MINISTRY OF HEALTH OF UKRAINE

ORDER

27.12.2012 No. 1130

Registered with the Ministry

of Justice of Ukraine

on January 21, 2013

under No. 133/22665

On approving the verification procedure for medicinal product manufacturing

compliance with the Good Manufacturing Practice requirements As per Article 9 Law of Ukraine "On Medicinal Products", paragraph 3 The Procedure for

State Registration (Reregistration) of Medicinal Products, as approved by the order of the Cabinet

of Ministers of Ukraine on May 26, 2005 No. 376, Procedures for State Quality Control of

Medicinal Products imported to Ukraine, as approved by the order of the Cabinet of Ministers of

Ukraine on September 14, 2005 No. 902 (as amended by the regulation of the Cabinet of Ministers

of Ukraine dated August 08, 2012 No. 793), I HE RE WIT H DE CREE :

1. To approve the verification procedure for medicinal products manufacturing compliance

with the Good Manufacturing Practice requirements that is attached.

2. To recognize the order of the Ministry of Health of Ukraine dated October 30, 2002 No.

391 "On Approving the Medicinal Products Manufacturing Certification Procedure" registered with

the Ministry of Justice of Ukraine on November 22, 2002 under No. 908/7196 as such that ceased to

be in force.

3. The Department for Medicinal Products and Medical Devices of the Ministry of Health of

Ukraine is to submit this order for state registration to the Ministry of Justice of Ukraine as

established by law.

4. The execution of this order shall be controlled by the Deputy Minister - Chief of Staff R.

Bohachov.

5. This order takes effect since the day of its official publication.

Minister R. Bohatyrova

APPROVED

Order of the Ministry

of Health of Ukraine

27.12.2012 No. 1130

Registered with the Ministry

of Justice of Ukraine

on January 21, 2013

under No. 133/22665

THE PROCEDURE

for verification of medicinal products manufacturing compliance with the Good

Manufacturing Practice requirements

I. General provisions

1.1. This Procedure has been developed based on the Law of Ukraine "On Medicinal

Products", taking into consideration the requirements of directives 2001/83/EU, 2003/94/EU of

European Parliament and the Council (hereinafter EU), the recommendations of the International

Pharmaceutical Inspection Cooperation Scheme (PIC/S) (document РІ 002) and the World Health

Organization (WHO TRS No. 908, 2003).

1.2. Verification of medicinal products manufacturing compliance with the good

manufacturing practice (hereinafter GMP) requirements applicable in Ukraine has been

implemented to prove that medicinal products are continuously manufactured and inspected in

accordance with quality standards pertaining to their intended use, as well as requirements of master

files or specifications for such products. Verification of active pharmaceutical ingredients

(substances) manufacturing compliance with GMP requirements is performed upon a applicant’s

request.

1.3. Verification of manufacturing compliance with GMP requirements for residents and non-

residents is performed by the State Administration of Ukraine on Medicinal Products by conducting

the expert examination of the documents submitted under this Procedure and inspecting the

manufacturing facilities in cases as provided for by this Procedure.

1.4. According to this Procedure the verification of manufacturing compliance with GMP

requirements is performed at the manufacturing sites, as per the respective request:

for issuing the GMP requirements compliance certificate according to Annex 1 to this

Procedure (hereinafter Certificate Application);

for issuing the opinion on GMP requirements compliance verification according to Annex 2 to

this Procedure (hereinafter Opinion Application) (in case a manufacturer has an official document

on the compliance of medicinal products manufacturing with GMP requirements issued by a

competent authority of PIC/S Member State).

1.5. Based on this Procedure the State Administration of Ukraine on Medicinal Products issues

the documents validating compliance of medicinal products manufacturing with GMP requirements:

GMP requirements compliance certificate;

opinion on GMP requirements compliance verification.

1.6. The definitions in this Procedure have the following meaning:

an active pharmaceutical ingredient (a medical substance, active substance, substance)

(hereinafter API or active substance) is any substance or a mix of substances intended for use in the

manufacture of product and which becomes its active ingredient during such use. Such substances

have a pharmacological or other direct effect on a human body, they are used in dosage forms for

treatment, diagnostics or prevention of diseases, for changing the state, structures or physiological

functions of an organism, for observation, treatment and improvement of symptoms;

a qualified laboratory - a laboratory for quality control and safety of medicinal products, which

was qualified by the State Administration of Ukraine on Medicinal Products according to the

Procedure for qualification of laboratories for quality control and safety of medicinal products, as

approved by the order of the Ministry of Health of Ukraine on January 14, 2004 No. 10 and

registered with the Ministry of Justice of Ukraine on January 30, 2004 under No. 130/8729;

manufacturer of medicinal products - an economic entity (a legal person) which performs at

least one of the manufacturing stages and has a license (authorization) for medicinal products

manufacturing (as provided for in the legislation of the state on the territory of which the

manufacturer's facilities are located);

medicinal products manufacturing - activities relating to batch production of medicinal

products, which involve all or at least one process stage, including purchase of materials and

products, filling, packing and/or labelling, storage, respective control, issue of batch releases, as

well as wholesale trade (distribution) of own products;

an opinion on the verification of medicinal product manufacturing compliance with GMP

requirements (hereinafter Opinion) - a document issued by the State Administration of Ukraine on

Medicinal Products which testifies that based on the results of conducted expert examination of

submitted documents an official document on compliance of medicinal product manufacturing with

GMP requirements issued by a competent authority of PIC/S Member State is considered as such

that proves the compliance of medicinal product manufacturing with GMP requirements applicable

in Ukraine;

an applicant - a legal or a physical person (economic entity) - is a holder of a registration

certificate (marketing authorization) and/or medicinal product manufacturing license, who submits

personally or through an authorized person (representative) residing in Ukraine an application to the

State Administration of Ukraine on Medicinal Products for the issue of Certificate or Opinion, and

who is responsible for reliability of submitted information and documents;

a sample from a batch - a part of a batch sampled in a way and at the amount that is

representative for the whole batch;

an inspector - an official of the State Administration of Ukraine on Medicinal Products and/or

specialist, who has a degree in one of the following specialties: pharmacy, industrial pharmacy,

pharmaceutical product technology, chemistry, biology, microbiology, biotechnology, has work

experience in medicinal products manufacturing, quality control, quality management (assurance)

or medicinal products manufacturing, and is attested in GMP issues or is trained in this regard;

inspection (check-up) - evaluation procedure for compliance of company's (manufacturing site)

quality assurance system and the actual medicinal products manufacturing conditions with GMP

requirements applicable in Ukraine at business location (manufacturing facilities location);

PIC/S Member State - a state which has an authorized body in the medicinal products quality

control sector, which is a member of International Pharmaceutical Inspection Cooperation Scheme,

PIC/S;

a critical discrepancy of GMP requirements - a discrepancy (nonconformity) of GMP

requirements of drug master file requirements, which resulted or may result in the manufacture of a

medicinal product with poor quality, wholesale and retail trade of low grade medicinal products that

can be harmful for human health or even life;

laboratory quality analysis of medicinal product samples - analysis of medicinal product

samples for compliance with quality specifications requirements based on quality control

techniques mentioned in the master file materials or techniques as established by the State

Pharmacopeia of Ukraine by means of

conducting respective tests in a qualified laboratory, which results in the issue of a written

statement on the medicinal product batch quality;

Good Manufacturing Practice, GMP - a part of quality assurance system which ensures that

medicinal products are persistently manufactured and inspected based on quality standards

pertaining to their intended use, as well as on the master file requirements and product specification;

other discrepancy of GMP requirements - a discrepancy (nonconformity) of GMP

requirements, which cannot result in the manufacture of poor quality medicinal product, wholesale,

retail trade of low grade medicinal products, and which does not belong to critical or major

discrepancies;

an official document on compliance of manufacture with GMP requirements issued by a

competent authority of PIC/S Member State - GMP compliance certificate or medicinal products

manufacturing license or other document on compliance with GMP requirements issued by a

competent authority of PIC/S Member State;

initial expert examination - inspection of completeness of submitted documents, determination

of necessity to specify the submitted or additional data performed by officials of the State

Administration of Ukraine on Medicinal Products;

verification of compliance with GMP requirements - the procedure for written verification of

compliance of medicinal product manufacturing with GMP requirements applicable in Ukraine

carried out by the State Administration of Ukraine on Medicinal Products;

Applicant's representative (an authorized person acting on behalf of an Applicant - a legal or a

physical person acting based on the respective mandate (power of attorney), in which the Applicant

entitles him to represent his interests when carrying out procedures for verification of medicinal

product manufacturing compliance with GMP requirements, registration, reregistration and/or

making amendments into medicinal products registration materials on the territory of Ukraine;

medicinal product prequalification - a standardized procedure for medicinal product quality

assessment implemented by the World Health Organization (hereinafter WHO) in order to assess

quality, safety and efficiency;

a product for restricted use (orphan product) - a medicinal product intended for diagnostics,

prevention or treatment of a rare disease, i.e. a disease that is life hazardous or results in disability

of normally up to 5 persons of each 10,000 residents by the moment an application is filed for state

registration;

in bulk products - any medicinal product intended for manufacture of a finished medicinal

product, which passed all process stages apart from filling and/or final packing and labelling;

a compliance certificate for GMP requirements (hereinafter Certificate) - a document issued by

the State Administration of Ukraine on Medicinal Products based on the inspection results, which

testifies the compliance of medicinal product manufacturing with GMP requirements applicable in

Ukraine;

a specialized expert examination - examination of documents submitted for compliance with

GMP requirements, analysis of their completeness and reliability of presented information;

a major discrepancy of GMP requirements - a discrepancy (nonconformity) of GMP

requirements that resulted or may result in the manufacture of low grade medicinal product,

wholesale and retail trade of poor quality products, but which cannot cause any harm to human

health of life, or a discrepancy (nonconformity) of product master file requirements, or combination

of several other discrepancies (nonconformities) neither of which can be categorized as major, but

which in total present a major discrepancy (nonconformity) and should be interpreted and defined

as such.

ІІ. GMP requirements compliance verification stages 2.1. Procedure for GMP requirements compliance verification includes the following stages:

submission of an Application for Certificate or an Application for Opinion and issue of a set of

documents as provided in this Procedure to the State Administration of Ukraine on Medicinal

Products;

reviewing and processing of submitted Application for Certificate or Application for

Opinion and a set of documents (including the initial examination and the specialized expert

examination carried out free of charge);

inspection (check-up) of the medicinal products manufacturing site in cases as provided for by

this Procedure;

adoption of a decision on the issue of a document for compliance of medicinal product

manufacturing with GMP requirements applicable in Ukraine or a well-reasoned conclusion on the

refusal to grant such;

making amendments into the existing document on compliance of medicinal product

manufacturing with GMP requirements applicable in Ukraine as stated in this Procedure.

2.2. To validate the compliance of medicinal product manufacturing with GMP requirements

the Applicant (Applicant’s representative) submits to the State Administration of Ukraine on

Medicinal Products an Application for Certificate on form as per annex 1 to this Procedure or

Application for Opinion on form as per annex 2 to this Procedure, with attachment of the following

documents:

1) a copy of an application on medicinal product state registration (reregistration) filed to the

Ministry of Health of Ukraine, certified by Applicant's signature and seal or his representative (if

any) - for medicinal products applied for state registration (reregistration) or when making

respective amendments relating to the change of manufacturer or his production facilities or

entering a new manufacturer into the registration materials of medicinal products registered in

Ukraine (if available);

2) a duly certified copy of an official document, which authorizes economic activity in the

manufacture of medicinal products issued by the respective state authority of the state where

production is located, the manufacturing site mentioned in the Application, and officially certified

translation into Ukrainian and English (for non-residents). If according to the laws of a

manufacturing state the manufacturing license exists only in e-form, the printouts should be given

with references to a respective official website certified by Applicant's signature/seal, and translated

into Ukrainian.

If the said document is added to EudraGMP database, the Applicant gives references to this

database. A copy of such a document is certified by the Applicant;

3) a duly certified copy of an official document issued by the state authority of the state where

production is located on compliance with GMP requirements of the manufacturing site mentioned

in the Application (if available); duly certified copies of annexes to this document listing the

medicinal products (if available) and officially certified translations into Ukrainian and English.

If the said documents are added to EudraGMP database, the Applicant gives references to this

database. A copy of such document with annexes (if available) is certified by the Applicant;

4) a duly certified copy of an official document on production compliance with GMP

requirements issued by a competent authority of PIC/S Member State (if available); duly certified

copies of annexes to this document listing the medicinal products (if available) and officially

certified translations into Ukrainian and English.

If the said documents are added to EudraGMP database, the Applicant gives references to this

database. A copy of such document with annexes (if available) is certified by the Applicant.

5) a copy of Site Master File and its translation into Ukrainian and/or English certified by the

Applicant (for non-residents, except manufacturers the production facilities of which are located on

the territory of PIC/S member states). In case of a repeated verification procedure on compliance

with GMP requirements the site master file copy is submitted if major changes are available;

6) a copy of a report certified by the Applicant that is made based on the results of last

inspection held by a competent authority of PIC/S member state (for non-residents, the

manufacturing facilities of which are located outside the territory of PIC/S member states).

Inspection should be held not later than 3 years before filing an Application. In case a manufacturer

refuses to present a copy of report, the Applicant can request the State Administration of Ukraine on

Medicinal Products if such a report could be given by a competent authority of PIC/S member state

that carried out the said inspection (a copy of manufacturer's letter of refusal is attached to the

request);

7) information on the last inspection carried out within the framework of WHO

prequalification program. The inspection should be carried out not later than 3 years before filing an

Application (for medicinal products supplied to Ukraine by the World Fund that were prequalified

by WHO (if applicable);

8) a statement on the quality of manufactured products, according to annex 3 to this Procedure;

9) a report on the manufacturing site inspection results carried out by state regulatory

authorities, on form according to annex 4 to this Procedure as stated in the Application;

10) the list of medicinal products registered in Ukraine and/or intended to be registered and the

production of which is already implemented (if applicable) or intended to be implemented at the

manufacturing site specified in the Application on form according to annex 5 to this Procedure.

Such a list is submitted in a written form and on the electronic media (Excel file);

11) copies of medicinal product certificate (CPP) for international trade (for nonregistered

medicinal products intended to be registered or obtain extended registration in Ukraine);

12) letters of commitment as per annex 6 (on Form 1 - major changes relating to the

manufacturing site that was validated for compliance of medicinal product manufacturing

conditions with GMP requirements; on Form 2 - on completion of the verification procedure or

submission of a report on the last inspection carried out by a competent authority of PIC/S member

state).

In case any of the documents from the said list submitted to the State Administration of

Ukraine on Medicinal Products in order to obtain an Opinion contains confidential information,

which the manufacturer cannot disclose to Applicant's representative in Ukraine, the manufacturer

can send these documents directly to the State Administration of Ukraine on Medicinal Products.

Upon receipt of these documents the State Administration of Ukraine on Medicinal Products

notifies in its letter the Applicant's representative on their examination within 10 working days or

places such information at the website of the State Administration of Ukraine on Medicinal

Products.

2.3. For non-resident manufacturers the verification of compliance with GMP requirements is

carried out by the State Administration of Ukraine on Medicinal Products based on the results of a

routine inspection for observing License provisions on maintaining economic activity in the

manufacture of medicinal products, wholesale and retail trade of medicinal products, as approved

by the order of MHO of Ukraine on October 31, 2011 No. 723 registered with the Ministry of

Justice of Ukraine on December 07, 2011 under No. 1420/20158 (hereinafter - a routine inspection

for observing License provisions) conducted in accordance with Control procedures for observing

License provisions on maintaining economic activity in the manufacture of medicinal products,

wholesale and retail trade of medicinal products, as approved by the order of MHO of Ukraine on

October 31, 2011 No. 724, registered with the Ministry of Justice of Ukraine on December 07, 2011

under No. 1421/20159.

If there are no critical discrepancies in the report for routine inspection of observing License

provisions the State Administration of Ukraine on Medicinal Products issues in accordance

with section V of this Procedure the Certificate to a license holder within 30 working days. To this

end the license holder submits within 10 working days after routine inspection to the State

Administration of Ukraine on Medicinal Products a list of products (medicinal products registered

in Ukraine) on form according to annex 5 to this Procedure (in a written form and on the electronic

media (Excel file)).

If any critical discrepancies are found during the last routine inspection for observing the

License provisions, and in case there is no documentary evidence on their elimination, the State

Administration of Ukraine on Medicinal Products makes a decision to refuse the issue of the

Certificate according to section V of this Procedure. If there is documentary evidence on the

elimination of critical discrepancies found during the last routine inspection for observing the

License provisions, the manufacturing site is inspected based on the application for certificate

submitted by a license holder.

2.4. Attached application and documents are accepted with the list of documents attached to the

Application for Certificate or Application for Opinion, according to annex 7 to this Procedure, the

copy of which is given to the Applicant stating the date when the documents have been accepted by

the State Administration of Ukraine on Medicinal Products and upon the signature of an authorized

person.

2.5. The State Administration of Ukraine on Medicinal Products makes an initial examination

of submitted documents to check their completeness and to analyze the scope of presented

information.

2.6. The State Administration of Ukraine on Medicinal Products may involve companies,

institutions and organizations in the conduct of laboratory analysis of medicinal product sample

quality and inspection (upon agreement).

2.7. For non-residents who have no official documents on production compliance with GMP

requirements issued by a competent authority of a PIC/S member state, or if medicinal products are

manufactured in the state with which Ukraine did not enter into the international agreement on

mutual recognition of production inspection results for compliance with GMP requirements, apart

from documents examination the manufacturing facility (manufacturing site) is inspected according

to section ІV of this Procedure.

2.8. For medicinal products prequalified by WHO, which are supplied by or intended to be

supplied by the World Fund, inspection for non-residents is not carried out.

2.9. When validating manufacturing compliance with GMP requirements all intermediate

manufacturing sites (including contract sites) engaged in the manufacture of finished medicinal

products should be specified. To validate manufacturing of finished medicinal products from in-

bulk form, all in-bulk products used in the manufacture of these medicinal products should have

Certificates or Opinions issued according to this Procedure except the cases as specified in subp.

2.9.1 and 2.9.2 hereof.

2.9.1. In case the certification of finished product batches and issuing of a marketing

authorization are performed on the territory of EU member state or on the territory of the state with

which EU entered into the agreement on mutual recognition of inspection results, and if a

competent authority of the said state is PIC/S member, the Applicant submits together with the

Application for Opinion the following documents:

the list of documents as per clause 2.2 of this section - for a manufacturer who issues batch

release authorization;

copies of documents certified by Applicant's signature and seal (if available) and their

translation into Ukrainian as specified in subp. 2 and 4 of clause 2.2 of this section - for

intermediate manufacturing sites, including contractual sites participating in medicinal product

manufacturing and located on the territory of EU member state, or on the territory of the state, with

which EU enters into the agreement on mutual recognition of inspection results, and also have

official documents on production compliance with GMP requirements, issued by a competent

authority of PIC/S member state;

copies of documents certified by Applicant's signature and seal (if available) or his

representative and their translation into Ukrainian as specified in subp. 2, 4, 6 of clause 2.2 of this

section - for intermediate manufacturing sites, including contractual manufacturing sites

participating in medicinal product manufacturing and located outside the territory of EU member

state and outside the territory of the state, with which EU entered into the agreement on mutual

recognition of inspection results, which have official documents on production compliance with

GMP requirements, issued by a competent authority of PIC/S member state. A copy of the

document specified in subp. 6 clause 2.2 of this section for intermediate manufacturing stage

(including contractual manufacturing site) is submitted not later than six months upon receipt of the

Opinion under Applicant's guarantee liabilities. If the Applicant fails to submit a copy of the

document specified in subp. 6 cl. 2.2 of this section within six months, the State Administration of

Ukraine on Medicinal Products makes a decision to declare the issued Opinion null and void or to

modify it by withdrawing such medicinal product from the list being an integral part of the Opinion.

Besides, the State Administration of Ukraine on Medicinal Products does not issue separate

Opinions for intermediate manufacturing sites (including contractual manufacturing sites).

2.9.2. In case the certification of finished medicinal product batches and release authorization

are made by a manufacturer who has an official document on production compliance with GMP

requirements issued by a competent authority of PIC/S member state, the Applicant submits

together with the Application for Opinion the following documents:

the list of documents specified by subp. 2.2 of this section - for a manufacturer who issues

batch release authorization;

the documents specified in subp. 2, 4, 6 clause 2.2 of this section - for intermediate

manufacturing sites, including contractual sites participating in medicinal product manufacturing,

which have official documents on production compliance with GMP requirements, issued by a

competent authority of PIC/S member state.

In this regard the State Administration of Ukraine on Medicinal Products does not issue

separate Opinions for intermediate manufacturing sites (including contract sites), which have

official documents on production compliance with GMP requirements, issued by a competent

authority of PIC/S member state.

For a medicinal product, the intermediate manufacturing stages (including contract sites) of

which are carried out at the manufacturing sites which have no official documents on production

compliance with GMP requirements issued by a competent authority of PIC/S member state, based

on the Applicant's guarantee liabilities on completing the verification procedure for production

compliance with GMP requirements within six months the State Administration of Ukraine on

Medicinal Products issues the Opinion. If the Applicant fails to fulfil the guarantee liabilities or the

State Administration of Ukraine on Medicinal Products makes a negative decision on the

verification of GMP requirements compliance, the State Administration of Ukraine on Medicinal

Products makes a decision to declare the issued Opinion null and void or to modify it by

withdrawing such medicinal product from the list being an integral part of the Opinion.

2.10. Verification of restricted use medicinal products (orphan products) compliance with

GMP requirements is carried out on a priority basis without inspection upon request of the

Applicant or the Ministry of Health of Ukraine (if applicable).

ІІІ. GMP requirements compliance verification terms

3.1. The term for initial examination of submitted documents performed by the State

Administration of Ukraine on Medicinal Products in order to check their completeness, conformity

of documents with applicable laws, as well as with requirements of this Procedure, makes up no

more than 5 working days after filing an Application.

3.2. A specialized examination by the State Administration of Ukraine on Medicinal Products

in order to make up a well-grounded opinion on the verification of production compliance with

GMP requirements is performed within the following terms:

provided an official document on production compliance with GMP requirements issued by a

competent authority of PIC/S member state is submitted - no more than 10 days after initial

examination;

provided the information on the last inspection conducted within the framework of WHO

prequalification is submitted - no more than 10 working days;

provided Ukraine has entered into international agreements on mutual recognition of inspection

results with the state where the Applicant's manufacturing facilities are located - no more than 10

working days after initial examination;

in all other cases - no more than 15 working days after initial examination.

3.3. In case of incompleteness or noncompliance with the requirements of this Procedure of the

documents attached to Application found during the initial or specialized examination, the

Applicant is given a written notification. Time needed to eliminate found discrepancies or to submit

the necessary documents is not added to the terms for initial or specialized examination.

3.4. If the Applicant does not eliminate found discrepancies or submit the necessary package of

documents as per the requirements of this Procedure within 30 working days upon receipt of such

notification, the Application is not reviewed, of which the State Administration of Ukraine on

Medicinal Products informs the Applicant in a written form. If there is a need to extend the terms

for presenting the necessary information, the Applicant should give a respective substantiation of a

reason and the required additional terms.

3.5. Copies of inspection plan and program are sent to Applicant's location of his representative

within the term not later than 5 working days before the date of inspection. The date of inspection is

appointed within six months upon filing an Application if there are no other terms suggested by the

Applicant.

3.6. Inspection of business location (manufacturing sites) should be no more than 15 working

days.

3.7. Report on the inspection results is made within 10 working days after finishing the

inspection.

3.8. Laboratory quality analysis of samples collected during the inspection is made within 14

working days after the collected samples are received by a laboratory for medicinal product quality

control and safety or within a term as specified by manufacturer's respective medicinal products

quality control techniques. It is the Applicant who provides the necessary reference substances. The

time needed for the Applicant to provide reference substances is not added to laboratory analysis

terms.

3.9. Execution and issue of the Certificate or the Opinion, or written notification on the failure

to issue the Certificate or Opinion are made within 10 working days after preparation of an

inspection report or obtaining the results of a specialized examination.

3.10. The draft Certificate or Opinion is sent to the Applicant via email or fax with the

respective list of medicinal products for approval. The Applicant certifies with his signature the

draft Certificate or Opinion with the respective list of medicinal products within not more than 5

days. The time needed for the Applicant to approve the draft Certificate or Opinion with the

respective list of medicinal products is not added to the terms for Certificate and Opinion execution

and issue.

3.11. Amendments in the Opinion, the Certificate, or the list of medicinal products to the

Opinion or the Certificate are made in a manner as specified by clause 5.10 section V of this

Procedure within a term not exceeding 10 working days.

ІV. Inspection procedure for compliance with GMP requirements

4.1. Inspection of production (manufacturing site) is carried out in order to validate medicinal

product manufacturing compliance with the requirements to medicinal products manufacturing in

Ukraine.

4.2. If needed, before inspecting the production (manufacturing site), the team of inspectors has

the right to review the registration materials for registered medicinal products and/or medicinal

products submitted for state registration (reregistration), or when making respective amendments to

registration materials of medicinal products registered in Ukraine.

4.3. Inspection of production (manufacturing site) is carried out:

on Applicant's request;

for non-residents who have no official documents on production compliance with GMP

requirements issued by a competent authority of PIC/S member state;

for facilities located in the states with which Ukraine has no agreement on mutual recognition

of inspection results;

in case decisions are made on withdrawal of medicinal product batches manufactured at this

site relating to the quality of a medicinal product;

in case it is found during the examination that it is possible to manufacture products which can

be hazardous for human health and life or which can result in serious consequences for human

health, or adulterated medicinal products.

4.4. Inspection of production (manufacturing site) is carried out according to inspection

schedule and program, in which the purpose, objects, dates of inspection are defined and an

inspector or team of inspectors are appointed. Copies of inspection plan and program are sent to

Applicant's location within the terms as defined by section ІІІ of this Procedure.

4.5. The State Administration of Ukraine on Medicinal Products may engage scientists and

specialists (upon their consent) to inspection of production, performing definite types of work and

participation in the study of separate issues.

4.6. Based on the inspection results an inspector makes a report in Ukrainian in two copies on

form as set forth in annex 8 to this Procedure. Additionally for non-residents a report can be made

in English or Russian within a term not later than 15 working days since compiling it in Ukrainian.

4.7. One copy of a report is given to the Applicant or his representative. Other copy of a report

and inspection materials are kept in files of the State Administration of Ukraine on Medicinal

Products during the validity term of Certificate or Opinion, but not less than three years.

4.8. If during an inspection samples are collected for laboratory analysis of their quality, the

following is attached to the report:

product sampling report;

reference for testing;

a draft of medicinal products quality control techniques provided by the Applicant;

a written conclusion of a qualified laboratory on the product batch quality (after providing

samples).

V. Decision making procedure on issuing or refusal to issue the Certificate or

Opinion 5.1. In case a positive decision is made based on the results of performed specialized

examination the State Administration of Ukraine on Medicinal Products issues the Opinion to the

Applicant (free of charge) on form according to annex 10 to this Procedure within the terms as

specified in section ІІІ of this Procedure.

The Opinion of the State Administration of Ukraine on Medicinal Products is issued for the

duration of an official document on production compliance with GMP requirements issued by a

competent authority being a member of PIC/S.

Duration of the Opinion is extended by a decision of the State Administration of Ukraine on

Medicinal Products up to six months in case the Applicant submits information on carrying out an

inspection for compliance with GMP requirements by a competent authority of PIC/S member state,

of which the State Administration of Ukraine on Medicinal Products informs the Applicant within

the period no more than 10 working days.

5.2. After inspection of production (manufacturing site) or examination of submitted

documents in case of a positive conclusion contained in the report, taking into consideration the

results of documents examination, the State Administration of Ukraine on Medicinal Products

issues to the Applicant within the terms as specified by section ІІІ of this Procedure the

Certificate on form according to annex 9 to this Procedure or the Opinion on form according to

annex 10 to this Procedure. The Certificate is valid for three years from the inspection date.

In case the period of license validity expired (for non-residents) when the Certificate is valid,

the Applicant submits a duly certified copy of a license to the State Administration of Ukraine on

Medicinal Products within three months since receipt of a license.

Should the Applicant fail to present a duly certified copy of a license, the State Administration

of Ukraine on Medicinal Products makes a decision to terminate the Certificate.

5.3. The State Administration of Ukraine on Medicinal Products orders to issue the

Certificate or the Opinion. The Certificate or the Opinion are attached by the list of medicinal

products which are registered or intended to be registered in Ukraine according to annex 11 to this

Procedure being an integral part of the Certificate or the Opinion.

5.4. If there are discrepancies (nonconformities) of GMP requirements in the report, the

Applicant should take measures to bring the production in compliance with GMP rules, to submit

corrective and preventive actions plan on the elimination of found discrepancies (nonconformities)

to the State Administration of Ukraine on Medicinal Products on form according to annex 12 to this

Procedure and documentary evidence on the elimination of discrepancies (nonconformities) within

90 calendar days. Should the Applicant fail to submit the corrective and preventive actions plan and

documentary evidence on the elimination of discrepancies (nonconformities) within the established

terms, the State Administration of Ukraine on Medicinal Products may adopt a decision to terminate

the Certificate according to clause 6.4 section VІ of this Procedure.

5.5. If during the validity of the Certificate or the Opinion the Applicant notifies the State

Administration of Ukraine on Medicinal Products of changes in the name of certified manufacturing

site or manufacturing license, including the change of Applicant's name, the State Administration of

Ukraine on Medicinal Products reissues the Certificate or the Opinion within the terms as specified

in section ІІІ of this Procedure. A reissued Certificate of Opinion is given to the Applicant, the old

Certificate of Opinion should be returned to the State Administration of Ukraine on Medicinal

Products.

5.6. For residents in case of manufacturing license cancellation, the Certificate is cancelled by

the order of the State Administration of Ukraine on Medicinal Products.

5.7. In case of a negative decision, the State Administration of Ukraine on Medicinal Products

informs the Applicant of the reasonable refusal to issue the Certificate or the Opinion within the

terms as specified in section ІІІ of this Procedure.

5.8. The decision on the refusal to issue the Certificate or the Opinion is executed by the order

of the State Administration of Ukraine on Medicinal Products and adopted in case:

unreliable information is found in the Application or documents attached to the Application

according to this Procedure;

critical discrepancies of GMP requirements are found during the inspection.

5.9. In case there are critical discrepancies (nonconformities) of GMP requirements in the

report, the Applicant takes measures on their elimination, submits corrective and preventive actions

plan on the elimination of found discrepancies (nonconformities) according to annex 12 to this

Procedure and documentary evidence on the elimination of discrepancies (nonconformities) to the

State Administration of Ukraine on Medicinal Products. The Applicant may submit a written

request to the State Administration of Ukraine on Medicinal Products on the conduct of inspection

in order to check the elimination of discrepancies (nonconformities). In case the elimination of

discrepancies (nonconformities) is confirmed based on the inspection results, the State

Administration of Ukraine on Medicinal Products makes a decision to issue the Certificate to the

Applicant according to annex 9 to this Procedure or the Opinion according to annex 10 to this

Procedure.

5.10. In case there is a need to make amendments in the Opinion or the Certificate, or the list of

medicinal products attached to the Opinion or the Certificate (extension of registration in Ukraine;

change in the name of a medicinal product, manufacturer or its location), the Applicant notifies the

State Administration of Ukraine on Medicinal Products.

Upon registration or reregistration of medicinal products or making amendments into

registration documents (in particular, change in production location) the Applicant submits the

respective notification, the list of products to the State Administration of Ukraine on Medicinal

Products with amendments according to annex 5 to this Procedure (in a written form and via

electronic media) and copies of marketing authorizations for medicinal products. The State

Administration of Ukraine on Medicinal Products makes up and approves the updated list of

medicinal products manufactured at the qualified site within 10 working days since receipt of

respective documents. One copy of such list is given to the Applicant, and the other is kept in files

of the State Administration of Ukraine on Medicinal Products.

The Applicant is obliged to return the original of the previous list of medicinal products not

later than the day he receives the updated one.

VI. Control of compliance with GMP rules during the validity of the Certificate or the

Opinion

6.1. The Applicant is liable for compliance with GMP rules during the validity of the

Certificate.

6.2. The production which according to this Procedure obtained verification of compliance

with GMP requirements is subject to unannounced inspection for compliance with GMP

requirements during the period of Certificate validity if there are reasons as specified in clause 6.3

herein.

6.3. The grounds for an unannounced inspection of production (or its part) in order to control

whether the Applicant complies with GMP requirements are as follows:

Applicant's request;

establishing facts of manufacturing medicinal products, which could be hazardous for human

health and life or which could result in serious consequences for human health;

presence of facts that low grade or adulterated medicinal products are manufactured (also if

there is a suspicion for possible manufacture of adulterated products);

expansion of the range of medicinal products manufactured in the certified production (if

applicable);

presence of instructions or decisions of state regulatory authorities on withdrawal of a

medicinal product which is manufactured at the manufacturing site (if applicable).

6.4. In case of nonconformity of medicinal products manufacturing with GMP requirements, or

the Applicant fails to submit the corrective and preventive actions plan and documentary evidence

on the elimination of discrepancies (nonconformities) of GMP requirements within the terms as

specified in clause 5.4 section V of this Procedure, failure to fulfil guarantee liabilities or

establishing the facts of manufacturing medicinal products not included to the list of

products (annex 5), the State Administration of Ukraine on Medicinal Products may adopt a

decision to terminate or cancel the Certificate or the Opinion and give instructions on the

elimination of discrepancies of GMP requirements stating the execution terms, and notifies the

Applicant within 10 working days after adopting the respective decision. After discrepancies of

GMP requirements are eliminated within the established terms the State Administration of Ukraine

on Medicinal Products may adopt a decision on the renewal of Certificate or Opinion validity (in

case of termination).

6.5. The grounds for unannounced inspection in case of changes in medicinal products

manufacturing that could influence the quality of products may be as follows:

expansion of the range of products manufactured at the site;

introduction of a new process stage, operation or a new unit of critical process equipment into

the production scheme;

changes in the process parameters of critical technological stages;

relocation of the manufacturing site, modernization of equipment, restructuring of the

manufacturing unit.

VII. Rights and responsibilities of an inspector in the course of GMP compliance

verification procedure 7.1. When inspecting production an inspector has the right:

to familiarize with all inspection-related documents concerning GMP requirements and master

file materials, and also to obtain the necessary data on the issues of his competence from the

Applicant and/or manufacturer;

to inspect freely according to the Law of Ukraine "On Basic Principles of State Supervision

(Control) in the Sphere of Economic Activity" the production, warehouse, auxiliary premises

(areas), quality control premises (areas) and other premises (areas) of the Applicant, to inspect them

in order to handle issues directly relating to Applicant's compliance with GMP rules;

to record according to the Law of Ukraine "On Basic Principles of State Supervision (Control)

in the Sphere of Economic Activity" the inspection process or any separate action by means of

audio and video equipment without interfering with the process;

to demand termination of actions that interfere with the procedure for GMP requirements

compliance verification;

to schedule an examination, obtain explanations, certificates, documents, materials, data on the

issues arising during GMP requirements compliance verification;

to collect samples of medicinal products for laboratory inspection of their quality according to

the laws of Ukraine in case of violations of production technology, quality requirements, conditions

and/or storage rules of medicinal products that could result in the manufacture of low grade

medicinal products and/or wholesale, retail trade of low grade medicinal products are found;

to obtain duly certified copies of necessary documents (excerpts) relating to production

inspection for compliance with GMP requirements;

to receive from the Applicant written explanations on the issues arising during the inspection.

7.2. In case the Applicant fails to fulfil his obligations as laid down in clause 8.3 section VIIІ of

this Procedure concerning provision of all the necessary information on inspector's request,

ensuring examination of the premises, equipment, quality control areas, interviewing manufacturer's

representatives (staff), scrutinizing the necessary documentation on quality system etc., a

notification is given to the management of the State Administration of Ukraine on Medicinal

Products and this fact is recorded in inspector's report.

7.3. Inspector should comply with requirements on:

keeping the data obtained from the Applicant and/or manufacturer confidential, including the

data collected during the inspection;

credibility, completeness and reliability of inspection results;

reliability of information contained in the report which is a basis for adoption of a decision to

issue the Certificate;

nondisclosure of confidential information and the information which is a commercial secret of

the Applicant that an inspector becomes aware of in the course of GMP rules compliance

verification.

7.4. Inspector is obliged:

to adhere to business ethics in relations with the Applicant and/or manufacturer;

not to interfere with the economic activity when validating medicinal product manufacturing

compliance with GMP requirements;

to submit a report based on inspection results to the State Administration of Ukraine on

Medicinal Products within the terms as specified by section IІІ of this Procedure.

VIIІ. Rights and responsibilities of the Applicant and/or manufacturer in the course

of GMP compliance verification procedure 8.1. Applicant and/or manufacturer are liable for credibility of presented information.

8.2. Applicant and/or manufacturer have the right:

to demand from inspectors compliance with the requirements of applicable laws of Ukraine;

to check inspector's service certificate or other identity document, and to obtain copies of

documents for carrying out an inspection;

to be present during the inspection;

to demand nondisclosure of confidential information and the information, which is a

commercial secret of the Applicant and/or manufacturer;

to obtain and review the report based on inspection results within the terms as established by

this Procedure;

to appeal decisions or illegal actions of the State Administration of Ukraine on Medicinal

Products or its employees as required by law.

8.3. Applicant and/or manufacturer are obliged:

to notify the State Administration of Ukraine on Medicinal Products of the changes relating to

the manufacturing site (including the change of medicinal products marketing authorization,

Applicant's name or his location);

to provide on inspector's request all the necessary information, ensure examination of

production, auxiliary, warehouse premises, equipment, quality control areas, interviewing

manufacturer's representatives (staff), scrutinizing the necessary documentation on quality system

etc.;

to fulfil the requirements of the State Administration of Ukraine on Medicinal Products on the

elimination of found violations of applicable laws of Ukraine;

to provide documents, product samples, explanations, certificates, data sheets, materials on the

issues arising during verification of GMP compliance as required by applicable laws of Ukraine;

to obtain a copy of the report based on inspection results within the terms as specified by this

Procedure.

Head of

Department for Medicinal Products

and Medical Devices

L.V. Konoshevych

Annex 1

to verification procedure for compliance of

medicinal product manufacturing conditions

with the Good Manufacturing Practice

requirements

State Administration of Ukraine on

Medicinal Products

APPLICATION

for issue of GMP compliance certificate

Date of submission:

"_____"______________ 20______

Filed under No. ___________

APPLICANT (name of a license holder or holder of a marketing authorization (trading license) for

a medicinal product or name of the applicant)

___________________________________________________

Location (residence) ______________________________________

Name, surname, job position of applicant's chief

________________________________________________________________________

Telephone, fax

________________________________________________________________________

MANUFACTURER (name of a company, manufacturing site/s) applied for GMP requirements

compliance verification procedure

________________________________________________________________________

________________________________________________________________________

Business location________________________________________

________________________________________________________________________

Name, surname, job position of company's director, tel/fax

________________________________________________________________________

Name, surname, job position of production chief, tel/fax

________________________________________________________________________

Name, surname, job position of quality service chief (authorized person), tel/fax

________________________________________________________________________

Name, surname, job position of quality control department, tel/fax

________________________________________________________________________

Other contact details (including e-mail) ____________________________________

The following documents are attached as per clause 2.2 section ІІ to this Procedure:

________________________________________________________________________

________________________________________________________________________

________________________________________________________________________

Hereby I guarantee that the presented information is true: ____________________________

________________________________________________________________________

(Name, surname, job position and signature of applicant's director (representative)

Made on "___"_________ 20__ Seal

Annex 2

to verification procedure for compliance of

medicinal product manufacturing conditions

with the Good Manufacturing Practice

requirements

State Administration of Ukraine on

Medicinal Products

APPLICATION

for issue of the opinion on GMP compliance verification

Date of submission:

"_____"______________ 20______

Filed under No. ___________

APPLICANT (name of a license holder or holder of a marketing authorization (trading license) for

a medicinal product or name of the applicant)

___________________________________________________

Location (residence) ______________________________________

Name, surname, job position of applicant's chief

________________________________________________________________________

Telephone, fax

________________________________________________________________________

MANUFACTURER (name of a company, manufacturing site/s) applied for GMP requirements

compliance verification procedure

________________________________________________________________________

________________________________________________________________________

Business location________________________________________

________________________________________________________________________

Name, surname, job position of company's director, tel/fax

________________________________________________________________________

Name, surname, job position of production chief, tel/fax

________________________________________________________________________

Name, surname, job position of quality service chief (authorized person), tel/fax

________________________________________________________________________

Name, surname, job position of quality control department, tel/fax

________________________________________________________________________

Other contact details (including e-mail) ____________________________________

The following documents are attached as per clause 2.2 section ІІ to this Procedure:

________________________________________________________________________

________________________________________________________________________

Hereby I guarantee that the presented information is true: ____________________________

________________________________________________________________________

(Name, surname, job position and signature of applicant's director (representative)

Made on "___"_________ 20__ Seal

Annex 3

to verification procedure for compliance of

medicinal product manufacturing conditions

with the Good Manufacturing Practice

requirements

CERTIFICATE

on the quality of manufactured products __________________________________________________________________________

(applicant's name)

for 20___ and 20___ (provide data for the last three years starting from the application date)

Item

No.

Data on product reclamations and recalls Total List of medicinal product names

and batch numbers

1 Number of reasonable claims to product

quality:

1.1 based on the state control results

1.2 upon applicants’ requests

2 Number of product withdrawals from the

distribution network in Ukraine:

2.1 according to instructions of state inspection

authorities

2.2 upon manufacturer's decision

3 Number of products withdrawn from the

distribution network of the state where

production is located (for non-residents):

3.1 upon instructions of state authorities of the

state where production is located

3.2 upon manufacturer's decision

4 Number of products withdrawn from the

distribution network in other countries:

4.1 upon instructions of competent state authorities

of the states where products were marketed

4.2 upon manufacturer's decision

Made on "___"_________ 20__

Company Director

_______________

(position)

_________

(signature)

________________________

(full name)

Seal

Chief of quality service

(authorized person)

_______________

(position)

_________

(signature)

________________________

(full name)

Annex 4

to verification procedure for compliance of

medicinal product manufacturing conditions

with the Good Manufacturing Practice

requirements

CERTIFICATE

on the results of inspections carried out by state inspection authorities at _____________________________________________________________________

(name of a manufacturing site and applicant)

for 20___ and 20___ (specify for the last three years before the application date)

Item

No.

Name of a competent

authority

Type of control

(inspection)

(scheduled,

unannounced)

Period,

dates

of

inspection

Report as

of_____

(date)

No.___

Inspection result

(provide reference to a

document and give the

summary stated in the

report)

1 State inspection authority

for medicinal products in

Ukraine

2 State or competent authority

for medicinal products

inspection in the state where

production is located (for

non-residents)

3 Competent authorities for

medicinal products control

being PIC/S members

4 Competent authorities for

medicinal products control

of other states

Made on "___"_________ 20__

Manufacturer's chief

_______________

(position)

_________

(signature)

________________________

(full name)

Seal

Chief of quality service

(authorized person)

_______________

(position)

_________

(signature)

________________________

(full name)

Annex 5

to verification procedure for compliance of

medicinal product manufacturing conditions

with the Good Manufacturing Practice

requirements

GENERAL LIST

of product range2

___________________________________________________________________________

(name of a manufacturing site)

___________________________________________________________________________

(address of production facilities (business location)

____________________________________________________________________________

(manufacturer's country)

Part

(А/В

)1

N

o

.

Trade name-3 Internati

onal

nonpropr

ietary

name

(INN)-4

Marketing

authorization in

Ukraine

Marketi

ng

authoriz

ation

(trading

license)

in the

state

where

products

are

manufac

tured,

dated

"__"___

_ ____

No. ___

Data on manufacturers5

trade

name

(Ua)

trade

name

(En)

dosag

e

form

(Ua)

dosag

e

form

(En)

nu

mb

er

yea

r of

issu

e

mo

nth

of

issu

e

day

of

issu

e

in-bulk

product

manufactu

rer

prima

ry

packi

ng

secon

dary

packi

ng

batc

h

rele

ase

auth

oriz

atio

n6

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

Made on "___"_________ 20__

Manufacturer's chief

_______________

(position)

_________

(signature)

________________________

(full name)

Seal

Chief of quality service

(authorized person)

_______________

(position)

_________

(signature)

________________________

(full name)

Production chief

_______________

(position)

_________

(signature)

________________________

(full name)

__________

The following is to be specified: 1 Part А - medicinal products registered in Ukraine or medicinal products intended to be registered

(reregistered) in Ukraine;

Part В - range of products of the site located in other countries (for part B columns 8-16 of the table

are not filled). 2 For non-residents this document is to be made in the language of the applicant's country, its

translation into Ukrainian and English has to be certified by the signature of the applicant or a duly

authorized person as well as the seal. 3 To specify the full name of a medicinal product mentioned in the master file submitted to a

competent authority of Ukraine or the state where production is located (in Ukrainian - in case a

medicinal product is registered in Ukraine, in English - in case a medicinal product is not registered

in Ukraine). 4 To specify (only in English) an international non-proprietary name of a medicinal product active

substance; to specify the list of all active substances for multicomponent (combination) medicinal

products. 5 These columns in a table are to be obligatorily filled in for all names of medicinal products in

order to add them to the list attached to the certificate on a form as provided in annex 11 to this

Procedure. 6 Name of a manufacturer the authorized person of which issues a product batch release.

Annex 6

to verification procedure for compliance of

medicinal product manufacturing conditions

with the Good Manufacturing Practice

requirements

LETTER OF COMMITMENT

Annex 7

to verification procedure for compliance of

medicinal product manufacturing conditions

with the Good Manufacturing Practice

requirements

State Administration of Ukraine on

Medicinal Products

INVENTORY No. ________

of the documents attached to the application for issue of GMP compliance certificate

(to the application for issue of GMP compliance opinion) from_____________________________________________________________________

(applicant's name)

Date and number of filing an application "_____" __________ 20____ No. __________

Ite

m

No.

Name of a document Number of

sheets in a

document

Note of availability of

documents (available,

unavailable)

Remarks

1 2 3 4 5

Accepted

by

_______________

(in numbers and

words)

documents

_____________________

(signature of a person in

charge)

_____________

(full name)

"_____"______________ 20____

Inventory copy accepted by

_______________________

(signature of applicant's

representative)

_________________

(full name)

"_____"______________ 20____

Annex 8

to verification procedure for compliance of

medicinal product manufacturing conditions

with the Good Manufacturing Practice

requirements

REPORT

on inspection results

Annex 9

to verification procedure for compliance of

medicinal product manufacturing conditions

with the Good Manufacturing Practice

requirements

CERTIFICATE

of GMP compliance

Annex 10

to verification procedure for compliance of

medicinal product manufacturing conditions

with the Good Manufacturing Practice

requirements

OPINION

on the verification of medicinal products manufacturing compliance with GMP

requirements

Annex 11

to verification procedure for compliance of

medicinal product manufacturing conditions

with the Good Manufacturing Practice

requirements

LIST

of medicinal products registered or intended to be registered in Ukraine1

Production of _____________________________________________________________2

to certificate/opinion No. _____________ valid till "____" __________ 20___

Ite

m

No.

Name of a medicinal product Marketing

authorization

(trading

license)

No.___

(in Ukraine)

trade name (in

Ukrainian)

trade name (in

English)

international non-proprietary name of active

substance(s) including their list - for

multicomponent (combination) products - in

English

________________

(position)

_______

_

(signatur

e)

_________________________

(full name)

"___"___________ 20___ Seal

Name,

__________ 1 In case of GMP compliance verification of foreign production the information in this annex has to

be presented in Ukrainian and English. 2 To specify the name of an applicant and the name of a manufacturing site(s).

Annex 12

to verification procedure for compliance of

medicinal product manufacturing conditions

with the Good Manufacturing Practice

requirements

PLAN

of corrective and preventive actions

Ite

m

No

.

Content of

nonconformity

(discrepancy)

Discrepancy

classification

(critical,

major, other)

Corrective/preventive

actions

Execution

period

Execution

note

Remarks