Effective pharmacovigilance is the cornerstone of any healthcare company, and a failure to have robust and transparent processes in place can result in heavy fines and revocation of license to operate. Pharmacovigilance (or PV) is a continuingly evolving science and requirements have seen notable advancement in recent years, most significantly in the European Union for which developments are ongoing.
Effective Medical provides a comprehensive range of regulatory-compliant PV services delivered by experts with many years of experience within the industry. Our services cover both the pre- and post-marketed stages of drug development and we pride ourselves in our ability to provide tailored and innovative solutions which exceed the requirements of our partners.
Pharmacovigilance services we offer include:
Signal detection/management activities
Signal detection and management activities are an essential step of proactive pharmacovigilance. Effective Medical have extensive experience of creating and managing comprehensive signal detection processes, including the creation of routine signal detection reports to support periodic aggregate reporting (PSUR, PBRER, ACO, etc.) and risk management planning.
Services include periodic and bespoke literature searches, literature tracking, and literature evaluation for Individual Case Safety Reports (ICSR) or inclusion in signal detection reports, aggregate reports, RMPs, etc.
Safety processes and SOPs
Whether setting up new processes or addressing existing procedures, our experts have many years’ experience in the pharmaceutical sector and will provide best practice recommendations to suit specific business needs.
Questions relating to the safety of a medicinal product or device can arise at any time or can be anticipated in advance at the time of regulatory activity (i.e. license applications or renewals). Whilst prevention with comprehensive clinical submissions and robust signal detection processes are better than resolving after the fact, if questions do arise it is essential to understand what is being asked and respond appropriately; failure to provide acceptable answers can lead to distrust from a regulator and costly delays in approvals.
Scientifically credible and accurate documentation is essential in these circumstances to ensure effective communication between healthcare companies and regulatory authorities. Effective Medical staff comprise of industry-experienced professionals who have spent many years working in-house at Top 10 pharma companies and who have extensive experience of reviewing and interpreting regulatory questions and compiling comprehensive and detailed responses. We are also able to provide a review and advice service for responses previously compiled in-house, and can produce pre-hearing presentations/documentation, and are able to provide world-wide on-location support during oral representations with regulators.
Development and implementation of compliant pharmacovigilance systems, including provision of an EU QPPV
Created entirely as a bespoke package to ensure the needs of our partners are fully catered for, services can include the creation of the Pharmacovigilance Systems Master File (PMSF), or conversions from the DDPS to PSMF, in addition to provision of a EU QPPV, deputy EU QPPV and a local QPPV (if required).
Case processing (data entry, narrative, causality assessment and MedDRA coding)
A fully validated, 21CFR compliant safety database is an essential part of Good Pharmacovigilance Practice, whist efficient and accurate case processing is essential for fulfilling electronic ICSR reporting requirements, signal detection, and aggregate periodic safety reporting.
Effective Medical can tailor case processing requirements to suit the needs of our partners, whether that be the provision of a fully outsourced case handling process or the provision of resource and expertise on all aspects of case processing and reporting.
Ad-hoc safety communications
During the lifecycle of a product the maintenance of a positive benefit risk profile is dependent on timely and accurate communications of new safety findings (both clinical and non-clinical) to regulatory authorities, investigators and healthcare professionals.
In addition to the general PV services outlined above, our experts also have extensive expertise in PV writing and the creation of high-quality safety documents which fulfil global regulatory requirements. The following examples outline some of the PV documents on which Effective Medical often provides writing expertise.
Periodic Safety Update Report (PSUR) & Periodic Benefit Risk Evaluation Report (PBRER)
The evolution from the PSUR to PBRER is one of the biggest changes to PV in the past few decades. The PBRER is the cumulative and periodic review of a drugs risk/benefit profile and is closely aligned with other PV documents (specifically the RMP and DSUR, below). Working closely with a variety of in-house teams (including safety, regulatory and clinical departments), Effective Medical routinely author and project manage the entire PSUR/PBRER production process, including the creation of integrated risk/benefit assessments.
Note that despite the move by the major regulatory regions to the PBRER format, some national regulators are still accepting ‘old-style’ PSUR format, in addition to summary bridging reports and PSUR addendums. Effective Medical are experienced in delivering the post-marketing safety reports in either format.
Periodic Adverse (Drug) Experience Reports (PA(D)ERs) and NDA Annual Reports
For each US-approved drug or biologics application, the FDA requires applicants to submit post-marketed periodic safety reports in the PADER (for NDA/ANDA applications)/PAER (for BLA applications) format. The reports must be submitted quarterly for the first 3 years following the US approval date and annually thereafter. The FDA also requires an applicant to submit an annual field alert report for every approved NDA and ANDA.
Effective Medical will assist with waiver applications (from either PA[D]ER to PBRER, or PSUR to PBRER) to ensure the most efficient reporting of aggregate safety data without duplication of effort and resource. Where a waiver is not appropriate, Effective Medical will create the PA[D]ER and NDA annual report swiftly with minimum disruption to everyday operations to ensure you remain compliant.
FDA Periodic Safety Reporting Requirements for NDA / ANDA (21 CFR 314.80)
FDA Periodic Safety Reporting Requirements for BLA (21 CFR 600.80)
Addendum to the Clinical Overview (ACO)
Written in support of licence renewals in the EU, the ACO comprise a critical discussion addressing the current benefit/risk balance for the product on the basis of a consolidated version of safety/efficacy data accumulated since the initial marketing authorisation application (MAA).
Effective Medical have extensive experience of authoring the ACO and Clinical Expert Statement (in addition to associated documents required at the time of a renewal), and can advise on the required format of the report to ensure efficient use of resource, budget and time.
Development Safety Update Report (DSUR) and IND Annual Reports
Similar to a PBRER, the DSUR provides a regulatory body with an update to safety and efficacy findings over the previous annual reporting period for every drug with ongoing clinical trials. In the US the FDA request this information be provided in an IND Annual Report, however in order to promote global harmonisation the FDA will also accept the DSUR to meet an IND application annual report requirements.
Effective Medical are skilled at authoring and project managing the entire DSUR / INA annual report production process, and will work together with in-house functions to ensure the harmonisation of data between the PBRER/PSUR and RMP as required.
Risk Management Plan (RMP) / Risk Evaluation and Mitigation Strategies (REMS)
With proactive pharmacovigilance now obligatory, a Risk Management Plan (RMP) is required for all products applying for marketing authorisation in the EU and is also often requested by other regulatory bodies and at specific times during a product lifecycle. Even after initial creation, the RMP is an evolving document that needs regular updating in order to maintain accuracy and compliance.
Since 2007 the Food and Drug Administration Amendments Act (FDAAA) gave the FDA the authority to require a Risk Evaluation and Mitigation Strategy (REMS) from manufacturers to ensure that the benefits of a drug or biological product outweigh its risks. REMS are similar to the risk minimisation measures discussed in an EU-RMP, and are essentially a strategy to manage a known or potential serious risk associated with a medicine and to enable patients to have continued access to such medicines by managing their safe use.
Effective Medical have expertise in the preparation of high-quality RMPs which comply with European standards, in addition to creating Risk Evaluation and Mitigation Strategies (REMs) to satisfy US requirements. We have also worked extensively with other regulatory agencies and have experience of providing RMPs and RMP Annexes which satisfy the requirements of counties in the Asia-Pacific region, the Far East and North America. Using our experience and judgement we are also able to project manage the entire process of RMP/REMS development, ensuing the coordination of input from many disciplines and guaranteeing the correct collaborators are engaged throughout the process.
Labelling Documentation Development (CCDS, SmPC, USPI, etc.) and the Maintenance of Reference Safety Information
The Company Core Data Sheet (CCDS) should provide a definitive description of the company core safety information (CCSI), appropriate usage guidelines and the basis for determining listedness for the purposes of regulatory reporting of a marketed medicinal product. Considered an internal document, the CCDS describes the agreed company position on the CCSI, which becomes the basis for the authoring of local labels for marketed products and global regulatory reporting.
The principals of proactive pharmacovigilance suggest the CCDS (and in turn local labels, e.g. SPC, USPI, etc.) should be developed during the clinical development phases and continually maintained throughout the lifecycle of a product to ensure the accuracy of the information.
Whatever the stage of product development Effective Medical has extensive expertise in the development and maintenance of core product information (in the form of CCSI in the CCDS, local labels and patient information documents) and in the creation and execution of processes to ensure the regular review of all CCSI.
Switching Documents (from POM to P or GSL)
One of the ways of making medicines more accessible to the public is to change the legal status from prescription only (POM) to a pharmacy medicine (P), or from a pharmacy medicine (P) to general sale (GSL). In order to reclassify a medication, stringent criteria are in place in terms of safety, efficacy and quality, including evidence that it can safely be used without the supervision of a doctor, and all documentation submitted to support of a switch application need to be clear and concise as to proving these criteria.
Effective Medical are skilled in providing detailed and accurate switching documentation with a proven track record of success.
Changing the Classification of a Medicinal Product for Human Use