use requirements and PV reporting and cooperation with health agencies outside Europe.
Comment: The EU, EMA and Member States are now very active in PV. The Good PV Practices modules are continually undergoing updates and changes. Revisions of required documents (e.g. PV System Master File) will force changes in procedures and IT in companies. As always it is unclear whether these changes produce better and faster PV benefiting the patients. This is rarely examined.