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As everyone who deals with the EU and the UK in drug safety knows, the EMA issued a new set of Good PV Guidelines to replace (largely) Volume 9A.  These are more than “guidelines” in the US sense where guidelines represent FDAs current thoughts on the matters addressed but are not binding.  In the EU, these guidelines are binding.

For the past several years the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) has been using a document called the Summary of Pharmacovigilance Systems (SPS or SPVS). See: https://www.mhra.gov.uk/home/groups/is-insp/documents/websiteresources/con2018030.doc  The SPS is very similar to the EMA’s equivalent Detailed Description of PV Systems (DDPS).

The Summary of PV Systems is a document that is prepared before an MHRA PV inspection of a sponsor, vendor, MAH etc.  It is a long and detailed document sent electronically (CD, DVD etc.) some six or so weeks before the inspection describing the PV/drug safety system in place at that company.  This is quite different from the way FDA handles inspections where no upfront information is requested or required from the company.

With the PV Guidelines a new document the Pharmacovigilance Systems Master File (PSMF) has been created which covers most of what the SPS and DDPS cover.  One might have thought that these two older reports would no longer be needed now that a master document exists that must be up to date and immediately available to the EMA and member states.

Yet this is not the case in the UK.  The SPS remains in place and is still required before an MHRA inspection even though the PSMF is also used.  It is necessary to be familiar with the for any company that has an MA in the UK.

But there is another, perhaps even more important reason to go over this document.  The SPS forces the writer to describe and detail the entire PV system in place in that company.  This then serves as a type of “internal audit” of the company’s PV system.  If everything is well in place as described in this document then the company will clearly have a very adequate PV system and should pass the MHRA inspection with flying colors.  If some items are not in place, it can serve as a type of “gap analysis” which can be used to prepare a Corrective Action, Preventive Action (CAPA) plan.

This document should be prepared, if used as a tool for an internal “gap analysis” along with the Compliance Report which was summarized in a previous Bart’s Corner posting.  Together these two documents (or the relevant parts of these documents) will give you a fairly good idea of how well your drug safety/PV system compares to the requirements of the health authorities.

Here is a quick review of the components of the SPS.

Section 1: Company Information. Contact information for the company and, in particular for the Qualified Person for Pharmacovigilance (QPPV).  Other names used by the company if they have product licenses (MAs) in other corporate names.  This will not necessarily be obvious to the drug safety department and they will most likely have to do a little digging with legal and finance to come up with this information.  Also required is the number of licenses (MAs) held in the UK and in the EU (centralized products).

Section 2. Company Structure & Operating Model. A brief description of the holding or parent company, world-wide subsidiaries, therapeutic areas and product portfolio – both investigational and marketed products, recent mergers and acquisitions and their impact on PV.  This too may not be evident to the PV department and some corporate searching may be needed.

A succinct overview of to how PV is managed.  Examples are given of the type of description wanted including this one:

Company X has one main PV site where the following are performed: data entry of ADR reports, preparation of PSURs, preparation of RMPs, signal generation, and answering all global safety related enquiries from regulator authorities. Expedited submissions to the EMA are managed by the global site.  The global site monitors compliance with reporting timeframes for expedited and PSUR submissions.

Local subsidiaries are responsible for maintaining a local database/tracking sheet, forwarding individual ADRs to the main site for data entry, submitting domestic and non-domestic ADR reports to their respective authority on an expedited basis, and submitting PSURs to their respective authority within 60 days of data lockpoint.

Section 3. PV System.  This is a summary of the PV activities done by the sites in the UK and the global PV department.  It is meant to summarize how the company ensures that all regulatory requirements are met.  Topics addressed should include:

They want to understand PV at the company: who, what, when, where, how and why.

Section 4. Computer Systems used for PV.   The present situation is described for all PV systems both global and local.  There should be details of the computer systems/databases for all AEs (spontaneous, trial, solicited etc.).  Detail should include:

This information too is not necessarily immediately available to the drug safety group and will require some hunting.  The legacy information going back 5 years may be hard to find even in the IT department!

Section 5. Quality Management System.  This includes:

The messages here are that the company has to have a quality management system and has to do or have done audits of the PV system(s).

Section 6. Training Records.  Describe the training record system and where the records are kept.  Also include CVs and job descriptions.

Section 7. Archiving. Describe the archiving activities for PV documents.  If out-sourced, give information.



This document requires an enormous amount of work to compile, particularly if the company is a medium to large global pharma.  Much of this data is siloed and hard to find.  When this document has to be prepared in 4 or 5 weeks for an upcoming  inspection, it can be a very painful “crisis” situation.

So several lessons can be drawn:

In the EU there is usually a month or so given to prepare this information and load it onto electronic media to send to the agency.  It may be in this form for the UK, in a similar form (though not necessarily all in English) for other EU member state agencies.  In the US, although a formal mass of information like this is not required to be submitted, most everything in this document is fair game for the FDA inspector.

For companies not in the EU directly, their partners in the EU may ask for this information if they are being inspected.  And they may not give you much time to gather it.

The bottom line conclusion is that the regulatory agencies are paying more and more attention to the details of PV.  Not just checking MedWatch/CIOMS I forms and PSURs but also the inner workings of the system, the quality of the data and whether “bad things” are being picked up in signaling.  Failure in these areas will lead to shame, public censure, penalties and even loss of MAs.

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