05.12.

2019

RESEARCH DEVELOPMENT BIRTH LIFE

1 - 2 yrs. 1 - 2 yrs. 1 - 3 yrs. 6 - 8 yrs. 1 - 2 yrs. Management of life cycle

Testing of

quality – efficacy - safety bioequivalence

1 YEAR

Data protection 10
yrs (centralised EU)
or 6 -10 yrs (in
INVESTMENT different countries*)
+ 1 yr in
case of new
1 - 3 yrs 7 - 10 yrs
therapeutic
0 3 12 indication
PRECLINICAL RESEARCH
MOLECULE CLINICAL TRIALS
IDENTIFIED

MARKETING AUTHORISATION Anna OLEÁROVÁ Patent protection

application Investment
Authorisation

€
Authorisation
during patent protection
period
€ €
PHARMACOVIGILANCE
[email protected]
Patent 20 years SmPC 5 years (Additional Generics
Protection Certificate

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LEGISLATIVE FRAME
Act No. 362/2011 Coll. On medicines and medical devices
§ 129 Act No. 362/ 2011 Coll. on Medicines and Medical Devices
• Market access authorisation of human medicines § 46-66 Scope of State Institute
Government Regulation No. 120/2009 Coll.
laying down analytical standards, toxicological-pharmacological standards,
clinical standards and protocols relating to the documentation of the results of
the pharmaceutical research, the toxicological-pharmacological research and (1) The State Institute is a state administration body in the field of human pharmacy and drug
the clinical trial carried out for the purpose of the marketing authorization of precursors.
medicinal products The State Institute is a budgetary organization and is headed by a director appointed and
Regulation (EC) No 726/2004 of the EP and of the Council dismissed by the Minister of Health.

laying down community procedures for the authorisation and supervision of

medicinal products for human and veterinary use and establishing a European
Medicines Agency
https://eur-lex.europa.eu/legal- (2) The State Institute
content/EN/TXT/PDF/?uri=CELEX:32004R0726&qid=1575537896791&from=EN
(e2) issues a marketing authorization for medicinal products for human use
Act No. 145/1995 Coll. On administrative fees (q) maintains a list of authorized medicinal products for human use and a list of authorized
Item 152 and registered medical devices

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ADVISORY BODIES EMA COMMITTEES

Committee for medicinal products Committee for Medicinal Products for Human Use (CHMP)

Subcommittee for generic medicines Pharmacovigilance Risk Assessment Committee (PRAC)

Subcommittee for phytopharmaceutics and homeopatics Committee for Medicinal Products for Veterinary Use (CVMP)
Committee for drug safety
Committee for Orphan Medicinal Products (COMP)
Pharmacopoeia Committee
Committee on Herbal Medicinal Products (HMPC)
Committee for drug quality
Ethics committees Committee for Advanced Therapies (CAT)

Committee for advertising Paediatric Committee (PDCO)

Pandemic team Working parties and other groups

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CLASSIFICATION OF HUMAN MEDICINES

AUTHORISATION OF HUMAN MEDICINES ACCORDING TO DISPENSING
Market access authorisation
Prescription medicines
Listing in the list of authorized medicinal products (Section 53 (1) of the Act) and
classification according to dispensing (§ 51)
Prescription medicines with limitations
All licensed medicines have to be authorised (§ 46)
Prescription medicine that have to be prescribed on
Decisions on a marketing authorization, a changes in a marketing authorization and a
special prescriptions with blu stripe
renewal of a marketing authorization are launched by

• SIDC in national or decentralised procedures – without period limit or for 5 years

Over-the-counter medicines
• European Commision (EC in centralised procedure and based on
recommendation of EMA (CHMP)

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AUTHORISATION PROCEDURES DOSSIER (AUTHORISATION DOCUMENTATION)

CP
Centralised
• EMA – validity in all
DCP Documentation on pharmaceutical, pharmacological-
toxicological research and clinical trial results
member states
• Required for: Decentralised MRP
• Medicines produced by procedure – validity in
biotechnological
methods
concerned states Mutual Recognition NP
• the applicant submits Procedure – validity in
• Medicinal products
containing an entirely
the application to concerned states National the applicant is required to report all results of the
new active substance
several selected
countries, one of
• the medicinal • SIDC – validity in SR research and trials as well as negative results and
product is already
which has not yet been
authorized in the EU and which is a reference authorized in any
only studies not completed
whose therapeutic member state (RMS) • National drug
member state and agencies – validity in
indication is treatment the applicant
• acquired one state
immunodeficiency
applies for
syndrome, recognition
• cancer,
• neurodegenerative
Common technical document (CTD) - 5 modules
disorder; or
• diabetes
• Orphan drugs

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DOSSIER DOSSIER
Module 1 a 2 Other draft of SmPCs in codified state language for professional public and SmPC
application approved in the European Union countries
• Administrative data,
• SmPCs - draft, requests
• Patients´ information leaflets – PILs - draft, draft for PILs in a codified form of the state language, a PIL approved in the EU
• Texts of inner and outer packages ( incl. Braille) countries where the medicinal product has already been authorized,
• Summaries of modules 3-5 (readability test - results of consultation with the target group of patients),
Module 3
proof of authorization to manufacture medicinal products in the country where it is
• it consists of chemical, pharmaceutical and biological data already manufactured,
• concern the manufacture and quality control of the medicinal product

Module 4 the evidence of the marketing authorization of the medicinal product in other
countries, where they are registered, a list of the countries in which the application
• the results of the pharmacological-toxicological studies carried out in laboratory animals for authorization was submitted and, if the authorization is refused, the reasons for
in relation to the toxicity and mechanism of action of the medicinal product the refusal,

Module 5 the manufacturer's data on the environmental performance of the medicinal product
• clinical trial information and on the disposal of the wastes containing the medicinal product or product.
• efficiency and safety

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APPLICATION REVIEW
Evaluation report

Comments - replies, completion of the application

In the case of centralised procedures, comments

are sent to the RMS and the requirements are not
met; refferal (CMDh) - arbitration scientific
discussion

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TYPES OF APPLICATIONS I. (Slovak legislative) TYPES OF APPLICATIONS II. (Slovak legislative)

COMPLETE DOSSIER APPLICATION (§ 48)

• it contains a complete set of data on the quality, safety and efficacy of the medicinal Referral application, medicine equivalent to a reference medicine authorized in the SR /
product, including pre-clinical and clinical studies with the medicinal product. EU medicine (generic medicine).
• innovative medicine, is a reference medicine for generic marketing authorizations
• the product is a generic medicine of the reference medicine which has been authorized in
COMPLETE DOSSIER BASED ON BIBLIOGRAPHY (§ 49 ods.1 písm. b)) at least one Member State for eight years (§ 49).
• a generic medicinal product is a medicinal product which has the same qualitative and
quantitative composition of the medicinal products and the same pharmaceutical form as
• a medicine which has been used in medical practice for at least ten years and has been the reference medicinal product and whose biological equivalence to the reference
proven, medicinal product has been demonstrated by adequate bioequivalence study.
• its efficacy and safety are confirmed or its composition is indicated in a relevant • salts, esters, ethers, isomers, mixtures of isomers, complexes or derivatives of a drug are
pharmacopoeia. considered to be the same drug unless their properties differ significantly in safety or
efficacy from the reference drug.
• additional information is required to demonstrate the safety or efficacy of the salts, esters
NEW FIXED COMBINATION OF KNOWN SUBSTANCES (§ 49 ods. 14). or derivatives of the authorized drug.
• new formulation of a medicinal product containing known medicinal products and Same indications, new indications, ! watch out for patent protection!
excipients that have not been used in a previously approved combination, the results of
the toxicological-pharmacological and clinical trials of the new formulation must be
submitted
• no submission of the results of the toxicological, pharmacological and clinical investigations
for the individual medicinal products and excipients shall be required

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SmPC – NOT
AUTHORISATION NUMBER, CODE OF SIDC PRESCRIPTION
INFORMATION ONLY
www.adc.sk
Authorisation number
www.sukl.sk
• xx / yyy / zz - S www.ema.europa.eu
• Indication group/ adminitrative number/ authorisation
year – Slovakia
https://www.medicines.org.uk/emc
http://www.mhra.gov.uk/spc-pil/
SIDC code

• a numeric code that uniquely identifies the drug in a

particular package

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AUTHORISATION NUMBER - EXAMPLE: AUTHORISATION NUMBER VS. SIDC CODE

07/ 0148/ 78 – CS 07/ 0148/ 78 – CS VS. 86051 AND 86052

07
• indication group (ANALGETICA - ANTIPYRETICA

0148
• administrative number

78
• Year of application submition

CS
• Czechoslovakia

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EUROPEAN (CENTRALISED) AUTHORISATIONS

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RATIONAL PRESCRIBING
CHANGES, SUSPENSIONS, CANCELLATIONS
RIGHT MEDICATION
 Based on correct diagnose
Change of market authorisation holder
RIGHT DIAGNOSE
 Indications • In case of fusions, or others...
RIGHT PATIENT
 Individual approach, taking into account age, restrictions, condition of the organism,
Changes in authorisation
contraindications, ...

RIGHT DOSE / APPLICATION FORM / ADMINISTRATION Suspensions of authorisation

ROUTE
 eg. GIT functions, eliminations organs functions, specifics (children, elderly, pregnant women,
dialyzed patients,...)
Market withdrawal
RIGHT TIME • based on the safety profile of the public health product
 Frequency, lenght of using
• if the marketing authorization holder fails to comply with the
conditions laid down by law
In accordance with SmPC!

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• Drug safety vigilance

(watch)
• The pharmacological
science relating to the
collection, detection,
assessment, monitoring,
and prevention of adverse
effects with
pharmaceutical products
• Aims
• to obtain new information
about risks connected with use
of medicines
• To avoid of patients damage
by adopting of prevention
actions
PHARMAKOVIGILANCE • Good Pharmacovigilance
Practice (GVP)

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SIDC – NATIONAL CONTACT

POINT TO REPORTING ADRS
1. Systematic
data collection
• SIDC in Slovakia is responsible:
• to collect and assessed ADRs reports
2. Spontaneous • To report ADRs to EudraVigilance
reporting database
system • To collaborate with Uppsala Monitoring

MEDICINES SAFETY Centre

• Participates in international cooperation

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SAFETY OF MEDICINAL PRODUCTS BLACK INVERTED TRIANGLE

Systematic data collection Spontaneous reporting system
„This medicinal product is subject to additional monitoring“
• During clinical trials • Healthcare pofessionals
• SUSAR - Suspected unexpected In PIL and SmPCs
serious adverse reaction
(mandatory)
Information, not warning symbol!
• Reported by sponsor • Patients (have an option)
All medicines are carefully monitored after they are placed on the EU
• DSUR - Development Safety Update
Report market after 01-Jan-2011
• Reported by sponsor If a medicine is labelled with the black triangle, this means that it is being
• Post authorisation monitored even more intensively than other medicines
• PSUR - Periodic Safety Update Report This is generally because there is less information available on it than on
• Reported by marketing authorisation
holder other medicines, for example because it is new to the market or there is
• Data from physicians and literature limited data on its long-term use
case reports It does not mean that the medicine is unsafe.

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SPONTANEOUS REPORTING SYSTEM OF

SUSPECTED ADRS ADRS REPORTING - SR
via national reporting points = national drug agencies!  http://www.sukl.sk/sk/bezpecnost-liekov
Healthcare professionals (mandatory)
Patients (have an option)
 https://portal.sukl.sk/eskadra/?act=EskadraN
ewAdv&mId=3

National Medicine EMA UMC

Agency

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ADRS REPORTING - EÚ
EudraVigilance
 http://eudravigilance.ema.europa.eu/human/index.asp

 http://www.adrreports.eu/sk/index.html

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ADRS REPORTING - GLOBAL DE, AT, GB

BfArM - The Federal Institute for Drugs and Medical Devices
(Bundesinstitut für Arzneimittel und Medizinprodukte)

Uppsala monitoring Centre AGES - Austrian Agency for Health and Food Safety
(Österreichische Agentur für Gesundheit und
 WHO Ernährungssicherheit)
 since 1978
MHRA - Medicines and Healthcare products Regulatory Agency
 http://www.who-umc.org

 in USA eg. MedWatch (by FDA)

https://www.ema.europa.eu/en/partners-networks/eu-partners/eu-member-states/national-competent-authorities-human

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GREECE, INDIA, USA

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https://humanweb.pei.de/index_form.php?PHPSESSID=aa1so4c5bso3u3o451fd2bevj52jlspn#calendar

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• Causality assessment is
difficult

MARKET WITHDRAWAL • Not all risks of drugs are

known at the time of
authorisation process
• Need to report ADRs
suspicions
• Contact point is SIDC/
national drug agency
• SIDC report ADRs
suspicion/ signals to
EudraVigilance database
• Global reporting - WHO
and CIOMS Uppsala
Monitoring Centre (UMC)

CAUSALITY • The drug could be

withdrawn when proven
the causality, severity and
frequency (Naranjo score)

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CAUSALITY ASSESSMENT (WHO) CAUSALITY ASSESSMENT (EMA)

A (probably) B ( possible) O (unclassifable) O1 (inconclusive) N (unlikely)

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USEFUL LINKS
www.sukl.sk

www.ema.europa.eu

www.uskvbl.sk

www.sukl.cz

www.fda.gov

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