Regulation and governance of

medicinal products and

pharmaceutical activities

Dr Patricia Vella Bonanno

• Regulatory Framework
(European and national)

- Legislation
- Policy

- Regulatory Authorities

2
The National Pharmaceutical Framework

Pharmacies Industry
Policy Makers
Wholesale Dealers

Healthcare
National
Healthcare
Professionals
Stakeholders Importers professionals
Patients and
Patient Organisations Patients &
Manufacturers consumers
Consumers

National
Legislation EU
Rational
Medicines
Pharmaceutical
Medicines
Use Regulation Legislation
National
Supply systems
Medicines
Policy
Essential Medicines Research
Medicines Policy
Medicines
Financing
Human
Resources Affordability
Monitoring &
Evaluation
Legislation

3
Regulation
National framework:
Maltese legislation
-Medicines Act came into force in Nov 2003 (Act 458 of 2003)
- Authorisation of medicinal products: quality, safety, efficacy
-Pharmacovigilance and post-authorisation activities
- Regulation of pharmaceutical activities

The EU framework
EU legislation and guidelines

The medicines supply chain starts from research and clinical trials,
and proceeds with marketing authorisation of the medicinal product,
manufacture, wholesale dealing, pharmacovigilance, prescribing,
dispensing and administration to patients.
These different steps are regulated so as to ensure that standards of
medicinal products and also of the different activities are maintained
4
Medicines Act CAP 458 (2003) Malta & S.L
• Licensing Authority
• The Medicines Authority
• Medicines Review Board
• General Provisions
• Marketing authorisation related to medicinal products
• Manufacture of medicinal products for human use
• Wholesale distribution and brokering of medicinal products for human use
• Pharmacies and related pharmaceutical activity
• Poisonous substances
• Other dealings with medicinal products

https://legislation.mt/Legislation
https://legislation.mt/eli/cap/458/eng

Subsidiary Legislation S.L. 458.xx

https://legislation.mt/eli/sl/458.xx/eng
 Medicines Act CAP 458 (Malta)
• “medicinal product” means any substance or
combination of substances –
(a) Presented as having properties for treating or
preventing disease in human beings; or
(b) Which may be used in or administered to human
beings either with a view of restoring, correcting
or modifying physiological functions by exerting a
pharmacological, immunological or metabolic
action, or to making a medical diagnosis

• “medical prescription” means any medicinal

prescription issued by a professional person
qualified to prescribe medicinal products by or
under this Act
 Prescriptions (Malta)

• In the community for medicines supplied

through the national health services (free)
- Prescriptions for free medicines (also
available as electronic prescriptions)
• Private prescriptions – medicines sold
through pharmacies
• Hospital in-patient charts
- Considered as prescriptions as well as
records of administration of medicines
 Investigational medicinal products

• “investigational medicinal product” means a

pharmaceutical form of an active substance
or placebo being tested or used as a
reference in a clinical trial, including products
already with a marketing authorisation but
used or assembled (formulated or packaged)
in a way different from the authorised form, or
when used for an unauthorised indication, or
when used to gain further information about
the authorised form
 Controlled drugs
Malta
CAP 31 Medical and Kindred Professions Ordinance
SL 31.18 Dangerous (Control) Regulations
SL 31.21 Registration of Drug Addicts Regulations
http://justiceservices.gov.mt/LOM.aspx?pageid=27&mode=chrono&gotoID=3
1

CAP 101 Dangerous Drugs Ordinance

SL 101.01 Raw Opium Rules
SL 101.02 Internal Control of Dangerous Drugs Rules
SL 101.04 Fees
SL 101.05 Substances used in the Illicit Manufacture of Narcotic Drugs and
Psychotropic Substances Rules
SL 101.06 Methadone Rules

http://justiceservices.gov.mt/LOM.aspx?pageid=27&mode=chrono&gotoID=1
01
 EU Legislation - EUDRALEX
The body of European Union legislation in the pharmaceutical sector is compiled in Volume 1
and Volume 5 of the publication "The rules governing medicinal products in the European
Union":
Volume 1 - EU pharmaceutical legislation for medicinal products for human use
Volume 5 - EU pharmaceutical legislation for medicinal products for veterinary use
The basic legislation is supported by a series of guidelines that are also published in the
following volumes of "The rules governing medicinal products in the European Union":
Volume 2 - Notice to applicants and regulatory guidelines for medicinal products for human use
Volume 3 - Scientific guidelines for medicinal products for human use
Volume 4 - Guidelines for good manufacturing practices for medicinal products for human and
veterinary use
Volume 6 - Notice to applicants and regulatory guidelines for medicinal products for veterinary
use
Volume 7 - Scientific guidelines for medicinal products for veterinary use
Volume 8 - Maximum residue limits
Volume 9 - Guidelines for pharmacovigilance for medicinal products for human and veterinary
use
Volume 10 - Guidelines for clinical trial
Medicinal products for paediatric use, orphans, herbal medicinal products and advanced
therapies are governed by specific rules.

10
EudraLex - EU Legislation | Public Health (europa.eu)
 Medicines Regulatory Agencies

• Malta Medicines Authority (Malta)

The mission of the Medicines Authority is to
protect and enhance public health through
the regulation of medicinal products and
pharmaceutical activities.

medicinesauthority.gov.mt
 European Medicines Agency

• The mission of the European Medicines Agency is

to foster scientific excellence in the evaluation and
supervision of medicines, for the benefit of public
and animal health in the EU

www.ema.europa.eu

Medicines authorised through the centralised

procedure have a marketing authorisation valid
across the EU
www.ema.europa.eu/en/human-
regulatory/marketing-authorisation
• Regulatory Framework
(European and national)

- Medicinal Products

- Marketing authorisation
- Post-authorisation monitoring product safety and
medication errors related to medicinal products
(pharmacovigilance)
- Safety features
13
• Regulatory Framework
(European and national)

- Medicinal Products

- Marketing authorisation
- Post-authorisation monitoring product safety and
medication errors related to medicinal products
(pharmacovigilance)
- Safety features
14
 EMA Guidelines for applicants of MA
• The European Medicines Agency's Committee for Medicinal
Products for Human Use (CHMP) prepares scientific guidelines in
consultation with regulatory authorities in the European Union (EU)
Member States, to help applicants prepare marketing authorisation
applications for human medicines.
• Guidelines reflect a harmonised approach of the EU Member States
and the Agency on how to interpret and apply the requirements for
the demonstration of quality, safety and efficacy set out in the
Community directives.
• The Agency strongly encourages applicants and marketing
authorisation holders to follow these guidelines. Applicants need to
justify deviations from guidelines fully in their applications at the time
of submission. Before that, they should seek scientific advice, to
discuss any proposed deviations during medicine development.

Scientific guidelines | European Medicines

Agency (europa.eu) 15
 Conditions for granting of a marketing
authorisation to a medicinal product
• Evaluation of the medicinal product
• Reached the required standards for
- Safety
- Quality
- Efficacy
Licensing of medicinal products

Evaluation

Benefits Risks
• Efficacy •Safety
• Use of •Side effects
medicines •Adverse drug
reactions
•Contra-indications

Quality of products •Classification (P/nonP)

Expiry dates •Labelling
Active Ingredients (API) •Patient information leaflet
Inactive ingredients •Summary of Product
Storage conditions Characterisitics (SPC) 17
Summary of Product Characteristics (SPC)
1. Name of 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 Interactions
4.6 Pregnancy and Lactation
4.7 Effect on Ability to Drive and Use Machines
4.8 Undesirable Effects
4.9 Overdose
5. Pharmacological Properties
5.1 Pharmacodynamic properties European Medicines Agency (European
5.2 Pharmacokinetic properties Marketing Authorisation – centralised )
5.3 Preclinical safety data
6. Pharmaceutical Particulars Malta Medicines Authority
Regulatory Data http://www.medicinesauthority.gov.mt/medi
cinesdatabase (national authorisation)
 Classification of medicinal products
Malta
• All medicines are sold from a pharmacy
• Medicines classified as Over the Counter (OTC) or
Prescription Only Medicines (POM); there is no GSL
• To date only medical doctors and dentist are
authorised to prescribe POMs
• Controlled drugs – narcotic drugs and psychotropic
substances

UK
• General Sale List (GSL)
• Pharmacy Only Medicines (P)
• Prescription Only Medicines (POM)
• Controlled drugs (CD)
Information on medicines authorised in Malta

http://medicinesauthority.gov.mt
www.maltamedicineslist.com

Medicines
• trade name
• chemical name
• license holder
• therapeutic class

Summary of
Product
Characteristics

Patient information
leaflet

Safety information
20
 Originator medicines and generic medicines
A
Originator U
Only Originator and
Medicines Research
T
H originator generic
O
Evaluation: R products on products on
Clinical studies I the market the market
Quality S
Safety A
Efficacy Development T Exclusivity Competition
I
O
N
AA
UU
Generic TT Originator
HH
Medicines OO and generic
RR products on
I I
Evaluation: SS the market
Quality AA
Bioequivalence TT
I I Competition
OO
NN

0 4 8 12 16 20 24 28

Years
21
Comparison between originator and generic medicines
Active ingredient/s There can be minor differences between
originator products and generic products, but
Essentially similar these are considered to have the same active
ingredient, as long as these do not significantly
impact on the properties with respect to safety
and/or efficacy.
Dosage forms Can have different shape, colour and size of
The same unit and different packaging and pack size.
Excipients Inactive substances usually do not effect the
Can be different patient, but patients maybe allergic to certain
inactive substances
Standards Evaluated in line with EU legislation.
Originator is evaluated on basis of full dossier,
The same including clinical trials.
Generic is evaluated on basis of a
bioequivalence study. No need to submit
clinical trials. Quality assessment is needed.
The requirements for the supply chain are the
same.
Name of product Different names. The name can be unique
(proprietary) or it can be based on the active
Different 22
ingredient and the name of the company (non-
proprietary).
 Bioequivalence
(applicable to most chemically-derived medicinal products)

• EMA Guideline on the investigation of

bioequivalence, CHMP/EWP/QWP/1401/98,
2010
• Two medicinal products containing the same
active substance are considered bioequivalent if
they are pharmaceutically equivalent or
pharmaceutical alternatives and their
bioavailabilities (rate and extent) after
administration in the same molar dose lie within
acceptable predefined limits. These limits are set
to ensure comparable in vivo performance i.e.
similarity in terms of safety and efficacy. 23
 Biosimilar biological products
• A biosimilar is a biological medicinal product that contain
a version of the active substance of an already
authorised original biological medicinal product
(reference medicinal product). A biosimilar demonstrates
similarity to the reference medicinal product in terms of
quality characteristics, biological activity, safety and
efficacy based on a comprehensive comparability
exercise.
• The standard generic approach of demonstration of
bioequivalence which is applicable to most chemically-
derived medicinal products is in principle not appropriate
to biological/biotechnology-derived products due to their
complexity.
24
 XXX ‘equivalence’
• Chemical equivalence:
- indicates that drug products contain the same active compound in
the same amount and meet current official standards
- inactive ingredients in drug products may differ

• Bioequivalence
- the drug products, when given to the same patient in the same
dosage regimen, result in equivalent concentrations of drug in
plasma and tissues

• Therapeutic equivalence
- indicates that drug products, when given to the same patient in the
same dosage regimen, have the same therapeutic and adverse
effects.

25
 Unlicensed / off-label medicines

• ‘Specials’ – manufacture and supply of unlicensed medicinal products to

meet special needs for individual patients
• Imports – imported from outside the EU; importation and supply of
unlicensed medicinal products for individual patients
• Extemporaneous preparations – medicinal product prepared in a
pharmacy. Extemporaneous compounding is the mixing together of the
ingredients of a prescription or drug formula and generally refers to a
manual process performed for individual orders by a pharmacist.
• “Hospital exemption” - manufacture and supply of unlicensed advanced
therapy medicinal products for individual patients
• Compassionate use – is a treatment option that allows the use of an
unauthorised medicine. Under strict conditions, products in development
can be made available to groups of patients who have a disease with no
satisfactory authorised therapies and who cannot enter clinical trials.
• Off label - use (or route) - outside the licensed indication or use of the
product; not in line with the SPC

Generally the responsibility for use of an unlicensed medicine, or a licensed

medicine for an unlicensed indication (off label), rests with the prescriber
 Liability

• Generally where a licensed medicine is

prescribed and administered in
accordance with the SPC the no liability
will be attached to the prescriber if:
- diagnosis is correct
- correct choice of medicine
- patient warned of potential adverse events
 Cover letter template for notification of ‘withdrawn products’ by MAHs

•Cover letter template for notification of "withdrawn products" by marketing authorisation holders
(< FROM MAH ON HEADED PAPER >)
<Date>
Name of regulatory authority,
Address
RE: Notification of "withdrawn product”
Dear <Name>,
Please find herewith enclosed our notification for a
• Centrally authorised medicinal product in accordance with Article 13 and 14b of Regulation 1027/2012
• Nationally Authorised medicinal product in accordance with Article 23a and 123 of Directive 2012/26/EC
<Product Name(s)>, <INN(s)>, <MAH>, <EVCODE>
To take the following action(s):
•Cease the marketing of a medicinal product (permanently or temporarily)
•Suspend the marketing of a medicinal product
•Withdraw a medicinal product from the market
•Request the withdrawal of a marketing authorisation
•Not to apply for the renewal of a marketing authorisation
I declare that the reason(s) for such action(s) are:
•Based on the grounds provided in Articles 116 and 117 of Directive 2001/83/EC;
•Not based on the grounds provided in Articles 116 and 117 of Directive 2001/83/EC.
I herewith confirm that together with this cover letter an Excel spread sheet (template EMA/445787/2013) entitled
<MAH file name> is submitted containing all the required information related to the medicinal product(s)
concerned.
Yours sincerely,
<Signature of authorised contact person>
<MAH>
cc:
<PTL for centrally authorised medicinal product>
<Rapporteur>
<Co-Rapporteur>
Encl(s) <Number> Excel file 28
• Regulatory Framework
(European and national)

- Medicinal Products

- Marketing authorisation
- Post-authorisation monitoring product safety and
medication errors related to medicinal products
(pharmacovigilance)
- Safety features
29
Safety issues post-authorisation

pharmacovigilance data and activities

Risk Benefit

evaluation of the risk/benefit balance

Variations to Withdrawal or
marketing suspension of
authorisations marketing
authorisations
30
The EU Pharmacovigilance legislation
Spontaneous Reporting of ADRs

• Definition of ADRs

A response to a medicinal product which is noxious and unintended.

Now includes:
• Medication errors that result in an ADR
•Uses outside the terms of the marketing authorisation including the
misuse and abuse of the medicinal product.

• Direct Patient Reporting

For Suspected ARs in Literature the burden for industry has decreased if the
product is listed in the EMAs list of monitored products

-Not be required to report the suspected ARs for medicinal products

containing the active substances referred to in the list of publications
monitored by the EMA.
31
 Pharmacovigilance guidelines

• HMA/EMA, Guideline on good

pharmacovigilance practices (GVP)

• EMA, Position paper on potential

medication errors in the context of benefit-
risk balance and risk minimisation
measures

32
Pharmacovigilance
EU legislation: Regulation (EU) No 1235/2010 of 15 December 2010
amending as regards pharmacovigilance of medicinal products for
human use, Regulation 726/2004
National legislation: S.L.458.35
Centralised EU database for Adverse Drug Reactions and
Medication Errors
Products subject to ‘additional monitoring’: Black triangle scheme for
new medicines and vaccines
Doctors and HCPs are encouraged to report ADRs
‘It shall be the duty of doctors and other HCPs to immediately report to the
Medicines Authority any suspected adverse drug reaction to a medicinal
product in Malta’ S.L.458.35 Sub-regulation 3(4)

Patients can report ADRs and Medication Errors to HCPs or directly

Marketing authorisation holders remain responsible for products on
the local market
33
Medicines under additional monitoring
• Medicines that contain a new active substance
• All biological medicines including biosimilars
• Medicines for which the marketing authorisation
holder is required to carry out a post-
authorisation safety study (PASS)
• Medicines given conditional approval or
authorised under exceptional circumstances and
medicines authorised with specific obligation on
the recording and monitoring of suspected
adverse drug reactions
34
35
36
• Regulatory Framework
(European and national)

- Medicinal Products

- Marketing authorisation
- Post-authorisation monitoring product safety and
medication errors related to medicinal products
(pharmacovigilance)
- Safety features
37
The Falsified Medicines Directive and Delegated Regulation

The Directive
Directive 2011/62/EU of the European Parliament and of the Council
amending Directive 2001/83/EC on the Community code relating to
medicinal products for human use, as regards the prevention of the
entry into the legal supply chain of falsified medicinal products.
• Published in January 2013
•‘falsified’ refers to all forms of falsification while ‘counterfeit’ refers to
infringement of intellectual property rights

The Commission Delegated Regulation (EU) 2016/161 details the

characteristics of the safety features, how medicine authenticity should
be verified and by whom.
38
 The Falsified Medicines Directive
•Defines Falsified Medicines as any medicinal product with a false
representation of:
a) its identity, including its packaging and labelling, name or its
composition as regards any of the ingredients and their strength,
b) its source, including the manufacturer, country of manufacturing,
country of origin, or its marketing authorization holder; or
c) its history, including the records and documents relating to
distribution channels used.
• Tougher rules on import of active pharmaceutical ingredients
• Strengthened record-keeping requirements for wholesale distributors
• A common, EU-wide logo to identify legal online pharmacies
• Regulated sales of medicines over the internet (established
authorised internet sites)
• Obligatory safety features – a unique identifier (UI) and an anti-
tampering device (ATD) on the outer packaging of medicines
39
• Regulatory Framework
(European and national)

- Pharmaceutical activities

- Clinical trials
- Manufacturing
- Distribution
- Pharmacies
- Regulation of falsified medicinal products
on the market 40
The Medicines Supply Chain, regulation and policies

Research, Manufacture, Prescribing,

Placing Use of
development wholesale Dispensing,
products on medicines by
and clinical dealing and Administration
the market patients
trials pharmacies to patients

Scientific & Authorisation & Inspection & Regulation of Information,

monitoring of licensing of advertising; access and
ethical medicinal pharmaceutical information on affordability of
evaluation products activities medicines medicines
41
 Pharmaceutical Activities and the relevant
principles of good practice
Activity
Clinical trials
Manufacturing of medicinal products
Manufacturing of Active
Pharmaceutical Ingredients (APIs)
Wholesale distribution
Pharmacies
Preparation of medicinal products in
healthcare establishments for
administration to patients
Pharmacovigilance activities
Principles of good practice
Good Clinical Practice (GCP)
Good Manufacturing Practice
(GMP)
Good Manufacturing Practice
(GMP)
Good Distribution Practice (GDP)
Principles of pharmacy practice
Good Practices for the preparation
of medicinal products in healthcare
establishments (Refer to PICS
Guide)
Good Pharmacovigilance Practice
(GPvP)
• Regulatory Framework
(European and national)

- Pharmaceutical activities

- Clinical trials
- Manufacturing
- Distribution
- Pharmacies
- Regulation of falsified medicinal products
on the market 43
• Clinical trials
(refer to lectures 3 & 4)

44
A scheme for new drug development
Years 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Chemistry
Synthesis Manufacturing Scale-up

Pharmacology
Pharmacology Drug
Screening
/side-effects interactions

Toxicology Sub-acute toxicology Chronic toxicology

Acute
toxicology & teratology Carcinogenicity

Pharmacokinetic
Animal Human
s metabolism metabolism

Pharmacy/ Formulation Packing & Long term

Pharmaceutical & stability dosage form stability tests

Medical Efficacy & safety Effic &

Pharmacology
dose ranging – safety –
Phase I Phase II Phase III
Registration
Consideration of regulatory needs Compilation of Product license
regulatory documents granted
Steps in a clinical trial
• Regulatory Framework
(European and national)

- Pharmaceutical activities

- Clinical trials
- Manufacturing
- Distribution supply chain
- Pharmacies
- Regulation of falsified medicinal products
on the market 47
 The legal medicines supply chain for
authorised medicinal products

APIs & Excipients

Wholesale
Dealing Pharmacies
& Distribution
(if within the EU)

Finished Dosage Form Brokers

Manufacturer

Import Patients
(if outside EU)

48
49
 Distribution activities
Distribution involves the stages of the supply chain from
the site of manufacture to the pharmacy.

In Malta medicines can only be sold from pharmacies.

• Free distribution within the European Union

• Parallel distribution
• Brokering
• Continued supply
• Prevention of penetration of falsified medicines into
the regulated supply chain
• Buying over the internet from unregulated sites
increases the risk of falsified products
• Free zones and free warehouses
• Regulatory Framework
(European and national)

- Pharmaceutical activities

- Clinical trials
- Manufacturing
- Distribution
- Pharmacies
- Regulation of falsified medicinal products
on the market 51
The Falsified Medicines Directive and Delegated Regulation

The Directive
Directive 2011/62/EU of the European Parliament and of the Council
amending Directive 2001/83/EC on the Community code relating to
medicinal products for human use, as regards the prevention of the
entry into the legal supply chain of falsified medicinal products.
• Published in January 2013
•‘falsified’ refers to all forms of falsification while ‘counterfeit’ refers to
infringement of intellectual property rights

The Commission Delegated Regulation (EU) 2016/161 details the

characteristics of the safety features, how medicine authenticity should
be verified and by whom.
52
 The Falsified Medicines Directive
•Defines Falsified Medicines as any medicinal product with a false
representation of:
a) its identity, including its packaging and labelling, name or its
composition as regards any of the ingredients and their strength,
b) its source, including the manufacturer, country of manufacturing,
country of origin, or its marketing authorization holder; or
c) its history, including the records and documents relating to
distribution channels used.
• Tougher rules on import of active pharmaceutical ingredients
• Strengthened record-keeping requirements for wholesale distributors
• A common, EU-wide logo to identify legal online pharmacies
• Regulated sales of medicines over the internet (established
authorised internet sites)
• Obligatory safety features – a unique identifier (UI) and an anti-
tampering device (ATD) on the outer packaging of medicines
53
Implementation of safety features under the FMD
• Rules applicable in the EU/EEA on 9th February 2019 (Article
50 of Commission Delegated Regulation (EU) 2016/161).
Greece and Italy benefit from an additional 6 year transitional
period.
•Prescription medicines placed on EU market will need to carry
safety features:
-unique identifier (UI) – bar code including serial number
-anti-tampering device (ATD) e.g. foil seal, breakable cap
•Repository system set by stakeholders: European hub and
national databases
•MAHs, wholesalers and those supplying medicines to the
public will need to scan medicines at different points of the
supply chain: introduce them into the repository, verify their
authenticity and decommission them from the database
(standards for pharmaceutical activities) 54
 Implementation of safety features
• Ensure medicines in EU carry safety features
• Information on safety features must be included in marketing authorisation application
• MAHs must sign contracts with National Medication Verification Organisations (NMVOs) in the MSs where they
Marketing market their products (in Malta MaMVO Malta Medicines Verification Organisation https://www.mamvo.org)
•
Authorisation MAHs or their manufacturers must store the required data on the unique identifier in the repository system
Holders • MAHs must also connect (onboard) to the European Medicines Verification Organisation (EMVO)

•
Manufacturing
and • Must keep records of the operations they perform with UI and together with MAH, ensure the
importation upload of the UI data via the European hub
authorisation
holders
(parallel
importers)

• must connect to national repositories to verify and decommission unique identifiers

• Verification of authenticity of UI is required for all products received from wholesalers who are
Wholesale not the MAH, manufacturer, or designated by the MAH
distributors • Any products returned by pharmacies or another wholesaler must also be verified
including • Wholesalers must decommission the UI of the products they export outside the EEA or on
parallel
distributors behalf of persons supplying medicines to the public

• Community pharmacies (at time of dispensing), hospital pharmacies (after

Persons receipt of medicines) and healthcare institutions (after receipt of medicines)
authorised or must verify the safety features and decommission the UI
entitled to
supply
medicines to
the public 55
• The pharmaceutical market
• Pricing and reimbursement of medicinal
products
• Health Technology Assessment

- National competence

56
Demand and supply in pharmaceutical markets

57
 The pharmaceutical market

Demand side Supply side

Consumers (patients) Manufacturers (originators, generics

Prescribers or both types)
Pharmacies Wholesalers
Health insurance schemes (private or Pharmacies (‘Brick and mortar’,
public) online, mail-order, hospital)

58
 Marketing authorisation and technology
appraisal
• Regulatory Agencies (e.g. Medicines Authority)
- Marketing authorisation of the medicinal product:
quality, safety, efficacy
- Does the product work?
- Is it safe?
- Pharmacovigilance

• Health Technology Appraisal (Ministry for Health in

Malta, NICE in the UK)
- cost-effectiveness
- How good is it ?
- How does it compare to other treatment?
- What is its value?
 Medicines within the National Health
Services in Malta
• SL 458.31 Availability of medicinal products within the
Government Health Services Regulations
http://justiceservices.gov.mt/DownloadDocument.aspx?app=lom
&itemid=11269&l=1

The Government Formulary List

Medicines which are available through the Government Health
Services
Protocols
Guidelines

https://deputyprimeminister.gov.mt/en/pharmaceutical/Pages/f
ormulary/formulary.aspx
 NICE (UK)
• Technology appraisal
- Guidance on the use of new and existing medicines
and treatments within the NHS in England and Wales

• Clinical guidelines
- Guidance on the appropriate treatment and care of
people with specific diseases and conditions within the
NHS

• Interventional procedures
- Guidance on whether interventional procedures used
for diagnosis or treatment are safe enough and work
well enough for routine use

https://www.nice.org.uk/about/what-we-do/our-
programmes/nice-guidance/nice-technology-appraisal-
guidance/process
 Medical Technologies covered by NICE
Technology Appraisal Guidance
• Medicinal products
• Medical devices (e.g. hearing aids, blood pressure
monitors)
• Diagnostic techniques (tests used to identify diseases
e.g. prostate cancer gene 3 (PCA3) assay)
• Surgical procedures or other therapeutic techniques
(e.g. repairing hernias)
• Health promotion activities (e.g. ways of helping
people with diabetes manage their condition)
• Systems of care
• Screening tools

https://www.nice.org.uk/about/what-we-do/our-
programmes/nice-guidance/nice-technology-appraisal-
guidance/process
Pharmaceutical product life-cycle

63
 Competition on innovation
• Innovation is driven by:
- the demand for new, more effective and safer medicines
- The life-cycles of medicines
- The threat of competition (Generic competition after loss of exclusivity

• Medicines have high development costs

• Relatively easy for competitors to copy a medicine
• Legislation grants originator companies various exclusivity mechanisms
to provide incentives to invest in R&D
• Patents and other exclusivities provide a period of protection against
generic products
• Exclusivities are limited in time – allowing entry of generic medicines at
the end of the exclusivity

• Enforcement in the pharmaceutical sector

- Antitrust rules – the prohibition of restrictive agreements and abuses of a
dominant position by pharmaceutical companies
64
- Review of mergers and acquisitions
 Patents
• The substance (active ingredient) in an originator medicine is
patented ‘compound’ or ‘primary’ patents.
• Patents provide the originator with an exclusive civil right to the
commercial exploitation of the invention for up to 20 years from the
patent application. Manufacturers usually apply for patents very
early in the development process.
• No competitor can sell a medicine can sell a medicine containing the
active ingredient which is patent protected.
• Supplementary Protection Certificates (SPC) can extend the period
of patent protection by up to 5 years. SPCs are created to
compensate for the period of exclusivity lost by the manufacturer
due to long periods needed to obtain MA for patented medicine.
• While the product is on the market manufacturers may continue to
improve its manufacturing process, pharmaceutical form and/or
composition. These improvements may result in patentable
innovation ‘secondary patents’.
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 Other exclusivities
• Market exclusivity
- The generic medicine cannot enter the market and compete with the
originator medicine until 10 years have passed from the date of the
MA to the originator medicine.
- Orphan medicines also benefit from a period of 10 years of market
exclusivity in which no similar medicine to treat the same disease
can be marketed.
- When medicines used by adults are adapted to meet the medical
needs of children, this may be rewarded by an additional period of
exclusivity (SPC, data or market exclusivity).

• Data exclusivity
The originator medicine enjoys 8 years of exclusivity over the data on
pre-clinical and clinical studies submitted to obtain the MA.
During the data exclusivity period companies (typically generic
producers) cannot apply for a MA for the same medicine by way of
an abridged MA procedure, which relies in part on the data for the
originator medicine. 66
• EPAR Cominarty

Comirnaty, INN-COVID-19 mRNA Vaccine

(europa.eu)

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