Social Pharmacy - Lecture 09

Authorisation
of medicinal products
(in the EU).

Institutional framework.

Authorisation procedures.

Quality of the medicinal products.

Drug switching.
JAMASOFT2017 1
JAMASOFT2017 2
To guarantee the highest possible level of public
health
and
to secure the availability of medicinal
products to citizens across the EU,
all medicinal products for human use
have to be authorised
either at Member State or Community level
before they can be placed on the EU market.

JAMASOFT2017 3
 The authorisation is based on the evaluation

of the
quality,
safety
and efficacy
of the medicinal product
and the assessment of its benefit and risk.

JAMASOFT2017 4
 The particulars and documents

which must accompany an

application for the authorisation for a medicinal
product
demonstrate that potential risks are outweighed
by the therapeutic efficacy of
the product.

JAMASOFT2017 5
 Competent authorities to grant an authorisation
in the EU are

1. national governmental institutions „medicines

agencies“ and

2. the European Commission (decision making) in

collaboration and shared responsibility with the
European Medicines Agency (application and
documentation evaluation).

JAMASOFT2017 6
 Authorisation of medicinal products in the
EU

Main stakeholders in the process are

- patients and consumers,
- healthcare professionals,
- healthcare providers, payers
(insurance companies) and
- applicants (pharmaceutical
companies).

JAMASOFT2017 7
The pharmaceutical industry
makes an important
contribution to Europe's and the
world's well-being.
It is a strategic sector due to
its economic as well as
its public health dimension.
JAMASOFT2017 8
 Life cycle
of a medicinal product:
• Research and development,
• Manufacturing
• Authorisation application: benefit-risk
• Obligations of the authorisation holder
• Post-marketing surveillance: quality and safety
(pharmacovigilance)
• Variations in the authorisation
• Validity of the authorisation and renewal
JAMASOFT2017 9
JAMASOFT2017 10
JAMASOFT2017 11
 The authorisation procedures

The European system for the authorisation of

medicinal products
for human and animal use was introduced in
January 1995
with the objective of ensuring that safe,
effective and high quality
medicines could quickly be made available to
citizens across the European Union.

JAMASOFT2017 12
EMA

JAMASOFT2017 13
The European Medicines Agency
is a decentralised agency of the European
Union, located in London.
The Agency is responsible for the scientific
evaluation of medicines developed by
pharmaceutical companies for use in the
European Union.

JAMASOFT2017 14
The European system offers several routes for the authorisation
of medicinal products:

• centralised procedure
• decentralised procedure
• mutual recognition
procedure
• purely national procedure
(one member state only)
JAMASOFT2017 15
 The Centralised Procedure.
Applications for the centralized procedure are
made directly to the European Medicines
Agency which issues and Opinion resulting
from the scientific assessment
of the quality, safety and efficacy of medicinal
products and further may lead to the granting
of an European marketing authorisation by
the Commission which is binding
in all Member States.

JAMASOFT2017 16
 The Decentralised Procedure

which was introduced with the

legislative review of 2004, is also applicable to the
majority of conventional medicinal products.
Through this procedure an application for the
marketing authorisation of a medicinal product is
submitted simultaneously in several Member States,
one of them being chosen as the "Reference
Member State".
At the end of the procedure national authorisations are
granted in the reference and in the concerned
Member States.
JAMASOFT2017 17
 The Mutual Recognition Procedure

which is applicable to the majority of

conventional medicinal products,

is based on the principle of recognition of an

already existing national authorisation by
one or more Member States.

JAMASOFT2017 18
 Special rules exist for
the authorisation of medicinal products for
paediatric use,
orphan drugs,
advanced therapy,
traditional herbal medicinal products,
vaccines,
homeopathics.

JAMASOFT2017 19
 A homeopathic medicinal product.

Only homeopathic medicinal products which satisfy all of

the following conditions
may be subject to a special, simplified registration
procedure:

administered orally or externally no specific therapeutic

indication appears on the labelling
there is a sufficient degree of dilution
to guarantee the safety of the medicinal product.

JAMASOFT2017 20
 Authorisation procedures.

The national authority closely examines the efficacy, risks and

quality of the medicine.

All important data about the medicine is reproduced in the

detailed product information sheet for doctors and
pharmacists (summary of product characteristics, SPC).

A summary for patients is also made, in the form of a package

leaflet. The national authority also decides on the product's
legal status.
(whether it can be obtained without prescription or may only be
dispensed on prescription).

JAMASOFT2017 21
 Once a medicine has been marketed,
the national authority
continues to monitor the medicine‘s
Adverse Event Reports.
It therefore always contains the most up-to-date
information about the efficacy and possible
adverse events of medicines.
If necessary, the authority can take steps like
modifying the package leaflet text or in the
most extreme case - suspending sales or even
withdrawing the medicine from the market
entirely.

JAMASOFT2017 22
The authorisation shall be refused,
if it is clear that:
(a) the risk-benefit balance is not considered to
be favourable, or
(b) its therapeutic efficacy is insufficiently
substantiated by the applicant, or
(c) its qualitative and quantitative composition is
not as declared.

JAMASOFT2017 23
 Medicinal product information

is an integral part of the authorisation !

• Information intended for healthcare professionals,
ongoing harmonisation in the EU therapeutic indications,
• posology and methods of administration,
• contra-indications,
• special warnings and precautions for use,
• interactions with other medicinal products,
• use during pregnancy and lactation,
• effects on ability to drive and to use machines
• undesirable effects,
• overdose,
• pharmacological (pharmacodynamic, pharmacokinetic) properties,
• preclinical safety data,
• pharmaceutical particulars.

JAMASOFT2017 24
 The official contents of Summary of Product Characteristics (SPC):
• 1. Name of the medicinal product
• 2. Qualitative and quantitative composition
• 3. Pharmaceutical form
• 4. Clinical particulars
• 4.1 Therapeutic indications
• 4.2 Posology and method of administration
• 4.3 Contraindications
• 4.4 Special warnings and precautions for use
• 4.5 Interaction with other medicinal products and other forms of interaction
• 4.6 Fertility, pregnancy and lactation
• 4.7 Effects on ability to drive and use machines
• 4.8 Undesirable effects
• 4.9 Overdose
• 5. Pharmacological properties
• 5.1 Pharmacodynamic properties
• 5.2 Pharmacokinetic properties
• 5.3 Preclinical safety data
• 6. Pharmaceutical particulars
• 6.1 List of excipients
• 6.2 Incompatibilities
• 6.3 Shelf life
• 6.4 Special precautions for storage
• 6.5 Nature and contents of container
• 6.6 Special precautions for disposal and other handling
• 7. Marketing authorisation holder
• 8. Marketing authorisation number(s)
• 9. Date of first authorisation/renewal of the authorisation
• 10. Date of revision of the text

JAMASOFT2017 25
 Medicinal product information
as an integral part of the authorisation.

• Patient information leaflet (PIL)

• Braille
• Challenges of multilingual texts

JAMASOFT2017 26
 Quality of the medicinal product.

The application shall be accompanied by the following

particulars and documents:

- descriptionof the manufacturing method,

- description of the control methods employed by the
manufacturer,
- a document showing that the manufacturer is
authorised in his own country to produce medicinal
products.

JAMASOFT2017 27
 Quality of the medicinal product

Member States shall take all appropriate measures to

ensure that:
(a) the competent authorities verify that manufacturers and importers of
medicinal products coming from third countries are able to carry out
manufacture in compliance

(b) the competent authorities may allow manufacturers and importers of

medicinal products coming from third countries, in justifiable cases, to
have certain stages of manufacture and/or certain of the controls referred
to in (a) carried out by third parties; in such cases, the verifications by the
competent authorities shall also be made in the establishment
designated.

JAMASOFT2017 28
 Good Manufacturing Practice (GMP)
is defined as

„That part of Quality Assurance which ensures that

products are
consistently produced and controlled to the quality
standards appropriate to their intended use.“
The competent authority may also carry out unannounced
inspections at the premises of manufacturers of active
substances used as starting materials, or at the premises
of the authorization holders whenever it considers that there are grounds for
suspecting noncompliance with
the principles and guidelines
of Good Manufacturing Practice.

JAMASOFT2017 29
 Authorisation and
Switching of Medicine-Status:
from
Prescription-only
To Over-the-counter
availability.

JAMASOFT2017 30
 In order to market
a medicinal product a manufacturer must first
obtain regulatory approval by conducting
clinical tests and trials to prove that the
product is safe and effective.

JAMASOFT2017 31
 Producers of generic medicines
are able to use the original manufacturer's
approval if they can demonstrate,
that the generic version is bioequivalent to the
approved medicine.

JAMASOFT2017 32
 Facilitating generic drug manufacturing.
Drug Switching.
As the global disease burden expands, the need for new, more effective
treatments is greater than ever.
Investing in drug research and development is, however, a costly, high-risk
endeavor.
Patents are intended to offer some guarantee of a return on investment, but
the patent system is also designed to balance the interests of inventors
with those of the public.
After a patent expires, a patented technology may be freely exploited by
anyone.
Drug switching refers to the practice of replacing a brand name drug with a
generic drug.
This practice is often used to reduce drug costs.

JAMASOFT2017 33
 Facilitating generic drug manufacturing:
Bolar Exemptions Worldwide.

To overcome this problem, many countries have

put into place legal exemptions (or research
exemptions) from infringement for certain
acts relating to the development and
submission of testing data to a regulatory
agency.
These exemptions are often referred to as
“Bolar” exemption.

JAMASOFT2017 34
 In patent law,
there is an exemption to the rights
conferred by patents,
which is especially relevant to drugs.

JAMASOFT2017 35
 Facilitating generic drug manufacturing:
Bolar exemptions worldwide.

Within Europe, there exists a defence to patent

infringement commonly referred to
as the “Bolar” exemption,
which applies to acts legitimately undertaken for the
regulatory approval of medicinal products.
Many nations have put similar exemptions in place,
but their nature and scope vary significantly
from country to country.

JAMASOFT2017 36
 The Bolar exemption
was a small part of a comprehensive reform of
the current European Union pharmaceutical
legislation proposed by the European
Commission in July 2001.

JAMASOFT2017 37
 Authorisation of Medicinal Products
and
Switching of Medicine-Status.

Prescription medicines are increasingly being

switched to over-the-counter
(OTC, nonprescription)
status
in the developed world,
with the support of government policy.

JAMASOFT2017 38
Thanks for your attention.

JAMASOFT2017 39