Are you ready for the new EU pharmacovigilance legislation changes? Part 2

Graeme Ladds


Continued from “Are you ready for the new EU pharmacovigilance legislation changes? Part 1

This afternoon, Graeme Ladds shares part two of his article about July 2012’s EU pharmacovigilance legislation changes and the effects this will have on pharmaceutical companies and manufacturers. This article explores quality management, the Pharmacovigilance Master File and a look towards the future for pharma.

There are 16 guidance documents to accompany the new legislation and part two of this article further explores some of these guidances, and their impact on pharmacovigilance (PV) conduct.

Quality management

Quality management and compliance was stated and expected in Vol IXa and a demonstration of compliance monitoring featured heavily in the EU Inspections.

The expectation of a quality management system under the direction of the EU QP for pharmacovigilance is a new guideline document in the proposed legislation for July 2012.

Although the principles were clearly laid out in Vol IXa, a change in emphasis from compliant reporting (reporting on time) has changed more to an emphasis on accuracy and the overall quality of the data to be submitted again under the watchful eye of the EU QP PV, who is the one person in the company responsible for the overall pharmacovigilance system and its functioning. This means the EU QP PV is responsible for all internal audits and findings from such audits that identify deficiencies in the overall approach to pharmacovigilance.


“…the EU QP PV is responsible for all internal audits and findings from such audits that identify deficiencies in the overall approach to pharmacovigilance.”


Overall, such deficiencies need to be viewed in terms of potential risk to patients with the company products and so a robust quality management system (QMS) ensures the continued progression of quality within the pharmacovigilance activities being performed by the company.

It is important at this juncture to differentiate the various quality activities that take place in PV so that it is clear what the regulatory expectation is:

Quality control (QC) is the element of checking to make sure that something has been accurately transcribed e.g. data review checks the information provided in data entry when a safety case is put into the safety database.

Quality assurance (QA) is the activity performed to ensure that the activity has been performed to a set standard e.g. that a PSUR confirms to the Regulatory template.

Quality management (QM) is the overall management of the system of QC and QA to ensure that the current level of performance or target is being met, looking for further improvements, and introducing new measures to increase accuracy and compliance.

The audits are conducted against the various QC and QA activities since they contribute to the overall QM. The EU QP PV is expected to have the QM presented at a high level within the company with any recommendations or improvements so that Senior Company Management can help the company achieve such goals and specifically in PV according to the new regulations. QM is not confined to PV activities and indeed a QM philosophy throughout the whole company is probably the best approach to fulfilling the new regulations.

As part of the activities of the EMA there are random checks on ICSRs submitted to the agency in connection with company quality systems.

The EMA will randomly sample (25) submitted reports to them and then check the quality of those reports, which is already in progress. Quality items will be ensuring all AEs, indications and medical histories are coded in MedDRA correctly. Information about dosage in the narrative is also presented in the XML drop down fields, that the case was submitted on time, that the case has been properly assessed by the company and that routes of administration (if mentioned in the narrative) also appear in the XML drop down fields.


“As part of the activities of the EMA there are random checks on ICSRs submitted to the agency in connection with company quality systems.”


The assessment will be given to the company and any potential errors identified will have to be investigated and then a report provided back to the agency. All of these measures are to test the company QM system.

If these random checks result in many errors and repeatedly then this may precipitate a regulatory inspection.

The Detailed Description of Pharmacovigilance Systems (DDPS) and the Pharmacovigilance Master File (PVMF)

Within the Vol IXa legislation there was a requirement to produce a document referred to as the DDPS. This document accompanied all new licence applications in the EU. It explained the system of pharmacovigilance in the company that would support the pharmacovigilance activities of the particular product being registered and detailed which company SOPs dealt with which particular aspects of the pharmacovigilance.

Under the present legislation, any SOPs referred to in the DDPS were available to be requested by the Agency assessing the licence and they had to be provided within 48 hours of request. Such a document was solely a European requirement, and if deficient, could hold up the licence approval.

Such a document under the new legislation is to be removed and replaced instead by the PVMF. The PVMF will again describe the pharmacovigilance system that operates in the Company but one key aspect of this document is also that it will include any outstanding activities following audits that have been performed on the pharmacovigilance system. Such information will remain in the PVMF until such time as the corrective action for the audit finding has been completed. Then it can be removed.

The PVMF will also be available to the regulatory authorities during inspections, which means that any outstanding audit finding activities will also be available to the regulators to see as well. This will be the first time that official internal outstanding audit findings will be freely available for the regulators to see.

The PVMF will be located where the main PV activities are performed and where the EU QP PV is located.


“Transitional arrangements are being put in place to support the introduction of the finalised guidance documents…”


For licence submissions, a summary of the POVMF will be submitted with the licence application.

If a regulatory authority requests to see the PVMF then it must be within 7 calendar days.

It is expected that the PVMF will be an accurate and up to date reflection of the PV activities of the company and so such a document needs careful quality assurance and monitoring in order to keep it maintained.

Additional warnings for products – ensuring patient safety and encouraging reporting

Much of the present legislation is designed to improve and encourage the reporting of potential adverse reactions to the regulatory authorities and to the pharmaceutical companies.

Changes within the SPC and Patient Information Leaflet (PIL) will advise HCPs and patients where to report adverse reactions, and those products subject to additional activities in relation to risk (risk management or minimisation plans) will have black symbols placed on the packaging and also mention that the product is subject to additional monitoring.

Additionally, and probably more controversially, the use of social media is mentioned in the new legislation as a mechanism for reporting. No one yet is quite sure what this will mean in terms of volumes of reports to the agencies or how much monitoring this will require from the companies and there is very little in the guidance about how to monitor this media.

What’s left?

The guidance notes are yet to be finalised and July is rapidly approaching. This gives Companies little time to finalise SOPs, train staff and produce the required documents (PVMF).

Transitional arrangements are being put in place to support the introduction of the finalised guidance documents which will occur between July 2012 and February 2013.

It is anticipated that further legislation may be introduced to support the two new laws (2010 / 84 &amp, 1235 / 2010) because of the magnitude and complexity of some of the new systems.

Certainly, pharma companies are expecting that the new legislation will require more resources to monitor the increased reporting and more in-depth knowledge of staff in producing detailed analyses of safety assessments for signal evaluation and benefit: risk determinations.


About the author:

This article was written by Graeme Ladds, and was commissioned by PiR Resourcing.

Graeme Ladds is the CEO of PharSafer® and has over 20 years experience in the pharma industry. His previous position in the industry was as Head of Global Drug Safety for a multi-national pharma company and as an EU Qualified Person for Pharmacovigilance (EU QP PV).

Graeme has worked as both a Pharmacovigilance and Medical Information Manager previously, and over the many years of working in the field of safety and medical services has written a modular book on multi-national pharmacovigilance (2006, 2010), written many articles on pharmacovigilance in peer reviewed journals, currently serves as editor on a multi-national pharmacovigilance journal, is a regular speaker at conferences, and active member of many international associations which include the DIA (and active member of SIAC), TOPRA, and ISOP.

PiR Resourcing is a brand synonymous with providing innovative senior resourcing solutions to international life science organisations. As a result of our exclusive focus on the sector, we have an understanding of many of the issues faced by pharmaceutical, biotechnology, diagnostic and medical device companies in the 21st century. PiR Resourcing offer a range of resourcing services, core to these are senior permanent and interim staff.

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How do you think pharma companies will react to the new legislation?