on amending and supplementing the annexes. 1, no.
2 and no. 3 Order no. 739 of July 23, 2012


Posted: 13/05/2016
in the Official Gazette

Nr. 128-133
Article No. 829

In accordance with article 11 of the Law on pharmaceutical activity nr.1456-XII of 25 May 1993 with subsequent amendments, Article 4 of the Law on drugs nr.1409-XIII of 17 December 1997, as amended and supplemented, in order to adjust the regulatory framework concerning the authorization of medicinal products through the European requirements, and under Section 9 of the Regulation on the organization and functioning of the Ministry of Health, approved by Government Decision nr.397 of May 31 2011, as amended and supplemented,

ORDER:

1. Annexes No.1, No.2 and No.3 to Order no. 739 of 23 July 2012 "On regulation of medicinal products for human approval and introduction of amendments post-authorization" (Official Gazette of the Republic of Moldova, 2012 nr.254-262, art.1555), as amended and supplemented, amended and supplemented as follows:
1) throughout the annexes the word "user" is replaced with the word "consumer" in the appropriate grammatical case;
2) in Annex 1 notes:
a) point 4, the word "Default" is replaced by "involving"
B) in Section 5, point 6 is amended to read as follows:
"6) active substances and excipients used as starting materials, except those manufactured in the country."
C) in Section 9:
following text the term "bioequivalence" is filled with a new term as follows:
"validated application - an application for which was confirmed completeness of the dossier by the presence of all documents and data necessary expertise; "
Term "GMP Certificate" is amended to read as follows:
"GMP Certificate - certificate confirming compliance manufacturer Rules of Good Manufacturing Practice, issued following inspection by the authorized body in accordance with recommendations of the World Health guide PIC / S concerning the rules of good manufacturing practice for medicines guide European Union on the rules of good manufacturing practice for medicinal products (issued for the interpretation of Directive 2003/94 / EC of 8 October 2003 laying down the principles and guidelines of good manufacturing practice in respect of medicinal products for human use and investigational medicinal products for human use) ";
Title of 'commission Medicines Agency under the Medicines and Medical Devices "is amended to read as follows:
" The Commission Medicines Agency under the Medicines and Medical Devices ";
Term 'drug designation "is amended to read as follows:
" drug name - the name given to a medicine that can be an invented name that does not lead to confusion with the common name international fold with a common name common or scientific name accompanied by the trademark or the holder; ";
Term 'proprietary name (INN) "is amended to read as follows:
' proprietary name (INN) - international non-proprietary name recommended by the World Health Organisation or, if such a designation does not exist, the usual common name; ";
After the term "efficacy" is filled with two new concepts as follows:
"labeling / marking - the information on the primary or secondary packaging;
"EudraGMDP - public database managed by the European Medicines Agency on behalf of the European Union, which are placed certificates of good manufacturing practice and good distribution practices issued by Member States";
Notion of "expertise" is amended to read as follows:
'expertise - complex process of drug research and related documentation's to assess completeness, authenticity and veracity of data and documents contained in the registration dossier and the quality of the product, to be registered in Moldova, conducted by a group of professionals (pharmacists, pharmacologists, clinicians), after which it is established compliance or noncompliance drug documentation and authenticity and data included therein; "

Terms' primary expertise "and" specialized expertise "are excluded;
Concept of 'materials authorization (licensing folder) "is amended to read as follows:
" materials authorization (authorization dossier) - information, documents, samples of finished product and reference substances, presented at Medicines and Medical Devices Agency to issue the registration certificate of the drug in Moldova ";
Term "drug" is amended to read as follows:
"drug - any substance or combination of substances presented as having properties for treating or preventing disease in human or any substance or combination of substances which may be administered people to making a medical diagnosis or to restoring, correcting or modifying physiological functions in humans; "
Term 'reference medicine' is amended to read as follows:
'reference medicine - medicine authorized in accordance with this Regulation, serving as comparison of the generic drug. Reference medicinal product can be a drug with well established, a drug which is a fixed combination of two or more active substances or drugs registered under informed consent, provided that these products were authorized under the documentation suite, complete - product original;";
Letter d) of the term "herbal medicine with traditional use" after "at least 30 years," is filled with the words "including at least 15 years within the European Union";
Term 'homeopathic medicine' is amended to read as follows:
'homeopathic medicinal product - any product prepared from products, substances or compositions called homeopathic stocks in accordance with a homeopathic manufacturing procedure described by the European Pharmacopoeia or in the absence thereof, by the pharmacopoeias currently used officially in the Member States of the European Union and other pharmacopoeia recognized in Moldova. A homeopathic medicinal product may contain a number of principles ";
Letter a) of the definition of 'immunological', is amended to read as follows:
"a) vaccines, toxins and serums shall cover in particular:
- agents used to produce active immunity, such as cholera vaccine, BCG, polio vaccines, smallpox vaccine;
- Agents used to diagnose the state of immunity, including in particular tuberculin and tuberculin PPD, toxins for the Schick and delayed hypersensitivity reactions Dick diphtheria and scarlet fever, brucellin;
- Agents used to produce passive immunity, such as diphtheria antitoxin, anti-smallpox globulin, globulin antilymphocytic ";
Following text the term "approval" shall be supplemented with two new concepts as follows:
"PIC / S (Pharmaceutical Inspection Co-operation Scheme) - scheme pharmaceutical inspections cooperation established between the competent authorities of the Member States in order to facilitate collaboration and exchange of information on drug good manufacturing practices;
Procedure for validation of the application - assessment procedure materials submitted for confirmation of documents and data required for the proposed medicinal product expertise file for approval ";
Title of 'Patient leaflet (package leaflet) "is amended to read as follows:
" leaflet: information for the consumer / patient ";
Concept "serious adverse reaction", the word "cause" is replaced by "cause";
D) Section 15 is amended to read as follows:
"15. Drugs submitted for authorization in the Republic of Moldova must be authorized in the country where the site or in the land registration certificate holder of the product.
Without this authorization, the drugs are to perform any of the following conditions:
1) to be licensed by the European Medicines Agency European Medicines Agency (EMA still);
2) to be licensed in at least one country in the European Economic Area or Switzerland, USA, Canada, Japan, Australia;
3) to be pre-qualified by WHO provided that the stage of submitting the file:
a) in the State List not found any such drug product or active ingredient is registered only one;

B) the stage of submitting the dossier, registered in the State List are also several medicines with active principle, but at the moment in Moldova is an exceptional situation (disasters, catastrophes, epidemics, epizootic diseases, mass poisoning, other cases that threaten human health);
C) the product was manufactured proposed for approval at the WHO inspected, according to the dossier evaluated by WHO (the same qualitative and quantitative composition, the same specification, method of manufacture, etc.). "
E) in paragraph 17, the words "Parts 3 and 4" are excluded;
F) in section 17, paragraph 2):
in the paragraph, the word "bioavailability" is replaced with the word "bioequivalence"
Final paragraph shall be completed with a new sentence as follows:
". In case, according to the guidelines referred bioequivalence can be presumed, during the file must be addressed this exemption as a report (in the summary overview, overview etc.); "
G) in point 29 April), after the words "Moldova" is filled with the words "or 15 years in the European Union";
H) of Chapter II "Section 8. Provisions applicable to drugs in bulk" is excluded;
I) of Chapter III, the title of section 1 is amended to read as follows:
"Section 1. The general procedure for authorization";
J) points 31, 32, 33, 34 and 35 shall be amended to read as follows:
"31. Medicines and Medical Devices Agency takes action to ensure that the procedure for issuing the certificate of registration of the drug is completed within 210 days.
32. Medicines and Medical Devices Agency issue a receipt within 5 days of submitting for approval.
33. The fee for authorization and collection of those amounts Medicines and Medical Devices Agency account within 10 days dossier completeness check by the presence of all documents in accordance with Annex 2 to the Regulation on the authorization of medicinal products. If the documentation and materials submitted by the applicant are in compliance with these regulations, the authorization request is validated.
If the documentation and materials submitted by the applicant are not in accordance with these regulations, the authorization request is rejected, the dossier is returned to the applicant, and the reason for rejection shall be noted in the evaluation sheet.
34. Medicines and Medical Devices Agency organizes expertise of the product and the documentation related to the reporting of results and decision making meetings Medicines Commission.
35. Authorization application for authorization documentation validated and are distributed group of experts and, where appropriate, Laboratory for quality control of medicinal products (LCCM) Medicines and Medical Devices Agency. "
K) Section 37 is amended to read as follows:
"37. If, during expertise is found that the documents and information submitted do not comply, the applicant shall submit the list of objections; the period of authorization is suspended (with "stop timer") to the applicant to supply additional information. "
L) point 40 shall be amended to read as follows:
"40. LCCM not perform quality control authorization stage:
1) for medicinal products registered by EMA or manufactured in one of the European Economic Area countries or Switzerland, USA, Canada, Japan, Australia;
2) for medicines, place of manufacture which has been inspected by one of the member states of the PIC / S, confirmed by the GMP certificate issued by regulators in that country. "
M) in paragraph 41, the words "under GMP rules" are excluded;
N) in section 44, after the word "suspended" is filled with words "(with" stop timer ")";
A) point 46 shall be amended to read as follows:
"46. When establishing objections from the expert group and / or completing the LCCM request, the applicant must respond fully to all the objections - within 90 days; given period may be extended upon written request of the applicant, for a reasonable period that should not exceed 30 days. If no objections are submitted within removed or if the result of the laboratory analysis is negative, the authorization procedure is interrupted by order of Medicines and Medical Devices Agency, then inform the applicant in writing within 20 days. "

P) of Chapter III, section 1 shall be supplemented by Section 11 as follows:
"11. Section 561
simplified authorization procedure. Medicines and Medical Devices Agency takes action to ensure that simplified authorization procedure is completed within 60 days.
562. When medicines are made by EMA or in at least one country in the European Economic Area or Switzerland, USA, Canada, Japan, Australia, the applicant submitted to the Medicines and Medical Devices Agency an application for dossier evaluation in simplified procedure. The request will be accompanied by product samples, reference substances, impurities and degradation products according to DAN. Notwithstanding the general rule, enclosing the following:
1) last folder EMA accepted by competent national authorities or the European Economic Area countries or Switzerland, USA, Canada, Japan, Australia, including all information submitted in support any variance that is granted at the time of application in Moldova;
2) affidavit of the applicant that the dossier is identical to that accepted by EMA or the competent national regulatory authorities in the European Economic Area countries or Switzerland, USA, Canada, Japan, Australia;
3) Pharmaceutical Product Certificate according to WHO recommendations (original) or Certificate of registration of the drug in the country producer or holder (copy notarized, authenticated and legalized, if applicable); Manufacturing authorization (copy notarized, authenticated and legalized, if applicable); GMP certificate for all producers, including the active substance (presented GMP certificate or certificate of compliance with Ph. Eur. (CEP)) production in bulk and poducătorul / her finished product (according to WHO recommendations) indicating the date and results of the last inspection (copies notarized, authenticated and legalized, if applicable). For producers who have GMP certificates registered in the database EudraGMDP not submit paper copies of the certificates. A reference to the electronic register EudraGMDP is considered sufficient;
4) Summary of Product Characteristics (SPC) in Romanian;
5) Draft patient leaflet in Romanian;
6) color graphic layout of primary and secondary packaging.
563. Medicines and Medical Devices Agency issue a receipt within 5 days of submitting for approval.
564. The fee for cashing authorization and the respective amounts to the account
Medicines and Medical Devices Agency, within 10 days dossier completeness check. If the documentation submitted by the applicant is in compliance with these regulations, the authorization request is validated.
565. If the documentation submitted by the applicant is not in compliance with these regulations, the authorization request is rejected, the dossier is returned to the applicant, and the reason for rejection shall be noted in the evaluation sheet. The procedure can be resumed at reapplication for authorization, accompanied by full documentation. "
Q) in section 57 point 4), after the word "and" insert the word "/ or" and the word "statement" is replaced by "one declared";
R) point 60 shall be amended to read as follows:
"60. Repeated authorization is requested within would not exceed 6 months before the expiry of the registration certificate of the drug. "
S) after point 60 is filled with section 601 as follows:
"601. Repeated authorization will be made by simplified procedure for medicines listed in Section 562. Conditions of authorization repeatedly mentioned drugs are identical to those presented in Chapter III, Section 11.
For medicinal products indicated in paragraph 562, the applicant submitted to the Medicines and Medical Devices Agency repeated a request for authorization module 1 and accompanied by an affidavit of the applicant that the information in the file held by the Agency fully Medicines and Medical Devices is updated and contains all changes made after the issuance of the registration certificate. "
T) point 61 shall be amended to read as follows:

"61. For products not listed in Chapter III Section 11 application is lodged and file in accordance with the requirements of this Regulation. Repeat the steps of the authorization procedure is identical to that presented in Chapter III, Section 1
The applicant shall submit the full volume of the file format modules 1-3 DTC / CTD and 4.5 modules will be replaced with the following information: | || 1) Post-authorization safety study results;
2) periodic safety update reports - Adverse reactions reported in last 5 years;
3) where the manufacturer has carried out additional studies and clinical pharmacological and toxicological aspects must submit expert reports updated for this type of documentation;
4) the list of variations in drug registration certificate of approval presented in chronological order (type and no. Variation, date of approval). "
U) paragraphs 62 and 65 are excluded;
V) in the first sentence in paragraph 66, the word "his" is replaced by "validity of the registration certificate of the drug";
W) section 661 shall be excluded;
X) Section 662 is amended to read as follows:
"662. For drugs for which the authorization repeated permitted import batch manufactured in accordance with the above provisions for 6 months from the date of expiry prior to and including the period after the expiry of the registration certificate to complete the licensing procedures repeated or 6 months after completion of the authorization procedure repeated if held until expiration previous registration certificate. "
Y) point 74 shall be amended to read as follows:
"74.Taxa paid shall not be refunded:
1) if the withdrawal;
2) if the application is not validated;
3) in case of withdrawal of the authorization procedure. ".
3) in Annex 2 of the Regulation on the authorization of medicinal products:
a) in paragraph 1:
heading 1.2.1. after the word "manufacturer" shall be supplemented with the words "or owner";
Position 1.2.2. is amended to read as follows:
"1.2.2. GMP certificate for all producers, including the active substance (presented GMP certificate or certificate of compliance with Ph. Eur. (CEP)) production in bulk and poducătorul / her finished product (according to WHO recommendations) indicating the date and results of the last inspection (copy notarized, authenticated and legalized, if applicable). For producers who have GMP certificates registered in the database EudraGMDP not submit paper copies of the certificates. A reference to the electronic register EudraGMDP is considered sufficient ";
Position 1.3.2. is amended to read as follows:
"1.3.2. Draft prospectus: information for the consumer / patient in Romanian ";
Position 1.3.3. is excluded;
B) in the text accompanying notes:
in point 1), the words "composed non DTC / non-CTD" are excluded;
In subparagraph 2), the words "parts" and "or some" exclusive;
4) in Annex 2 of the order:
a) Section 6 shall be completed at the end a new sentence as follows:
"It allowed minor variations in design primary and secondary packaging, as such as registration numbers in different countries, bar-code, codes pharmaceuticals (Pharmcode) symbols, including trademark, icons, holograms, security elements of packaging and other minor changes in the movement of text (distance between rows changing the place of the Barcode, the logo) with the Medicines and Medical Devices Agency informed by letter informative explanation and reasoning clear divirgenţelor packaging and presentation layouts in the current version and proposed on paper and electronically. "
B) in Schedule 1 to the Regulations on the management of post-authorization variations, compartment type II variation, on "Human NTA format (Notice to Applicants)" shall be excluded;
5) in annex 3 notes:
a) Section 1 is amended to read as follows:
"Information and documents accompanying an application for authorization to market medicinal placement shown in four chapters in accordance with the conditions laid down in this Annex and taking into account national regulations. "
B) Section 2 is amended to read as follows:

"CTD-presentation is applicable for all types of applications for authorization, regardless of the procedure applied and whether they are based on a full or abridged application.
It also applies to all types of products including new chemical entities (NCE), radio-pharmaceuticals, plasma derivatives, vaccines, medicinal herbal products etc. "
C) point 11 point 4), letter a) is amended to read as follows:
"a) Pharmaceutical Product Certificate according to WHO recommendations (original) or Certificate of registration of drug producer or holder in the country ( copy notarized, authenticated and legalized, if applicable) or certificate of registration of the drug in at least one country in the European Economic area or Switzerland, USA, Canada, Japan, Australia (copy notarized, authenticated and legalized, if applicable) or confirmation prequalification by the WHO ";
D) point 11 point 4), point b) is amended to read as follows:
"b) Manufacturing Authorizations (copy notarized, authenticated or legalized, if applicable) and GMP certificate for all producers including active substance (presented GMP certificate or certificate of compliance with Ph. Eur. (CEP)) production in bulk and poducătorul / her finished product (according to WHO recommendations) indicating the date and results of the last inspection (copy notarized, apostil or legalized, if applicable). For producers who have GMP certificates registered in the database EudraGMDP not submit paper copies of the certificates. A reference to the electronic register EudraGMDP is considered sufficient; "
E) point 12 shall be supplemented by paragraph 121 as follows:
"121. Information on the SPC in Romanian approved in Romania supports Moldova provided the same series of drugs to be marketed simultaneously in both countries (producing common for Moldova and Romania), and changes to the SPC, leaflet and labeling to be presented in Moldova after approval to Romania. "
F) in section 14:
point in the title, after the word "user" is filled with the word "/ patient";
Point 1) a), the second sentence is amended to read as follows:
"common name shall be included where the product contains only one active substance and if its name is an invented name ; "
Point 4) b) the words "mode, and, if necessary, route of administration" is replaced by "route of administration and, where appropriate, the administration";
G) after point 14 shall be supplemented by paragraph 141 as follows:
"141. Information Prospectus in Romanian approved in Romania supports Moldova provided the same series of drugs to be marketed simultaneously in both countries (producing common for Moldova and Romania), and changes to the SPC, leaflet and labeling to be presented Moldova after approval to Romania. "
H) 15:
point 1):
in point a), "followed by concentration" is replaced with the word "concentration" and at the end of the text, after the words "common name" is supplemented with the word "usual";
Point d), the word "label" is replaced with the word "packaging";
Letter e), the words "manner of administration and, if necessary, route of administration" is replaced by "route of administration and, where appropriate, the administration";
Point f), the words "the reach and sight of children" is replaced by "accessible to children";
Point i), the words "special" and "where appropriate" are excluded;
Letter l) is excluded;
In point 3):
after "small" is filled with words "(up to 10 ml)";
Point a) the words "according to the letter a), point 1) of this section and, if necessary, route of administration" are excluded;
Letter c), the word "how" is replaced with the word "path";
After letter c) is completed with the letter c1) as follows:
"c1) contents by weight, volume or units";
Subpart 4) c), the words "manner of administration and, if necessary, route of administration" is replaced by "route of administration and, where appropriate, the administration";

Subpart 5) c) the 4, the word "manufacturer" is replaced with the word "owner";
I) sections 152 and 153 shall be amended to read as follows:
"152. Information on secondary packaging of drugs is given in Romanian or Romanian and other / s language / languages.
The information on primary packaging is exposed in Romanian and / or other / s language / languages.
For drugs for which there is a common name (INN) unique in Moldova issued under prescription drugs, hospital medicines, medicines for special therapy, cancer, rare diseases, substitution therapy, vaccines and orphan drugs etc., primary and secondary packaging accepts the language / foreign languages ​​/ e and are exempt from the provisions of this Regulation.
153. Drug name must appear on the packaging in Braille format. "
J) paragraph 153 is filled with section 154 as follows:
"154. Information labeling in Romanian approved in Romania supports Moldova provided the same series of drugs to be marketed simultaneously in both countries (producing common for Moldova and Romania), and changes to the SPC, leaflet and labeling to be presented Moldova after approval to Romania. "
K) in paragraph 53, the words "parts 1-2 non-DTC format / CTD" are excluded;
L) in paragraph 54:
point 1):
letter a), after the word "used" is filled with the words "regular use in patients";
B), after the word "substance" is filled with the words "taking into account the extent to which substance was used in practice, the use a geographical area and the extent to which use of the substance was monitored system pharmacovigilance or other methods ";
Second paragraph, second sentence is amended to read as follows:
"However, the time required to determine a well established medicinal use of a component of a drug must be at least 10 years after first use systematic and documented use of that substance as a medicine in Moldova and the European Union. "
Point 2) shall be completed at the end with a new sentence as follows:
"must be appended copies of the full text of scientific monographs."
After point 2) is supplemented by point 21) as follows:
"21) EPAR type reports, made public by the competent authorities for reasons of transparency, it can not be regarded as a source of supply information sufficient to meet the requirements that relate to drugs with well established medicinal use. "
M) in paragraph 55, the words "parts 3-4 non-DTC format / CTD" are excluded;
N) in paragraph 56, the words "parts 1-2 non-DTC format / CTD" are excluded.
2. This order is published in the Official Gazette of the Republic of Moldova.
March. Control over execution of this order'm willing to take.