However pharmacovigilance IS expensive. And pharmaceutical companies ARE companies and do have to make a profit, even the most responsible pharma company knows that it is answerable to its shareholders and stakeholders as well as the regulatory authorities.

So what to do?

Well one solution is to outsource some or all of the drug safety surveillance activities or to bring in consultants. Is this wise? Well it might be but it depends where the work goes and why the work is being outsourced in the first place.

It costs money to recruit staff and keep them permanently. It costs a LOT of money to set up a pharmacovigilance system. For example a full working drug safety database on its own can cost in excess of £200,000 before the staff to run it are even notified of vacancies.

2.) PROVIDING FLEXIBILITY

A lot of companies strike a balance between permanent staff and hired hands by bringing in consultants to provide flexibility during periods of higher workloads. This enables them to meet their regulatory requirements while at the same time ensuring that there isn’t an excess of staff during quieter times.

3.) COVERING FOR OTHERS

Sickness, maternity leave and all sorts of other factors can leave temporary gaps in the workforce. Just because employees are not present doesn’t mean the work goes away and inevitably it may be necessary to bring in temporary cover for absent colleagues.

4.) PROVIDING EXPERTISE

From time to time specific, highly specialized, expensive skills are required to carry out pharmacovigilance effectively. Those who can do the work may then not be needed for a period of time before they are next required, if they are required at all. Rather than having pharmacovigilance experts sitting around twiddling their thumbs and drawing a wage, it can make a lot more sense to temporarily draft in help when needed in order to gain their support and expertise that is not currently available in-house.

Almost all of the functions and work of a pharmacovigilance department can be outsourced effectively. This includes both the work for clinical trials and post-marketing spontaneous adverse event reporting.

This includes receiving the safety data from the public and from health professionals, triage of routine cases to determine seriousness, entry of the data into a validated pharmacovigilance database, coding the narrative and providing medical review and surveillance of cases.

EXPEDITED REPORTING:

All reports of serious adverse events have to be reported to regulatory authorities within strict timescales. This expedited reporting includes electronic reporting such as Eudravigilance and usually include both expected as well as unexpected serious events.

ROUTINE REPORTING:

All reports of adverse events, serious and non-serious, expected and unexpected, must be submitted periodically to the regulatory authorities. These reports include periodic safety update reports, US periodic reports and annual safety reports. The preparation of these reports can be outsourced.

DETECTING SIGNALS:

As well as reporting events, pharmacovigilance staff must carry out exercises in signal detection to see if there are any underlying trends or issues that need to be reported.

LITERATURE SCREENING:

Likewise pharmacovigilance professionals need to carry out regular searches of the peer-reviewed literature to ensure that any mentions of their product are duly noted and reported to the competent authorities. This includes searching for potential safety issues as well as individual case reports.

QUALIFIED PERSON:

In the EU, each marketing authorisation requires there to be a single point of contact, with a deputy, that is available 24-7 to act as the Qualified Person for Pharmacovigilance for Europe. Elsewhere a local Qualified Person is often required. The QP’s job is to co-ordinate the pharmacovigilance response to any safety issues that occur. QPs are required due to the complicated and convoluted structures of many pharmaceutical companies which may mean that it can be difficult to ascertain which subsidiary of which company is responsible for which product. Requiring appointment of a QP bypasses these complications.

RISK – BENEFIT:

All pharmaceutical products are supposed to bring benefits. All pharmaceutical products are associated with risks. Balancing the one against the other is the job of the pharmacovigilance  professional and of course as products stay on the market and their safety profile becomes better known, so the risk profile of a product will change.

RMP, RiskMAP, REMS

Risk management planning has become an essential part of pharmacovigilance with the requirements of submission of a Risk Management Plan in the EU and, in the US, establishment of a Risk Minimizarion Action Plan as part of a Risk Evaluation and Mitigation Strategy. Setting up and maintaining these strategies can be outsourced to pharmacovigilance specialists.

Every marketing authorisation in the EU has to come with a detailed description of the pharmacovigilance system being employed by the pharmaceutical company in addition to any risk management plans that will be employed. This has to include proof that there is a QP and that the QP is available as well as proof that you as a marketing authorisation holder can deal with adverse events properly – collecting and notifying the competent authorities in the correct manner.

Safety Data Exchange Agreements

Safety Data Exchange Agreements are controlled documents to be shared between business partners and other third parties so that clear lines of communication may be established for safety data. This is particularly important given the requirements of expedited reporting. Most reporting timescales are 15 days from when the company OR IT’S EMPLOYEES AND BUSINESS PARTNERS become aware of events. It is therefore absolutely vital that safety data be transmitted in a timely as well as secure manner. Setting up these agreements can be effectively outsourced.

Training in pharmacovigilance and inspection readiness

Training in pharmacovigilance is something that can always be contracted out since only the very biggest pharmaceutical companies will have in-house resources that can carry out training in such a specialized area. There are also trainers who will train in inspection readiness as there are a few trainers who are former regulators and former senior pharmacovigilance officers in the industry – in a few rare cases they are both. Pharmacovigilance inspection readiness training ensures that your staff know what to expect in the event of a pharmacovigilance inspection by a regulatory authority as well as how to ensure that they have the data to hand when such an inspection is carried out.

Organisation setup and change

Often establishment of a pharmacovigilance department can require new structure within a company as well as changes to how existing departments function, oversight of these changes can be contracted out to consultants who are experienced in change management and setting up pharmacovigilance departments.

Preparation of SOPs and other controlled quality documents

All businesses require standard operating procedures but in industries as heavily and tightly regulated as pharmacovigilance, well written, up-to-date, comprehensive SOPs and other quality documents are absolutely vital. They will be investigated during any pharmacovigilance inspection and it will be expected that they are up to date and that all staff are trained in them. Bringing in outside help to prepare these documents therefore makes perfect sense.

System and database evaluation and validation

Your whole pharmacovigilance system, including the database, need to be evaluated as fit-for-purpose. Consultants who specialise in this area can provide a useful insight into what you should be doing and can carry out the evaluation and validation tasks as well as ongoing maintenance of the system and database.

Pharmacovigilance audit, development and implementation of corrective action

Pharmacovigilance auditing should be carried out on a regular basis to ensure that the pharmacovigilance operation is fit for purpose. Where there are problems it will be necessary to develop and implement a corrective action plan. In the US this is known as CAPA – Corrective Action and Preventative Action.

CCSIs, DCSIs and labelling

Different regulatory authorities have different requirements for labelling and the work of evaluating labelling along with regional variations plus the preparation of Company Core Safety Information and Development Core Safety Information can be outsourced.

Responses to safety enquiries from regulatory authorities.

Two things:

1 when the regulator has questions you’d better have answers and

2 if the regulator has questions you’ve already missed something. Prevention is better than cure and while it is of course possible to outsource the responses to enquiries from regulatory authorities, it is better to have already pre-empted and dealt with any potential issues by bringing the right consultants in earlier.

Product Registration dossiers

When a license application is submitted for a medicinal product a product registration dossier or brochure will be submitted as part of this application. Experienced pharmacovigilance specialists can assist in ensuring that the dossier is compliant and also that it matches up to the standards of dossiers that they have seen previously.

Crisis management

Of course prevention is better than cure but sometimes a crisis will come out of left-field and there’s nothing you can do to avert it. In these cases a steady hand a wise head can be invaluable. It may be the end of the world to you but to an experienced pharmacovogilance expert may well have seen this sort of event several times before. Their knowledge and expertise may make the difference, helping bring successful resolutions to awkward problems.

Medicolegal support and defence against litigation.

You may need a pharmacovigilance specialist to help argue your side in court. They may be able to help build a defence and even to enable your company to deal properly with legal issues.

Helping to evaluate your options when it comes to pharmacoepidemiology studies

Since the MEDdra-fication of pharmacovigilance, it has become increasingly possible and indeed useful to carry out pharmacoepidemiology studies. But as with the rubbish-in rubbish-out model, just because you are using pharmacoepidemiology studies doesn’t mean they will be worthwhile. A pharmacovigilance expert will help to enable you to carry out meaningful pharmacoepidemiology investigations.

Assessment of published reports

Do they affect your product? Should they? Does your product interfere with another product in a way that needs to be reported? All of these questions come to mind with published reports ans it helps having an expert on hand to keep you informed of the true nature of any potentially challenging reports.

However if a client wished to outsource the majority of their pharmacovigilance activities – both the routine work and the one-off activities – contracting in would not be appropriate. Instead such a client would use a contract organisation or, in this case, a “PV service provider”. Some of these service providers will be the big CROs (Contract Research Organisations) – Parexel, Quintiles for example – whose main specialism is clinical research but who also do pharmacovigilance as well. Others will be the specialist pharmacovigilance service providers like PrimeVigilance Ltd, PharSafer, Vigilex who are equipped to run all the pharmacovigilance activities but do not engage in clinical trials. When

At the other extreme of the spectrum, the client may wish to outsource most of the pharmacovigilance activities, routine and non-routine, to a contract organisation (a “PV service provider”). These companies may be very large Contract Research Organisations (CROs) such as Quintiles or Parexel, that concentrate on clinical research, but carry out pharmacovigilance activities as well. There are also specialist PV service providers, such as PrimeVigilance Ltd, PharSafer and Vigilex, that carry out all pharmacovigilance activities but do not perform clinical trials.

In other cases the requirements are more finely grained. A client might need a more limited range of the routine work to be covered – activities such as the processing of individual cases, expediting reports to the regulatory authorities in accordance with their expedited reporting timescales and preparing PSURs – but may prefer other elements to remain either in-house or subject to their current practices. In such cases the cost of using one of the larger CROs might be prohibitive although they would certainly have the capacity to do the work. In cases such as this a dedicated pharmacovigilance provider might be able to deliver an approach that returns competitive cost-effectiveness without jeopardising quality. There are also several companies with bases in India that offer to perform some of this basic work. Such solutions may seem very competitive and costs may be far lower than any of their competition. However when something seems to be too good to be true, it may well be because it is. Firstly there may be concerns about how easy it would be to keep effective control of quality and of events from such great distances. Secondly there is the issue of knowledge and training – the pharmacovigilance requirements in India, such as they exist, are far removed from those in the West; India is still a developing nation and governments have higher priorities. Consequently in practice they tend not to legislate for any more than rudimentary medicine safety. Doctors trained in such an environment going in to a pharmacovigilance outsourcer might struggle to come to terms with the exacting nature of the regulatory environment in the West.

One problem with smaller, dedicated pharmacovigilance consultancies is that they won’t have the facilities to provide safety databases and expedited reporting but there are a few who can offer it, mainly through arrangements with third parties who will perform these functions on the consultant’s behalf. Amongst these consultancies the depth and range of expertise will vary widely. Some consultancies, for example the UK-based Elliot Brown Consulting, will have medically trained staff and will involve a global network of pharmacovigilance associates including former senior regulators and industry specialists. Pietrek Associates operate in a similar way. Companies such as these can often provide high end consulting, helping to deal with serious safety issues that can affect pharmaceutical products, in addition to the more run-of-the-mill pharmacovigilance activities which would include writing and review of PSURs and auditing. With such companies the costs of these consultants can seem high but it must be borne in mind that they can often turn work around faster. More experienced contractors may be able to complete a project faster than their less experienced counterparts thanks to their greater experience and knowledge.

In the end it must be remembered that the responsibility for product safety lies with the pharmaceutical company. It doesn’t matter whether you use a pharmacovigilance service provider or bring in contractors or consultants. The company that holdes the marketing authorisation (EU) – or manufacturer (US) is free to delegate some or even most of its pharmacovigilance responsibilities but overall control and responsibility lies with the pharmaceutical company itself. Therefore, all outsourcing of pharmacovigilance must have clear and proper accountability with transparent organisational strucutre and a decision making process for the client company that is robust. There also needs to be contract documentation that is both comprehensive and detailed in terms of dictating which party is to carry out which of the many pharmacovigilance activities. This is the only way that patients’ interests can be protected and that all of the company’s legal obligations may be met. satisfied and the patients’ interests protected.