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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!