Drug safety has moved into the media spotlight and now more than ever it is essential that patient safety is seen to be of utmost importance to regulators as well as pharmaceutical companies. Outsourcing in the pharmaceutical market has grown vastly over the last 10 years, with PV market estimated to reach $5billion in 2019, at a Compound Annual Growth Rate (CAGR) of 12.9% from 2013 to 2019.It has become almost standard practice among multinational companies to develop global sourcing programs. The outsourcing of pharmacovigilance tasks provides a flexible solution to the ever changing demands of running a specialist pharmacovigilance team. Duties usually be performed in-house are contracted to a dedicated service provider, whether it is on a full service, partial or project basis. The trend seen in drug safety services has largely paralleled the trends seen in the clinical research and product development services.
When Outsourcing helps?
· When we need to have short term additional resources.
· When we need to have readymade troop of skilled and trained resources.
· When we need the flexibility to respond to varying workloads.
· Outsourcing approach of ‘pay as you go’ allows you to respond fully to regulatory obligations, without the need of retaining a full pharmacovigilance team on the payroll.
· The benefits of outsourcing include reduced costs due to less effort needed for staff recruitment, management and training. With stricter regulatory requirements, the hiring of experienced safety personnel has become highly competitive.
What services can be outsourced?
Company size, the size of the pharmacovigilance department and existing license or development partnerships influence outsourcing decisions. It is possible to outsource an entire pharmacovigilance (end to end) or medical information department or just individual elements, depending on your requirements.
The range of contracted services is determined by the type of safety service providers, including individual consultants, specialty Clinical Research Organizations (CROs), large, full-service CROs and global service providers under the umbrella of business process outsourcing (BPO). Life science companies, CRO’s, KPO’s, and BPO’s shifted for doing this business. These companies come up with robust technology and mature processes to effectively address risks and concerns associated with delegating responsibility to service providers. The negotiations between the pharmaceutical company and the regulatory authorities on the risk management program had been unsuccessful over several years so the pressure has increased of late, in order to comply with evolving regulations worldwide. Regulatory observation along the entire product life cycle has seen a substantial increase, with all areas of the business being affected.
Examples of outsourcing consultation trends include:
· Full PV service outsourcing (ICSR management & reporting of cases).
a. Small biotech companies typically have no drug safety department and routinely
Outsource all safety services including the safety database.
b. Mid-sized pharma companies generally have the knowledge and resources to cater
to the demands of the global pharmacovigilance environment. They face challenges to meet fluctuating resource needs associated with a changing product development.
c. Large pharma companies have comprehensive expert pharmacovigilance
departments with global infrastructure and databases.
· Case processing (Regulators requested an active surveillance study to detect
rare and serious adverse events for risk minimization).
· Literature screening (Usually provide flexible end-to-end literature search and review solutions that assist companies and individuals to meet their regulatory goals).
a. Literature review help users to stay updated in their research.
b. Provides complete picture of today’s global clinical research in clinical medicine which is enabled by broad coverage with numerous access point, extensive search capabilities and coverage of immense data.
c. Save research time by providing one source for variety of research data including abstracts, author’s name, contact details and information per bibliographic record than in other resources.
· Signal detection/ benefits risk assessment (Contracted experts are external, they can provide an unbiased view, may have special value in decision making process involved in signal detection and risk management activities required for the drug.
· MedDRA coding and writing risk management plans.
· Aggregate reporting(PSURs/PADERs/PBRERs/DSURs)
a. Periodic benefit/risk evaluation reports (PBRERs)
b. Periodic safety update reports (PSURs)
c. Periodic adverse drug experience reports (PADERs)
d. Summary bridging reports
e. Developmental safety update reports (DSURs)
f. Pharmacovigilance risk assessment committee (PRAC) responses/health authority responses.
· Aggregate reports may include following contents:
b. Worldwide market authorisation status (dates of MAH, limits on indications if relevant to safety , treatment indications and special populations covered by the market authorisation, lack of approval, including explanation, by regulatory authorities, trade name(s), withdrawal by the company of a licence application submission if related to safety or efficacy, dates of launch when known.
c. Update of regulatory authority (MAH actions taken for safety issues). The safety related reasons that led to these actions should be described and documentation appended when appropriate; any communication with the health profession (e.g., Dear physician letters) as a result of such action should also be described with copies appended.
d. Changes to the RSI’s (reference safety information). It should be numbered, dated and appended to the PSUR and include the date of last revision. The revised labelling document should be used as the reference for the next report and the next period.
e. Patient exposure (An estimation of accurate patient exposure should cover the same period as
the interim safety data).
f. Presentation of individual case histories: Case presented as line listing, the line listing(s) should include each patient only once regardless of how many adverse event/reaction terms are reported for the case. If there is more than one event/reaction, they should all be mentioned but the case should be listed under the most serious ADR (sign, symptom or diagnosis), as judged by the MAH. An aggregate summary for each of the line listings should usually be presented.
g. MAH’s Analysis of Individual Case Histories: This section may be used for brief comments on the data concerning individual cases. Discussions can include: serious or unanticipated findings (their nature, medical significance, mechanism, reporting frequency, etc.). The focus here should be on individual case discussion and should not be confused with the global assessment in the overall Safety Evaluation.
h. Studies: All completed studies (non-clinical, clinical, and epidemiological) yielding safety information with potential impact on product information, studies specifically planned or in progress, and published studies that address safety issues, should be discussed.
i. Overall safety information: A change in characteristics of listed reactions, e.g. severity, outcome, target population. Serious unlisted reactions, Non-Serious unlisted reactions. An increased reporting frequency of listed reactions. Drug abuse/misuse/overdose/interactions. Pregnancy, breastfeeding related safety concerns. Effects on vulnerable patients.
j. Conclusion: indicate which safety data do not remain in accord with the previous cumulative
experience, and with the reference safety information (CCSI), specify and justify any action recommended or initiated.
· Electronic reporting set up (By E2B format).
· Contractual agreement production and maintenance
· Risk management planning and services.
· Due diligence support activities (The due diligence should be supplemented with data on the tenure of the staff and management team).
· Provide insight and overview of global regulations.
· PV Training (The sponsor drug safety team provided initial training to the CRO staff at the beginning of the relationship, the CRO is responsible for training new staff (train-the-trainer principle).
· Quality compliance training and review (Reducing costs through low-cost or off-shore outsourcing results in quality issues and regulatory non-compliance and deviations. It is pertinent to maintain the necessary oversight and engagement with the outsourcing partners or the vendors).
· Audit and inspection readiness and preparation. (A track record of regulatory compliance and low non-conformity rates usually indicates a robust quality management system. Audits during the cooperation either by in-house staff or an external auditor are the best tools to reconfirm that the provider meets quality standards and implements adjustments in a changed regulatory environment.
· Clinical safety assessment (Whether you are seeking an experienced QPPV (Qualified Person) service only, LPVRP (Local Pharmacovigilance Responsible Person) service, report writing services or an entire team, service providers are able to provide subject matter expertise for matters pertaining to complex global pharmacovigilance and Medical Information regulations, expertise which may not be readily available in house). Most countries have requirement of LPVRP/QPPV. If you are exporting your drugs to any international market, it is critical to have their respective supports. Regulators prefer dealing with senior professionals experienced in pharmacovigilance. Regulators prefer having a single point of contact to address their queries and concerns. It is helpful if these are in charge of the entire pharmacovigilance operations in their region. Should be 24×7 available. The role of QPPV and/or the deputy can be outsourced, however this must form part of a formal agreement which will have clear definitions of the responsibilities of each party, moreover confidentiality must be maintained.
· A QPPV has a central role focused on ensuring the company is meeting all of its PV responsibilities and ultimately the safety of the public using the medicine is maximised.
· Labelling documents/ RSI’s Updating revision (CCDS/CCSI/PIL/SPC assessments)
· SOP writing/updating/ Training (SOPs are important and can impact cost, adherence to the
sponsor’s SOPs can be advantageous. Sponsor’s SOPs, user manual and entry/coding conventions).
Outsourcing pharmacovigilance activities is a standard business practice in a rapidly expanding market segment. It can be successful provided:
a. The service provider has the qualification for the pharmacovigilance services.
b. Contractual agreement includes well defined responsibilities.
c. Transparency maintained at project start.
1. Pharmaceutical information and Pharmacovigilance association retrieved from http://www.pipaonline.org/Pharmacovigilance-Competencies on 24-Oct-2015.
2. Report to the European Commission on Pharmacovigilance audits carried out in the Irish Medicines Board in Ireland from 21-SEP- 2012 to 20-SEP-2013 retrieved from
3. https://www.hpra.ie/docs/default-source/publications-forms/corporate-policy-documents/ie_summary-of-pharmacovigilance-system-audit-report-results_2013_final-(1).pdf?sfvrsn=2 on 27-Oct-2015.