Pharmacovigilance
EU Qualified Person for Pharmacovigilance (QPPV)
Within the EU, each Marketing Authorisation Holder should ensure to have at his disposal a single point of contact, with a deputy, who is available 24/7 to act as the Qualified Person for Pharmacovigilance (QPPV). The QPPV has the following prime responsibilities:
Detailed Description of the Pharmacovigilance System
EU Directive 2001/83/EC requires that every Marketing Authorisation Application should include a Detailed Description of the Pharmacovigilance System being employed by the pharmaceutical company that filed the application (to be replaced by the Pharmacovigilance System Master File). Additionally, for certain products as described in Volume 9(A) (Notice to Applicants), a Risk Management Plan should be submitted. Finally, the applicant should provide proof that there is a Qualified Person for Pharmacovigilance at his disposal and that this QPPV is available. The DDPS/summary of the PSMF is intended to provide the competent authorities with proof that the applicant as a (future) Marketing Authorisation Holder is capable to deal with adverse events properly, including collecting and notifying the competent authorities.
Read more: Detailed Description of the Pharmacovigilance System
Safety reports processing from clinical trials and post-marketing sources
DADA is capable of receiving safety data on your behalf from the public, from health professionals, competent authorities, clinical trials and literature sources, amongst others. The experienced team at DADA will conduct triage of case reports to determine seriousness, enter the data into our pharmacovigilance database, code the medical information according to standardised MedDRA terminology and provide medical review and ongoing surveillance of case reports.
Expedited reporting of case reports to Competent Authorities, EudraVigilance, FDA, Ethics Committees, Institutional Review Boards and Investigators
One of the most common causes of critical findings in Pharmacovigilance Inspections is non-compliance with the expedited reporting (15 day) of spontaneous serious adverse drug reactions. DADA has a quality system implemented to ensure that expedited reports are reported in time to competent authorities. Reports may be submitted electronically or by hard copy as required by local regulations. DADA is registered with EudraVigilance to facilitate electronic reporting. EMA-trained staff ensure compliance with the rigorous requirements of such a system.
Periodic reporting, through (Addendum) Periodic Safety Update Reports (PSURs), Summary Bridging Reports (SBRs), and Annual Safety Reports (ASRs)/Developmental Safety Update Reports (DSURs)
The major goal of pharmacovigilance is to ensure continuous monitoring of the safety profile of medicinal products. To verify that MAHs live up to these obligations, competent authorities require the submission of periodic safety reports wherein an overview of the safety findings is presented. For products in clinical trials, FDA requires submission of Investigational New Drug (IND) reports, whereas EMA requests Annual Safety Reports (ASRs) or annual Developmental Safety Update Reports (DSURs). For products that have received marketing authorisation, Periodic Safety Update Reports (PSURs) are required. As specified in Volume 9A, the periodicity of these reports may be different depending on the age of the product, from 6 month-intervals to three years. Addendum PSURs may be submitted to cover periods to extensive to be covered in a line listing, but too short to necessitate submission of a regular PSUR. Summary Bridging Reports (SBRs) are generally submitted during a renewal, to present the competent authorities with a short overview of the information presented in the PSURs and/or Addendum PSUR that are bridged by the SBR.
Global and local literature screening and review
The MAH is required to regularly screen the published medical and scientific literature, to ensure that any mention of their products is duly noted and reported to competent authorities. DADA pharmacovigilance staff is experienced in carrying out this activity on your behalf and can comprehensively manage your literature screening requirements in a cost-effective manner in conjunction with writing periodic safety reports and signal evaluation documents for your products. Our weekly search is not only limited to identification of individual case safety reports, but also includes detection of potential safety issues. Per your requirements, we can also conduct local literature screening in our territories.
In addition, we carry out ad hoc literature searches for purposes of signal evaluation or for identifying safety concerns for inclusion in PSURs.
Risk Management Plans (RMPs)
Risk management planning is an essential part of pro-active pharmacovigilance. In the EU, Risk Management Plans (RMPs) have to be submitted during application for a marketing authorisation for certain medicinal products. In the US, Risk Minimization Action Plans (Risk MAPs) may have to be written as part of a Risk Evaluation and Mitigation Strategy (REMS). In close cooperation with our clients, DADA can write and submit these product specific risk management documents to the competent authorities.
Signal detection and evaluation – benefit/risk assessment in safety review meetings
Signal detection and evaluation is an ongoing process, supported by case processing and expedited and periodic reporting. The purpose of signal detection is to identify underlying trends or safety issues that need to be reported to competent authorities. Any changes to the established benefit-risk balance require re-assessment of the product’s safety. In this context, it can be a relatively simple matter of reviewing accumulating evidence and confirming that little has changed. On the other hand, when there is a newly identified important risk, or when new evidence for diminished efficacy arises, the issues can be extraordinarily complex. At such a time, preparation of a comprehensive benefit-risk assessment, involving the concepts presented in the CIOMS IV guideline, facilitates decision-making.
Significant changes to benefit-risk balance must be notified to the competent authorities. This may be a matter of extensive discussion between various stakeholders in the company. At such times, having expert independent input to the debate can be crucial.
Read more: Signal detection and evaluation – benefit/risk assessment in safety review meetings
Safety Data Exchange Agreements
The QPPV should have oversight of the global safety profile of the MAH’s medicinal products. Competent authorities want reassurance that safety information is exchanged effectively between different departments (e.g. Regulatory and Pharmacovigilance), between affiliate and headquarter companies and from one end of your organisation (for instance, your distributor in the Middle East) to the other (your US headquarters), and that the European Qualified Person for Pharmacovigilance will be updated with all safety issues and emerging safety concerns in real time.
Communication with National Competent Authorities
When regulatory authorities have questions about the safety of your products, they require answers fast. DADA can help you in understanding the questions, identifying the necessary resources for the response, develop the strategy and contribute to, write or review and comment on the response document.
To prevent is better than to cure and DADA has all the necessary procedures in place to ensure early identification of potential safety concerns and their effective management through adequate signal evaluation and communication at the time of safety findings.
Training in pharmacovigilance
DADA can train client staff members ranging from basic pharmacovigilance for general awareness within the company, via advanced pharmacovigilance training for employees of the client’s pharmacovigilance department, up to dedicated training sessions on topics such as MedDRA coding, pharmacoepidemiology, or inspection readiness, to name a few of the different activities as described in this document.
Depending on your training requirements, DADA will prepare a training covering those pharmacovigilance topics you wish to be discussed. DADA pharmacovigilance staff regularly attends courses and seminars to stay up-to-date on current approaches and changes in regulation, to always present updated information during the pharmacovigilance training.
Audits preparation
DADA can assist you in preparing for an inspection. Our Pharmacovigilance inspection readiness training aims to ensure that your staff will know what to expect in the event of a pharmacovigilance inspection by a competent authority as well as how to ensure that they have the data at hand when such an inspection is carried out and advise on inspection activities, coupled with one-to-one training on interview techniques for all your inspector-facing staff. DADA has been involved in MHRA inspections of their client’s pharmacovigilance system and has implemented their experiences into practice-based inspection readiness training.
Organisation set-up and changes
For clients who conduct their own pharmacovigilance activities, DADA may function in an advisory role to review the pharmacovigilance system as described in the client’s DDPS/PSMF. If the advisor finds topics that may not be audit-proof, DADA can assist the client with updating the pharmacovigilance system to match competent authorities expectations and legislation.
DADA may also be consulted during the establishment of a pharmacovigilance department within the client, to assist in determining the necessary new communication channels and responsibilities of those departments that will need to interact with the pharmacovigilance department.
Preparation of pharmacovigilance SOPs and other controlled operating instructions
DADA can assist in the preparation and/or review of standard operating procedures (SOPs) and other quality controlled operating instructions to facilitate the creation of a pharmacovigilance system or improvement of a pre-existing system. In the tightly regulated world of pharmacovigilance, well-written, up-to-date and comprehensive SOPs and other quality documents are absolutely essential. These will be focussed upon during an inspection and all staff conducting the procedures described within should have documented that they were trained prior to initiating the procedure. DADA has a full suite of SOPs and work instructions to describe all the pharmacovigilance activities we conduct on behalf of our clients. Our experienced staff can help you in ensuring that you too will have an adequate description of activities in line with current pharmacovigilance legislation.