Revised ABPI Guidance for PV in Market Research

As reported in Safety Observer N°150 of November 2018, the ABPI (Association of the British Pharmaceutical Industry) has worked with BHBIA (British Healthcare Business Intelligence Association) to produce a revised version of their guidance on collecting Adverse Events, Product Complaints and Special Situations Reports during Market Research Programmes (MRPs). This is Version 4 of this valuable guidance document, which was first issued in October 2009.

In addition to changes related to Personal Data Protection, the main change concerns the collection of contact details when information is collected directly from patients/consumers in order to enable the appropriate follow-up of Adverse Events by the MAH.

For those who are not familiar with this document, it includes a series of useful annexes including example wording for the contract with the Market Research Agencies, templates for Data Collection and Reconciliation Forms, as well as interview scripts covering a range of scenarios.

The information presented on the BHBIA website also includes the Microsoft Word templates for the Data Collection and Reconciliation Forms, as well as suggested wording for Market Research Materials and a series of “Quick Guides”.

→       Link to ABPI News Release

→       Direct link to BHBIA/ABPI Guidance on PV in MRPs

→       Link to BHBIA Page

Thierry Hamard is a Pharmacist with more than 15 years of Global Pharmacovigilance Auditing experience and over 200 PV Audits performed since his company PV Focus was established in 2004.

Thierry is also Chief Editor of Safety Observer, a provider of Regulatory Intelligence services for Pharmacovigilance since 2005.

Established products to exit EU list of Black Triangle Products ?

As reported in Safety Observer N°148 of September 2018, the EMA has published the minutes of the 100th Management Board meeting, which took place on 06 and 07-Jun-2018.

The Board discussed a great variety of topics, including Brexit and lessons learnt after the first EMA Public Hearing. It also included a discussion on a report exploring the experience made with the list of products subject to additional monitoring, also known as the list of Black Triangle Products.

As described in GVP Module X, all medicines on the list must be identified with an inverted Black Triangle, which is displayed in their package leaflet and in the SmPC. This system was derived from the Black Triangle scheme already in place in the UK to highlight the medicines under close scrutiny by the authorities, which was expanded throughout Europe with the implementation of the 2010 Pharmacovigilance Legislation. The EMA published the list for the first time in April 2013 and it is reviewed every month by the PRAC.

There are a few reasons that can make a medicine enter the list, knowing that it should remain on the list for 5 years unless the PRAC decides otherwise:

• It contains a new active substance or a new biological/biosimilar product

• It has been given a conditional approval, or approved under exceptional circumstances or with specific obligations on the recording of suspected ADRs

• The company that markets the medicine is required to conduct a post-authorisation safety study (PASS)

One of the main conclusions of the report discussed by the Board is that the latter criterion has led to the inclusion of a large number of established products in the list (see item B.9 in the minutes). This is reportedly of limited value and the PRAC supports that this category of products should be removed from the scope of additional monitoring.

Based on the current list (i.e. Revision 58 dated 25-Jul-2018), there are 57 out of 346 active substances that are on the list only because of a required PASS. They are not all established products but those are easy to spot because the number of products and MAHs concerned is so large that they need to be presented in Annexes separate to the list. For example, the list of Domperidone-containing medicinal products (Annex X) is 6 pages long. Even though each formulation / MAH / Country is presented, it still concerns a large number of products indeed.

Based on the report and the opinion of the PRAC Committee, this may change in the future and these products would no longer qualify for the Black Triangle scheme in the EU. Following endorsement by the Heads of Medicines Agencies (HMA), the report will be sent to the European Commission for further consideration and decision by the European Parliament and Council.

→       Link to EMA Management Board Meeting Page

→       Direct link to EMA Management Board 100th Meeting Minutes

→       Link to EMA Page: Medicines under additional monitoring

→       Link to EMA Page: List of medicines under additional monitoring

Thierry Hamard is a Pharmacist with more than 15 years of Global Pharmacovigilance Auditing experience and over 200 PV Audits performed since his company PV Focus was established in 2004.

Thierry is also Chief Editor of Safety Observer, a provider of Regulatory Intelligence services for Pharmacovigilance since 2005.

EMA Guidance on ICSR data from EudraVigilance

Everybody should know by now but in case you missed it, the EMA published much-awaited guidance over the summer to clarify the obligations of MAHs to record information on ICSRs they can access in EudraVigilance.

Since the implementation of the New EudraVigilance on 22-Nov-2017, MAHs are given access to all ICSRs contained in the EudraVigilance database. The MAHs are now responsible to access EudraVigilance to retrieve all ICSRs related to their medicines and first received by National Authorities.

There was however no guidance regarding the obligations of MAHs in relation to ICSRs submitted to EudraVigilance by other MAHs or regarding those ICSRs available in EudraVigilance prior to 22-Nov-2017. This has caused a lot of pain and confusion, especially for MAHs of generic products who could not exclude ownership of the suspected products in many ICSRs they became aware of.

This gap has now been closed by the EMA and the Note for Clarification published on 23-Jul-2018 brings much needed guidance:

• Regarding the ICSRs available in EudraVigilance prior to 22-Nov-2017, the Note clarifies that MAHs have no obligation to screen EudraVigilance for cases that they do not already have in their own database. In the same way, the MAH have no obligation to record in their database those ICSRs they become aware through activities related to Signal Management in EudraVigilance.

• Regarding the ICSRs submitted by other MAHs to EudraVigilance, the Note clarifies that MAHs have no obligation to record these in their own database.

Although some will argue this took a long time and could have been better anticipated, this should come as a relief for the industry. It also sets a clear standard for Regulatory Inspections.

→ Link to EMA Page: Access to EudraVigilance data

→ Direct link to Note for Clarification

Thierry Hamard is a Pharmacist with more than 15 years of Global Pharmacovigilance Auditing experience and over 200 PV Audits performed since his company PVFocus was established in 2004.

Thierry is also Chief Editor of Safety Observer, a provider of Regulatory Intelligence services for Pharmacovigilance since 2005.

Medication Errors in France: Q&As now published !

The publication of the new version of the French Good Pharmacovigilance Practices in February 2018 brought some confusion regarding the obligation for Marketing Authorization Holders (MAHs) and "Exploitants" to submit specific reports to regulatory bodies outside of the EudraVigilance network.

As mentioned earlier (link to our June2018 post here), we questioned the French Agency about the apparent additional requirement to submit Reports of Medication Errors with no Adverse Reaction, as well as Reports of Abuse or Dependence to medicines containing psychoactive substances.

The response we received brought valuable information and announced the imminent release of a Questions & Answers Document to address the need for clarification. The wait was short and the ANSM has now published this Q&A Document, which provides additional information on the role and obligations of the MAH and "Exploitant".

In line with the response shared earlier, it confirms that there is no obligation for Pharma Companies to submit Medication Errors without adverse reactions to the dedicated ANSM Medication Error Desk. As already mentioned, all confirmed Medication Errors (with or without Adverse Reactions) must be assessed in the corresponding PSUR and taken into account in the evaluation of benefits and risks of Medicinal Products.

In the same way, the Q&A Document clarifies that there is no obligation for MAHs and "Exploitants" to submit reports of abuse or dependence to medicines containing psychoactive substances to the Dependence Evaluation and Information Center (CEIP).

These clarifications will be reflected in the French Good Pharmacovigilance Practices, which should be revised accordingly in the near future.

Please note that the Q&A Document also clarifies the expectations regarding additional aspects of the local Pharmacovigilance System including the responsibilities of the local contact person for Pharmacovigilance, local PSMF, local Signal Detection activities and Risk Management, etc.

➝ Link to ANSM Q&A on the French GVPs (in French)

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Raphaëlle KUHN is a Pharmacist with over 9 years of experience in the pharmacovigilance and clinical trial safety area. She has been working as a Pharmacovigilance Consultant within SUNNIKAN Consulting for 6 years where she supports clients in quality management activities and has conducted over 80 audits internationally.

Raphaëlle also contributes to the monthly Pharmacovigilance Regulatory Intelligence bulletin Safety Observer with regards to the French announcements.

About the reporting of Medication Errors in France...

Although mostly in line with the European legislation, the new version of the French Good Pharmacovigilance Practices published in February 2018 introduced a few new requirements for Marketing Authorization Holders and "Exploitants". As specified in article 4.32, these new obligations include the submission of:

• Reports of Medication Errors with no Adverse Reaction to the dedicated ANSM Medication Error Desk,
• Reports of Abuse or Dependence to medicines containing psychoactive substances through the Dependence Evaluation and Information Center (CEIP-A).

Since the reporting of Medication Errors without Adverse Reactions was not required for Marketing Authorization Holders and "Exploitants" prior to February 2018 and no information on the modalities of reporting were provided (i.e. timelines and format), we contacted the French Agency to request some clarifications. We also asked confirmation regarding the duplicate submission of Reports of Abuse or Dependence to medicines containing psychoactive substances, as those cases are already required to be reported to EudraVigilance (see articles 4.13, 4.14 and 4.15 of the French GVPs).

We have just received a response from the Medication Error Desk, which clarifies that pharmaceutical companies do not have any obligation to report Medication Errors without Adverse Reactions to the ANSM Medication Error Desk. A Questions & Answers Document should be published by the Agency shortly, pending the correction of article 4.32 of the French GVPs. The response included a reminder that confirmed Medication Errors associated or not to an Adverse Reaction must be assessed in the PSUR, as specified in the EU GVP Module VI (see VI.B.6.3). Medication Errors and the risk of Medication Errors must also be taken into account in the framework of the monitoring of the safe use of medicines and the assessment of risks and benefits.

Below is a copy of the response we received from the ANSM Medication Error Desk (in French !):

"Nous vous remercions pour votre message. Nous tenions à vous préciser que les industriels n’ont pas d’obligation à déclarer les erreurs médicamenteuses sans effet indésirable au Guichet Erreurs Médicamenteuses de l’ANSM.

Une Foire aux questions sera prochainement publiée par l'agence dans l'attente d'un rectificatif de l’article 4.32 du chapitre 4 des BPPV.

Néanmoins, l’ensemble des erreurs médicamenteuses avérées ayant entraîné ou non un effet indésirable doivent être évaluées dans le rapport périodique de pharmacovigilance. Il est important que tout signalement d’erreur ou de risque d’erreur soit pris en compte dans le cadre du suivi de la sécurité d’emploi et de l’évaluation du rapport bénéfice/risque."

At this time, we have not received a response regarding reports of abuse or dependence cases, and we will update this blog when this information becomes available.

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Raphaëlle KUHN is a Pharmacist with over 9 years of experience in the pharmacovigilance and clinical trial safety area. She has been working as a Pharmacovigilance Consultant within SUNNIKAN Consulting for 6 years where she supports clients in quality management activities and has conducted over 80 audits internationally.

Raphaëlle also contributes to the monthly Pharmacovigilance Regulatory Intelligence bulletin Safety Observer with regards to the French announcements.