Processing of Adverse Reactions
Post Marketing Safety and Clinical Safety
PharSafer® has extensive experience in multi-national drug safety reporting for both post-marketing spontaneous reports and for clinical trial reporting. Safety reporting for globally registered products or for multi-national clinical trials, can require both a complex and diverse set of rules and timelines to be observed. Such reporting can extend to additional reporting in clinical trials with Institutional Review Boards (Ethics Committees) and investigators.
Our personnel have extensive knowledge and training of the various country requirements for safety reporting to enable our clients to report individual cases correctly, and in an appropriate timeframe to remain compliant with the legislation.
Our clients are provided with up to date safety reporting plans for their products. Devised by PharSafer®, the safety reporting plans identify by country the various requirements for safety reporting both for post-marketing and clinical trial situations. They are version controlled and dated documents, monitored too by our internal QA, to ensure that any changes to legislation by any country can be adapted into the reporting plan to ensure continuing compliance.
We have experience of conducting such safety reporting for clinical trials and post-marketing products, on a global basis, for many Companies. Our experience covers medicines, devices and vaccines. Our Clinical trial experience ranges from Phase I – IV multi-national studies for the EU, USA, Canada, South America and South East Asia. We have worked on blinded studies, worked with Independent Data Monitoring Committees (IDMC, DSMB) set up by clients and Risk Management/Minimisation Studies.
PharSafer® has also worked with marketing departments conducting marketing studies, research outcome activities and Patient Support Programmes (PSPs), which capture adverse events. They ensure that all safety related information has been properly reported into the Company and Regulators.
- Post Marketing Safety and Clinical Safety
- Individual Safety Case Reports (ICSR)
- Literature Searching
- Compassionate Use/Named Patient Studies
- Electronic Reporting of ADRs / Eudravigilance Registration
- Medical Device Safety
- Device/Drug Combinations and Drug/Device switches
- Vaccine & Biological Safety
- Advanced Therapies
Individual Safety Case Reports (ICSR)
Individual case processing is the beginning of signal detection. The necessity to be accurate, compliant, to obtain detailed follow-up in order to assess the seriousness, causality and expectedness of a case cannot and should not be under-estimated.
The process includes: data entry, data quality check, medical review, reportability assessment, electronic/paper reporting, follow up, case closure and case file archiving. This can be performed for post-marketing and clinical trial cases (SAEs and SUSARs) and captured within the PharSafer® secure, validated Global Safety Database. The database can generate reports electronically or in printed format, for submission to the Regulatory Agencies. We are also able to produced metrics reports for our clients to demonstrate their compliance statistics.
Similarly the database can generate, periodic summary tabulations, line-listings and perform analyses for identifying potential signals and tabulations and specialised queries used in safety reviews. PharSafer® has detailed procedures for the production, management, assessment and reporting of individual case safety reports (ICSRs) and suspected, unexpected, serious adverse reactions (SUSARs) globally.
We are also responsible for obtaining follow up information for adverse reaction reports (ADRs). Comprehensive information is obtained by our staff to allow a proper determination of both causality and the possible mechanism by which the reaction occurred, thereby, looking to prevent or minimise its reoccurrence.
Our case processing accuracy enables all other activities including safety review, PSUR/PBRER/DSUR writing and Risk management activities to be undertaken with confidence that the data being used in these documents has been properly assessed.
PharSafer® is experienced in performing global literature searching on behalf of its clients for both safety and efficacy related articles. Currently, in the EU, and in accordance with the regulations, such searches are conducted at least weekly. We agree search content with our clients and set up those weekly search streams to automatically capture all types of articles involving the client company products. Literature searching is performed using MeSH terms to enhance possible safety issue identification. PharSafer® is performing such searches for Companies in the USA, Canada, the EU and South East Asia.
We have a system in place for the ordering of articles to perform expedited reporting, signal detection, benefit risk assessments and analyse Class related events, which may be used in PSURs/PBRERs or DSURs.
Additionally, PharSafer® performs competitor analyses to assess products treating the same indications, same class of products, disease treatments and for products in development to assess current gold standard treatments versus the Company product.
All of our staff are extensively trained in literature searching and all literature search streams are internally reviewed and approved by a physician, pharmacist and safety scientist as well as the client.
Compassionate Use/Named Patient Studies
PharSafer® has worked in many situations involving compassionate (named patent) use programmes, either as extensions to clinical trial studies or for use during the products post-marketing phase in countries where licenses have yet to be obtained.
There is a need for such programmes to follow the varied country legislation in terms of safety monitoring and PharSafer® has multi-national experience of conducting very large compassionate use programmes including using such data as supportive data in further license submissions.
Electronic Reporting of ADRs / Eudravigilance Registration
Since 20th November 2005, there has been a requirement in Europe to report ADRs electronically (legislation 726/2004). Europe is moving ever further to a single simple system for safety reporting, PharSafer® can ensure that you are properly registered and reporting electronically to the various Regulatory Authorities within the EU and outside the EU, ensuring maximum compliance to the EU legislation and other countries that have employed electronic data submission of ADRs.
To begin the process of electronic reporting in the EU, a company must apply to perform the electronic reporting with the EMA and test with the EMA first. Once this has been approved, then the company can proceed to country specific reporting according to National legislation. To register with the EMA, the details of the EU QP PV must also be declared.
PharSafer® is performing this activity for many clients across the EU, Canada, Japan, South East Asia and the USA. We have carried out Eudravigilance registration for many Companies from the EU, USA and Japan.
Additionally, proof of registration to Eudravigilance is a requirement of the Pharmacovigilance Systems Master File (PSMF) and without proof of this, the company will not be granted a license. Similarly, lack of notification of the EU QP PV will prevent the license being assessed.
Many other countries are starting to require electronic reporting of ADRs. PharSafer® has experience with the FDA (USA), Health Canada and the Middle Eastern Countries, where the requirements are changing regularly. PharSafer® can help you remain up to date with your electronic reporting needs globally.
Medical Device Safety
The Medical Devices industry has grown progressively globally over the last 30 years and continues to expand.
The legislation regarding Medical Device Safety is no less stringent than the Pharmaceutical medicines requirements around the world.
PharSafer® has been involved and continues to be involved in multi-national medical device reporting of adverse incidents.
The Medical Device definition regards any product that does not perform its main activity via a pharmacological activity to be a Medical Device. The reporting requirements for Medical Devices are very different to the medicines legislation and the class categorisation of the medical device depends either upon the level of invasiveness of the device for the patient or the perceived risk to the patient concerning the placement of the device, which also varies around the world.
The PharSafer® validated safety database also captures and reports medical device reports for global safety reporting. All staff have been trained on medical device reporting and there are standard operating procedures in place in the Company to not only report medical device reports but also for the assessment of possible unexpected incidents and assessments of conformance and possible changes required to the device, its packaging or labelling.
PharSafer® is well aware of the variety of global medical device legislation which sees annual inspections in Europe via the Notified Bodies through to the differing schemes in the USA, Canada and other countries, as well as the different categories of Class of Device and reporting rules.
Experienced PharSafer® staff compile safety reporting plans to allow reporting of medical device incidents using the various Regulatory Authority incident forms globally.
There is no global system for Medical Device classifications, meaning that a single medical device may have varying classifications around the world, possibly being classed as a drug in some countries and a device in others. Either way, PharSafer® knows the reporting rules to keep their clients compliant.
Device/Drug Combinations and Drug/Device switches
Increasingly there has been a new group of products being licensed which are either drug-device combinations, requiring specialist knowledge in both disciplines, and devices which are drugs in some regions and devices in others.
Experienced PharSafer® personnel can ensure that you have the correct assessments of your products to ensure Regulatory compliance.
Importantly, for drug-device combinations, PharSafer® can ensure that what needs to be reported as an adverse drug reaction or a device incident will be correctly assessed.
Vaccine & Biological Safety
PharSafer® also works with vaccine companies. The PharSafer® safety database will capture and report all types of vaccine reports globally.
As part of the legislation and in order to monitor possible batch related safety issues, PharSafer® endeavour to get all batch numbers and identify whether there are batch related safety issues. These assessments form part of the routinely conducted safety review.
PharSafer® works with a number of companies who have developed Advanced Therapy products. This is a vital and new area of research in the Pharmaceutical Industry which pushes the current knowledge and methods of safety assessments because the products do not fit the normal pharmacological response model exhibited by many standard medicines.
The Regulatory Agencies have recognised this too with special requirements for safety reporting, the mode of license submissions and Risk Management activities.
PharSafer® has procedures in place, in line with the most up to date legislation in this area, for the accurate interpretation of potential adverse events and any long term safety assessments in this particular sphere of treatment.