investigational product (imp) (drug and medical device)

Investigational product (IMP)

(Drug and medical device)

Cristiana Sessa

GCP – Investigator Level

Content

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• Definition of drug and medical device

• Handling, storage, documents, distribution

• Labelling

• Documents and accountability

Investigational product and pharmaceutical

compounds (IMP)

1. A pharmaceutical form of an active ingredient or placebo being tested

or used as a reference in a clinical trial

2. If a product has a marketing authorization it could be an IMP when it is

used for an unapproved indication

• When assembled (formulated or packaged in a way different from

the approved one

• To gain further information about an approved use

3. A drug without a marketing authorization

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IMP

Information requested

4

Preclinical Phase

• Adequate information on toxicology and antitumor activity

• Clinical data to justify new features of the protocol (schedule of treatment eligibility criteria, schedule of investigations)

Investigator

Sponsor Compilation and

update of the

Investigator

Brochure (IB)

(ICH7)

Responsibility

Competence in the

interpretation of the

data

Investigator Brochure (IB)

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Definition

A compilation of the clinical and non clinical data on the investigational product relevant to the study of the investigational product in human subjects (ICH GCP 1.36)

Purpose

To provide to the study team the information to justify the rationale for and their compliance with many key features of the protocol (schedule, dose, safety procedures)

• To improve compliance and clinical management

• To enable the clinician to make his /her own unbiased risk-benefit assessment

Format

Concise, simple, balanced, non–promotional form

Extent of information according to the stage of clinical development

For marketed compound the package leaflet may be an appropriate alternative

Specific IB for a new indication

Annual revision

Investigator Brochure (IB)

Content

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Summary

Introduction

Physico-chemical characteristics, information preclinical and pharmacological clinical relevant for clinical development and the study protocol (also toxicity and antitumor activity)

Instructions for storage and handling

Post-marketing clinical information

Summary and recommendations for the investigator

Knowledge of potential risks and toxicities of

the treatment and of the measures to decrease

their occurrence

Medical Device (WHO)

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Instrument, apparatus, implement, machine, appliance, implant, reagent

for in vitro use, software, material or other similar or related article to be

used for human beings for specific medical purpose(s)

Diagnosis, prevention, monitoring treatment or alleviation of disease

Diagnosis, monitoring, treatment, alleviation for or compensation for

an injury

Investigation, replacement, modification or support of the anatomy or

of a physiological process

Providing information of means on in vitro examination of human

specimens

Doesn’t achieve its primary intended action by pharmacological

immunological or metabolic means but which may be assisted in its

intended function by such means.

Medical Device

Essential requirements

The main mechanism of action is physical

Should be for clinical use

Should have a medical indication

Could be a software if it meets the above requirements

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Medical Device

Classification

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Based on the indication and other factors such as:

Duration of use: Transitory < 60 minuti

Short-term ≤ 30 giorni

Long-term > 30 giorni

Invasive or surgically invasive

Implant needed or already active

Local vs systemic effects

Medicated or non-medicated

Medical Device

Classification (EU) according to risk

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Class Risk Example

Class I Low Colostomy bag

Class II (a) medium MRI, syringe for infusion pump

Class II (b) Medium/high Ureteral stent, defibrillator

Class III High Medicated stent, heart valves,

pacemakers, hip-joint implants

Medical Device

Requirements and indication for use

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The amount of data required is proportional to the risks

The indication for use define the class of risk, the

requirements and the clinical data required

The indication for use should be reported in the label, in the

leaflet and in the promotional materials

Medical Device

Essential requirements for CE marking

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Risk should be acceptable when weighed against the

benefits to the patient

The device must be designed and manufactured reflecting

the latest scientific and technical knowledge

Should be used according to indications for use of the

manufacturer

Should be evaluated clinically according to appropriate

investigations (class II,III)

A C

bears a conformity marking

and

It is used in accordance with the instructions

Doesn’t have a conformity making

It is not used in accordance with the intended purposes specified in the instructions

Use prohibited in Switzerland

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Medical Device (OSRUm Art. 20)

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Clinical studies Categories Criteria of assessment

Clin

ica

l stu

die

s

OS

RU

mMedicinal products A B C Registration, professional

informations, international

directives

Medical Device A C CE marking, instructions for use

Other clinical

investigations

A B Risks, inconveniencies,

internationals directives

non-c

linic

alstu

die

s

OR

Um

Collection/sampling

of biological

materials/ health

personal data

A B Risks, inconveniences

OSRUm OSRUm-Dmed ORUm

Omologazione,

informazione

professionale,

direttive intl.

Rischi,

incomodi

direttive

intl.

Marchio di

conformità (CE),

istruzioni d’uso

Categorizzazione in base a

rischi e incomodi

LRUm

Autorità coinvolte in base all’oggetto dello

studio e alla categoria

Sperimentazioni cliniche con agenti terapeutici o con dispositive medici

Comitato etico

Categoria A

Categoria B

Categoria C

Swissmedic

Categoria B

Categoria C

Categoria A

Altre sperimentazioni cliniche: Comitato etico

Studi clinici con dispositivi medici- categorizzazione e procedura

(definizioni OSRUm-Dmed Cap 2 e MDR Cap III; NEW: tempistiche)

Utilizzato conformemente a

istruzioni per l’uso, con

procedure supplementari

invasive o gravose

Com

ita

toetico

Classi IIa invasivo, IIb, III

Non utilizzato conformemente

a istruzioni per l’uso

Classi I, IIa non-invasivo

(definizioni MDR Cap III)

Classi I, IIa non-invasivo

Iniz

iost

ud

io

EUD

AM

ED, se

per

ottene

rem

ach

iodi co

nform

ità

Non utilizzato conformemente

a istruzioni per l’uso

Classi IIa invasivo, IIb, III

(definizioni MDR Cap III)

Studio clinico

con

Dispositivo

Medico (MD);

procedure

diverse se

per ottenere

o no il

marchio di

conformità

MD

con

cert.

CE

MD

senza

cert.

CE

Utilizzato conformemente a

istruzioni per l’uso, senza

procedure supplementari

invasive o gravose

Sw

issm

ed

ic

A1

A2

C1

C2

C3

C4

Eccezioni

possibili

Eccezioni

possibili

Medical Device

Conformity mark

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It is a legal mark:

The manufacturer declares that the product complies with the

EU health, safety and environmental requirements of the

relevant directives (MDR 2017/745).

The product can be placed on the market of all the EU

members of the European community

Medical Device

Notified bodies

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Organizations designated by an EU country to assess the

conformity of certain products before being placed on the

market according to principles laid down in Decision

768/2008/EC

Must operate in a non discriminatory, transparent, neutral,

independent, and impartial manner

More rigid criteria for the designation and control on the

activities of the notified bodies (MDR 2017/745)

New regulation on medical device (MDR

2017/745)

Main changes

Implementation of an authority responsible for the assessment, designation

and notification of conformity assessment bodies and for their monitoring

Re-certification for some MD

Greater pre-marketing control on high risk MD

European data base of MD with an identification code (UDI)

Clear and defined rules for clinical data, with an European coordination for

the authorization of multicentric studies

More rigid criteria of post-marketing surveillance

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Mandatory from May 2021

Investigational Medicinal Product (IMP)Handling of IMP in a clinical study

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Sponsor/CRO

PI

Pharmacy

Subject

IMP lost% compliance

IMP = medicinal product or placebo or control

Written documentation

of all stepsPI can delegate all or

some of the

responsibilities to the

pharmacist

Investigational Medicinal Product (IMP)

Manufacturing and labelling

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Sponsor responsibility (GCP 5.13.1)

The sponsor should ensure that the IMP (including comparator) and

placebo (if applicable) is characterized as appropriate to the stage of

development and is manufactured in accordance with applicable GMP and

is coded and labelled in a manner that protects the study blinded

The labelling should comply with applicable regulatory requirements


Responsibilities of the investigator

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Accountability

Storage

Distribution and administration

Return of non used IMP to the sponsor

Redistribution

Final accountability

Keep always a registry


Accountability (ICH 4.6)

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Responsibility of the investigator

The investigator and/or a pharmacist or other appropriate

individual, designated by the investigator, should maintain

records of the product’s delivery to the trial site, the inventory

at the site, the use by each subject, and the return to the

sponsor or alternative disposition of unused product(s).

These records should include dates, quantities, batch/serial

numbers, expiration dates (if applicable) and the unique code

numbers assigned to the investigational products and trial

subjects


Accountability record

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Storage and use according to protocol

(ICH GCP 4.6)

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The investigator is responsible for the storage of IMP at the conditions

specified by the sponsor (temperature, protection light), storage times,

reconstitution fluids and procedures, and devices for product infusion, if

any

The investigator should explain the correct use of IMP to each subject

and should check, at intervals appropriate for the trial, that each subject

is following the instructions properly


Storage in the pharmacy

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In a locked cabinet or in an area with a safe storage space and limited

controlled access

In a space separate from those of drugs non used in trials

In a space storage different for each study

with a constant monitoring of temperature (internal for the fridge and

external for the room)


Distribution and administrance

Responsibilities of investigator

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Administer the IMP only to patient entered in the study and

according to protocol

Verify patient’s compliance

Assure and control

Patient diary

Hospital patient records

Accountability registry

Source documents


Compliance and accountability

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Compliance is a measure of how much the patient has been

treated according to protocol

The evaluation of compliance could define to which extent

negative results could be caused by a low compliance or by other

factors

Thank you for your attention

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