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. The 6-month period should be counted from the start of the national implementation phase, i.e. from the deadline of submission of the DHPC or its Hungarian translation to OGYÉI for approval as determined by the communication plan. 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:
· A Coordinator is appointed in the communication plan, as agreed by the PRAC or the Lead Member State
· 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.
Similarly to single-MAH DHPCs, the 6-month period should be counted from
the start of the national implementation phase, i.e. from the deadline of
submission of the DHPC or its Hungarian translation to OGYÉI for approval as
determined by the communication plan.
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 version that is
submitted for OGYÉI approval (it is not acceptable to include any codes following 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: farmakovigilancia@nngyk.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 farmakovigilancia@nngyk.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 farmakovigilancia@nngyk.gov.hu.
In case of dissemination via email,
OGYÉI (farmakovigilancia@nngyk.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 farmakovigilancia@nngyk.gov.hu.
