Pharma jobs: Frequently asked questions for Good Pharmacovigilance Practice "D"

This section provides answers to frequently asked questions relating to Good Pharmacovigilance Practice.

For specific questions and answers on the new pharmacovigilance legislation please refer to the following links:

European Medicines Agency Q&As (external link)
MHRA Q&As
For questions or comments specifically regarding MHRA’s implementation of the new legislation, email pharmacovigilance@mhra.gsi.gov.uk. Please note, however, that not all enquiries will be answered directly and may instead be used to develop further questions and answers on this webpage.
The EMA also has an email address for enquiries regarding the new legislation: p-pv-helpdesk@ema.europa.eu

Further guidance

Are marketing authorisation holders (MAHs) expected the monitor these Q&A sites on a regular/ongoing basis?
Will the MHRA be inspecting MAHs against GPvP comments/guidance/advisory notes posted on these web sites?

With regards to the frequently asked questions section on the MHRA GPvP web pages, these contain previous questions discussed at symposia, Pharmacovigilance Consultative Committee meetings and others received by the Pharmacovigilance Inspectorate. These FAQs have been compiled to provide all MAHs the opportunity to review previous questions the Pharmacovigilance Inspectorate has received.
They aim to provide information on the expectation of the MHRA and additional clarification on existing legislative requirements and associated guidelines and do not include additional requirements that the MAH must comply with. They aim to educate the MAH on the current thinking on a specific topic and expectations on how existing requirements can be fulfilled.
The FAQs are reviewed and updated periodically and we encourage MAHs to regularly review them. We have now implemented an email alert service to notify subscribers when the GPvP webpages are updated. Users can subscribe to the email alerting service via the stay connected section of the website
The MHRA is not the author of the European Medicines Agency post-authorisation guidance included on their website and therefore cannot specifically comment on this. However, on review of these Q&As (in relation to pharmacovigilance) the objective seems similar to the MHRA web pages in which these provide clarification on existing legislative requirements and associated guidelines and do not introduce any new requirements that would be subject to inspection. The expectation is that the advice contained in the European Medicines Agency Q&As should be followed, unless the MAH can provide good justification for deviating from this advice.

2. Where can I find more guidance about pharmacovigilance, the inspection process and findings? How does the MHRA determine when to inspect an MAH?
In November 2008, the MHRA published the “Good Pharmacovigilance Practice Guide” which provides practical guidance to individuals and organisations involved in pharmacovigilance. The guide is intended to complement currently available EU legislation and guidance.

It is available from the Pharmaceutical Press (external link)

3. How does the MHRA determine when to inspect a marketing authorisation holder? - Updated April 2010
From April 2009, the GPvP Inspectorate has implemented a formal risk-based inspection process. Full details regarding the process are provided in the Good Pharmacovigilance Practice risk-based inspections section of our website.

4. How often will an MHRA pharmacovigilance inspection be performed on an MAH? - Updated July 2012
This is determined by the information provided on the risk-based inspection compliance report and the findings from the previous inspection. If the inspection results in a critical finding it is likely the MAH will be re-inspected within 12 months, with a particular focus on corrective actions agreed following the last inspection. If no critical findings are identified there is no specific timeline by which an MAH must be inspected again. However, an inspection may be performed at any time if a specific trigger is identified.

5. What are the size of inspection teams and duration of inspections to small/medium sized companies? How does the MHRA decide the number of inspectors that are sent out to a site and is this number of any significance? - Updated April 2010
The size of the inspection team varies depending on the type of products marketed by the company, the complexity of the pharmacovigilance system and type of inspection (eg routine systems, triggered, national or requested by the Committee for Medicinal Products for Human Use (CHMP)). Information from the risk-based inspections compliance report is used to determine an approximate amount of time required to perform the inspection.

However, if the organisation of the pharmacovigilance system is complex or if serious issues are identified, more time may be spent on site and additional site visits may be performed. A routine systems inspection may involve between one and four inspectors for between one and five days. Occasionally observers eg from the MHRA Pharmacovigilance and Enforcement Groups or other Competent Authority Inspectorates may also participate in an inspection.

6. Are there any plans to publish the trends identified from pharmacovigilance inspections in the future? If so, will these be available on the net? - Updated April 2010
Anonymised findings from MHRA pharmacovigilance inspections are presented at MHRA symposia and conferences at which inspectors present. Inspection metrics summarising data from 2006 can be found in the pharmacovigilance inspections metrics section of the website.

7. Where a company has several MAHs with separate company numbers, but no pharmacovigilance activities are conducted in the UK, but in the EU, would they be subject to a pharmacovigilance inspection by the MHRA? Updated July 2012
Any MAH with a UK marketing authorisation is subject to pharmacovigilance inspection by the MHRA. If pharmacovigilance activities are performed within the EU but outside the UK, the MHRA may ask company personnel from other EU sites to participate in an inspection at a UK site and/or may request inspectorates in other Member States to perform an inspection at site(s) in their country or to share results from recent inspections. If the MAH does not have a UK site, then a ‘virtual’ inspection may be performed. This may involve the MAH hiring temporary office space in the UK, or alternatively, the inspection being performed via teleconferences.

If a group of associated MAHs share the same pharmacovigilance system, the inspectors would examine the agreements between the companies to determine whether the agreements clearly describe the responsibilities for pharmacovigilance activities.

8. If the MHRA has performed a pharmacovigilance inspection, is it likely that another EEA competent authority will wish to also perform an inspection? Updated July 2012
In relation to inspections performed at UK sites by the MHRA, mutual recognition exists with other EEA Member States. EEA Competent Authorities can request copies of inspection reports for inspections performed by the MHRA. Other EEA Competent Authorities would contact the MHRA, if they wish a site to be inspected in the UK by the MHRA.

However, the performance of a pharmacovigilance systems inspection by the MHRA at a site in the UK does not preclude other EEA member states from performing pharmacovigilance inspections at sites in their own country or in third countries (in order to fulfill national statutory obligations). For CHMP requested inspections the competent authority of the Member State in whose territory the MAH has located the pharmacovigilance system master file (PSMF) will perform the inspection.
The new pharmacovigilance legislation strengthens the requirement for sharing of information on inspections between Members States and The Agency:

Article 111 of Directive 2010/84/EC states that “The competent authority of the Member State concerned shall, in cooperation with the Agency, ensure that the legal requirements governing medicinal products are complied with, by means of inspections, if necessary unannounced, and, where appropriate, by asking an Official Medicines Control Laboratory or a laboratory designated for that purpose to carry out tests on samples. This cooperation shall consist in sharing information with the Agency on both inspections that are planned and that have been conducted. Member States and the Agency shall cooperate in the coordination of inspections in third countries.”
GVP Module III (Pharmacovigilance Inspections) provides additional detail on the role of The Agency in co-ordinating inspections of MAHs with centrally authorised products.

9. Would senior executives be interviewed during an inspection?
Inspectors normally interview operational personnel that are involved in pharmacovigilance activities or activities associated with safety reporting. All MAH staff should be aware of their obligations with respect to safety reporting and should receive appropriate training.

If considered necessary eg if serious issues are identified relating to a business area that a senior executive is responsible for, it might be necessary to interview a senior executive and senior executive(s) might be requested to attend the closing meeting.

10. Will a contract research organisation (CRO)/PV Service Provider be inspected on its own or only as part of an inspection of a marketing authorisation holder (MAH)? - Updated July 2012
Article 111 of Directive 2010/84/EU includes the provision for the MHRA to “inspect the premises, records, documents and pharmacovigilance system master file of the marketing authorisation holder or any firms employed by the marketing authorisation holder to perform the activities described in Title IX”.

At the current time pharmacovigilance service providers are inspected as part of an MAH inspection. The MHRA is in the process of developing a programme of standalone pharmacovigilance inspections of service providers. These inspections would be independent of any MAH for whom the service provider worked, providing assurance to both the MHRA and MAHs that the service provider was operating in compliance with the applicable legislation.
Inspection of service providers (independent of MAH inspections) is in line with the MHRA philosophy of reducing regulatory burden. At this current time one service provider who provides a service to several MAHs will be inspected on multiple occasions. This creates duplication of effort and is not the best use of resource.

11. A critical finding from a pharmacovigilance inspection relates to ‘overall system failure’. What does this mean and can you provide specific examples?
An overall system failure can sometimes mean that there is no pharmacovigilance system in place, but more commonly it relates to multiple serious deficiencies leading to an inadequate pharmacovigilance system. Two examples of what would constitute overall system failure are provided below.

Example 1:
Company X has no global pharmacovigilance system due to inadequate safety data exchange with affiliates/subsidiaries for products with different invented names but containing the same active substance. There are no timescales or formal arrangements for transfer of individual case safety reports (ICSRs) or other safety information. This results in either lack of or late expedited reporting of ICSRs and periodic safety update reports (PSURs) containing incomplete safety data. There is also no quality assurance auditing of the affiliate companies.
Example 2:
Company Y does not have a back-up for processing ADRs if the safety officer is absent and there is a lack of follow-up on ADRs and pregnancy cases. There is no formal process for the transfer of adverse drug reactions from medical information to the pharmacovigilance department. There is no reconciliation between these departments and others (eg product complaints department). Key personnel have not been adequately trained in pharmacovigilance. The company does not perform any signal generation/trend analysis of cumulative safety data. In addition, Summary of Product Characteristics are not being updated in a timely manner. There is no policy for retention of source documents.

12. Do changes in pharmacovigilance legislation have an impact on the conduct of MHRA pharmacovigilance inspections? Updated July 2012
The general inspection process does not change when pharmacovigilance legislation is updated. However, the questions we ask and the documents we request during inspections are modified to ensure that we can assess if the company is compliant with new requirements. We may also ask the company questions to determine if they have understood the impact of new legislation and may request legislation implementation plans.

13. What kind of recommendations has the Inspection Action Group (IAG) made to date? Do they intend to take actions for non-compliance? If so, what? Have they taken any enforcement action since they started conducting GPvP inspections? Updated July 2012
The Pharmacovigilance IAG is a non-statutory, multi-disciplinary group constituted to advise the Director, IES Division and/or the Director, VRMM Division and/or the Director, Licensing Division on any recommendations or enforcement action appropriate to the Division(s). The group meets regularly, usually monthly, to deal with ongoing business and to consider new referrals. Criteria to be met for making referrals to the IAG in relation to pharmacovigilance inspections include, but are not limited to:

conditions that are likely to cause or lead to a significant risk to public health
an inspection identifies one or more unresolved critical deficiencies.

IAG recommendations to date have consisted of:

early re-inspection: this has been the most common recommendation to date - in most cases on re-inspection, adequate progress has been observed; in some cases, a further re-inspection has been required and a minority of cases have been referred back to IAG for consideration of other actions,
sharing of information with other competent authorities and the European Medicines Agency; this has previously led to a CHMP-requested EU inspection,
amendments to the safety information contained on MAH websites,
sending a warning or compliance commitment letter,
meetings with MAH senior representatives to discuss the issues and consequences of continued non-compliance,
additional questions raised during the processing of marketing authorisation applications, where the applicant is found to have a seriously non-compliant pharmacovigilance system,
recalls and temporary suspensions of release of an authorised product e.g. when the product information was found not to contain up-to-date safety warnings,
referral to the MHRA Enforcement group for criminal investigation.

Actions for the future may include:

referrals under the EU Infringement Regulation (fines) in relation to centrally authorised products,
application of conditions to marketing authorisations in accordance with Articles 21a and 22a of Directive 2010/84/EC,
rejection of new marketing authorisation applications where the applicant is found to have a seriously non-compliant pharmacovigilance system,
suspension of marketing authorisations where considered appropriate,
serving of Infringement Notices in cases of serious and persistent non-compliance (new guidance on this option is in development).

For GCP and clinical trials some additional actions have been taken for non-compliance eg suspension of CTA and of pending applications.
There have been no criminal prosecutions to date as a result of MHRA pharmacovigilance inspections.

14. What communication occurs between European Medicines Agency and National Competent Authorities regarding the timing of GPvP inspections? Do Competent Authorities communicate information regarding planned/completed inspections? – Updated July 2012
Communications on national programmes has become more formal, particularly from 2008 onwards. On a quarterly basis, Member States provide to the European Medicines Agency (EMA) updated details of planned and conducted national inspections. This information is circulated to all Member States.

EMA also maintains a spreadsheet containing details of routine and triggered pharmacovigilance inspections (requested by CHMP) of MAHs with centrally authorised products.
Critical and substantial major findings from inspections conducted as part of the EMA’s four-year plan of routine pharmacovigilance inspections of MAHs with centrally authorised products are routinely shared with the EMA and other EU competent authorities. This is described in the following publication:
Procedure for the Preparation of a Risk-Based Programme for Routine Pharmacovigilance Inspections of MAHs Connected with Human Centrally Authorised Products (CAPs) (external link)
The new EU pharmacovigilance legislation states:
“If the outcome of the inspection referred to in paragraph 1(d) is that the marketing authorisation holder does not comply with the pharmacovigilance system as described in the pharmacovigilance system master file and with Title IX, the competent authority of the Member State concerned shall bring the deficiencies to the attention of the marketing authorisation holder and give him the opportunity to submit comments. In such case the Member State concerned shall inform the other Member States, the Agency and the Commission”.
New mechanisms for the sharing of inspection findings with other Member States, EMA and the Commission are to be developed following the implementation of the new legislation.

15. Are there similar communications with the FDA regarding planned/completed inspections, as with the European Medicines Agency and individual Member States? - Added February 2008
An agreement is in place between the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) which provides high-level details on regular exchange of listings of Pharmacovigilance inspection information (including performed and planned inspections). The FDA normally provides at least two weeks notice of pharmacovigilance inspections which they intend to conduct at sites in the UK.

At the current time, there is no formal coordination of inspections between the MHRA and the FDA. Mechanisms are in place for discussion of topics of mutual interest. It should be noted that there tends to be a difference in focus between US and EU pharmacovigilance inspections (partly as a result of the differences in legislative frameworks). Further information on this agreement can be accessed from the Inspections section of the European Medicines Agency website.

16. What mechanisms are in place for MAHs to provide feedback after an inspection? - Updated July 2012
The Pharmacovigilance Inspectorate welcomes ongoing feedback on the conduct of inspections, which can either be sent directly to inspectors, to one of the Operations Managers or to our mailbox gpvpinspectors@mhra.gsi.gov.uk. In addition, the Inspectorate has a programme of sending out questionnaires to all organisations inspected within a defined time period, which are then returned to the Quality and Standards Manager for analysis. Questionnaires are sent relating to each GxP on a rotational basis.

Qualified Person responsible for pharmacovigilance (QPPV)

17. When you say the QPPV should be permanently available, what exactly do you mean? Can you explain - eg 24/7, dedicated mobile? Updated July 2012
The QPPV should be the main point of contact for pharmacovigilance issues, for EEA competent authorities. The QPPV (or their backup) must be permanently and continuously available. To meet this requirement, there must be an adequate procedure for out-of-working hours contact (provision of a mobile phone number and testing of the contact system may be sufficient for this purpose).

The procedure should enable the QPPV (or their back-up) to contact other personnel who may be required to assist with obtaining information to respond to urgent safety queries eg product medical experts and personnel who can search the company's pharmacovigilance database.
A suitably experienced back-up should be designated to cover for the QPPV when they are absent or otherwise unavailable. The name and contact details of the QPPV and any changes to these details must be notified to the EEA competent authorities and to the European Medicines Agency.
The MAH should ensure that the name and contact details of the QPPV are entered into the eXtended EudraVigilance Medicinal Product Dictionary (XEVMPD). See Electronic submission of information on medicines (external link)

18. Is it expected that compliance metrics for expedited reporting are maintained in countries that are not part of the EEA (eg USA)? - Added February 2008
The MHRA is interested in expedited reporting to EU/EEA Competent Authorities. It is expected that the QPPV will receive compliance metrics from non-EEA offices, in relation to the compliance of affiliates/partners when sending cases to the case processing centres, in order to ensure that cases will be reported on time within the EEA.

While the MHRA has no remit to ensure that reporting to the FDA is performed in compliance with US requirements, there may be circumstances where this activity is reviewed on inspection, eg to ascertain if the processes for ensuring compliance in the EEA are different from those employed in the US.

19. Is it acceptable for a QPPV to reside in the Isle of Man or the Channel Islands? - Updated July 2012
As noted in GVP Module I section I.C.1.3, the QPPV must reside and operate in the EU. Residents of the Isle of Man and the Channel Islands are not considered to be resident within the Community and therefore, it is not acceptable for a QPPV to reside or operate in these locations.

Pharmacovigilance database

20. Does the MHRA expect the same level of validation for medical information databases? Updated July 2012
As with all databases used to support pharmacovigilance activities, the company is expected to have taken steps to ensure that the database is fit for the intended purpose and document the steps that have been taken to achieve this. The level of validation expected for medical information databases will depend on, for example, whether source information relating to suspected adverse drug reaction reports is captured directly in the medical information database.

21. When a validated ADR reporting database is on the company server in the USA, what additional validation (if any) is required to be done in the UK, when used by the UK company for the reporting of ADRs in the EU?
The level and type of user-testing/validation to be done in the UK depends on the type of application, how it is used and whether the application is installed locally or solely resides on a company server in the USA. Therefore, it is not possible to provide a general response to this question.

Standard guidance documents for validation of computerised systems, eg PIC/S, GAMP, ACDM/PSI, should be referred to when assessing the level of validation/user-testing to perform. Inspectors will examine the appropriateness of the testing that has been performed to ensure that the system works as intended and in a consistent way.
The inspectors may ask to examine validation documentation from validation activities performed outside the UK.

22. For a company with a low volume of ADR reports - is it acceptable to have a paper-based system for logging and reporting ADRs? - Updated July 2012
The MAH is required to take appropriate measures in order to collect and collate all reports of suspected ADRs. Whatever system for pharmacovigilance is implemented by the MAH, it must be sufficient to allow compliance with applicable regulations and guidelines.

Although the regulations do not state that a database is required, in practice, use of a database is one of the best mechanisms to ensure that information is collected and collated in order to be accessible at least at one point in the EEA. A database may also facilitate trend analysis and electronic reporting. However, the computer application used does not have to be complex and, in some circumstances, an electronic spreadsheet (with appropriate security and quality controls) may be sufficient.
A paper-based system for logging and reporting ADRs would be acceptable if the MAH is able to demonstrate compliance with the applicable legislation and guidelines. Although a spreadsheet is acceptable for the collection, collation and analysis of ADRs the MAH should ensure that they have the capability to report cases to Eudravigilance in electronic format.
Additional guidance on this topic is provided in Chapter 2 of the Good Pharmacovigilance Practice Guide.

Record retention

23. Is there a time limit for keeping records ('over a long period' was mentioned at the symposium)? How long do we have to archive for? Updated July 2012
GVP Module I section I.C.2.4 states how long pharmacovigilance documentation should be retained.

In applying the requirements set out in I.B.9.1. in the EU, the marketing authorisation holder shall put in place the following additional specific quality system processes for ensuring:

the retention of minimum elements of the pharmacovigilance system master file (PSMF) (see IR Art 2 and Module II) as long as the system described in the PSMF exists and for at least further 5 years after it has been formally terminated by the marketing authorisation holder [IR Art 12(2)];
the retention of pharmacovigilance data and documents relating to individual authorised medicinal products as long as the marketing authorisation exists and for at least further 10 years after the marketing authorisation has ceased to exist [IR Art 12(2)].

Destruction of records should still be based on a risk assessment and the above are minimum retention periods. There may be specific circumstances where competent authorities request MAHs to retain pharmacovigilance data and documents for longer time periods.

24. For archiving purposes does hard copy source documentation need to be kept or will scanned versions of source documents be acceptable? - Updated July 2012
If paper copy records are being transferred to electronic media sufficient evidence should exist that the process retains all the information present in the original in a legible manner and that the media used for storage will remain readable over time. GVP Module I section I.C.2.4 contains further detail on the retention of documents in electronic format.

Spontaneous case processing and literature cases

26. For ADRs received from partner companies what should be defined as day zero for regulatory reporting purposes?
GVP Module VI Section VI.B.7 states “The clock for the reporting of a valid ICSR starts as soon as the information containing the minimum reporting criteria has been brought to the attention of the national or regional pharmacovigilance centre of a competent authority or of any personnel of the marketing authorisation holder, including medical representatives and contractors. This date should be considered as day zero.”

Day zero is therefore defined as when the partner company receives the ADR and not the MAH.

27. Regarding section VI.A.2.3 of GVP Module VI: “Medical documentations (e.g. laboratory or other test data) provided by a consumer that support the occurrence of the suspected adverse reaction, or which indicate that an identifiable healthcare professional suspects a reasonable possibility of causal relationship between a medicinal product and the reported adverse event, are sufficient to consider the spontaneous report as confirmed by a healthcare professional.”
What is and what is not acceptable as ‘medical documentation’ eg what about ECGs, x-rays, CAT scan results, photos of rashes taken by a patient etc?
In general terms, the confirmatory document(s) provided should appear to come from a medical source and should include clear confirmation that an adverse reaction has occurred (rather than providing information that requires a separate assessment, eg an ECG tracing without an associated written confirmation of the abnormality). The document should provide confirmation that the adverse reaction occurred in relation to the concerned patient.

The MAH has to judge whether sufficient information is available to make the case valid for reporting at that time (a conservative approach should be adopted, ie if the documents appear to provide health care professional confirmation, this should be accepted, but appropriate follow up should be performed).
However, MAHs should note that certain serious consumer reports should be reported to the MHRA (in addition to HCP reports) as detailed in the ADR reporting section of the MHRA Q&As.
If the patient has taken the trouble to provide confirmatory documentation, it is probable that the patient will provide permission for the case to be followed up with the relevant health care professional. Therefore, we would expect to see that the company has made appropriate attempts to follow up the case.
Patients can also submit adverse reaction reports directly to the MHRA, even without confirmation from a health care professional via the Yellow Card scheme

28. Is medical review of a recognised ADR for an old, established product with a well-established safety profile really necessary in non-serious cases?
The MAH should decide, based on risk assessment, what type of medical review of non-serious ADR reports is appropriate. A number of factors will be involved in the decision-making process, eg the type of product, the safety profile of the product, the expectedness of the reaction etc.

Inspectors will examine the management of these cases during inspection. Even if pharmacovigilance physicians do not review expected non-serious cases on an individual basis, physicians should be involved in the company's trend analysis processes, which should include review of non-serious data.

29. If the MAH receives a serious adverse drug reaction report from a Competent Authority within the EEA, should this be expedited to the MHRA? - Updated July 2012
For medicinal products authorised through the mutual recognition or decentralised procedures the MAH is responsible for ensuring that all serious adverse reactions received from Competent Authorities within the EU are reported to the MHRA when the UK is the Reference Member State.

In addition, if the product is under intensive surveillance in the UK (denoted by a black triangle), these should also be expedited to the MHRA (regardless of the procedure under which the product is authorised), if it meets the definition of a spontaneous report or a report from a non-interventional study.
For current MHRA requirements see: ADR reporting and signal management

Miscellaneous

30. For Investigator Initiated Studies, what would be expected in relation to the transfer of safety information between the MAH/company and the investigator? - added September 2008
This would depend on any arrangement between the MAH/company and the investigator. If the MAH/company is providing product or any other assistance to the investigator, it would be expected that there would be written provisions in place outlining clearly defined requirements for the exchange of safety-related information to the MAH/company.

It should cover the immediate exchange of significant new safety concerns as a minimum. Additional detail contained within a formal agreement will depend on the specific arrangements relating to the study and the type of product. It is not possible to provide a response that covers all situations, as each case should be assessed individually.
The MAH/company should perform a risk assessment based on the type of trial and type of product, to determine what type of information should be exchanged and within what timeframes. This risk assessment should be documented. Where appropriate, exchange should be a two-way process eg if the MAH/company becomes aware of significant new safety concerns relating to their product, which may be relevant to the trial being conducted by the investigator, the MAH/company should promptly communicate this to the investigator.
For clarity, the agreement should identify the responsibility for expedited reporting of SUSARs (which is the ultimate responsibility of the sponsor of the study).

31. Is there a set number of inspections or a set period of time required for a new MHRA pharmacovigilance inspector to be considered competent? Updated July 2012
When a new inspector joins the MHRA they undergo a training and accreditation process, during which they have to demonstrate they have the requisite skills and knowledge to perform inspections in accordance with MHRA procedures and in compliance with applicable legislation.

The aim is for new inspectors to gain accreditation within six to 12 months, but it is very much dependent on the individual’s background. Training plans are tailored to each inspector, and there is no set number of inspections required.
Feedback is provided to the trainee and mentor at the end of each inspection by the most senior inspector present. Accreditation involves a recommendation by the mentor and operations manager, compilation of a detailed package of information and assessment of the trainee by an expert or designated senior pharmacovigilance inspector.

32. Translation of documents: are certified translations required?
Translation of documents into English must be performed/overseen by an individual with an appropriate background and with adequate knowledge of both languages. The appropriateness of the individuals/procedures used for translation may be assessed during inspection. EU legislation does not require ‘certified’ translations (although companies may choose to obtain certificates to provide evidence of the process that was used).

33. Will the MHRA require a type II variation for changes to the Detailed Description of Pharmacovigilance System (DDPS) eg change of QPPV? What is the MHRA position on type II variations for the DDPS? For example, if the QPPV changes, is a type II variation required or is it sufficient to inform the European Medicines Agency? - Updated July 2012
Until the MAH has produced a pharmacovigilance system master file and submitted variation(s) to replace the DDPS with the pharmacovigilance system summary for all relevant authorisations, the requirement to maintain a DDPS and submit appropriate variations to update the DDPS remain.

Guidance regarding this topic can be found in the classification guideline on variations from the EMA website (external link).
The MHRA has also produced guidance on variations: Variations to licences

34. What is the MHRA’s expectation of companies in relation to assessment of business partner/licensing partner quality management systems (QMS) that support PV activities? In light of consultation MLX 345, can the MHRA provide any guidance on the assessment of risk associated with business partners? If issues are identified what do they expect companies to do to ensure issues are addressed when contracts are not typically signed by QA departments? If serious issues are raised do they expect feedback from the company auditing the business partner? - Updated July 2012
The MAH may subcontract pharmacovigilance activities to a third party, but responsibility for the fulfilment of pharmacovigilance responsibilities in compliance with the legislation ultimately lies with the MAH. Audits are a mechanism by which the MAH can gain assurance that a third party is performing subcontracted activities appropriately. However, as indicated by EU GVP Module I section I.C.1.5, audits are not the only method that could be used.

For example, the MAH could:

Review procedures for, and timeliness of exchange of ICSRs, (how many are transmitted within specified timeframes?) as well as quality of service/information provided.
Check whether all cases have been transmitted as required (ie these may be identified during data reconciliation).
Hold regular meetings with partner companies to discuss general processes and SDEA commitments.
Perform individual risk assessments of each partner company using information gathered from 1) to 3) as well as perhaps using a regular compliance questionnaire, with questions on a range of topics including the partner company’s own internal audit process and perhaps top-line audit/inspection results relevant to the SDEA in place. It would then be for the MAH to determine whether a formal audit is required.

An audit is not the definitive activity that can be used to assess a partner company’s compliance with a safety data exchange agreement.
If the MAH does decide to conduct audits, the type and frequency will depend on the activities being conducted by the business partner/licensing partner (and the risks associated with those activities). In general, there is an expectation that some review of how a business partner/licensing partner is able to meet or is meeting its commitments will be made, and audit may be an appropriate way to address this. It is the responsibility of the MAH to ensure that appropriate corrective actions are taken (not specifically the responsibility of the QA department).
The contract should be worded in such a way so as to facilitate audits and implement necessary corrective actions. All parties to the contract should commit to take action to address non-compliances, and audit reports should be shared with the parties, as appropriate. MLX 345 mentions business partners in relation to risk because the MHRA has observed that serious non-compliance is often found where there are complex and numerous business partner relationships.
It was also noted that it is the responsibility of the QPPV to ensure that contracts with business partners are appropriate with respect to pharmacovigilance activities.

35. What is the Inspectorate's expectation of timeframes for publication and distribution of updated SPCs and PILs?
One of the major risk communication tools used by companies to inform patients and prescribers about risks and benefits is product information, in particular, the patient information leaflet (PIL) and Summary of Product Characteristics (SPC). Timely risk communication is essential in order to protect patients and companies should adopt appropriate standards for the timely publication and distribution of new SPCs and PILs once they have been approved by a Competent Authority.
The MHRA GPvP Inspectorate has identified numerous examples of approved safety updates which have not been communicated to patients, prescribers and relevant marketing authorisation holder (MAH) personnel in appropriate timeframes. Therefore, in order to ensure consistency across MAHs, recommended timeframes for completing specific activities are described below. This list should not be taken as exhaustive.
Note: These timeframes are considered as maximum recommendations for “routine” safety updates. Immediate communication to concerned parties may be necessary in the event of Urgent Safety Restrictions (USRs) and MAHs should always follow the timeframes for risk communication set out by the Competent Authority. For centrally authorised products the timeframes for implementation of safety variations generally commences from the point that the CHMP opinion is received. However, there may be instances where the MAH will need to wait for the Commision Decision before implementing. For further details MAHs should refer to section 3.8 of the EMA post-authorisation procedural advice for users of the centralised procedure.

1.Communication to MAH personnel
A number of different departments within the company will need to be notified of updated product information for use within their area of responsibility. This may include staff within the medical information and pharmacovigilance departments, sales representatives, marketing staff and website coordinators. It is expected that each MAH will define relevant distribution channels within the company and that appropriate staff will be notified no later than 10 working days following approval of updated product information.
2. Company-sponsored websites
Any company sponsored websites which contain published copies of SPCs and PILs should be updated within 10 working days of approval of new product information. Companies should maintain a record of websites where product information has been published to ensure that all relevant websites can be updated in a timely manner.
3. External publication
MAH’s may choose to publish product information with a number of external sites (eg the electronic medicine’s compendium (eMC)) or to notify external organisations (eg the BNF, MIMS etc). Where applicable, the MAH should submit the update request to these organisations no later than 10 working days after approval of new SPCs and PILs. It is acknowledged that external providers will have their own timeframes for checking and publishing new product information, but it is expected that updated documents will have been submitted for the publication process within the specified timeframe.
4. Implementation of patient information leaflets in product packs
Once new packaging components have been approved by the MHRA these must be introduced into packed stock being certified for release to the market by the Qualified Person in accordance with Directive 2001/83/EC (as amended) within three to six months, unless MAHs have been advised of the need for earlier introduction of the new components for safety reasons. The Qualified Person should not certify a medicinal product for release to the market if the packaging components, at the time of certification, have not been updated within three to six months following approval.

See more here

Pages

Hot Jobs

Looking for Career in Pharmacovigilance/ Clinical Research. Enter details here.

Monday, 3 March 2014

Frequently asked questions for Good Pharmacovigilance Practice "D"

Further guidance

Qualified Person responsible for pharmacovigilance (QPPV)

Pharmacovigilance database

Record retention

Spontaneous case processing and literature cases

Miscellaneous

Further guidance

Qualified Person responsible for pharmacovigilance (QPPV)

Pharmacovigilance database

Record retention

Spontaneous case processing and literature cases

Miscellaneous

No comments:

Post a Comment

Subscribe to us

Pages

Hot Jobs

Looking for Career in Pharmacovigilance/ Clinical Research. Enter details here.

Monday, 3 March 2014

Frequently asked questions for Good Pharmacovigilance Practice "D"

Further guidance

Qualified Person responsible for pharmacovigilance (QPPV)

Pharmacovigilance database

Record retention

Spontaneous case processing and literature cases

Miscellaneous

Further guidance

Qualified Person responsible for pharmacovigilance (QPPV)

Pharmacovigilance database

Record retention

Spontaneous case processing and literature cases

Miscellaneous

No comments:

Post a Comment

Subscribe to us

100% Free.

No Spamming.

Unsubscribe anytime.