Focused Exclusively On Pharmacovigilance

Ashfield Pharmacovigilance5003 South Miami Boulevard, Durham, NC 27703T: +1 919 401 8003E: info@ashfieldhealthcare.com

As the EU/PV legislation becomes fully effective in July 2015, Ashfield Pharmacovigilance can help navigate the sometimes complex requirements associated with this new directive. Our medical writing and regulatory team prepares numerous documents each year, including PSMF and associated annexes. This group of healthcare and regulatory professionals produces comprehensive reports and monitors updates to ensure compliance with changing regulatory requirements. Our experts can help update items from the Detailed Description of Pharmacovigilance Services into the new ‘living document’ format, while ensuring frequent communication with clients to keep annexes up-to-date.

PSMF services include:

• Creation• DDPS to PSMF transition• Managing PSMF updates• Template and SOP development• Consultancy and training

PSMF Services

As a part of Ashfield Pharmacovigilance’s signal detection program, you have access to our Safety Evaluation Committee (SEC). The SEC is comprised of our Chief Safety Officer, highly experienced safety physicians, medical writers and representatives from global aggregate reporting. The SEC is responsible for lifecycle signal detection and analysis as well as recommendations and proposals to clients regarding findings and additional analysis.

Our signal detection program consists of the following tiered approach:

• Tier 1: Routine proactive signal identification,

prioritization, analysis and reporting o Daily medical analysis of serious ICSRs o Safety signal tracking and trending over periodic

intervals as defined by product risk and client preference

o Production of formal analysis reports• Tier 2: On-demand proactive signal detection and

data mining o Utilize external passive reporting databases

(AERS and WHO Vigibase) for disproportionalityanalysis

o On-demand access to the Safety EvaluationCommittee (physicians, epidemiologists,pharmacists, biostatisticians, etc.)

o Weekly SEC meetings to discuss and strategizeemerging potential signals from aggregate analysis

o Qualification and quantification of data o Safety data review of reports

• Tier 3: Strategic risk management planning o Development of risk management and

communication plans o Risk minimization action plans

Ashfield Pharmacovigilance has been afforded the opportunity to work with the world’s leading pharmaceutical organizations to help form our industry-recognized signal detection and management best practices. Our information technology strategy incorporates the latest thinking in next generation data mining, analysis and information delivery. Ashfield's own Signalytics® program allows for concise identification, workup, evaluation and communication of all signals.

Database & IT Services

A pharmacovigilance program is only as good as the IT infrastructure on which it’s built. Ashfield Pharmacovigilance provides a global safety database, IT infrastructure and IT services that are secure, compliant and designed to ensure the integrity of your data.Our IT services portfolio encompasses a broad spectrum of services around Safety reporting. Our experienced technologists will work with you to ensure that you have the highest possible level of safety reporting through meticulous design & implementation.

Key elements of our IT services portfolio include:

• A strong understanding of the regulatorylandscape that allows us to work with you tocreate appropriate and compliant systemsthat are audit-ready and meet your businessrequirements

• Consultative services that can assist you insupplementing your existing IT infrastructureor provide comprehensive infrastructure andsafety database solutions

• E2B compliance• A global delivery model to support your

safety programs in the North America,Europe, Asia Pacific, and ROW regions

• Worldwide e-submission capability

Our complete suite of pharmacovigilance-specific service offering includes implementation, custom development, testing and validation, data warehousing and business intelligence (BI), data migration, reporting and training.

Pharmacovigilance Consulting

For over 15 years, Ashfield Pharmacovigilance has been a dedicated pharmacovigilance services provider. This experience allows us to offer you guidance in how to structure outsourcing programs that maximize the use of all internal and external resources. Knowing that you are under constant pressure to reduce costs while maintaining quality and efficiency, we can work with you in a number of different capacities.

Examples of outsourcing consultation include:

• Signal surveillance and management• Risk management services• Due diligence evaluation• Providing insight and overview of

global regulations (i.e. ADR reporting,literature, clinical and post-marketrequirements)

• Evaluating metrics management• Quality compliance training and review• Audit readiness and preparation• PV training

Signal Surveillance Activities

Pharmacovigilance

Comprehensive Case Management

We believe that exceptional pharmacovigilance begins at the individual case report level with high-quality, consistent data capture and management practices. With today’s expanding regulations and growing enforcement, it is more important than ever to utilize proven methodologies and best-practices for managing your adverse event case load.

With Ashfield Pharmacovigilance, you have access to the tools and experience needed to provide a fully compliant drug safety program and a wide array of pharmacovigilance services. From clinical trials safety to post-marketing surveillance, Ashfield Pharmacovigilance manages data collection, triage, tracking, and reporting of your adverse events from start to finish.

Analyzing, assessing and reporting important safety data requires best practices for data entry, follow-up and query, quality control, medical review and quality assurance. Ashfield Pharmacovigilance adheres to industry-recognized best practices for data management, coupled with thoughtful, business metrics and workflow for enhanced efficiencies.

Program Management

Ashfield Pharmacovigilance has been managing pharmacovigilance work from small, medium, and large pharmaceutical companies for over 15 years. We believe that strong program management is a critical element in ensuring the success of any outsourcing initiative. The Program Director acts as your primary Ashfield Pharmacovigilance contact through the ramp-up period and also during ongoing drug safety and pharmacovigilance projects.

Program management oversight includes:

• Ensuring a successful project start-up• Supervising team performance for quality

and productivity• Tracking of key milestones• Monitoring ongoing project performance• Investigating future needs for PV & drug

safety solutions• Development of project-specific SOPs and

other documents, as required• Managing deliverables, project scope and

budget• Providing periodic updates, metrics, reports

and communication, as required• Attending teleconferences and face-to-face

meetings• Conducting annual client audit meeting and

preparation

With thousands of adverse event cases processed each year, we can provide you unprecedented case and account management support.

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Global Aggregate Report Development

Our Global Aggregate Reporting group consists of a professional team of physicians and regulatory experts that work with you to assist with the continuous cycle of preparing global aggregate regulatory reporting.Our team has expertise in both pre and post-marketing drug safety regulations, global marketing authorization applications, variations and renewals and carefully developed due diligence strategies. Ashfield Pharmacovigilance is able to lead all global regulatory report generation and submission services designed to align with electronic or paper submissions.

Reports delivered:

• Global periodic safety reporting (PADER,PSUR/PBRER)

• Provide support for ASR/DSUR• NDA and IND submissions (supporting

preparation of IND/NDA annual reports, NDAISS sections and clinical study reports)

• Regulatory report submissions to appropriateauthorities

• Medication error and drug abuse/misusereporting

• Toxicology report management• Medical writing support for report generation• Other special reports required by regulatory

authorities (e.g. risk management associatedreports and other post-marketingcommitments)

Risk Management Services

• Pre-inspection auditing, planning, andtraining

• Review, audit, train and/or develop keyprocesses and procedures:o Pharmacovigilanceo Contractual agreements with partners,

affiliates, and vendorso Regulatory agreementso Quality Management System (QMS)o Internal, partner, affiliate, and vendor audit

programso Document control, records management,

and records retentiono CAPA and deviation managemento Quality objectives and metrics to measure

performance of QMSoComputer system validation

• Review current regulatory findings and key focus areas for inspections

Ashfield Pharmacovigilance physicians and safety experts are critical to the accurate and efficient clinical safety and pharmacovigilance programs we provide you. Our medical professionals ensure that all of your safety surveillance activities are conducted to the highest medical, ethical and safety standards.

Ashfield Pharmacovigilance’s Risk Management Services include:

• Development of RMPs• Pharmacovigilance plans• Reference safety information reviews/revisions

(e.g. core label, SPC, PI, CIB)• Annual and ad hoc safety signal evaluations• Medical assessment and analysis for Periodic

Safety Update Report (PBRUR) and PeriodicADE Report (PADER)

• Position papers• Health hazard analysis• Medical monitoring• Case narrative company assessment/clinical

evaluation comments• Causality assessments• Risk benefit assessments• Analysis of Similar Events (AOSE)• Integrated Summary of Safety Sections (ISS)• NDA annual report safety sections• Product expectedness lists• Development of innovative pharmacovigilance

interventions to proactively identify,characterize and prevent risks

Literature Search Services

Ashfield Pharmacovigilance conducts weekly, monthly, and quarterly internationally qualified scientific review of adverse events from multiple databases to ensure that you have complete and diligent product case management and reporting. We conduct periodic search and review on articles, manuscripts, abstracts, excerpts, bibliographic searches for Individual Case Safety Reports (ICSR), PSURs, annual reports, risk management analysis, and other ad hoc safety reports.

Standard literature search includes:

• Monthly or weekly searches of Adis, Medlineand Embase

• Ad hoc or customized literature searches tomeet specific needs

• Standard search criteria to generate initiallistings of references and abstracts

• Expert screening by PV specialists to identifyspecific citations that are potentially reportableICSRs

• Concise and timely communications to clientsregarding search findings

• Retrieval of full text articles• English translation services are available

Additional literature archiving services include:• Automatic client literature searches generated

on a weekly or monthly basis with all resultsstored electronically

• The electronic text files of searches performedand the archive of full text articles are readilyavailable for internal, client or regulatoryinspection

Audit and Inspection Readiness Services

• Aggregate PADER/PSUR/PBRER reportingincluding:

• Tracking of reporting periods andsubmission dates

• Generation of tables and listings from safetydatabase

• Analyze line listings and prepare relevanttables

• Analyze previous aggregate reports for theproduct

• Compose case summaries and analysis• Draft report for client review and approval• Medical review of each report

We also work with you to provide ad hoc solutions for any specialized regulatory request.