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Drug Regulatory System in
Hungary
Hilda Kőszeginé Szalai Hilda PhD
Dep. Director-general
February 16. 2015
ABOUT HUNGARY
Location: Central Europe,
93.000 sqkm, no see
Population: 10 million
Capital: Budapest, 2 million
State: founded 896,
state form: republic
Religion: Christian (Roman
Catholic and Reformed)
Member of EU (2004),UN,NATO
13 Nobel prize winner
scientists
Pharmaceutical Industry in Hungary
123 manufacturing sites (spread all over Hungary)
27 finished product manufacturing companies
4 big companies (export 70%, domestic:30%)
9 medium size, wide range of products mainly
for domestic market
14 small companies (4 radiopharmaceutics,
3 herbal, 3 medical gases, 3 biologics,1
vitamins)
Some other data
• 2 GMP biotech manufacturing sites
• 27 API manufacturing sites
• 70 GLP testing sites
• 350-400 clinical trials/year
• 15 Accredited Phase I Clinical sites
• 4 medical universities:Pharmaceutical faculties
Budapest Technical University : chemist,
drug chemist and biotechnology engineers ,
4 universities of sciences: chemists, biologists
6113 6527
7451
8477 8857
8487 8297 8276
0
2000
4000
6000
8000
10000
2008
2009
2010
2011
2012
2013
2014
2015
Number of authorised allopathic medicinal products (strengths and dosage forms counted separately)
About the market of medicines
About the market of medicines
4
16 13
26 18
26 33
30
14
32 19
32
61
46
99
46
68 63
79
68
0
20
40
60
80
100
120
1995
1997
1999
2001
2003
2005
2007
2009
2011
2013
Number of centrally authorised products (strengths and dosage forms counted as one product)
Cca. 800 products
1871 1st edition of the Hungarian Pharmacopoeia
1927 Regulatory drug control by the Chemical
Section of National Institute of Public Health
(NIPH)
1933 Drug registration by NIPH
1962 National Institute of Pharmacy
a complex drug regulatory authority for
marketing authorization, supervision
of manufacturing, wholesale and retail trade
and market surveillance of the medicines.
Supervised by the Ministry of Health
Milestones of drug regulation in Hungary
Milestones of drug regulation in Hungary
1976 Signing the Pharmaceutical Inspection
Convention
1999 Signing the Convention on the Elaboration
of the European Pharmacopoeia
2005 New act on medicinal product
(harmonised with the new EU law)
2011, 2015 Re-organisation of NIP, integration
with other institutions
Legal framework for regulation of
the market of medicines
EU Commission/EMA/ ICH
Scientific and procedural
guidelines
Ph.Eur.Commission
monographs,
general chapters
EU Institutions
regulations, directives,
delegated acts, decisions
MSs:national acts, decrees
ECJ, national CJ
decisions
Regulatory activities in Hungary
Authorisation
- MA of medicines (incl.variations,renewals
- Batch specific authorisations
- Clinical trials
- Import of non-licenced medicines
- Off-label use of medicine
- Authorisation of the Manufacture of medicines
- Authorisation of Wholesaling
- Paralell import
Supervision
- Supply of medicines
- Quality of medicines
(market surveillance,
investigation of quality
defect reports, anti-
counterfeit )
-Pharmacovigilance
-Advertisement
-Manufacturers (GMP)
- Wholesalers (GDP)
- GLP inspections
- GCP inspections
Other
- Scientific advice
-Pharmaceutical methodology
-Pharmacopoeia authority
-National Formulary
Marketing Authorisation
Aims:
• increase of RMS-ships (new and RMS transfer)
• increase of assessments in centralized procedures
• 900 renevals
• 15 000 variations
26 36 6 17 51 34
308
169
114
40
0
100
200
300
400
500
600
2013 2014/I. félév
Nemzeti
CMS - DC
CMS - MR
RMS – MR
RMS – DC
Authorisation of alternative forms of supply
and use of medicines
Authorisation of the parallel import of medicines
(10-20/year)
Batch specific authorisations: cca 1200/year
Authorisation of the individual import of non-licenced medicines (cca.13.000/year), authorisation of the import and use of batches products without MA in case of shortage
(3-5/year)
Authorisation of the off-label use of medicines (cca. 3000/year)
Authorisation of other medicine related
activities
Authorisation of manufacturing and whole
sale activities (20/25 licence/year) total
sites of 123/168
Accreditation of Phase I clinical sites
Authorisation of Clinical Trials (cca.350-
400/year)
Authorisation of GMO plants and activities
Aims: To keep/increase the number of
clinical trials, especially BE studies
Supervision of the market of medicines
Pharmacovigilance activity (ADRs, PSURs: single assessment, DHPC letters, signal detection (43 substances), RMPs
981 1124
1641 1419
807
1614
1027 1136
833
1666
2010 2011 2012 2013 2014/I. félév2014/I. félév duplán
ADR notifications (new and follow up)
Supervision of the market of medicines
314 295
271 268
138
88
150 146
197
88
18 27 17 26 14
2010 2011 2012 2013 2014/I. félév
Recalls 4,5% 6,1% 4,1% 5,6 % 6,2%
Quality defect reports (local notification, RA, recall)
Supervision of the market of medicines
4 5 4 8 4 4 4 2
37 38 49 65
17
47
55
48
0
50
100
2010 2011 2012 2013
Market surveillance of authorised products Centrally authorised EDQM organised non-CAP Nationally selected Nationally selected radiopharmaceutical
2010 2011 2012 2013
PANGEA OTHER CIVIL PERSON POLICE
NHS CUSTOMS)
94 141
187
348
• 64%
1
• 56%
• 54%
7% 13
ILLEGAL /COUNTERFEIT PRODUCTS TESTED IN THE LABORATORY
Supervision of the market of medicines
Supervision of medicine supply
• Publication and risk management of supply discontinuation and shortage notifications
• RM Tools: active data collection, monitoring of stocks, individual import licence, batch specific licence, ex-officio MA, regulation of distribution, prohibition of export, sanctions
Supervision of the market of medicines
Supervision/monitoring of GMP, GCP, GLP, GDP compliance and Pharmacovigilance activity
(pharmacies are also supervised by National Public Health Service)
Certification of GMP and GLP compliance
Supervision of advertisment of medicines to health care professionals (20-30/year), co-authority in the advertisement to the public (120/year)
Supervision of the market of medicines
Other activities
Editing and amending of the
Hungarian Pharmacopoeia (1 volume/2 years, 3-5 resolutions)
Editing and amending of the national
formulary : Formulae Normales
Expert opinion on medicines to other authorities, e.g.customs, police, consumer protection authority : 150/year
Preparatory and advisory activity in the national pharmaceutical legislation
Other activities: information
Web site www.ogyi.hu, periodical (Our
Medicines)
Maintaining a direct telephon information
service on medicines (2000-3000
calls/year)
Other activities: relationships
• Establishing and maintaining international
relations regarding our competency (EU
Commission, EMA, WHO, EDQM, Ph.Eur.
Commission, OECD)
Establishing and maintaining relations
with partners and clients (organisations of
patients, industry, professionals)
Basic rules of MA
Directive 2001/83 Article 6
(1) No medicinal product may be placed on the
market of a Member State unless
- a marketing authorisation has been issued by
the competent authorities of that Member
State or
- an authorisation has been granted in
accordance with Regulation (EC) No
726/2004.
Exceptions
• Magistral and officinal preparations
• Medicines without MA in Hungary, imported on a
named patient basis
• Import of a specified quantity of medicines without MA
in case of drug shortage
• Temporarily authorised distribution of an
unauthorised medicinal product (spread of pathogic
agents, toxins, nuclear radiation)
• Medicines from donations
• Medicines used in clinical studies
Common features of MA
Administrative procedure, including assessment
of the dossier by experts of the authority/agency
Assessment: Compliance of submitted data
package with legal and scientific/technical
requirements in terms of
• Quality
• Efficacy, Safety
• GMP,GCP, GLP compliance
Types of MA procedures
• By the initiation of MA procedure
• By the way of demonstration of efficacy
and safety (legal basis)
• By the level of international cooperation
Types of MA procedures
By the initiation of MA procedure
• applicant established in the community
• competent national authority (ex officio)
Types of MA procedures (content)
Legal basis
Own non-clinical and
clinicaL studies
Reference
8(3) full dossier,
stand alone
YES NO
10.1 generic
YES (BE)
original product
authorised in
the EU
10.3 hybrid YES original product
authorised in the
EU
10.4 biosimilar YES original biologic
product authorised
in the EU
Types of MA procedures (content)
Legal basis
Own non-clinical and
clinicaL studies
Reference
10c informed
consent
NO product of same
composition
Line extension
(YES)
own product
Traditional herbal NO own or other
product of similar
composition used
30/15years
10a well established
use
NO products of the
same AS, 10 years
Scientific literature
Types of MA procedures (content)
Legal basis
Own non-clinical and
clinicaL studies
Reference
Fixed combination YES NO
Mixed (full, FC)
YES (limited)
Scientic literature
on similar products
Homeopathic
without indication
NO
Scientic literature
on homeopathy
Temporary,
Exceptional
YES, but have not finished
YES but in the lack of
sufficient number of
patients
No or Scientific
literature
Types of MA procedures (cooperation)
National: MA is applied for in one member state,
the same product is not authorised or is not
under review in another MS
- different MAH- not the same product
- line extension may be granted nationally even
if the same product is authorised or under
review in another MS
Types of MA procedures (cooperation)
Mutual recognition:
• valid MA(s) in EU, reference MS selected
• updated AR
• submission of dossier and AR in all CMSs
• 90 day for recognition, refusal on ground of
SRPH
• in case of disagrement referral to
CMD(h), EMA, Commission decision
Types of MA procedures (cooperation)
Decentralised (210 day): no valid MA in EU
• RMS selected
• PRAR is prepared by RMS day70
• SRPH and other concerns raised by
CMSs (day100)
• Q&A Ass. Q&A Ass. Q&A Ass.
• agreement, FAR, National phase (30 days)
disagreement, referral CMD(h), EMA, Comm.
Types of MA procedures (cooperation)
Centralised: Coordination EMA
Mandatory for : products of gene technology
advanced therapy, new API in cancer , AIDS,
diabetes,viral, neurodegenerative, immune
system diseases, orphan products
Assessment: experts of MSs, (Co)-Rapp, PRAC
Rapp., Peer review, CHMP members
EMA recommendation, Commission decision
Special national requirements in Hungary
• Sample of the product and API for
assessment (except for CP)
• Declaration on the equivalence and
substitution in pharmacies
• classification of medicines in terms of
prescribing (specialist or GP, normal or special
prescription) and use (out patient, in-patient
setting)
• Control of the specimen of the first batch to
be marketed
Special EU requirements for non-EU
manufactured products
• Applicant and MAH established in the EU
• Finished product manufacturers: valid GMP
certificate issued by CA of EU MS
• EU batch release of the finished product
(EU batch release site included in MA)
• API : written confirmation on compliance with
EU GMP issued by the CA of exporting
country or entry on the list of countries;
EU QP or 3rd party audit (CoI!!!)
Co-operation of the Hungarian
authority with non-EU manufacturers
The Hungarian regulatory authority on request
undertakes:
• Reference membership in marketing auth.
• Inspections and GMP certification of finished
product manufacturers
• Inspections and GMP certification of API
manufacturers
Thank you for your attention!