H-1051 Budapest, Zrínyi u. 3.

Tel.: (1) 8869-300, E-mail: ogyei@ogyei.gov.hu

Mail: 1372 P.O. Box: 450.

MAGYAR

Direct Healthcare Professional Communication (DHPC)

Direct Healthcare Professional Communications (DHPCs), which prompt about significant new drug safety information that influence the benefit-risk balance and/or the conditions of use of medicinal products require urgent dissemination. Marketing authorization holders (MAHs) are obliged to deliver this information without delay, in an efficient manner, directly to healthcare professionals.

Guidance to MAHs is provided below in a Question and Answer format about the national and international requirements of the preparation and dissemination of DHPCs.

1.       When is dissemination of a DHPC required?

DHPC is an important notification that draws attention to a newly identified drug safety concern well before the update of Product Information and provides recommendation on how to manage and minimise risks. Guideline on good pharmacovigilance practices (GVP) Module XV – Safety communication lists the circumstances when the dissemination of a DHPC is mandatory or needs to be considered.

Due to its importance, DHPCs should be reserved for the circumstances listed in the module. MAHs are requested to abstain from communication of commercial decisions via DPHCs. These scenarios may include market launch of a product or withdrawal of a marketing authorisation due to commercial reasons, or notification of a temporary drug shortage with no detrimental effects on patient care due to the availability of alternative therapies. Furthermore, DHPCs should not be used as a cover letter (e.g. accompanying the distribution of educational materials).

2.       How does the MAH become aware that a DHPC needs to be distributed for one of its medicines?

When the obligation to prepare and distribute a DHPC is established by the National Institute of Pharmacy and Nutrition (OGYÉI) an email notification is sent to the local (Hungarian) pharmacovigilance contact person of the concerned MAH; in absence of a local contact person the EU-QPPV is notified. Therefore, it is important that MAHs keep OGYÉI informed of their contact details and any changes thereof. (According to Decree 15/2012 (VIII. 22.) of the Ministry of Human Capacities, the appointment of a local pharmacovigilance contact is mandatory in Hungary whenever the EU-QPPV does not reside in the country. More information on how to notify the Authority on the details of contact persons is provided here).

In all other cases, it is the responsibility of the MAH to monitor relevant sources of information in order to identify proactively and in a timely manner any emerging DHPC requests concerning its medicinal products. OGYÉI monitors every regulatory procedure, which may lead to a DHPC request, but will only issue a notice if the MAH fails to submit the application on national implementation by the deadline.

Hereunder we provide some practical advice for MAHs on how to obtain information on an upcoming DHPC obligation in time.

The European Medicines Agency (EMA) and OGYÉI share the view that MAHs should exercise due diligence and proceed proactively in any issues potentially concerning their authorised medicines. To facilitate the flow of information, prior to the Pharmacovigilance Risk Assessment Committee (PRAC) meeting all concerned EU-QPPVs are notified of the signals to be discussed. In addition, the detailed agenda for the meeting is published on the EMA website prior to the PRAC meeting. In this document MAHs can check if there are safety issues planned to be discussed that concern any active substances contained in their authorized medicinal products. If the MAHs have not been actively involved in the procedure and/or have not been notified by the EMA, they can contact the EMA or OGYÉI whether a DHPC obligation have been imposed in the concerned procedure. Minutes of the meeting are usually inappropriate for monitoring DHPC requests as they are finalised and published only two months after the meeting, whereas DHPCs usually require urgent communication.

MAHs should note that DHPC requests may also arise from mutual recognition or decentralized procedures, independently of the PRAC.

Irrespective of the source of the DHPC obligation, if the decision on dissemination is referred to national competence, MAHs are obliged to contact OGYÉI to determine whether the DHPC is required or can be waived.

It may occur that the DHPC obligation is imposed on the originator, but the originator does not have a marketing authorization in Hungary. In such instances, MAHs of the active substance in Hungary are obliged to contact OGYÉI and request information on how to proceed.

3.       What to do if the concerned medicine is authorised but not marketed in Hungary?

If the medicine concerned by the DHPC is not marketed in Hungary, the Hungarian translation should still be prepared and submitted to the Institute for approval. The approved Hungarian translation is published on the Institute’s website. This new approach follows recent changes in the publication of DHPCs on the Institute’s website. Currently DHPCs appear assigned to medicinal products rather than exclusively as a single list. Thus, if DHPCs were not published for non-commercialised medicinal products this could suggest a false impression that the product is not associated with any safety concern.

Nevertheless, dissemination of the DHPC is required only if the concerned medicinal product is administered to at least one patient in Hungary. Pertinent information should be submitted to the Institute beforehand. In case no patient receives the medicinal product, the dissemination will be deferred to a date when the product becomes available. If the product is placed on the market within 6 months from the date of the DHPC obligation, the DHPC should be made available to healthcare professionals at the same time as the product is placed on the market. In such cases, the MAH should inform the Institute in advance. OGYÉI will pay special attention to check whether information provided by MAHs on market status are valid at the end of the 6-month period. If the medicinal product is not marketed in Hungary, but it is administered to patients, the dissemination of the DHPC and the determination of the target population are subject to a case-by-case evaluation.

The DHCP obligation also applies to parallel distributors, provided that the above mentioned requirements are met.

4.       What to do if several MAHs are involved simultaneously (so-called joint DHPC)?

If several MAHs are involved in the procedure (e.g. the subject of the DHPC is a drug interaction, or it refers to a group of drugs or numerous generic medicinal products contain the concerned active substance), it should be avoided that healthcare professionals receive several letters with different content from various MAHs. Multiple dissemination may cause confusion in the target population and thus, decrease the effectiveness of DHPCs. It is the explicit request of the Institute that in these cases MAHs liaise with each other and a single DHPC is distributed to healthcare professionals.

4.1 How can MAHs find out if other MAHs are affected by the same DHPC obligation?

Simultaneously with the DHPC request, MAHs can check the OGYÉI website (Drug Database, available only in Hungarian) whether there are any other products authorized in Hungary that meet the criteria of the DHPC request and thus, whether there are any other MAHs involved. In case of uncertainty, the position of the Institute may be requested.

4.2 Is it mandatory for MAHs to participate in the preparation and dissemination of joint DHPCs?

Contribution in a joint DHCP is not mandatory, but refusal of participation is contrary to the recommendations of OGYÉI and the EMA (see section 4). Nevertheless, if a MAH rejects to participate in the preparation and distribution of the joint DHPC, then this decision should be communicated to OGYÉI without any delay. Non-contribution to a joint DHPC does not waive the MAH from the obligation and the DHPC should be prepared and distributed to the target group individually.

4.3 Which MAH is responsible for coordinating DHPC-related tasks? (Proposed criteria for selecting a Coordinator)

The safety information communicated in a DHPC can sometimes affect several products and MAHs. In order to ensure that the joint DHPC is drafted efficiently and smoothly, it is recommended to designate one of the MAHs as Coordinator to align and manage DHPC-related tasks. The designation of the Coordinator should be based on the common agreement of the participating MAHs. OGYÉI should be notified in an email on the appointment of the Coordinator.

When selecting the Coordinator, the following aspects may be considered:

·         An appropriate volunteer assumes the role of the Coordinator

·         The MAH of the originator product will be the Coordinator

·         The MAH that is marketing products in Hungary or marketing the highest number of products in Hungary will be the            Coordinator

·         The MAH that has the highest number of products authorized in Hungary will be the Coordinator

·          The MAH with the highest market share will be the Coordinator

It is recommended that the Coordinator be appointed from among MAHs that commercialize their products in Hungary.

If, despite the above criteria, the MAHs cannot decide who should take the Coordinator role, they should immediately inform OGYÉI in writing. In this case, OGYÉI appoints a Coordinator.

4.4 What are the roles of the MAHs involved in the preparation and dissemination of the joint DHPC?

The role of a MAH involved in a joint DHPC depends on whether it is the Coordinator, and whether it is marketing its product(s) in Hungary.

The latter requires that, at the start of the procedure, all concerned MAHs declare whether they are marketing their product(s) in Hungary or intend to launch them on the market within the next 6 months. The relevant information need to be forwarded to the Coordinator, who should immediately inform OGYÉI. The validity of declarations about the marketing status will be extensively checked by OGYÉI at the end of the 6-month period.

4.4.1 Tasks of the Coordinator:

The Coordinator acts on behalf of all the MAHs involved in the joint DHPC as the single official contact point. It manages and coordinates all DHPC related activities (e.g. translation, preparation of the communication / implementation plan, distribution, etc.) and communicates with the Institute and the represented MAHs.

The joint DHPC is signed by the representative of the Coordinator on behalf of all concerned MAHs.

4.4.2 Tasks of the MAHs involved in the process, if they are marketing their product(s) in Hungary or planning a market launch within 6 months:

Upon the Coordinator’s request, these MAHs should participate in the preparation or translation of the DHPC, the translation check, the development of the communication plan, the distribution of the DHPC and the verification of the effectiveness of distribution.

If the MAH does not market the product but plans to introduce it within 6 months of the obligation being incurred, its tasks are the same as that of the MAHs already marketing their products.

4.4.3 Tasks of the MAHs involved in the procedure, if they NEITHER are marketing their product(s) NOR intend to launch them in Hungary within 6 months:

Upon the Coordinator’s request, these MAHs should participate in the preparation or translation of the DHPC and in the translation check, as the DHPC is uploaded on OGYÉI's website and attached to all concerned products independently from their marketing status.

However, these MAHs do not need to participate in the dissemination.

Please note that during an inspection, all participating MAHs should be able to demonstrate that they have fulfilled all their obligations.

4.5 How can participants of a joint DHPC get in contact with one another?

MAHs may use each other's public contact points for communication. In case of difficulty, the Coordinator may contact OGYÉI for assistance. There is no legal mandate for OGYÉI to publish a list of national contact points or EU-QPPVs.

Please note that there is no need to designate a pharmacovigilance contact at national level, if the products are not yet marketed in Hungary. Correspondence with MAHs of such products may be arranged via the EU-QPPV in English.

4.6 How should the concerned MAHs and their products be indicated in the DHPC?

Sometimes, there are numerous products and MAHs concerned by a joint DHPC rendering it difficult to provide such information in a clear and organised way. Furthermore, extensive lists may distract attention from the content of the letter. In order to prevent this, the relevant products, their MAHs and their contact details should be included in a separate annex. Please clearly distinguish the products based on their market status in Hungary (i.e. marketed, not marketed, or planned to be launched within 6 months).

4.7 What to do if there is disagreement among the participating MAHs?

OGYÉI does not undertake the settlement of internal disputes. In case of disagreement on the content of the letter or the communication plan, the position of OGYÉI may be requested.

5.       What aspects to consider regarding the content and format of DHPCs?

Regarding the preparation and wording of the DHPC, MAHs should follow the guidance provided in the Guideline on good pharmacovigilance practices (GVP) Module XV – Safety communication and the DHPC template included in its annex.

5.1 Graphical elements

OGYÉI does not recommend the placing of company/medicine logos in the DHPC, nor on the envelope (if any).

5.2 Inverted black triangle

If any of the drugs mentioned in the DHPC is under additional monitoring, the inverted black triangle should be displayed next to the name of the medicine and the letter should include the explanatory text. For more information, how to display the inverted black triangle, please click here.

5.3 Corporate document codes

Internal company document codes should only appear at the end of the letter, as footnote, in such a way that they do not distract attention from the content of the letter. The internal company code should already be included in the first version that is submitted for OGYÉI approval.

6.       Is it possible to deviate from the DHPC or communication plan agreed by the PRAC (e.g. in terms of the target group or deadlines)?

Deviations from centrally agreed DHPCs and communication plans, in terms of either target groups or deadlines, can only be allowed in justified cases.

It may be justified, for example, to bring the final DHPC or the communication plan in line with the characteristics of the Hungarian health care system.

Modifications of the format or style that do not affect the content but improve clarity are generally acceptable. In case of translation, the special features of the Hungarian language should be observed. Loan translation of the English language is not acceptable.

If the MAH deems that substantial deviation from the original DHPC or communication plan is required, it should submit the proposal for amendment together with a justification to OGYÉI for assessment and approval.

7.       How should DHPCs be submitted for approval and what documents need to be attached?

The proposed text, the target population, way and date of dissemination of the DHPC should be approved by the Institute in advance. To ensure quick and efficient processing of the request for approval, the communication package should be sent to the following email address: adr.box@ogyei.gov.hu. The communication package should include the followings:

·         draft DHPC (i.e. the text intended for dissemination) in Hungarian and in English in word format and if applicable, all annexed materials;

·         communication plan that contains

o   the timetable (e.g. deadline for comments, approval of translation and final letter, DHPC distribution and follow-up)

o   the proposal regarding the target group(s) of healthcare professionals and

o   the proposed channels of dissemination;

·         the preview of the envelope

·         other related documents, if applicable (e.g. press releases);

·         draft plan for the post-communication strategy and the intended method to assess the effectiveness of the DHPC, if applicable;

·         the contact details of the person submitting the DHPC;

·         information on whether the medicinal product is marketed in Hungary or it is administered to any patient; or a statement in case of joint DHPCs that the products are expected to be marketed in 6 months

Please always indicate in the application the regulatory procedure in which the DHPC request has been imposed.

The Institute approves the communication package within the deadline included in the communication plan and provides suggestions for modifications if considered necessary.

8.       What requirements apply to the dissemination of DHPCs?

DHPCs can be disseminated via various channels (e.g. via email, postal letter or packed together with professional journals for healthcare professionals). The MAH should consider the most efficient way to cover the entire target population; nonetheless, combination of various communication channels can also be applied. The MAH is required to demonstrate that the target groups have actually received the letters in every case. The Institute expects a proven rate of receipt of at least 75% in the total target population (if target groups are significantly different, then the minimum 75% dissemination effectiveness applies for each target group separately, if feasible). The data concerning the effectiveness of dissemination should be submitted to the Institute via adr.box@ogyei.gov.hu within 2 months after initiation of the dissemination. In case of a receipt rate lower than 75%, the causes thereof should be investigated by the MAH and in consultation with the Institute corrective actions may be required.

Furthermore, the Institute requests that the MAH indicates the sentence 'Important drug safety information' on the envelopes or in case of electronic delivery, in the subject of the email; thus, facilitating the easier differentiation of DHPCs from other correspondence, in order to ensure that more healthcare professionals read its content.

The name of the medicinal product and the active substance might appear on the envelope (considered on a case-by-case basis); however, the company logo may not be inscribed.

In case of delivery via email, the text of the DHPC should appear directly in the body of the email, and not as an attachment.

9.       Is the MAH required to notify the Institute that the dissemination of the DHPC has taken place?

The MAH is obliged to notify the Institute on the exact start date of dissemination prior to or simultaneously to the launch of the DHPC. Furthermore, the MAH should return a final, signed copy of the DHPC in pdf format to the Institute via an email sent to adr.box@ogyei.gov.hu. In case of dissemination via email, OGYÉI (adr.box@ogyei.gov.hu) should be included in carbon copy.

The Institute publishes the final, signed DHPC on its website on the first day of dissemination, at latest.

The Institute also publishes DHPCs that do not need to be disseminated, so the requirement of returning the final signed copy to OGYÉI is applicable to such letters as well.

10.   In general, how much time is given to the MAH to prepare, translate, and disseminate the DHPC?

Because DHPCs are used for urgent information sharing, the corresponding deadlines are generally short. There is no universal schedule for DHPCs, they are always tailored to the procedure, the nature and urgency of the drug safety issue, thus, communication plans are developed on a case-by-case basis.

GVP module XV refers to minimum time frames for each step, which are usually measured in days. In practice, it has occurred that from the date of the translation submission to the Authorities, the MAH had only a few days to finalize the DHPC and to begin or complete the dissemination. As these are not exceptional cases, MAHs should implement their DHPC management process so that is adequate for the management of short term, urgent cases. OGYÉI gives high priority to cases where compliance with deadlines was not observed by MAHs in the communication of urgent safety issues.

11.   Who is responsible for managing DHCPs within the MAH’s organisation?

It is up to the MAH to determine in its own processes who is responsible for managing DHPCs within the company, and whether or not the local pharmacovigilance contact is involved. However, performing this task without qualified pharmacovigilance specialists does not discharge the MAH of the responsibility to know and apply the current pharmacovigilance legislation when preparing DHPCs or producing any pharmacovigilance-related documents.

OGYÉI communicates with the appointed local pharmacovigilance contact or the EU-QPPV in any pharmacovigilance issues, including the management of DHPCs. It is the company's sole responsibility to promptly forward the information from the contact person to the professionals assigned to the task. The authority may check the adequacy of the communication process during an inspection.

12.   Where can queries be placed on DHPCs?

Any further questions regarding the preparation or management of DHPCs may be sent to adr.box@ogyei.gov.hu.

Last updated: 2019.10.04 10:34