PHARMACOVIGILANCE

Encompassing Pre-Marketing Pharmacovigilance Services:

  • Safety Data Exchange Agreements (SDEA):
  • The Global Drug Safety Database:
  • Pharmacovigilance System Master File (PSMF):
  • Pharmacovigilance Audits:
  • SOP Writing:
  • Training:
  • Medical Consultancy:
  • Risk Management Plan in Pharmacovigilance:
  • Responding to regulator safety enquiries:
  • Assessment of Benefit-Risk:
  • Safety Concerns and Safety Communication:
  • Data Safety Monitoring Boards (DSMB):
  • Provision of a Qualified Person for Pharmacovigilance:

Post-marketing: Pharmacovigilance Operations

  • Individual Case Safety Reports (ICSRs):
  • PSUR / PBRER – Periodic Safety Update Report:
  • Literature screening:
  • Safety signals:

Clinical trials: Pharmacovigilance Operations

  • Case processing (SAEs):
  • Expedited reports:
  • Clinical trial safety
  • Periodic reporting (DSURs)

Encompassing Pre-Marketing Pharmacovigilance Services:

The pharmacovigilance services we provide can help you implement any corrective actions that may be necessary. ACRO PharmaSolutions offers all the components required to help ensure drug safety, for your compliant and effective pharmacovigilance system. ACRO PharmaSolutions can provide a Qualified Person for Pharmacovigilance, and a validated safety database, electronic reporting to Eudravigilance, your Standard Operating Procedures and safety data exchange agreements. A one stop shop to provide a wide range of Pharmacovigilance services by top specialists to assist the production of risk management plans (RMPs), responding to regulatory enquiries, helping with assessment of benefit and risk and assisting in responding to safety concerns. As specialist Pharmacovigilance service providers, we also carry out training and have world-class experience in performing audits.

Safety Data Exchange Agreements (SDEA):

Safety Data Exchange Agreements are legal written contracts ensuring that all safety data regarding a licensed product makes its way quickly and reliably back to the marketing authorization holder so that they may fulfill their legal obligations to aggregate safety data and to submit safety reports in a timely manner.

Pharmacovigilance outsourcing and contracting-out drug safety and regulatory activities can massively reduce expense and workload for any pharmaceutical marketing authorization holder (MAH). However, overall responsibility and oversight of the pharmacovigilance system always remains with the MAH and the EU QPPV. Specifically, it is the responsibility of the MAH to correctly receive process and, where required, expedite reports of adverse events and other safety reports. Even where all pharmacovigilance activities are outsourced, the overall responsibility lies with the MAH. The legal and regulatory responsibility for any failure on the part of a pharmacovigilance outsourcing provider to correctly follow pharmacovigilance legislation lies with the MAH, not the company to whom pharmacovigilance has been outsourced.

The inbound flow and management of this safety information is governed by Safety Data Exchange Agreements (SDEA) and they are a legal requirement in all cases where safety data might be received by any third party – i.e. not the license holder.

The types of safety data received can be very varied, they can be reports of adverse events but equally they can be other safety data: reports of abuse, misuse, overdose, medication error, use in pregnancy, lack of efficacy – and others. The MAH has to have a system in place to receive these reports, the 3rd party must have processes in place to transmit these reports to the MAH and there must be an SDEA in place to control and guarantee that no safety data falls through any “gaps”. It is imperative that all the data gets through and there needs to be a system of acknowledgement of receipt and reconciliation of data sent and received.

The treatment of safety data varies somewhat between the US, EU and other areas, however in general the obligation to expedite safety reports of serious suspected adverse reactions to the competent authorities is at least similar across territories. The timeframe within which reports must be received begins when the report is received by the 3rd party subcontractor / outsourcing provider, NOT when the report reaches the MAH. Therefore it is in the interests of the MAH that reports are forwarded on to them (or to the service provider), to reach them as quickly as possible so that they may be processed properly and on time.

SDEAs will vary depending on the role being carried out by the 3rd party. If the third party is only carrying out sales activities their exposure to safety data may only require simple instructions on what to do if they encounter reports of issues. If the third party is more involved, a distributor, co-marketing company, co-developing company or licensee, the SDEA will be more detailed. Where the activity being outsourced is pharmacovigilance the SDEAs have to be more detailed still, since it is vital that all involved parties are aware of their responsibilities and processes with regards to safety reporting.

Depending on the relationship, the SDEA may have to include assignation of responsibility for EU QPPV, PSUR writing, literature searching, the submission of reports to regulatory authorities, answering regulatory authority questions, handling product complaints, signal detection, hosting the safety database and ongoing benefit-risk evaluation. If some or all pharmacovigilance activities are being outsourced, including Medical Information, Call Centers’, Adverse Event Processing, the SDEA needs to be comprehensive, detailing which parties are responsible for which activities, even though the ultimate responsibility lies with the MAH. None of the above lists are exhaustive – the types of data and activities governed by SDEAs will differ from company to company and from product to product.

All of the SDEAs must be part of the MAH’s quality management system and the writing, approval and documentation of each SDEA and each type of SDEA must follow company SOPs and be auditable. This is a regulatory requirement and SDEAs are inspected during pharmacovigilance inspections and audits.

  • Are Safety Data Exchange Agreements required by the regulations?

Yes. SDEAs can be requested for inspection under EU drug safety regulations and equivalent FDA legislation within the US. They must be produced within a certain timescale and within the EU they need to contain a specific list of key details, for example, details of the Qualified Person, etc. Our team constructs robust, reliable agreements to ensure there is a mechanism whereby the correct data can reach the correct destination within a prescriptive and compliant timescale, ensuring that all activities occurring throughout the transit process are compliant with the regulations governing them. For a consultation on SDEAs, please contact the team in confidence alternatively, you may prefer to email: info@ACROpharmasolutions.com

                                                                 Safety Data Exchange Agreements: Compliant and Comprehensive

Just one of the pharmacovigilance services from ACRO PharmaSolutions. For more information contact ACRO PharmaSolutions today

References

Cooper T. Licensing arrangements – global regulatory framework. Pharmacovigilance Rev (2007) 1, 13-15

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The Global Drug Safety Database:

A ‘21CFR’ compliant, fully validated safety database is an essential part of Good Pharmacovigilance Practice. An accurate and accessible database allows rapid assessment of data for signal detection, aggregate report production and statutory electronic reporting of cases to the regulatory authorities. Following many years of experience with the available databases ACRO PharmaSolutions can provide a proven system as an option for all operational contracts. As an experienced user we are able to offer an immediate and cost effective database system removing the need for either expensive installation or set-up in house or the requirement for employing and training staff to perform data entry, quality control and database searches using a hosted system.

All Database workflow associated with the particular product

Managing multiple variants of products, for e.g. medicines, vaccines, combination products, medical devices etc.

  • Reception of new data as it arrives
  • Data entry
  • Data assessment with full multi-lingual support
  • Coding & reporting
  • Follow up
  • Storage of adverse event reporting at any stage of the product life cycle

Key features include the ability to handle:

  • Security Measures

Personnel using the drug safety database are assigned roles which ensure maximum security. This means staff is automatically assigned appropriately different levels of access to functions and data to ensure maximum security for sensitive information. Reports are correspondingly generated and distributed allowing only authorized users to view them or, only where approved, to amend reports.

  • Compliant Pharmacovigilance Terminology

The database is configured to browse and code using multiple versions of MedDRA® and the World Health Organization Drug Dictionary as required. It can also be configured to work with third party coding applications.

  • User Friendly Features

Cases are presented only to the correct staff and are represented on case assessment screens where all key information appears on just one screen. Cases can be approved and locked.

The system will accommodate single case reporting sets in a format rapidly providing all information in an adverse experience report. There is a standardized set of management reports, with Business Objects to facilitate ad hoc reporting.

  • Drug Safety Reporting

The system is designed to facilitate reporting to regulatory bodies from the moment it is implemented for your company. It will also distribute and track cases to third parties according to pre-configured criteria. The system supports a variety of formats including E2B, CIOMS and MedWatch.

For a free consultation on how ACRO PharmaSolutions pharmacovigilance services could implement this industry standard drug safety database for your company, call the team in confidence alternatively, you may prefer to email: info@ACROpharmasolutions.com

                                                             ACRO PharmaSolutions – for Compliant and Validated database –

                                                    Just one of the pharmacovigilance services from ACRO PharmaSolutions

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Pharmacovigilance System Master File (PSMF):

EU Directive 2010/84/EU (amending 2001/83/EC) require each application for Marketing Authorization (MA) for the EU to have a Pharmacovigilance System Master File (PSMF) in place including the named Qualified Person responsible for Pharmacovigilance within the EEA. The PSMF is a modular document containing all of the details of the pharmacovigilance system for the product. It must be made available to a Competent Authority on request, within 7 calendar days.

  • Why companies need help to compile or revise their PSMF’s

A PSMF is required to be in place for all marketing authorization holders who hold Marketing Authorizations (MA) within the EEA. It is required to be in place at the time of submission of all new applications for Marketing Authorizations (MAs).

The structure of the PSMF is strictly controlled by the guidelines of the GVP, Module II. The PSMF must contain specified sections with details of the pharmacovigilance system. It is expected that:

    The PSMF exists as a dynamic document with Annexes kept meticulously up to date at all times

    The PSMF forms the basis of the pharmacovigilance system, as it describes the system as a whole

    Therefore the PSMF is to be considered as a key reference document for the company’s personnel, on all aspects of day to day drug safety operations. The PSMF contains all of the details of the pharmacovigilance system for the MAH and their products. It is therefore an important tool for providing oversight of the pharmacovigilance system and can be used by the EEA QPPV to assist with their oversight.

    The PSMF, the standard operating procedures and training derived from and the operational guidelines implementing the standard operating procedures form the cornerstone of all pharmacovigilance activities

Consequently, the PSMF plays a pivotal role and requires expert knowledge to meet all of the regulator’s requirements.

  • PSMF Content

The content of the file is defined in GVP Module II. There is no standard template; however ACRO PharmaSolutions has an established template in place. The following sections are provided as a generalized guideline to indicate the broad nature of the required content:

  • Details of the qualified person responsible for pharmacovigilance (QPPV)
  • Details of the organization structure of the company that actually holds the Marketing Authorization
  • Details of all of the sources of the relevant safety data
  • Details of all electronic (computerized) systems and databases
  • Details of all pharmacovigilance processes
  • Details of the performance of all drug safety systems
  • Details of all quality control systems

Additional annexes can be required and in all cases the content must be meticulously documented for compliance. All companies are advised to seek advice from professional pharmacovigilance service providers to ensure the content of the Pharmacovigilance System Master File complies with the regulatory requirements. For more information, call the team in confidence alternatively, you may prefer to email: info@ACROpharmasolutions.com

                                                             ACRO PharmaSolutions – for Compliant and Validated PSMF –

                                                    Just one of the pharmacovigilance services from ACRO PharmaSolutions

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Pharmacovigilance Audits:

Pharmacovigilance audits are an essential component of any pharmaceutical company’s Quality Management System. If carried out correctly, auditing provides an unbiased opinion of operational performance of the Pharmacovigilance system, measuring the system against its own procedures and against the regulatory guidelines, and ensuring that the system itself remains compliant with the regulations.

  • Why are good Pharmacovigilance Audit practices so vital?

Statutory Pharmacovigilance inspections by regulatory authorities – especially in the EEA – have become increasingly intensive and wide in scope in recent years. GVP Modules III (Pharmacovigilance Inspections) and Module IV (Pharmacovigilance Audits) provide detailed requirements for the establishment of a good auditing program by a Marketing Authorization Holder. Moreover, effective pharmacovigilance audits help to identify and resolve compliance issues in a cost-effective, planned manner, before the regulatory inspectors impose punitive and costly demands on companies to carry out urgent remedial actions.

  • Risk Based Pharmacovigilance Audits

Risk Based Pharmacovigilance Audits are conducted according to the need to identify problems at different stages of the drug safety processes. Expert advice is required to adequately develop and implement three distinct elements of good practice in order to gain the benefits of a comprehensively planned approach versus the cost of remedial actions.

1. Strategic long term planning

A 2 to 5 year high level scheme which lists audits, topics to be examined, the methods to be employed and the theoretical approaches underpinning this work. Your strategy should address all aspects of drug safety work, including:

  • All routine and extraordinary processes and tasks involved
  • The quality system which provides the framework for these activities
  • Liaison with interested parties both within the company and externally
  • Liaison with regulatory authorities

2. Developing a Robust Program

The development of an approximately 12 month plan which forms the latest phase of the audit program. This needs to deliver on the principles, structure and practices to be followed as stipulated throughout the Strategic Plan. The Program needs to address areas which have required further input in the past, and those areas where a higher risk potential has been identified. It should then be the driver for all pharmacovigilance processes and tasks, the controls which operate around those and the relevant quality system. In accordance with legislation, these tactical audits must take place at regular intervals and reliable professional advice will therefore be required to ensure all practices are compliant.

3. Individual Audits

Each one needs an unequivocal and individualized plan from the very start. Every step, every aspect must be adequately documented, with clear evidence of the timeframes involved and the manner in which the work is to be undertaken, including standard methodologies and communications practices.

4. Reporting and Remedial Action

The results of audits must be communicated to upper management and regulators according to the highly specific framework lay down by EU drug safety law. The formulation of responses from the company to regulators in relation to inspections requires a high level of expertise. Devising and implementing the appropriate Corrective and Preventive Action Plan (CAPA) is also an issue where professional support should be sought.

ACRO PharmaSolutions consultants and executives have many years of experience of conducting pharmacovigilance audits worldwide, and develop programs with client companies to ensure that all elements of their pharmacovigilance system are covered as appropriate.

The team can audit pharmacovigilance operations at headquarter, national affiliate, distributor and partner level, with follow-up audits if required to ensure corrective measures are completed appropriately. The correct support at the correct time offers a superior strategy – one that is far more cost effective and reliable.

                                                                                         For audits: Compliant and Prepared

                                                                Just one of the pharmacovigilance services from ACRO PharmaSolutions

                                                                       For more information contact ACRO PharmaSolutions today

References

1. Brown EG, Goldman SA. Preparing for regulatory inspection of company pharmacovigilance systems and practices in the European Union and United States. In Good Clinical, Laboratory and Manufacturing Practices: Techniques for the QA Professional. Royal Society of Chemistry, 2007

Brown EG Preparing for a European pharmacovigilance regulatory inspection. Pharmacoepidemiol Drug Safety 2002 11 S238

  • Corrective and Preventative Actions:
  • What is a CAPA and why is it required?

Corrective And Preventative Actions (CAPA), also sometimes termed Corrective Action Plans (CAPs), is compiled from the findings of inspections and audits. Inspections are carried out by regulatory authorities, audits can be carried out internally or they can be conducted by an external party.

Where audits and inspections identify parts of the pharmacovigilance system that are non-functional and issues that are being encountered, CAPs will then:

  • Describe in detail how the company proposes to remedy each individual issue
  • Describe in detail the timescales and mechanisms by which this will be done
  • Describe in detail how those actions relate and contribute to the system as a whole

The prospect of executing corrective actions following findings of an inspection or audit can be particularly daunting task for companies. A purely hypothetical example here could be as follows:

An Individual Case Study Report of a serious event is submitted to the regulatory authorities outside the legally required timescale, triggering an inspection. The findings of the inspection then require an adequate response from the company, in the form of a CAPA, which addresses any and all issues within the

Pharmacovigilance operations which have contributed to that delay. The inspection could also have identified numerous other issues of concern. Each would need to be individually addressed, with a response adequately reflecting the level of severity, formulated in sufficient detail and using the correct terminology.

Addressing Major and/or Critical Findings from Regulatory Audits

Within the European Union (EU), when the findings of a drug safety system audit bring to light major or critical findings, both the findings AND the resulting CAPA are required to be held in the Annex of the Pharmacovigilance System Master File (PSMF) for that marketing authorization until the issue has been fully resolved to the regulator’s satisfaction.

  • What do CAPA’s compel companies to do?

CAPAs can demand anything. They are a formal response to a major or critical finding within the pharmacovigilance system. Whatever they do demand has to be:

  • Specific
  • Detailed
  • Achievable within a defined timeframe
  • And have assigned responsibility

They may need prior investigation with root-cause analysis before being drafted. Possible courses of action required can include:

  • Modification or rewriting of certain Standard Operating Procedures (SOPs)
  • Training for staff to be received in those specific new procedures
  • That all SOPs must be rewritten or that an entirely new set replace them
  • That staff receive training in all those new procedures

However, it is also possible that within a specified timescale:

  • Modifications to Quality Management processes are required on a large scale
  • A Safety Database is required to undergo important modifications
  • A Safety Database is required to be updated

And finally, where there have been serious systemic failures in compliance with EU drug safety laws:

  • The entire pharmacovigilance system may be required to be overhauled
  • New components may need to be added to that system
  • Departments could need to be reorganized
  • In rare cases entire companies could need to be reorganized
  • Why use ACRO PharmaSolutions for formulating and implementing CAPAs?

Our consultants have been extensively involved in interpreting inspection and audit findings and can pitch the response at the appropriate level. Indeed many of our consultants are former regulators and have in-depth knowledge of what regulators expect. For example, it is essential that the findings are explored appropriately to determine whether they are manifestations of underlying problems or isolated events. The response to the findings is crucial in ensuring that suitable remedies – with achievable commitments – are offered. Getting this wrong can cost companies enormous sums in activities that may be either too superficial or too intensive and wide-ranging.

The implementation of a corrective and preventive action plan can be challenging in the extreme and expert advice and support can make the difference between a vicious cycle of repeated inspections (or worse) and a rapidly achievable compliant system that is acceptable to auditors and inspectors. To speak to one of our expert staff about how we can support you with all aspects of Corrective and Preventative Actions or Corrective Action Plans,

                                   For more information, call the team in confidence alternatively, you may prefer to email: info@ACROpharmasolutions.com

                                                                         ACRO PharmaSolutions – compliant and taking the right actions

                                                                  Just one of the pharmacovigilance services from ACRO PharmaSolutions

                                                                          For more information contact ACRO PharmaSolutions today

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SOP Writing:

Where the GVP (for the EU) and specific legislation in other territories refers to “the quality processes”, they are referring to Standard Operating Procedures (SOPs). These fit into the overall information structure of the company like this:

SOPs are the quality control documents which implement company policy. Working practice documents are then derived from the SOPs to provide detailed guidance to staff in the execution of the tasks outlined in the SOPs. For those working within a pharmacovigilance system, training on SOPS would also be expected as well. The implementation of SOPs is audited, inspected and regulated by the competent authorities in accordance with Quality Management Guidelines contained in the EMA’s GvP. Your SOPs are therefore a pivotal component of your drug safety system.

  • Generic templates alone are not adequate

SOPs are always product and company specific. Your overall company policy will clearly be the driving agent dictating the nature of these documents for individual medicinal products / marketing authorizations. It is not appropriate to use a generic template because each pharmaceutical company is different, each marketing authorization is different and each product is different. If your company working practices are going to be specific for your company, they cannot be derived from “generic” SOPs.

Standard generic templates are therefore inadequate without proper advice and modification. In order to comply with EU pharmacovigilance laws, each Standard Operating Procedures document must be:

  • Extremely detailed
  • Written using the correct terminology
  • Of an adequate length (possibly extending to some 20 or 30 pages)
  • Reflective of your specific company structures and practices

In order to put together a set of compliant SOPs you need a highly experienced, responsive and flexible pharmacovigilance service provider for advice on cost effective compliance. For example, whilst 2 or 3 SOPS could adequately describe an entire pharmacovigilance process for one product in one company, other systems elsewhere could require more than a dozen.

  • Why choose ACRO PharmaSolutions to help write your SOP?

Our consultants have written compliant SOPs for many years for a highly diverse range of companies and medicinal products and processes. No matter what size and shape your company is your SOPs are all controlled, comprehensive and specific:

  • Controlled:
  • Each SOP release must be controlled and numbered
  • All document circulation and distribution must be accurately controlled
  • Versioning must allow for vital comparisons and control of modifications at every stage

    The SOPs must be kept up to date and must be current, specifying current practice rather than reflecting obsolete procedures which are no longer used or no longer valid or compliant.

  • Comprehensive:

 All activities and processes carried out by the company must be covered by a SOP. They have to be checked to ensure that they are comprehensive and that there are no “process gaps” – areas of activity not covered by an SOP.

  • Specific:
  • Responsibilities must be allocated to named personnel
  • Timescales must be clearly established
  • Regular review and progress monitoring is essential
  • Compliant and timely documentation of this review and monitoring is essential
  • Documentation must be accompanied by flowcharts
  • There must be cross-reference made to other SOPs wherever appropriate

Your SOP can be seen as the broader description of activities and processes. Then your pharmacovigilance Working Practice Documents are the vital fine detail which consistently explains everything you do.  They must:

  • Detail every facet of the work to be undertaken, in minute, precise and step by step detail
  • Be accompanied by screenshots and instructions where appropriate

We recommend expert advice at every step of your SOP journey. The process of creating and reviewing SOPs is ongoing: drafting, reviewing, approving, training, implementation and periodic review are all part of the overall process. They are audited and inspected as part of a pharmacovigilance system. To find out more about our cost effective, complaint and controlled Standard Operating Procedures writing services,

                               For more information, call the team in confidence alternatively, you may prefer to email: info@ACROpharmasolutions.com

                                                                                 SOP writing – Documented and compliant

                                                            Just one of the pharmacovigilance services from ACRO PharmaSolutions

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Training:

  • Why invest in outsourced Training?

Quality training is ultimately a compliance issue. The current guidelines on Good Pharmacovigilance Practice clearly emphasize the link between meeting regulatory quality standards and having adequately trained personnel1. Modern drug safety practice relies on professionals who are fully versed in all the relevant processes and regular communication between those professionals and relevant third parties such as regulatory authorities. There is an expectation that well trained employees should be constantly updated with appropriate continual professional development. Training must be appropriate to the role to which employees are fulfilling and competency assessment should be undertaken to ensure understanding. The commitment to the highest quality training should be a prime driver within all company activities in this arena.

Professionals are expected to demonstrably acquire and maintain:

• An appropriate level of qualification.

• A thorough working knowledge of pharmacovigilance obligations in relation to their particular role and how that relates to the overall processes.

• The working knowledge of how to practically respond to issues of drug safety concern.

There must also be a commitment to training for employees who are not directly placed within a company’s pharmacovigilance unit, but whose work has a direct relationship to it. Examples here could include diverse professional teams such as sales staff, legal team and customer services personnel dealing with certain types of complaints, etc. Please note this list is not exhaustive but serves to illustrate the wide scope of need for high quality training on an ongoing basis. Furthermore, there should always be checks and balances in place to ensure that the training everyone has received meets their operational needs.

  • Why train with ACRO PharmaSolutions drug safety trainers?

ACRO PharmaSolutions consultants are among the world’s leading pharmacovigilance educators. They have trained company employees and regulators in many countries on basic and advanced aspects of pharmacovigilance. They have lectured on regulatory compliance and risk management as well as offering training on MedDRA® at all levels. They have been instrumental in writing the guidelines, developing the processes as regulators, using what they teach as part of their daily work. They have lectured on these subjects at academic institutions, published papers and spoken at and chaired international conferences on all of these subjects: these are people passionate about their subject.

  • Operational Drug Safety Training

Whether you require aggregate report training (DSURs and PSURs), risk management workshops, Pharmacoepidemiology support, or other types of training, we can help. Our consultants can carry these out at your company locations – and they are all seasoned experts in their particular field.

  • Pharmacovigilance Inspection Training

ACRO PharmaSolutions can also offer inspection preparation training, with intensive courses on the regulations, advice on inspection activities, coupled with one-to-one training on interview technique for all your inspector-facing employees1. Additionally we offer back room support during inspections. But we can do more; by educating senior management on how effective pharmacovigilance is life insurance for your Company.

By bringing these educational activities to the Company premises the need for expensive and time-consuming travel for employees is reduced and can be at a low cost per trainee.

                                                                  Training: Compliance and Know-How

                                              Just one of the pharmacovigilance services from ACRO PharmaSolutions

                                                     For more information contact ACRO PharmaSolutions today

References

  1. Brown EG. Preparing for a European pharmacovigilance regulatory inspection. Pharmacoepidemiology Drug Safety 2002 11 S238

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Medical Consultancy:

We offer expert and comprehensive medical consultancy services.

ACRO PharmaSolutions offers Medical Consultancy services providing companies medical support by a physician group experienced in all areas of Clinical Safety, Post Marketing and Medical Information.

ACRO PharmaSolutions’s Medical Team currently consists of on board-certified physicians. Some of our physicians have more than 20 years’ experience in the clinic and the pharmacovigilance arena. As a team we can cover all therapeutic areas and support clients in different tasks such as:

The development of risk management strategies to help on following up on important signals and development risk minimization measures including the development of Post-Authorization Safety Studies,

  • Responses to Regulatory Authority requests, e.g. responding to EMA referrals
  • Benefit-Risk analyses, Clinical Expert Statements
  • Provision of therapeutic area and product training
  • Development and update of Reference Product Information.

                                                  Just one of the pharmacovigilance services from ACRO PharmaSolutions

                                                         For more information contact ACRO PharmaSolutions today

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Risk Management Plan in Pharmacovigilance:

All applications for marketing authorization in the EU must include a detailed and complex Risk Management Plan (RMP). In addition, renewals for older or generic products require an RMP.

A new or updated Risk Management Plan in Pharmacovigilance may be required where there are certain variations to the marketing authorization. This requirement depends on the nature of the variation and may not be necessary in all circumstances. Our expert medical writers and Pharmacovigilance risk benefit specialists can advise both on the need for an abbreviated RMP and on its content. ACRO PharmaSolutions can help our clients determine important identified and potential risks for both detailed and abbreviated risk management plans.

ACRO PharmaSolutions, has extensive experience in writing RMPs, assessing risk benefit analysis, RMP maintenance, and in line with GVP Module V can advise or perform analysis of the effectiveness of the risk minimization activities.

                                                                   Risk Management Plan: Compliant and Proactive

                                              Just one of the pharmacovigilance services from ACRO PharmaSolutions

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Responding to regulator safety enquiries:

When regulatory authorities have questions about the safety of your products or about the effectiveness of your pharmacovigilance system, you had better be able to come up with the answers. And who better to help with the response than ACRO PharmaSolutions experts and pharmacovigilance consultants who have “sat on the other side of the table”?

  • We can help interpret the questions

Since our consultants have served extensively as regulators themselves they can help you to better understand the type of information and response the regulatory authorities need. Our staff and consultants include those who have been members of the committees which created much of the original drug safety legislation. Understanding the legislation and responding with exactly what is required saves you time, substantial costs and a tremendous amount of unnecessary effort.

  • We can identify the necessary resources for the response

Our consultants can pinpoint the correct next step for you – whether that means advising on the precise resources needed to respond to an issue that is subject to legislation, to advise on the pharmacovigilance services that are required or the data, literature searches, etc. There are many areas that you could need to focus on – a clear vision of what to present to the authorities means your response is faster, more accurate and more appropriate.

  • We can develop your strategy

Experience on the regulatory bodies means our people know not only the type of response you need to give but also what monitoring, changes to Marketing Authorizations or other actions that may be appropriate. We can contribute to, write or review and comment on the response document. ACRO PharmaSolutions consultants can help companies prepare with pre-hearing rehearsals, or attend and support during oral representations with the regulators. Regulators need coherent responses, not ‘stock scripted answers’, but rather an understanding of what it is they are asking that results in a meaningful response.

Inadequate responses can result in unnecessary damage to products and significant expense to the company and the reverberations can result in a vicious cycle of continuing questions and responses.

But prevention is better than cure and early identification of potential safety concerns and their effective management, assisted by ACRO PharmaSolutions consultants, may help to pre-empt the regulators’ questions. And we can help you put in place the necessary crisis management procedures just in case those difficult questions do arise.

                                                                Regulatory Authority interactions: Compliant and coherent

                                                          Just one of the pharmacovigilance services from ACRO PharmaSolutions

References

Brown EG Methods and Pitfalls in Searching Drug Safety Databases Utilizing the Medical Dictionary for Regulatory Activities (MedDRA). Leading article. Drug Safety 2003, 26(3):145-58.

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Assessment of Benefit-Risk:

The EU regulations and Guideline on Good Pharmacovigilance Practices require companies to continuously monitor the benefits and risks of their marketed medicines. This involves various activities requiring pharmacovigilance experience and expertise including:

  • Screening the worldwide global medical and scientific literature weekly for articles relevant to drug safety
  • Regular review of adverse events – and other information, such as reports of lack of efficacy – recorded on the company drug safety database and on the Eudravigilance database for purposes of signal detection
  • Monitoring findings relevant to drug safety and efficacy from ongoing and completed clinical trials and other studies
  • Preparation of the Periodic Safety Update Report (PSUR) at the intervals specified in the pharmacovigilance regulations.

The processes required for each of these activities are described in depth in the various modules of the guideline on Good Pharmacovigilance Practices – for example, in GVP Module IX, Signal Management and Module VII, Periodic Safety Update Reports.

For new products and those with new therapeutic indications, dosage forms etc., there are requirements for companies to prepare a Risk Management Plan, in accordance with EU regulations and using a specific template. The Risk Management Plan includes a Safety Specification, a Pharmacovigilance Plan and Risk Minimization action plan. The Safety Specification states what is known for the product in terms of drug safety, as well as what is uncertain and what important safety information is still needed. Thus, it describes the important ‘identified risks’, ‘potential risks’ and ‘missing information’ for the product.

The Risk Management Plan describes the pharmacovigilance system and, for each identified and potential risk and item of missing information, states whether routine pharmacovigilance activities will be sufficient or whether additional activities (such as post-authorization safety studies) are needed to fill the gaps in the knowledge about drug safety. These considerations are all described in depth in the Pharmacovigilance Plan section of the Risk Management Plan.

For each ‘important’ identified and potential risk, the Risk Management Plan indicates whether the company proposes routine risk minimization activities – such as statements relevant to drug safety in the product information – or if additional activities are required, such as educational programs for prescribers, patient support schemes, etc. In each instance, the company has to specify how it will monitor whether the efforts to minimize risk actually work in practice.

The routine monitoring of benefits and risks of a product may generate new signals and safety concerns which then lead to an updating of the Risk Management Plan for the product. Signals are also described in the PSUR and any changes to the drug safety profile of the product any new information regarding its benefits are considered in detail in that document. Complying with the requirements of the guideline on Good Pharmacovigilance Practices for a critical integrated benefit risk evaluation can be a challenging exercise for any pharmacovigilance department.

  • Why Choose ACRO PharmaSolutions for managing continuous monitoring of benefit-risk for your products?

The fulfillment of this regulatory obligation activity is routinely inspected by regulatory authorities and it requires a systematic approach, with robust processes and involving experienced pharmacovigilance personnel: ACRO PharmaSolutions has the necessary expertise and experience for this activity. Effective monitoring of benefits and risks is also a form of “life insurance” for companies, prescribers and patients: if there are indeed problems with drug safety these need to be identified and addressed at the earliest opportunity. The critical evaluation of benefits and risks within companies may be contentious and identifying appropriate strategies difficult: at such times it can be invaluable to have access to top flight independent expertise which ACRO PharmaSolutions can also provide.

                                             ACRO PharmaSolutions – compliant and getting the right balance

                                         Just one of the pharmacovigilance services from ACRO PharmaSolutions

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Safety Concerns and Safety Communication:

Reports of issues regarding the safety of your medicinal products may come in from many different sources. Most pharmacovigilance professionals expect spontaneous reports to come in from GPs and regulatory authority but there are other sources:

  • Members of the public
  • ‘Front line’ healthcare professionals
  • ‘Non-front line’ healthcare professionals
  • Patients themselves
  • Regulatory authorities
  • Literature Searches
  • Your Spontaneous Reporting System
  • The media
  • Other sources

Additionally, there is no time limit within which problems will come to light: concerns can be raised within a short time of a product’s launch onto the market – or several decades later. It could be that there are issues that only become apparent following extensive searching for safety signals within current and previously existing data.

No matter how a potential or actual safety signal arises, the most important issue is how your company then processes it. You need to do so:

  • In a timely manner
  • In full compliance with EU pharmacovigilance laws
  • In a manner which ensures the best possible outcome for all parties concerned

Dealing with safety signals promptly and correctly, regardless of their source, will lead to the best possible outcome in any given situation, both for you, your product and most importantly your patients. With the ability to call in a team of senior former-regulators from the EU and elsewhere, ACRO PharmaSolutions provides reassurance to your management that products and patients are in the safest of hands. Our consultants have experience in all aspects of emerging safety concerns, from signal evaluation, through risk management, to assistance in preparing for regulatory authority hearings. All that may be needed is a few hours of advice, or there may be extensive involvement, with assistance in preparing responses for the regulatory authorities. The ability to bring top level regulatory and medical expertise – from people who have experience of these problems from “both sides of the table” – can be the difference between make and break for both product and company.

  • EU Regulations Apply To All Drug Safety Concerns

The European Medicines Agency’s Module XV (‘Safety Communication’) of the Guideline on Good Pharmacovigilance Practices (GVP) is a key document dealing with communication and processing of safety issues.  It lays out twelve key points on the requirements for the Quality Systems concerned with safety communication. There is an expectation from regulators that the company should be considering communication of this nature:

  • Throughout all of its risk assessment and risk management procedures
  • Throughout all of its working procedures

Regulators also expect clear and comprehensive communication between themselves, any public health bodies involved and the Marketing Authorization Holder (i.e. – your company). Professional advice should be sought to ensure that the right messages are reaching the right audience at the right time according to all the regulations. You also need to ensure that the regulators would consider all communications you issue are considered appropriately formulated for their intended audience. When presenting information about potential and known risks, you need to include information which is:

  • Adequately contextualized
  • Accurate
  • Relevant
  • Extremely detailed including seriousness, severity, frequency, risk factors, time to onset, reversibility of potential adverse reactions, expected time to recovery – and uncertainties
  • Comprehensive including information on any competing risks

Regulators will expect particular care to be taken when communication concerns uncertainties.  Continual care should be taken to consult with appropriate parties evaluate the effectiveness and appropriateness of communications prior to release wherever possible, following release, as Safety Concerns are resolved, as any recommendations are updated. Finally, professional advice should be sought to ensure that all communications comply with data protection legislation.

For comprehensive advice that ensures your communications strategy is always compliant and effective, speak to one of our drug safety experts today.

Simply call in complete confidence for a complete assessment of your company’s needs. Please note professional advice should always be sought on all aspects of safety concerns including compliance with legislation; the overview provided here cannot function as any type of substitute.                                     

                                                                ACRO PharmaSolutions – Compliant and protecting patients and products

                                                                    Just one of the pharmacovigilance services from ACRO PharmaSolutions

Reference

Guideline on good pharmacovigilance practices (GVP). Module XV. Safety communication.

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Data Safety Monitoring Boards (DSMB):

A Data Safety Monitoring Board, or Data Monitoring Committee (the terms are used interchangeably), is a committee used to monitor safety in clinical trials. They enable safety monitoring to be carried out while maintaining the blinding of the trial so that the blinding is not broken and the trial remains valid.

A DSMB is a group of experts formed outside of the pharmaceutical company or CRO commissioning or conducting a particular clinical trial. The aim of the DSMB is to provide impartial safety advice, often in the context of benefit and risk. CHMP Guidelines define a Data Monitoring Committee as “a group of independent experts external to a study assessing the progress, safety data and, if needed critical efficacy endpoints of a clinical study. In order to do so a DMC may review unblinded study information (on a patient level or treatment group level) during the conduct of the study. Based on its review the DMC provides the sponsor with recommendations regarding study modification, continuation or termination”.

Under clinical trial conditions patients tend to be monitored far more closely than would be the case in day-to-day medicine. Consequently issues will be picked up earlier than in standard spontaneous reporting pharmacovigilance. However this close monitoring does lead to adverse events being reported that are not caused by the trial drug. Under normal clinical conditions on the other hand, adverse reactions are vastly under-reported. DSMBs are not compulsory in clinical trials and their use depends on the nature of the drug being trialed, the condition being treated, and length of trial, number of patients and a host of other factors. A DSMB may be just one of several teams with oversight of clinical trials. The EU expects DSMBs to be appointed if, for example, there are potential safety concerns or potentially life-threatening reactions and publishes guidelines on how a DMC should be appointed, what its responsibilities would be and how it would operate.

  • When and why is a Data Monitoring Committee vital?

The need for a DMC should generally be discussed during the planning of any clinical trial program. They would be expected to have been formed in all trials involving a life-threatening disease and are also a consideration when trials involve certain groups within the population, for example, children, the elderly, people who are pregnant. DMCs are a consideration when there is a suspicion the treatment has the potential for higher levels of risk of harm, for complex trial designs and where there is a probability that study modifications may be needed.

  • A DMC is likely to take at least several weeks of valuable time to set up.

DMCs are an important safeguard for patients and clinical trial sponsors alike. It is vital that the board is formed from those who understand and have experience with clinical trial safety overall, not just experts in particular therapeutic areas or with specific types of drug. ACRO PharmaSolutions and its consultants have been involved in setting up, chairing and sitting on DMCs in a variety of therapeutic areas. They can help strike the balance between over-anxiety about findings that are perhaps not of major importance and the failure to detect signals through lack of experience with this type of data. Involving experienced pharmacovigilance consultants can also help to ensure that the DMC sticks to the remit established in its charter and do not stray into areas that may not be relevant.

                                                                   ACRO PharmaSolutions: Monitoring data, protecting patients and products

                                                                      Just one of the pharmacovigilance services from ACRO PharmaSolutions

References

Committee for Medicinal Products for Human Use Guideline EMEA/CHMP/EWP/5872/03 of 27th July 2005 on Data Monitoring Committees. European Medicines Agency.

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Pharmacovigilance Process Development:

The Good Pharmacovigilance Practice (GVP) modules and other drug safety regulations set out exacting standards for you to meet without exception and the quality documentation required for your systems and activities is extensive and specified in GVP Module I. Due to the level of complexity, most companies find they face challenges e.g.:

  • Accurately & adequately interpreting the regulations
  • Applying them appropriately
  • Creating appropriate systems that will meet with regulators’ approval during inspections and auditing
  • Maintaining those systems in accordance with regulations

You could outsource these operations in their entirety to an external pharmacovigilance services provider such as ACRO PharmaSolutions. An expert team working on your behalf eliminates the risk of non-compliance – avoiding difficult and costly penalties by the regulatory authorities. However, there are those companies who understandably prefer to complete this essential work in-house. The risk they run is that the laws are so complex and detailed that staff is unable to allocate adequate time to keep abreast of the current laws and the changes to them that inevitably come with time.

  • Why Choose ACRO PharmaSolutions?

Our expert consultants can show you the ‘middle way’. All are drug safety professionals with many years of experience in the field. Some have helped to draft the regulations themselves and some have been on regulatory bodies. All are highly adept at working directly with companies to ensure you always:

  • Meet your legal obligations
  • Follow current best practice
  • Work in the most cost effective way possible

Many of our clients choose the ACRO PharmaSolutions ‘middle way’, keeping operations in-house yet drawing on our support for specific tasks as the need arises. From help formulating your Standard Operating Procedures (SOPs) through to help to build your drug safety department itself, our team is right behind you. For us, Process Development means a supportive third party to develop your vital processes in a more intelligent, advanced and insightful way.

  • Why Use Our Pharmacovigilance Process Development Services?

There are many reasons why working with ACRO PharmaSolutions can streamline your operations, making them more time- and cost-effective. For example, GVP VI states that literature searching should be conducted weekly for adverse drug reactions. However, you need to know precisely how to conduct those searches – since explicit guidance is not contained within the Annexes. GVP Module VII provides another good example. It describes the objective of searching in broad terms without any operational guidelines to ensure a consistent approach across the company and, hence, your consistency is drawn from your SOPs. However, formulating those is time consuming and requires a process of iterative compilation.

ACRO PharmaSolutions consultants assist with process mapping and process development for documents such as these. We offer a comprehensive suite of template Standard Operating Procedures in relation to clinical trial and post marketing pharmacovigilance and risk management. All are designed to be specifically adapted to your precise requirements. Whereas preparation of SOPs can take many weeks and represent a considerable investment of your resources, our templates can result in significant time and cost savings.

Our approach works for individual SOPs and operational guidelines; it works for whole suites of SOPs and it even works where you need an entire Drug Safety Department to be built from scratch, including taking care of your needs for:

  • An EEA Qualified Person for Pharmacovigilance (QPPV)
  • Suitably skilled personnel for literature screening
  • A system to receive events and process them
  • A safety database
  • A Pharmacovigilance System Master File (PMSF)
  • Safety Data Exchange Agreements (SDEAs)

ACRO PharmaSolutions’s Process Development is the process by which each of these elements is meticulously planned and organized to help you define your needs and provide you with expert advice on how to proceed at every stage. We can also produce your SOPs and other operational guidelines so that your staff always has clear and consistent instructions to follow for each process – ensuring that all your operations stay completely compliant. Finally, you may prefer to have ACRO PharmaSolutions handle the work in its entirety as your named contracted comprehensive drug safety services provider.

To find out more about how our team can help yours, simply call us today in confidence or alternatively, you may prefer to email: info@ACROpharmasolutions.com

                                                       Pharmacovigilance Process Development – documented and compliant

                                                 Just one of the pharmacovigilance services from ACRO PharmaSolutions

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Provision of a Qualified Person for Pharmacovigilance:

ACRO PharmaSolutions offers experienced Qualified Person for Pharmacovigilance and Deputy Qualified Person for Pharmacovigilance with extensive knowledge and experience of the industry. Your medicinal products cannot be marketed within the EU without a Qualified Person for Pharmacovigilance (QPPV) that is personally responsible in law for the fulfillment of key functions:

  • Establishing and maintaining your pharmacovigilance (PV) system, including all activities which contribute to the detection, assessment, understanding and communication of safety information, as well as risk management activities
  • Overseeing the safety profiles of your company’s marketed products and any emerging safety concerns
  • Acting as a single point of contact for the EMA and EU Competent Authorities on a 24-hour basis, and the contact point for inspections
  • Ensuring and verifying that the pharmacovigilance system master file (PSMF) is constantly an accurate and up-to-date reflection of that safety system

Your QPPV must reside with the EEA and be permanently and continuously at the disposal of the marketing authorization holder (MAH) and must be experienced in all aspects of pharmacovigilance.

  • Why Outsource Your Qualified Person for Pharmacovigilance?

Recruiting and appointing your QPPV can consume a great deal of your time and resources. Our support allows for greater economy without sacrificing quality.

ACRO PharmaSolutions QPPVs have extensive knowledge and experience of the industry and reside in more than one EU member state.

Our experienced QPPV’s can work within your PV system which has been outsourced to ACRO PharmaSolutions. ACRO PharmaSolutions can audit your existing QPPV and PV system and identify gaps in oversight and advice on optimal arrangements, recommending corrective actions to ensure your PV system meets the requirements of the legislation.

ACRO PharmaSolutions also offers an extensive network of National Persons Responsible for Pharmacovigilance (NPRP – also known as local QPPVs or Local Contact Persons) who are the primary contact person for their local competent authority and work closely with the EEA QPPV e.g. the German Stufenplanbeauftragter or Graduated Plan Officer as defined in section 63a of the German Drug Law.

                                                                  Just one of the pharmacovigilance services from ACRO PharmaSolutions

                                                                            For more information contact ACRO PharmaSolutions today

References

1European Medicines Agency. 22 June 2012 EMA/541760/2011. Guideline on good pharmacovigilance practices (GVP) Module I – Pharmacovigilance systems and their quality systems. 2Brown EG. The Qualified Person for Pharmacovigilance for Europe: a compliance and quality perspective. Leading article. Int J Pharm Med 2005; 19 (1): 7-14

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Pharmacovigilance Operations – Post-marketing:

Individual Case Safety Reports (ICSRs):

‘ICSR’ refers to Individual Case Safety Reports which must be compiled for each instance of a suspected or confirmed adverse event and each reception of a report about one to the Competent Authority (CA) of the Member State.

From 22 November 2017, the upgrade of EudraVigilance by EMA will become effective. This means that all adverse reactions (serious and non-serious) experienced with the EU will be submitted to EudraVigilance only

ICSR format is precise and exacting and includes:

  • References for administration and identification purposes, including where the report came from and who received it
  • All information from primary sources
  • Characteristics of the patient concerned
  • Description of the relevant events
  • Results of clinical tests and procedures
  • Characteristics of the medicinal product in question
  • Narrative style summary of the case
  • Any further relevant supporting information

It is expected that each ICSR should be:

  • Validated before reporting
  • Submitted within extremely strict and rapid timescales – starting from the time when minimal information is brought to your attention as the Marketing Authorization Holder – and this includes your Sales representatives and any contractors
  • Rapidly re-submitted as new or updated information becomes available which has an impact on the original submission

You also need to be sure that detailed Safety Data Exchange Agreements (SDEAs) exist regarding relevant information exchanges (including information from periodic Literature Searching) with any of your contractors. SDEAs must be formulated to ensure compliance with the interim and final arrangements.

  • Why Choose ACRO PharmaSolutions for your ICSRs?

Advice from our drug safety services consultants ensures:

  • You and your staff stay abreast of all the changes
  • Your submissions remain seamlessly compliant throughout the transition from interim to final arrangements
  • You avoid onerous and costly penalties accrued through non-compliance

ACRO PharmaSolutions uses a validated safety database – the Industry standard – and our employees have been processing Individual Case Safety Reports (ICSRs) and drug safety data for many years. Our system server is secure, with appropriate back-up and disaster recovery programs in place. We offer a cost-effective solution for managing your legacy safety data as well as taking care of your company’s future needs for processing ICSRs. Our experienced pharmacovigilance physicians are involved in reviewing MedDRA coding and in the medical assessment of all cases. We carry out full quality control on each report.

We have a specialized submissions team who are qualified users of EudraVigilance for electronic reporting. Case disposition is tracked and contributes to metrics for regulatory and quality compliance monitoring. Regulatory intelligence is key part of this team’s role to ensure we keep abreast of any changes in the regulations and update our core regulatory reporting requirements table accordingly.

We understand the need for keeping to time, for making the right decisions about expedited reporting and for keeping the appropriate people in your company informed if necessary we can tailor our established standard practices to your specific requirements. The whole system is subject to internal audit and is also open to your scrutiny.

However, entering data into a safety database is only a small part of the requirements for pharmacovigilance. Regular management reports, routine signal detection, database searches for signal evaluation, periodic safety update reports or responses to regulatory authority enquiries all attract the same attention to quality and application of medical expertise. At ACRO PharmaSolutions, if it needs a medic we use a medic, but it need not cost you the earth.

                                                                                       For ICSRs: Compliant and Complete

                                                              Just one of the pharmacovigilance services from ACRO PharmaSolutions

Reference

1. European Commission. Vol 9a of The Rules Governing Medicinal Products in the European Union – Guidelines on Pharmacovigilance for Medicinal Products for Human Use.

PLEASE NOTE: EU drug safety laws are complex here and changing – this document is provided for education purposes and cannot be interpreted as any statement of meaningful professional advice.

Expedited reports:

Remaining compliant throughout all the changes to EU legislation can be a challenging endeavor for any company. This is particularly the case with Expedited Reporting – one of the pillars of all EU pharmacovigilance work.

  • Fact:

EU pharmacovigilance laws mean that ALL spontaneous reports regarding serious adverse reactions must be expedited within 15 days. In addition, from 22nd November 2017 all non-serious adverse reactions, with an origin within the EU, will require expediting to EMA within 90 days.

  • Fact:

These laws will mean that ALL suspected reactions provoked by a medicinal product must be expedited – regardless of seriousness.

  • Fact:

One of the most common causes of critical findings in Drug Safety Inspections is the non-compliance with the expedited reporting of spontaneous adverse drug reactions

Non-compliance can result in time-consuming and costly remedial work and/or penalties imposed by regulators. These can include inspections, CAPAs and suspensions of Marketing Authorizations.

  • What Is Expedited Reporting?

In the EU post-marketing environment, an Individual Case Safety Report (ICSR) may involve a serious or non-serious adverse reaction – regardless of expectedness. Such cases must be submitted to the regulatory authorities within 15 days or 90 days respectively. As a Marketing Authorization Holder, you need to be fully versed in each change to the drug safety laws in concerned territories around expedited reporting as and when it happens. Including the responses you need to introduce to remain fully compliant. With the right support you can rapidly respond to the challenges in line with your Standard Operating Procedures.

  • Post-Marketing Phases

Any clinical trials including post authorization studies during the post marketing phase of a product will need to be correctly processed and expedited according to regulatory requirements.

  • Why Choose ACRO PharmaSolutions For Your Expedited Reporting?

ACRO PharmaSolutions drug safety services consultants place particular emphasis on the timely reporting of post-authorization case reports. With a fully validated E2B compliant safety database highly effective SOPs and operating guidelines, thorough employee training and a constant quality management system ‘on time’ reporting is a major priority. Reports may be made electronically or by hard copy as required by local regulations. ACRO PharmaSolutions may register and run electronic reporting systems such as EudraVigilance. Our EMEA trained employees to ensure compliance with the rigorous requirements’ of such a system.

                                                     ACRO PharmaSolutions – Trained and on Time ‘No missing of timeline’s

                                                    Just one of the pharmacovigilance services from ACRO PharmaSolutions

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PSUR / PBRER – Periodic Safety Update Report:

Periodic safety update reports (PSUR) are required for all products that have marketing authorization in the EU.

PSUR in pharmacovigilance represents a fundamental document and basic requirement for majority of regulative proceedings.

A PSUR in pharmacovigilance provides an overview of safety and efficacy (GVP Module VII) over a defined interval: they require careful preparation according to a standard format in order to comply with the regulations and must meet tight deadlines for submission. Periodic safety update reports (PSUR) can also be submitted to the US FDA following a waiver from the need to submit US-style reports; alternatively we can write the US periodic adverse drug experience report (PADER).

  • PSUR Pharmacovigilance

PSURs are considered important pharmacovigilance documents by the authorities and they are subject to intense scrutiny at the time of inspection in the EU. A PSUR in pharmacovigilance that fails to examine and critically review the safety of the product often lead to punitive demands from regulators for additional time- and resource-intensive cumulative analyses.

The regulations PSUR Pharmacovigilance are complex, and effective timetabling for multiple products can be difficult and lead to costly duplication of effort.

Development Safety Update Reports (DSUR) for clinical trials is required for studies with centers in any EU country: again, there is a standard requirement for content and for time of submission.

ACRO PharmaSolutions consultants and staff have years of experience of planning and writing periodic safety update reports, PADERs and DSURs in a cost-effective way. Whether it is a single simple DSUR or PADER or complex PSURs, we can meet the need.

                                                                          Periodic reports: Compliant and Thorough

                                                            Just one of the pharmacovigilance services from ACRO PharmaSolutions

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Literature screening:

  • Why Are Correct Screening Procedures So Important?

GVP Module VI makes it clear that regulators expect consistent screening to be an integral part of your day-to-day drug safety operations. For each marketing authorization you hold, you are expected to:

  • Understand which publication databases are most relevant to each medicinal product
  • Systematically monitor these for publications worldwide at least once a week
  • Systemically monitor all “active substances” for which you hold Marketing Authorizations within the EU (where not listed by the EMA)
  • Monitor articles published locally in each territory where your product is marketed
  • Route the results of this activity to the appropriate departments within your company
  • Understand and comply with the time deadlines that apply to Individual Case Safety Reports Literature Screening – even if a third party is completing your screening
  • Avoid reporting duplicate ICSRs within literature
  • Describe and analyze any “new and significant safety findings” in the medicinal product’s PSUR
  • Understand and comply with the requirement to immediately notify regulators of new safety information from screening

ACRO PharmaSolutions operates a comprehensive Worldwide Pharmacovigilance Literature Screening Service as part of the suite of drug safety services offered by the company. Features include:

  • Conduct of searches via validated databases e.g. Medline and Embase – Screening of Abstracts for identification of potential ICSRs
  • Screening of Abstracts for identification of potential new and significant safety findings for inclusion in PSURs
  • Pregnancy outcomes (including termination) with no adverse outcomes
  • Use in pediatric populations
  • Compassionate supply, named patient use
  • Lack of efficacy
  • Asymptomatic overdose, abuse or misuse
  • Medication error where no adverse events occurred
  • Important non-clinical safety results. Ordering selected full publications for evaluation of ICSRs or safety issues
  • Targeted Literature Screening for Safety Assessments and Benefit Risk Analysis

ACRO PharmaSolutions’s system for monitoring literature currently screens different INNs & MLM and is constantly increasing. Significant cost savings are incurred when multiple clients share the same INN &MLM. Results may be sent directly to you if you prefer.

Your service may be extended to full or part service including:

  • Entry of identified cases onto a validated safety database
  • Full medical review of ICSRs
  • Regulatory reporting of ICSRs
  • Signal Detection and Benefit risk analysis
  • Medical Assessment of safety issues
  • Why Choose ACRO PharmaSolutions For Your Pharmacovigilance Literature Screening Service?

The requirement to proactively screen the published medical and scientific literature as part of a pharmacovigilance system can lead to difficulties: the screening can be time-consuming and resource intensive; inadequate searches are a common finding during regulatory authority inspections; and the identified cases can be complex and difficult to evaluate and to enter onto the safety database.

One benefit of contracting ACRO PharmaSolutions to carry out your Literature Screening for you is that we have been offering it as part of our range of drug safety services for a number of years. Our staff has extensive experience in this arena and can comprehensively manage your literature screening requirements in a cost-effective manner. Involving medical review of cases rather than adopting a mechanistic approach can also help to identify important signals in the literature. We can also utilize our existing international network to establish screening of the local, non-indexed medical and scientific literature.

We can also carry out literature searches for purposes of signal evaluation or for identifying safety concerns for inclusion in PSURs.

                                                      -Extensive literature search through various databases-

                                            Just one of the pharmacovigilance services from ACRO PharmaSolutions

References

Guideline on good pharmacovigilance practices (GVP) Module VI – Management and reporting of adverse reactions to medicinal products

Guideline on good pharmacovigilance practices (GVP) Module VII – Periodic safety update report

21CFR314.80 Post-marketing reporting of adverse drug experiences

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Safety signals:

  • Business-Critical Responses – Processing of Safety Signals-All drugs safety monitoring activities involve the collection and processing of tremendous amounts of drug safety data. When it comes to processing data related to Adverse Reactions, your work must demonstrably meet with both EU regulations and best practice guidelines. Patterns that could suggest new safety information must be swiftly and accurately identified – without exception. Within your pharmacovigilance system, timely identification and appropriate evaluation of possible signals of new adverse reactions and safety concerns for products are essential for:
  • The protection of patients
  • Protecting your company against litigation and action taken by regulators

By the same token, it is vital to evaluate safety concerns appropriately, if products are not to be unnecessarily damaged or even lost.

This area of practice is subject to stringently defined expectations as far as drug safety laws are concerned across the EU. Formal guidelines on Signal Detection can be found in GVP Module IX which also refers to CIOMS VIII.

  • Why choose ACRO PharmaSolutions for Safety Signals Management Services?

Our consultants include former regulators and industry experts who have long been at the forefront of this activity, not only are we adept at identifying and evaluating signals, we bring a common-sense approach to the methodology that can simplify the process and ultimately reduce your costs.

If your signals are evaluated and thought to represent real new concerns that may affect the balance of benefits and risks for a product, expert advice is essential. Again, ACRO PharmaSolutions has access to world-class pharmacovigilance experts who can carry out benefit-risk analysis, advice on strategy and help to effectively communicate the message about new safety concerns both to top levels within your company and any necessary regulatory authorities.

  • Why Can Safety Signals Management Become So Complex?

Signals can indicate the potential for new risks associated with a particular medicinal product or the potential for the expected risks to have changed. The data which informs the signal detection process can come from a truly diverse range of sources, including but not limited to:

  • The Spontaneous Reporting System
  • Clinical Trials – pre or post marketing
  • Pharmacovigilance Literature Screening
  • Other types of non-clinical non-interventional studies
  • Systemic reviews and meta-analyses
  • Other forms of active monitoring including risk-benefit monitoring Databases such as EudraVigilance
  • Periodic Safety Update Reports (PSURs)
  • Media reports carrying information not channeled through the Spontaneous Reporting system for some reason

In addition, the regulations which address this vital drug safety activity are highly specific, necessarily complex to reflect the nature of the work – and subject to periodic review and change over time. You need to demonstrably work within the regulations not only for detection, but also for the:

  • Prioritization of tasks and responses
  • Robust and timely analysis of all potentially and actually relevant data
  • Validation and confirmation processes for signaling
  • Assessment of findings
  • Recommendations for next steps – consistently compliant with both EU regulations and best practice guidelines

ACRO PharmaSolutions pharmacovigilance services consultants ensure your Safety Signals Management activities are consistently comprehensive and your responsive action always timely, sensitive, accurate and compliant.

                                                                  Signal Detection: Compliant and Protective

                                                   Just one of the pharmacovigilance services from ACRO PharmaSolutions

References

Brown EG. Effects of coding dictionary on signal generation: a consideration of use of MedDRA compared with WHO-ART. Drug Safety 2002, 25(6), 445-452.

Stahl M, Lindquist M, Edwards IR, Brown EG. Introducing Triage Logic as a New Strategy for the Detection of Signals in the WHO Drug Monitoring Database.Pharmacoepidemiol Drug Saf. 2004 Jun;13(6):355-63.

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Pharmacovigilance Operations – Clinical trials:

Case processing (SAEs):

The data generated from clinical trials tends to be more complete than that received through typical channels of spontaneous reporting. Likewise the steps for follow-up are often far easier to take. Nonetheless, you will need to demonstrate consistently that your reporting process is adequately specified and resourced to the task.

  • Why choose ACRO PharmaSolutions for your clinical trial case processing?

ACRO PharmaSolutions bring a wealth of experience to the interpretation of case reports within the necessary pharmacovigilance legal frameworks. Our expertise ensures your submissions to regulators are always compliant and on time. The following outlines just some of the reasons why companies choose our staff:

  • Expedited Reporting Timelines

Serious adverse events (SAEs) must be reported to the regulatory authorities within very strict timelines. During any clinical trial, the onus is on your company to explicitly specify for the investigator which events are deemed serious and unexpected within your clinical trial. Your investigator must also make you aware of specific types of non-serious adverse events or laboratory findings. All clinical trial Suspected Unexpected Serious Adverse Reactions (SUSARS) must be reported to regulators within 7 days if they are classified as fatal or life-threatening. Those which are non-fatal, non-life-threatening must be reported within 15 days.

  • Defining Serious and Non-Serious Adverse Events

Expedited reporting requirements dictate that your standard operating procedures (SOPs) must involve the accurate grading of events within a suitable timescale. Our staff has the experience to advice on the grading process to ensure accurate and timely compliance. Their input is also crucial when it comes to demonstrating your analysis of risk-benefit ratios.

  • Appropriate Formats For Double Blind Trials

Since majority of late phase clinical trials involve a double-blinded protocol, your team will need to understand how to appropriately un-blind the trial before engaging in expedited reporting. It is also vital that the correct personnel undertake this task to prevent jeopardizing the integrity of the trial and/or presenting non-compliant data to the authorities.

  • Completing Your Causality Assessments

You will also need to demonstrate an adequate and compliant causality assessment procedure when completing your case processing for clinical trials.

  • Demonstrating Your Ceaseless Commitment To Clinical Trial Safety

As your trial progresses, you will need to demonstrate the continual evaluation of risk-benefit balance, enabling you to determine whether or not to allow the trial to continue. Where companies have outsourced part or all of the tasks associated with the trial, for example to a 3rd party Contract Research Organization (CRO), the responsibility for correct Case Processing for SAEs still lies with the company as far as the regulations are concerned. Suitable SDEAs (Safety Data Exchange Agreements) and/or Safety Management Plans (SMPs) must be in place and must have been agreed and established accordingly.

  • Formatting Your Reporting & Documentation

You will need to keep detailed records on all clinical trial related data including regulatory submissions which can be reviewed on request by regulators during inspections. For other purposes such as: the marketing authorization application itself, product Pharmacovigilance Master System File (PMSF), etc. your staff will need to be trained and kept up to date on EudraVigilance terminology used in all reporting. Comprehensive SOPs must be in place to cover these operations.

Non-compliance can result in costly remedial processes to complete tasks that should have been completed correctly in the first instance. It can even pose risks to the product’s ability to reach or stay on the market due to simply having presented data in a way which does not meet the regulations. To find out more about our clinical trial safety services, call us today in complete confidence. Our support is provided by consultants who have assisted on regulatory authorities; those who have worked for years within the pharmaceutical industry and now help companies navigate the complex waters of pharmacovigilance laws.

                                                 – Compliant and Consolidated- Clinical trial case processing–

                                        Just one of the pharmacovigilance services from ACRO PharmaSolutions

Reference

Communication from the Commission — Detailed guidance on the collection, verification and presentation of adverse event/reaction reports arising from clinical trials on medicinal products for human use (‘CT-3’). 2011/C 172/01).

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Expedited reports:

Electronic Reporting of Suspected Unexpected Serious Adverse Events (SUSARS) is now mandatory in many global territories.

As part of the service ACRO PharmaSolutions offers the facility to delegate the onerous task of registration and set up of the electronic reporting routes for the pharmacovigilance system. Experienced and EMA trained personnel ensure that expedited reporting meets the regulatory requirements in each trial territory. Whether electronic or hard copy ACRO PharmaSolutions offers consolidated expedited reporting services.

  • What is Expedite reporting?

A SUSAR that meets the seriousness criteria of life threatening and/or results in death must be reported within seven (7) calendar days. A SUSAR which if not life threatening or does not result in death must be submitted to the regulatory authorities within fifteen (15) calendar days.
In addition to the regulatory authorities, a SUSAR may also need to be reported to other recipients including ethics committee and investigators.

As a Sponsor, you need to be fully versed in each change to the drug safety laws around SUSAR reporting as and when it happens. Including the changes you need to introduce to remain fully compliant. With the right support you can rapidly respond to the challenges in line with your Standard Operating Procedures.

  • PRE-MARKETING CLINICAL TRIAL PHASES

ACRO PharmaSolutions has considerable experience advising on the submission of ICSRs for clinical trial phases 1 -3. The focus will inevitably vary from trial to trial but it should be noted that any SUSAR is subject to extremely strict deadlines for submission. ACRO PharmaSolutions can advise on when, who and how to submit and when to insert information within a Development Risk Management Plan, the Development Safety Update Reports and End of Study Reports.

  • POST-MARKETING PHASES

Adverse reactions reported during clinical trials in the post marketing phase e.g. Post Authorization Safety Studies (PASS) and all spontaneous reports will also need to be correctly expedited.

ACRO PharmaSolutions places particular emphasis on the timely reporting of SUSARs. With a fully validated E2B compliant safety database, highly effective SOPs and operating guidelines, thorough employee training and a constant quality management system ‘on time’ reporting is a major priority. Reports may be made electronically or by hard copy as required by local regulations. ACRO PharmaSolutions can register and run electronic reporting systems such as EudraVigilance. Our EMEA trained employees ensure compliance with the rigorous requirements of such a system.

                                                           Compliant and Timely submission of expedited reports

                                                Just one of the pharmacovigilance services from ACRO PharmaSolutions

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Clinical trial safety

Maintaining safety within clinical trials is of paramount importance to any pharmaceutical company wishing to bring new products to the market place or diversify their existing products.

Compliant pharmacovigilance procedures during your pre- and post- marketing clinical trials are the key to the eventual success of those trials and the granting of any Marketing Authorization. Demonstrating this compliance requires a very specific set of skills to be constantly updated in line with regulatory changes.

  • Why choose ACRO PharmaSolutions to manage your Clinical Trial Safety?

Pharmaceutical companies around the world face ever greater challenges in their quest to bring new drugs to market, including:

  • Meeting strict budget requirements
  • Ensuring staff have sufficient time available.
  • Ensuring those staff has the core competences needed.
  • Ensuring that outsourced activities are appropriately managed and of high quality

You need to conduct clinical trials, and the safety aspects of these involve a plethora of skills to be deployed in a timely manner to ensure not only regulatory compliance but also that best drug safety practices are enforced. Resources may not be immediately available within the company and you may be working within the EU or any given global location. While contracting-in external resources to provide pharmacovigilance services may seem a more obvious choice for medium-sized pharmaceutical companies, the challenges nonetheless remain for even the largest of corporations.

For example, will you have the full range of resources, personnel, skills and time consistently available throughout the studies to satisfy the increasingly complex global regulatory frameworks – in a cost effective manner?

  • Medical Review & Reporting

Our Clinical Trial Safety Services recognize the need to demonstrate your commitment to patient safety to regulators, your shareholders and stakeholders and the general public on an on-going basis. In addition to routine processing of individual case safety reports, we provide a comprehensive medical review of cases from your trials which meet with both good pharmacovigilance practice standards and regulators expectations.

We can also:

  • Compile and prepare your reports to trial investigators and Ethics Committees.
  • Report to regulatory authorities – within the EU and around the world
  • Prepare signaling reports, Development Safety Update Reports and IND Annual reports

Failure to implement and follow adequate reporting practices can at best result in costly and time consuming remedial work in order to satisfy the needs of the regulatory authorities. It can jeopardize or delay your product’s application for Marketing Authorization. It can also place your product at risk of losing its authorization during the post-marketing phase. It is of course necessary to establish and follow adequate Standard Operating Procedures in order to perform your ongoing monitoring of clinical trial safety but it is also essential to have an adequate understanding of the complexities of international regulations and pharmacovigilance laws in relation to clinical trials. Our services include:

  • Working with you to establish your SOPs on clinical trial pharmacovigilance – available for every step of the processes involved, helping you to establish clinical trial data safety monitoring boards if these are required
  • Developing your Risk Management Plans in full compliance with EU & worldwide drug safety regulations
  • Writing the Development Core Safety Information for each investigational product, if this is considered necessary by your company
  • Preparing and submitting your Development Safety Update Reports
  • Preparing and submitting your IND Annual reports if required
  • Supporting you to assess risk-benefit ratios throughout the trial and updating your Investigator Brochure as necessary
  • An industry-standard safety database

You need your database to be fully capable and compliant when it comes to managing serious adverse events from clinical trials. All of the above services are supported by our validated safety database. Our expert personnel have years of experience using safety databases which has become the Pharmacovigilance Industry gold standard. Alternatively, we can use your own safety database and enter data on that system.

Our services include:

  • Entering individual cases into the database, including quality and medical review
  • Database searches, retrieval and presentation
  • Registration with Eudravigilance Clinical Trial Module
  • Code break and submission of expedited reports world-wide

Whether you require particular advice on individual aspects of clinical trial safety or a comprehensive package of support services to allow your trial to operate, we can help you.

To find out more, simply call our team in complete confidence. We look forward to helping you achieve your pharmacovigilance goals in a far more cost effective way in the short, medium and longer term.

                                                           –Clinical trial safety: Compliant and Credible–

                                             Just one of the pharmacovigilance services from ACRO PharmaSolutions

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Periodic reporting (Development Safety Update Reports (DSURs))

Additionally to the need for expedited reporting of SUSARs, Development Safety Update Reports (DSURs) should be submitted to regulatory authorities and Ethics Committees throughout the clinical trial or on request. The DSUR takes into account all new available safety information received during the reporting period.

DSURs must be submitted at yearly intervals from the date of the CTA approval. For trials with marketed products, the date is the first marketing authorization granted in the EU.

The DSUR is a complex document written according to ICH E2F and includes the following:

  • Executive Summary
  • Introduction
  • Worldwide Marketing Authorization Status
  • Update on Actions Taken in the Reporting Period for Safety Reasons
  • Changes to Reference Safety Information
  • Status of Clinical Trials Ongoing and Completed During the Reporting Period
  • Estimated Exposure:
  • Cumulative subject exposure in clinical trials (Phase I-IV)
  • Patient exposure from marketed setting
  • Presentation of Safety Data from Clinical Trials
  • General considerations
  • Interval line listings of Serious Adverse Reactions (SARs)
  • Cumulative summary tabulations
  • Deaths in the reporting period
  • Subjects who dropped out in association with any adverse event in the reporting period
  • Significant Findings from Clinical Trials during the Reporting Period
  • Completed trials and any interim analyses
  • Ongoing clinical trials
  • Other therapeutic use of investigational drug
  • New safety data related to combination therapies
  • Relevant Findings from Non-Interventional Studies
  • Relevant Findings from Other Studies
  • Safety findings from marketing experience
  • Other Information:
  • Non-clinical data
  • Long-term follow-up
  • Literature
  • Other DSURs
  • Significant manufacturing changes
  • Lack of efficacy
  • Phase I protocol modifications
  • Late-Breaking Information
  • Overall Safety Assessment:
  • Evaluation of the risks
  • Benefit-risk considerations
  • Conclusions
  • Summary of important risks

Consolidated safety reporting systems at ACRO PharmaSolutions, together with extensive in-house medical expertise provide the means for accurate and through DSUR production.

                                                           – Accurate and Thorough- Development Safety Update Reports (DSURs)

                                         Just one of the pharmacovigilance services from ACRO PharmaSolutions

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