Annex 4 to Item 4

Annex 4 to Item 4.1.2 of the Procedure for Conducting Clinical Trials of Medicinal Products and Expert Evaluation of Materials Pertinent to Clinical Trials

Application form

request for authorization of clinical trial oF medicinal product to theStatePharmacologicalcenterMoH Ukraine and for opinion of the ethics committee

For restricted use of the StatePharmacologicalCenter MoH Ukraine and Ethics Committee:

Request received on: / Additional information requested on: / Grounds for negative opinion:
Information to make it valid requested on: / yes  / no 
If yes, date:
Date of valid application:
Date of start of procedure: / Date of receipt of additional/amended information: / Positive opinion/authorization:
yes / no 
If yes, date:
The State Pharmacological Center MoH Ukraine (SPhC MoH Ukraine) or Ethics Committee registration number:

To be filled in by the applicant:

Thisformiscommonforgetting authorizationfromSPhCMoHUkraineandEthicsCommittee. Please indicate the relevant purpose in a box below.

Request for Authorization of the SPhC MoH Ukraine:



Request for Opinion of the Ethics Committee:



А. Trial Identification

Full title of trial:
Sponsor’s protocol code number, version, and date[1]:
EudraCT[2] number
Nameorabbreviatedtitleoftrial,whereavailable:
ISRCTN[3] number, if available:

С. APPLICANT IDENTIFICATION(please tick appropriate box)

С1. Request to SPhC MoH Ukraine /  / С2. Request to the Ethics Committee / 
- Sponsor /  / - Sponsor / 
- Legal representative of the sponsor /  / - Legal representative of the sponsor / 
- Personororganizationauthorizedbythesponsorto make the application. In that case complete below: /  / - Personororganizationauthorizedbythesponsorto make the application. In that case complete below: / 
-Organization: / - Organization:
-Name of contact person: / - Name of contact person:
-Address: / - Address:
-Telephone number: / - Telephone number:
-Fax number: / - Fax number:
-E-mail: / - E-mail:
-Investigator in charge of the application Investigator in charge of the application:
• Coordinating investigator (for multicenter trial where available) / 
• Principalinvestigator(forsinglecentertrial) / 
When the application is submitted to the Ethics Committee by investigator,complete below:
-Name:
-Address:
-Telephone number:
-Fax number:
-E-mail:

D. Informationoninvestigationalmedicinalproduct(s) beingusedinthetrial: medicinal product being tested or used as comparator

Information on each “bulk product” before trial specific operations (blinding, trial specific packaging and labeling) should be provided in this section for both the medicinal product being tested and the product being used as a comparator. Information on placebo, if relevant, should be provided in section E.If the trial is performed with several investigational medicinal products (IMP), use extra pages and give each IMP a sequential number; information should be given for each product, likewise if the product is a combination product information should be given for each active substance.

Indicatewhichofthefollowingisdescribedbelow, thenrepeatasnecessaryforeachofthenumberedIMPstobeusedinthetrial (assignnumbersfrom 1-n):
Information refers to the IMP number: (...... )
IMPbeingtested / 
IMPusedascomparator / 

D.1. Status of the investigational medicinal product to be used in the trial

D.1(a) Has the IMP to be used in trial a marketing authorization (MA): / Yes / No / If yes, specify the following
Trade name[4] / Name of the MA holder4 / MA number 4
• in Ukraine /  / 
• in another country. If yes, please, specify: /  / 
D.1(b) SituationwheretheIMPtobeusedintheCThasaMAinUkrainebuttheprotocolallowsthatanybrandoftheIMPwithaMAinUkrainebeadministeredtothetrial subjectsanditisnotpossibletoclearlyidentifytheIMP(s) inadvanceofthetrialstart: / Так / Ні
Inthe protocol,istreatmentdefinedonlybyactivesubstance?
- if yes, go to D.2 /  / 
Intheprotocol,treatmentregimensallowdifferentcombinationsofmarketedproductsto be usedat some or all clinical bases
-If yes go to D.2 /  / 
Theproductstobeadministered asIMPsaredefinedasbelongingtoanATCgroup
- if yes give the ATC group (level 3 or more to the level that can be defined) of the applicable authorized codes in the ATC code field in D.2 of this form555 /  / 
Other:
- if yes, please, specify: /  / 
Hastheuseof the investigationalmedicinalproductbeenpreviouslyauthorizedina clinical trial in Ukraine?
Yes / No
Hastheuseoftheinvestigationalmedicinalproductbeendesignatedinthisindicationasanorphandrug?
Yes / No
If yes, give the orphan drug designation number[5]:

D.2. Description of the investigational medicinal product

Product name[6]:
Product code (where applicable)[7]:
Nameofeachactivesubstance (INNorproposedINNif available, specify whether proposed or approved INN):
Otheravailablenameforeachactivesubstance (CAS, currentsponsorcode(s), other descriptive name, etc.: provide all available):
АТС code, if officially registered[8]:
Pharmaceuticalform (use standard term):
Methodofadministration (use standard term):
Strength(specifyallstrengthstobe usedintrial):
- concentration (number):
- concentration unit:
- concentrationtype (underline the appropriate: «exact number», «range», «more than» or «up to»)
Type of medicinal product
Does the investigational medicinal product contain an active substance:
- of chemical origin? / Yes  / No
- of biological/biotechnological origin[9]? / Yes  / No
Is this:
1) a celltherapymedicinalproduct9? / Yes  / No 
2) agenetherapymedicinalproduct9? / Yes  / No 
3) aradiopharmaceuticalmedicinalproduct? / Yes  / No 
4) an immunological medicinal product9? / Yes  / No 
5) aherbalmedicinalproduct? / Yes  / No 
6) a homeopathic medicinal product? / Yes  / No 
7) a medicinal product containing a genetically modified organisms9? / Yes  / No 
Ifyes,
- Hastheauthorizationforcontaineduseorreleasebeengranted? / Yes  / No
- Or is it pending? / Yes / No
8) another type of medicinal product? / Yes  / No
If yes, specify:

D.3. Biological/biotechnologicalinvestigationalmedicinalproducts

Type of product
- Extractive / Yes / No
- Recombinant / Yes  / No 
- GMO / Yes  / No 
- Blood and plasma derived products / Yes  / No
- Others / Yes  / No 
If others, specify:

D.4. Somaticcelltherapyinvestigationalmedicinalproduct (nogeneticmodification)

Origin of cells

- autologous / Yes  / No 
- allogeneic / Yes  / No 
- xenogeneic / Yes  / No 
Ifyes,specifyspeciesoforigin:
Type of cells
- stem cells / Yes  / No
- differentiated cells / Yes  / No
Ifyes, specifythetype (keratinocytes, fibroblasts, chondrocytes, etc.):
- Others: / Yes  / No
If others, specify:

D.5. Genetherapyinvestigationalmedicinalproduct

Gene(s) of interest:
In vivo gene therapy: /  / Ex vivo gene therapy: / 

Typeofgenetransferproduct

- Nucleicacid (e.g., plasmide): / Yes  / No 
If yes, specify
- if naked: / Yes  / No 
- or complex: / Yes  / No 
- Viral vector: / Yes  / No 
Ifyes, specifythetype: adenovirus, retrovirus, AAV, etc.:
- Others: / Yes  / No 
If others, specify:

Е. Informationonplacebo (if more than one used – repeat for each)

Is there a placebo used: /  Yes  No
Information refers to placebo number № (...... )
WhichIMPisitaplacebofor? (specifynumber(s) of investigational product fromD)
Pharmaceutical form:
Method of administration:
Composition apart from the active substance(s):
- is it identical to the IMP?
- ifnot,specifymajoringredients: / Yes  No 

F. Authorized manufacturing site responsible for the release of the investigational medicinal product

Thissection deals withfinishedinvestigationalmedicinalproduct and comparator product, i.e. medicinalproductsrandomized, packaged, labeledandreleasedforuseintheclinicaltrial. If there is more than one site or more than one IMP is released, use extra pages and give each IMP its number from D or E for any placebo. In case of multiple sites, indicate the product released by each site.

WhoisresponsibleforthereleaseofthefinishedIMP (please tick the appropriate box):
Thismanufacturingsiteisresponsibleforreleaseof (specifythenumber(s) fromDof the IMP and E for the placebo): ……....
- Manufacturer / 
- Importer
- Both manufacturer and importer / 

- Name of organization:
- Address:
- Please give the manufacturer or importer authorization number:
If no authorization, give the reason:
Hasthesitebeeninspectedbycompetentauthorities? / Yes  / No 
Ifyes,date of most recent inspection and who performed it:

G. General information on the trial

Pathological state or disease under investigation

Specify pathological state (free text):
ICDclassificationcode (ICD-10)[10]:
MedDRA classification code[11]:
Is it a rare disease[12]? / Yes  / No 

Objective of the trial

Main objective:
Secondary objectives:
Principal inclusion criteria (list most important)
Principalexclusioncriteria(list most important)
Primary end point(s):
Scope of the trial — tick all the boxes where applicable
- Diagnosis / 
- Prophylaxis / 
- Therapy / 
- Safety / 
- Efficacy / 
- Pharmacokinetics / 
- Pharmacodynamics / 
- Bioequivalence / 
- Dose response / 
- Pharmagenomics / 
- Pharmacoeconomics / 
- Other / 
If others, specify:
 Humanpharmacology (Phase I)
Is the trial:
 First administration to humans
 Bioequivalence study
 Comparative pharmacodynamic study /  Therapeutic exploratory
(Phase II) /  Therapeutic confirmatory
(Phase III) /  Therapeutic use
(Phase IV)
 Comparativeclinicaltrial (generics)
 Other: please specify:
Design of the trial
Randomized: / Yes / No 
Controlled: / Yes / No  / If yes, specify:
Open: / Yes / No
Single blind: / Yes / No  / Double blind: / Yes / No 
Parallel group: / Yes / No  / Cross over: / Yes / No 
Other: / Yes / No  / If yes, specify:
Specify the comparator:
- (an) other medicinal product(s) / Yes / No
- placebo / Yes / No
- other / Yes / No
If other, specify:
Single site (see also section I): / Yes / No
Multiple site (see also section I): / Yes / No 
Multiple trial: / Yes / No 
Maximumdurationoftreatmentofasubjectaccordingtotheprotocol:
Maximum IMPdoseallowed (specify: perdayortotal):
Definitionoftheendoftrialandjustification,inthe case whereitisnotthelastvisitofthelastsubjectundergoingthetrial[13]:
Initial estimate of the duration of the trial (years and months)[14]:
- in Ukraineyearsmonths
- in all countries concerned by the trial yearsmonths

Н. Population of trial subjects

Age span:
 under 18 years
If yes, specify: /  Adult (18–65 years) /  Elderly (> 65 years)
 In Utero
 Preterm Newborn Infants (up to gestational age 37 weeks)
 Newborns (0–27 days)
 Infants (28 days – 24 months)
 Children (2 – 11 years)
 Other juveniles (12–16 years)
 Minors (16–18 years)
Gender:
 Female /  male

Population of trial subjects

Healthy volunteers / Yes  / No 
Patients / Yes  / No
Specificvulnerablepopulations
- women of childbearing age / Yes  / No 
- pregnant women / Yes  / No 
- nursing women / Yes  / No 
- emergency situation / Yes  / No 
- subjectsincapableofgivingconsent personally / Yes 
If yes, specify: / No 
- others / Yes 
If yes specify: / No 
Plannednumberofsubjectstobeincludedintrial:
- in Ukraine
For a multinational trial:
- for the whole clinical trial
Plansfortreatmentorcareafterthesubjecthasendedtheparticipationinthetrial[15] (if it is different form the expected normal treatment of that pathological state):
Уточніть:

I. Proposed clinical trial sites in Ukraine

I.1. Clinicaltrialsite, principalinvestigator (forsinglecentertrial) and/orcoordinating investigator (for multi-center trial)
(see comments in section С2)
Name and address of the clinical trial site / Principal investigator or coordinating investigator
Name / Qualification
I.2. Principalinvestigators (for multi-center trial; where necessary, use other forms)
Name and address of the clinical trial site / Principal investigator
Name / Qualification
I.3. Centraltechnicalfacilitiestobeusedintheconductofthetrial (laboratoryorothertechnicalfacility), inwhichthemeasurementorassessmentofthemainevaluationcriteriaarecentralized (repeatasneededformultipleorganizations)
Organization:
Name of contact person:
Address:
Telephone number:
Dutiessubcontracted:
I.4. Organizationstowhomthesponsoror his legal representative havetransferredtrialrelateddutiesandfunctions(repeatasneededformultipleorganizations)
Hasthesponsor or his legal representative transferredanymajororallthesponsor’strialrelateddutiesandfunctions toanotherorganizationorthirdparty?
Yes  / No 
If yes, specify:
Organization:
Name of contact person:
Address:
Telephone number:
Duties/functions subcontracted:

J. SPhCMoHUkraine / Ethics Committee in Ukraine

IfthisapplicationisaddresstoSPhCMoHUkraine, please,ticktheEthicsCommitteeboxand give information on the Ethics Committee concerned and vice versa
SPhC MoH Ukraine / 
Ethics Committee / 
Name and address:
Date of submission: /
Authorization /opinion: /  to be requested  pending
 given
If given, specify: / Date of authorization/opinion:
 authorization accepted/opinion favorable:
 not accepted /not favorable.
If not acceptable /not favorable, give:
- reasons
- eventual anticipated date of resubmission

K. Checklistoftheinformationappended to the application form

InformationthatSPhCMoHUkraineandEthicsCommittees (EC)of Ukraine require according to item 4.1 and sub-item 5.2.1 of item 5.2 of this Procedure
EC / SphC[16]
 /  / Cover letter
 /  / Application form
 /  / Receiptofconfirmationof EudraCT number (when available)
 /  / Protocol with all current amendments
 /  / Investigator’sbrochureoritsequivalent
 /  / Investigational Medicinal Product Dossier (IMPD)
 /  / Simplified IMPD for know products
 /  / SummaryofProductCharacteristics (for medicinal products registered in Ukraine)
 / Case report form (except for multinational clinical trials)
 /  / Copy of Ethics Committee opinion (where available)
 /  / Letter of authorization enabling to act on behalf of the sponsor (if applicant is not the sponsor)
Additional information for special situations
 / Copyofauthorizationforcontaineduseorreleaseofgeneticallymodified organismsinenvironment (whenapplicableandavailable)
Subject-related information
 /  / Subject information leaflet andinformed consent form
 /  / Othersubjectrelatedinformation (diary, checklists, case histories, etc., list appropriate):
 / Arrangement for recruitment of subjects
Protocol-related information
 /  / Summary of the protocol
 / Expert evaluation of clinical trial (when available)
 / Ethicalassessmentmadebytheprincipal/ coordinating investigator
 / SignedanddatedcurrentCVsof principal investigators of each site
IMP related information
 /  / Examplesoflabelwith product information in understandable language
 /  / Applicableauthorizationstocovertrialsorproducts with special characteristics (if available) eg. genetically modified organisms (GMO), radiopharmaceuticalproducts
 / TSE certificate (when applicable)
 /  / Certificateofanalysisfortestproduct
IfIMPmanufacturedoutsideUkraine
 /  / Declarationthatthemanufacturingsiteworksincompliancewith good manufacturing practice(GMP), or its equivalent
If IMPmanufactured in Ukraine
 / Copy of manufacturing authorization stating the scope of this authorization;
 / Informationabout IMPsiteofmanufacturing
 / CertificateofIMPorigin
 / Informationaboutproduction techniqueanddocumentationformanufacturingandqualitycontrolof medicinal product;
 /  / Declarationthatthemanufacturingsiteworksincompliancewithgoodmanufacturingpractice (GMP) oritsequivalent
IfsiteisnotincludedtotheMoHUkraineapprovedListofhealthcaresettingswhereclinicaltrialscanbeconducted and planned to be usedin clinical trial once only:
 /  / Applicationletterfromprincipalinvestigator (freetext) toincludeclinicaltrialsiteinthegivenclinicaltrial
 /  / Card of certification of clinical site
 /  / SignedanddatedcurrentCVsof investigators
Finance-related information
 /  / Documentconfirmingpatients’ (healthy volunteers’) lifeandhealthinsurance
 /  / Other documents

L. Signature of the applicant in Ukraine

Iherebyconfirmthat, |confirmonbehalfofthe sponsorthat (deleteinappropriate):
-the information given in this request is correct;
-thetrialwillbeconductedaccordingtotheprotocol, nationalregulationsandprinciplesofgoodclinicalpractice;
-it is reasonable for the proposed clinical trial to be undertaken;
-IwillsubmitafinalstudyreporttotheSPhCMoHUkraineandtherelated EthicsCommitteewithin 1 yearaftertheendofstudyinallcountries(iftrialismultinational);
-Iwilldeclaretheeffectivedateofstartoftrial[1]7totheSPhCMoHUkraineandEthicsCommittee.
Applicant of the request to SPhC MoH Ukraine
Date: / Applicant of the request to the Ethics Committee
Date:
Signature: / Signature:
Print name: / Print name:

V.T. Chumak

Director,

State Pharmacological Center MoH Ukraine

[1]Any translation of the protocol should be assigned the same date and version as those in the original document.

[2]Stated if available.

[3]ISRCTN - International Standard Randomised Controlled Trial Number.

[4] Available from the Summary of Product Characteristics.

[5]AccordingtotheCommunityregisteronorphanmedicinalproducts (regulationEC №141/200) another International register (please specify).

[6]Intheabsenceofa tradename, thisisthe name routinely used by the sponsor to identify the IMP in the CT documentation (protocol, investigator’s brochure, etc.).

[7] Intheabsenceofa tradename, thisisa code designated by the sponsor which represents the name routinely used by the sponsor to identify the product in the CT documentation. This code is potentially used in the case of combination of medicinal products or medicinal products and devices.

[8] Available from the Summary of Product Characteristics.

[9] Complete also sections D.3, D.4 or D.5.

[10] Source: World Health Organization.

[11] The information on the ICD-10 and MedDRA (the Medical Dictionary for Regulatory Activities) classification is optional. Whenbothclassifications codes areavailableonlyoneshouldbeprovided; in this it is recommended to provide the MedDRA classification code.

[12] Points to consider on the calculation and reporting of the prevalence of a pathological state for orphan drug designation: COM/436/01 (

[13] If not provided in the protocol.

[14] from the 1st inclusion until the last visit of the last subject.

[15]If not specified in the protocol previously.

[16] Tick all boxes to show information provided to the Ethics Committee concerned and SPhC MoH Ukraine.

[1]7 Inclusion of the 1st patient in Ukraine (inclusion starts with the informed consent signature).