Moldova

Population of Moldova is about 3.5 million people. More than 80% of pharmaceutical market is covered by imported products. Market volume of medicinal products and medical devices is growing from year to year. In 2016-2017 Government of Moldova took a number of actions for increasing the number of reimbursed medicinal products attracting international manufacturers and improving competition in the pharmaceutical market as well as expanding the network of pharmacies in rural areas.

Republic of Moldova has its own national regulatory affairs system but requirements for medicinal products and medical devices are in active harmonization with legislation of European Union. Simplified registration procedure can be applied for medical products authorized in EU countries and other countries with strict regulatory requirements.

Marketing Authorization Holders should apply for registration (authorization) procedure of medicinal products before their importation to Moldavian market. Medical devices are subjected to state registration based on conformity assessment procedures prior to entering the Moldavian market. Special purpose food products are subjected for  registration procedures and should comply with requirements of Sanitary Regulations on food supplements. Imported cosmetic products are certified in process of customs clearance.

 

Medicinal products

Main legislative acts regulating processes of registration and marketing of medicinal products in Moldova are as follows:

• Law of the Republic of Moldova No. 1456-XII “On Pharmaceutical Activities” dated 25 May 1993.
• Law of the Republic of Moldova No. 1409-XIII “On Medicinal Products” dated 17 December 1997.
• Order of the Ministry of Health of the Republic of Moldova No. 739 “On Authorization of Medicinal Products for Human Use and Approval of Post-Marketing Changes” dated 23 July 2012.

Registration of medicinal products is coordinated by Ministry of Health of the Republic of Moldova; examination of registration materials is performed by Medicines and Medical Devices Agency (http://amed.md/).

Applicant for registration is an entity appointed and authorized by Marketing Authorization Holder (MAH) as its representative during registration procedure for medicinal products in the Republic of Moldova. Marketing Authorization Holder of the medicinal product is an inventor, manufacturing site or any other legal entity authorized by them responsible for efficacy, quality and safety of medicinal product. Applicant can be only a resident of the Republic of Moldova, while MAH can be both resident and non-resident.

MAH is responsible for quality, efficacy and safety of marketed medicinal product and its compliance with requirements of Specification.

Medicinal product submitted for new registration in the Republic of Moldova should be registered in country of manufacturing site, or in the country of MAH or in one of the countries of European Economic Area, Switzerland, USA, Canada, Japan, Australia.

 

Registration procedure consists of the following stages:

1. filing of Application form as well as registration dossier, samples of medicinal product and reference standards by Applicant to the Medicines and Medical Devices Agency.
2. issuing invoices by the Medicines and Medical Devices Agency  to the Applicant for registration fee payment.
3. conducting of primary examination after receipt of registration fee payment:
   dossier is checked for completeness. In case of positive result of primary examination the application form is considered as validated; in case of negative result the file is returned to the Applicant.
4. distribution of validated application form for registration and registration materials to the group of experts and if necessary to laboratory for quality control of medicinal products.
5. conducting specialized examination of registration dossier.
6. conducting laboratory analysis of the samples of medicinal product according to Specification and methods of control.
7. issuing observations (if available) from experts or from laboratory;Applicant should provide complete response to observations within 90 days. Timelines for reply may be extended by a written application of the Applicant for not more than 30 days.
8. base on examination results decision to conduct inspection at manufacturing site, preclinical/clinical trial sites as well as to check the Marketing Authorization Holder or its representative office for compliance of pharmacovigilance system can be issued. Registration procedure is suspended for the period of conducting the relevant inspection but not more than for 12 months.
9. submission of positive reports on specialized examination and laboratory analysis to the Commission on Medicinal Products for making decision on the approval of the medicinal products for registration.
10. drafting an order on authorization of the medicinal products by the Medicines and Medical Devices Agency  and its approval and signing by the Ministry of Health.
11. after signing the order, issuing of original of Registration Certificate.

Medicinal products listed in the order of the Ministry of Health are considered as entered into the State Register of the medicinal products authorized in the Republic of Moldova from the date of signing the corresponding order.

Duration of the specialized examination is up to 210 days. However, these timelines do not include (a) actions  performed prior to the start of examination: obtaining and payment invoices with registration fee, primary examination, (b) time required for the Applicant to prepare replies to observations, (c) time required for conducting inspections at manufacturing site, preclinical/clinical trial site, pharmacovigilance site, (d) actions to be taken after getting decision on approval of the medicinal product for registration: drafting and signing order of Ministry of Health, entering data about medicinal product into State register, issuing the original Registration certificate.

Applicant has the right to suspend the authorization process for up to 5 years.

Laboratory analysis is not required for:

• medicinal products registered by EMA, or produced in one of the countries of the European Economic Area, or in Switzerland, USA, Canada, Japan, Australia.
• medicinal products manufacturing site of which was inspected by one of the countries-members of PIC/S and confirmed by GMP certificate issued by the authorized body of that country.

Validity period of Registration Certificate is 5 years. Medicinal product may be used in medical practice until its expiry date.

Registration Certificate may be revoked by the Ministry of Health in the event if medicinal product has not been supplied to the country within three (3) years from the date of issue of the Registration Certificate.

 

Simplified registration procedure

Simplified registration procedure is stipulated by legislation of Moldova for medicinal products registered by the EMA  in at least one of the countries of European Economic Area or registered in Switzerland, USA, Canada, Japan, Australia.

Obvious advantages of the simplified procedure are shortened examination timelines of up to 60 days, no need to provide registration samples and standards, no need in laboratory analysis.

Simplified registration procedure is applicable in case if submitted registration dossier is completely identical to the latest dossier accepted in one of the mentioned above countries. In case of filing the dossier specific for the market or region, medicinal product should be submitted according to standard registration procedure.

 

Requirements to registration dossier

Registration dossier should be submitted in CTD format:

• Module 1 should be submitted in paper form. Administrative part should be properly legalized. Eudra certificates are allowed to be submitted without notarization.
• Modules 2-5 should be submitted on an electronic media.

Documents can be submitted in Romanian or English or Russian language.

SmPC should be submitted with translation into Romanian.

Draft of package leaflet should be prepared in accordance with the national form in Romanian language.

Package labeling should is submitted in Romanian language as well. Additional languages are allowed in case if information is identical to the text in Romanian.

For medicinal products intended for administration by healthcare personnel, for example: for hospital preparations (anesthetics, solutions for infusion, vaccines, radiopharmaceuticals, blood derivatives or blood serums), or orphan drugs, or drugs used for substitution therapy, primary and secondary packaging in the language/ languages of international importance is allowed.

 

Variations

During validity of Registration certificate MAH is obliged to notify the Medicines and Medical Devices Agency regarding any changes to registration materials and obtain authorization from them.

The types of changes in Moldova are adjusted to those of the EU:

• Urgent safety restriction.
• Change in the content (terminology).
• Type IA variations.
• Type IB variations.
• Type II variations.
• Transfer of Registration Certificate.
• Extension of the product line (changes that lead to the issuing of the new Registration Certificate).

Every variation should be submitted by a separate Application form, except for supplementary variations (changes resulted by another variation).

The approved variations should  be implemented within a period not more than 6 months from the date of their approval. The MAH is required to inform the Medicines and Medical Devices Agency on the date of introduction of new batches produced according to the relevant approved post-registration variations.

 

Renewal (repeated registration)

Within a period not more than 6 months before the expiration of the Registration Certificate, the Applicant may submit the application form for renewal (repeated registration) to the Medicines and Medical Devices Agency.

The list of documents required for renewal is shorten comparing to new registration. During renewal the Applicant should confirm the absence of variations or additionally apply for variations to obtain their approval.

During renewal it may be required to provide laboratory quality control of registration samples. Such control is not performed in case if there are no changes to finished product specification and if there has not been any rejection of import during last 5 years.

 

Pharmacovigilance

Pharmacovigilance system in Moldova is organized based on international standards, namely, Guidelines of the International Conference on Harmonization (ICH) and Directive of the Council of the European Economic Community on Pharmacovigilance No. 75/319.

Medicines and Medical Devices Agency is the competent authority responsible for adverse events supervision, recording, systematization and analysis of data on adverse reactions in Moldova.

Information on adverse reactions/effects of medicinal products should be submitted to Pharmacovigilance  Department by:

• healthcare specialists and pharmacists of all medical institutions of the Republic of Moldova, regardless of the form of ownership.
• manufacturers/Marketing Authorization Holders or their authorized representatives.
• authorized international organizations (WHO: World Health Organization, EC: European Community, etc.).
• from medical information sources and scientific publications.
• public organizations representing interests of consumers of medicinal products as well as citizens.
• ethics Committees (during conducting clinical trials of medicinal products).
• investigators of clinical sites involved in conducting of clinical trials of medicinal products.

According to regulations Applicant should appoint Authorized person responsible for pharmacovigilance in the territory of Republic of Moldova. Application form for a medicinal product registration should be accompanied by curriculum vitae of the authorized person.

In case of change of the Authorized person Applicant should apply for relevant variation to Medicines and Medical Devices Agency.

Manufacturers/MAHs or their representatives should report information on any adverse event of the medicinal product approved in Moldova to Pharmacovigilance Department during the first 5 years after obtaining Registration Certificate.

Report on an unexpected serious adverse drug reaction identified in the territory of Moldova and other countries should be submitted within 15 days from the receipt of information.

During validity period of Registration Certificate of medicinal product, MAH should provide the Medicines and Medical Devices Agency with Periodic Safety Update Reports (PSURs) for the registered medicinal product. Periodicity of PSURs submission is the following:

• every six months during first two years after placing the medicinal product on the market;
• once a year during next three years;
• then every 5 years: at the stage of next registration (renewal).

Medicines and Medical Devices Agency may require inspection at MAH or its representative on compliance with the regulatory requirements and pharmacovigilance system, with following completion of assessment report within 30 working days and its submission to the council of the Commission on Medicines.

 

Medical Devices

All medical devices are subjected for mandatory marketing authorization prior to entry to Moldavian market. Marketing authorization is performed:

• if medical device has CE marking: by notification.
• if medical device doesn’t have CE marking: by national conformity assessment and registration.

Medical devices authorized in EU (bearing CE marking) should pass simplified procedure for admission to the market of Moldova by notification. Th

The device is placed on the market without national SM conformity marking. However, before marketing the product it is necessary to:

1. appoint an authorized representative in Moldova for which manufacturer should assign the necessary rights to resident legal entity in the country by means of power of attorney or contract;
2. perform registration of medical device by notification Medicines and Medical Devices Agency;
3. assure that all requirements of regulations are met if medical device is subjected to another technical regulations;
4. comply with relevant regulatory requirements to package labeling and instruction for use (user manual).

 

Medical devices not marketed in EU should be submitted for passing conformity assessment procedure in accordance with regulatory requirements of Moldova. Then data on authorized medical devices are entered in the State Register of Medical Devices.
For authorization of such medical devices the following activities should be provided:

1. to appoint the authorized representative in Moldova, for which purpose the manufacturer must transfer the necessary rights to the resident legal entity of Moldova by means of the power of attorney or contract.
2. to comply with the necessary legislative requirements for package labeling and instruction for use (user manual).
3. depending on the class of medical device:
   1. for class I (non-sterile, without measurement functions) to compile technical file and issue declaration of conformity to the requirements of Regulations on setting conditions for placing medical devices on market.
   2. for products of other classes to choose procedure for assessing conformity (for one batch, with inspection, etc.), to submit Application form and required technical documents to designated conformity assessment authority, to perform prescribed activities and obtain certificate of conformity.
4. to assure that all requirements of regulations are met if medical device is subjected to another technical regulations;
5. to perform registration of medical device by notification to the Medicines and Medical Devices Agency.
6. to place the national sign (mark) of conformity SM.

 

Authorized representative of manufacturer

If manufacturer of medical device is not a resident of the Republic of Moldova such manufacturer must appoint the authorized representative. The authorized representative is appointed by means of the contract or power of attorney. The authorized representative may be entitled to initiate conformity assessment procedures.

Responsibilities of authorized representative are as follows:

• to place its name and address on authorized medical devices;
• to register in the Medicines and Medical Devices Agency and to provide description of medicinal products in scope of its activities for entering the relevant data into Agency’s database.
• to receive information about incidents from the Agency and to take necessary actions.
• to take necessary actions in case of detection of medical devices without proper labeling.
• to keep documentation and provide the Agency with access to it during 5 years from the time of placing medical device on the market:
  • declaration of conformity.
  • technical file.
  • changes in technical file.
  • decisions and documents of the designated authority.

 

Package labeling and instruction for use (user manual)

Information in product labeling may be indicated as international symbols. Labeling text of medical device and instructions for use (user manual) should be provided in Moldavian (Romanian) language. Thus in the labeling text of medical device which contains international symbols it is necessary to indicate the following information in Romanian language:

• name or brand name of the manufacturer, name and address of authorized representative in the Republic of Moldova.
• trade name of medical device and other data necessary to identify the device and content of its package.
• if a device is made on a by-order basis, the following should be indicated in the labelling: “dispozitiv fabricat la comandă”.
• If a device is intended for clinical trials, the following should be indicated in the labelling: “exclusiv pentru investigaţii clinice”.
• any special conditions for storage and/or handling.
• any special operational instructions.
• any warnings and/or precautions to be taken.
• information that product contains substances derived from human blood if applicable.

National conformity mark SM (Securitatea conform cerinţelor esenţiale Moldova) indicates that manufacturer or its authorized representative responsible for placing this mark has checked conformity of products to all main requirements applied in technical regulations and that the products have passed conformity assessment procedures conducted according to all applicable technical regulations.

 

Graphic representation of SM mark	Specifications (proportions) applied to SM mark

National conformity mark should be followed by identification number of designated authority if the specified authority participated in the conformity assessment procedure. Identification number of the authority shall be placed by the authority itself or at direction of the authority by manufacturer or its authorized representative.

 

Special purpose food products

Food products for special purpose may be placed on the market of the Republic of Moldova only if they meet requirements of Sanitary Regulations on food supplements. Prior to placing on the market, food supplements are subjected to notification procedures (vitamins and/or minerals) or registration (food supplements containing other substances).

Registration of food products for special purpose is performed by the Ministry of Health of the Republic of Moldova on the basis of examination results and report of National Center of Public Health.

Notification form with a copy of the label is submitted (in the original and translated into Romanian) to the National Center for Health Care for notification.

For registration of food products relevant application form and dossier should be submitted according to the regulations approved by the Ministry of Health. National Center of Public Health evaluates the documents and submits the report with recommendations on product registration to the Ministry of Health, which issues the order for registration (or denial of registration) with inclusion into the “List of notified/registered food additives”.

Texts for labeling and instructions for use should be provided in Romanian.

 

Cosmetic products

Cosmetic products should be certified at importation stage. Registration of cosmetic products is not required.

Labelling text should be provided in Romanian language.

 

The company Cratia offers provision of services for state registration of medicinal products, development and maintenance of the pharmacovigilance system, marketing authorization (notification, conformity assessment, registration) of medical devices, registration of special purpose food products in Moldova.