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, 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 31 May 2011, amended and supplemented,
ORDER:
Order no. 739 of 23.07.2012 "On regulation of medicinal products for human approval and introduction of amendments post-authorization" (Official Gazette of the Republic of Moldova, 2012, no. 254-262, art. 1555), with amendments made by Order no. 58 of 01.29.2015, amended and supplemented as follows:
1. Throughout Annexes 1 and 3 notes, the terms "or parts of the dossier in a 1-2 non-DTC / CTD", "or parts 3-4 non-DTC / CTD", "parts 1-4 format and non- DTC / non-CTD '' and parties formed 1-4 non-DTC / non-CTD "" format or 2-3 non-DTC / CTD "," or parts 1-2 non-DTC / RTD "in case grammatically properly excluded;
2. In Annex 1 to order:
1) in paragraph 11, subparagraph 1) after the word "paper" is supplemented by "(only Module 1)";
2) paragraph 16 shall be amended to read as follows:
"16. When the owner of the certificate of registration of the drug different from the drug manufacturer, presents supplementary agreement between the two sides copy notarized, authenticated or legalized, as appropriate. When the owner of the certificate of registration of the drug and drug manufacturer are members of the same group of companies presented a letter of confirmation evidencing ownership holder and manufacturer in the same company group, copy notarized, authenticated or legalized, as appropriate. "|| | 3) point 33 shall be amended to read as follows:
"33.Agenţia Medicines and Medical Devices shall issue a receipt within 20 days after accepting the application for authorization valid."
4) in paragraph 34 the word "primary" shall be excluded;
5) point 39 shall be amended to read as follows:
"39. LCCM to be made within 20 days of receiving full materials needed, analyzing samples submitted in accordance with the specifications and control methods attached file for authorization. "
6) paragraph 40 shall read as follows: || | "40. LCCM not perform quality control at the stage of approval to products manufactured and registered in one of the European Economic Area countries or Switzerland, USA, Canada, Japan, Australia. "
7) in section 41 the words "no" and "conducting quality control serial number" are excluded;
8) paragraph 42 shall be excluded;
9) paragraph 50 shall be supplemented by "During inspection authorization procedure shall be suspended until this inspection report, but no more than 12 months after the inspection request".
10) in paragraph 66 the phrase "not more than 12 months after the expiry of the certificate of registration" is replaced by "until the expiration date of the drug."
11) after point 66 shall be supplemented with sections 661, 662, 663 as follows:
"661. The amendments to the certificate of registration of the drug, approved by the Medicines and Medical Devices Agency as a result of re-authorization of a medicinal product to be implemented by the holder of the certificate of registration within 6 months from the date of issue documents certifying approval of the amendments.
662. The manufacturer can import series of drugs manufactured in accordance with the previous issue documents certifying approval of those changes by the deadline set out in section. 661 and can be marketed until expiration date.
663. The series of drugs manufactured in accordance with the original registration certificate may remain in the therapeutic to the expiration date of the drug, according to the period of validity stated on the product packaging manufactured in accordance with the original certificate. Registration certificate holder is obliged to inform the Agency of Medicines and Medical Devices date of introduction of the new series corresponding registration certificate. "
March. in Annex 2 of the Regulation on the authorization of medicinal products:
1) in 1:
a) in the title of the paragraph, the phrase "for drugs manufactured in accordance with the rules of Good Manufacturing Practice (GMP)" are exclude;
B) in paragraph 1.2.1 after the word "original" words "or notarized copy" shall be excluded;
B) of paragraph 1.2.2 the phrase "(WHO format)" is replaced by "(according to WHO recommendations)";
C) in sections 1.2.1; 1.2.2; 1.2.3 after "notarized copy" is filled by "apostil or legalized, as appropriate";
D) 1.3.1 after "(RCP)" the words in Romanian;
E) Section 1.3.2 shall read as follows:
"Project patient leaflet in Romanian";
F) Section 1.3.3 shall read as follows:
"Information on the finished product labeling in Romanian";
G) 1.3.4. will be as follows:
"1.3.4. Color graphic layout of primary and secondary packaging (Please present stage presentation file) ";
H) Section 1.3.5 shall read as follows:
"1.3.5. SPC home and / or in countries where the drug is approved (if applicable). "
2) paragraph 2 shall be excluded;
4. In Annex 2 of the order:
1) in Section 3 the words "Ministry of Health" is replaced by "Medicines and Medical Devices Agency";
2) after paragraph 4 is completed by paragraphs 41, 42 and 43 as follows:
"41. The amendments to the certificate of registration of the drug, approved by the Medicines and Medical Devices Agency as a result of changes in post-marketing approval of a drug must be implemented by the holder of the certificate of registration within 6 months from the date of issue documents certifying approval of the amendments.
42. Until the time limit set out in item 41, the manufacturer can import and commercialize series of drugs manufactured in accordance with the previous issue documents certifying approval of the amendments.
43. The series of drugs manufactured in accordance with the above provisions may remain in the therapeutic to the expiration date of the drug, according to the period of validity stated on the product packaging manufactured. Registration certificate holder is obliged to inform the Agency of Medicines and Medical Devices date of introduction of the new series corresponding to the approved post-authorization changes. "
3) Section 7 shall be supplemented as follows:
" In some cases, common admit an application for the same product more variations, filed simultaneously. "
4) in Section 8 the number "5" is replaced by "7";
5) paragraphs 20, 36 and 45 the phrase "appropriate point 2)" shall be excluded;
May. In Schedule 1 to the Regulations on management of post-authorization variations:
1) In section "Changes type IA and type IB"
a) in the title, after the words "Tick the appropriate change required" is filled with the words "and deletes all those changes which are not applicable. Variation / em applicable / s will / will be subject to variations in demand. Applications for variations unclassified (unprecedented), the holder must declare such variations as "other variations" ( "z") using the section of the list corresponding to the most detailed description of the amendment, including the type of variation proposed in this case. "
b) CI I shall be supplemented with letters d), e), f) as follows:
"
d)
Changing or adding a packaging design primary and / or secondary drug product
e)
Minor changes in the SPC and package leaflet for the user, where, registration certificate holder does not file additional new data
f)
Major changes in the SPC and package leaflet for the user, where, holder of the registration certificate filed new additional data
"
June. In Annex 2 of the Regulation on the management changes posautorizare:
heading "Application for transfer of registration certificate" shall be supplemented by a new section reads as follows:
"
11. Name and address of the company authorized to pay the tax and tariff changes
Name: _________________________
Address: ________________________
Country: __________________________
Phone: ________________________ Type of currency (MDL, USD, EUR)
E-mail: _________________________
"
July. Annex 3 to the order:
1) point 12 shall read as follows:
. "12 SPC:
SPC under Article 11 of Directive 2001/83 / EC of the European Parliament and of the Council establishing a Community Code relating to medicinal products for human use, in the order shown below contains the following information :
1. name of the product followed by the strength and the pharmaceutical form;
2. qualitative and quantitative composition in active substances and constituents of the excipient, knowledge of which is essential for proper administration of the drug. Use common name or chemical description;
March. pharmaceutical form;
4. Clinical information:
4.1. therapeutic indications;
4.2. dosage and method of administration for adults and, to the extent that is necessary for children;
4.3. contraindications;
4.4. Special warnings and precautions for use and, for immunological, special precautions applicable to persons handling such products and administering them to patients, together with the precautions taken by the patient;
4.5. interaction with other drugs and other forms of interaction;
4.6. use during pregnancy and breastfeeding;
4.7. effects on ability to drive and use machines;
4.8. side effects;
4.9. overdose (symptoms, emergency procedures, antidotes);
May. pharmacological properties: 5.1
. Pharmacodynamic properties;
5.2. pharmacokinetic properties;
5.3. Preclinical safety data;
June. Pharmaceutical information:
6.1. the list of excipients;
6.2. major incompatibilities;
6.3. shelf life, when necessary after reconstitution of the product or when the immediate packaging is opened for the first time;
6.4. special precautions for storage;
6.5. nature and contents of the pack;
6.6. special precautions for disposal of medicines used or waste materials derived from such products, if appropriate;
July. registration certificate holder;
August. registration certificate number or numbers;
September. date of the first authorization or approval repeated;
10. date of revision of the text;
11. for radiopharmaceuticals, full details of internal radiation dosimetry;
12. for radiopharmaceuticals, additional detailed instructions for extemporaneous preparation and quality control of such preparation and, where appropriate, maximum storage time during which any intermediate preparation such as an eluate or radiopharmaceutical ready to use satisfies the requirements. "
2) point 15 shall read as follows:
"15. Information concerning labeling:
1) outer packaging of medicinal products or, where there is no secondary packaging, the primary packaging must appear the following information:
a) name of the product followed by its strength and pharmaceutical form and, case, whether it is intended (babies, children or adults); if the product contains up to three active substances included is the international non-proprietary name (INN) or, where there is the common name;
B) active substances expressed qualitatively and quantitatively per dosage unit or according to the form of administration for a given volume or weight, using their common names;
C) the pharmaceutical form and the contents by weight, volume or number of doses of the product;
D) a list of those excipients known to have a recognized action or effect and included in the Guide recognized the excipients to be mentioned on the label and the package leaflet of medicinal products. If injectable drugs, topical or ophthalmic use, all excipients must be stated;
E) the method of administration and, if necessary, route of administration. It provides a space to indicate the prescribed dose;
F) a special warning that the product should be kept so that the reach and sight of children;
G) a special warning if necessary for the medicinal product;
H) the expiry date in clear terms (month / year);
I) special storage conditions, if any;
J) specific precautions relating to the disposal of unused medicinal products or waste derived from medicinal products, where appropriate, as well as reference to any appropriate collection system in place;
K) the name and address of the holder of the registration certificate and, where appropriate, of the representative appointed by the holder to represent him;
L) of the drug registration certificate number (not required);
M) batch number;
N) for medicines not issued on prescription, instructions for use.
2) placement in primary packaging secondary packaging must bear the following information:
a) name of the product according to the letter a), point 1) of this section;
B) the name and / or logo of the drug registration certificate holder;
C) batch number;
D) expiry date;
3) small packages must be marked at least the following information:
a) name of the product according to the letter a), point 1) of this section and, if necessary, route of administration;
B) the name and / or logo of the drug registration certificate holder;
C) the administration;
D) expiry date;
E) batch number;
4) Provisions applicable to homeopathic medicinal products. In addition to the clear mention of the words "homeopathic medicinal product", the labeling and, where appropriate, package medicinal products referred to pct.26, Section 7, Chapter II, Annex 1 to the Order no. 739 of July 23, 2012 shall bear the following information:
a) the scientific name of the stock or stocks followed by the degree of dilution, using the symbols of the pharmacopoeia. If homeopathic medicinal product is composed of two or more stocks, the scientific names of the stocks on the labeling may be supplemented by an invented name;
B) the name and address of the holder of the registration certificate, and, where appropriate, of the manufacturer;
C) method of administration and, if necessary, route of administration;
D) the expiry date in clear terms (month, year);
E) the pharmaceutical form;
F) contents of the sales presentation,
G) special storage precautions, if any;
H) a special warning, if it is necessary for the drug;
I) batch number;
J) a special warning 'Homeopathic medicinal product without approved therapeutic indications ";
K) registration number (not required);
L) a warning advising the user to consult a doctor if symptoms persist.
5) The provisions applicable to medicinal products containing radionuclides:
a) secondary packaging and container of medicinal products containing radionuclides shall be labeled in accordance with the regulations for the safe transport of radioactive materials laid down by the International Atomic Energy Agency. The labeling must comply with the provisions set out in subparagraphs b) and c) of this subsection;
B) label on the shielding shall include the information specified in paragraph 1 of this point. Also, the label on the shielding shall explain in full the codings used on the vial and shall indicate, as appropriate, for a given time and date, the amount of radioactivity per dose or per vial and the number of capsules, or, for liquids, the number milliliters in the container;
C) bottle label must contain the following information:
- name or code of the product, including the name or chemical symbol of the radionuclide;
- Batch identification number and date;
- The international symbol for radioactivity;
- Name and address;
- The amount of radioactivity in accordance with paragraph b) of this subsection;
D) In the packaging of radiopharmaceuticals, radionuclide generators, radionuclide kits or radionuclide precursors introduced a detailed instruction leaflet. The text of this leaflet shall be established in accordance with paragraph 14 of this Schedule. Also, the leaflet shall include any precautions to be taken by the user and the patient during the preparation and administration of the medicinal product and special precautions for disposal of packaging and its unused contents. "
3) after paragraph 15 is filled with paragraphs 151, 152 and 153 as follows:
"151. Carton and leaflet may include symbols or pictograms designed to clarify certain information mentioned in paragraphs 15 and 14 of this Annex and other information compatible with the summary of product characteristics that are useful for patient exclusion of any element of a promotional nature.
152. Information on secondary packaging of drugs is given in Romanian or Romanian language and in another language / international languages so that information in all languages is identical.
The information on primary packaging is exposed in Romanian and / or one of the international languages. For products intended for administration by health professionals eg .: products for hospital use (anesthetics, infusion solutions, vaccines, radiopharmaceuticals derived from human blood or plasma) or orphan drugs or used in substitution therapy), it accepts the primary and secondary packaging in English / foreign languages.
153. Name of product, referred to in subparagraph a) 1, paragraph 15, must appear on the packaging in Braille format. Registration certificate holder shall ensure that the package information leaflet is available on request from patients' organizations in formats appropriate for the blind and partially sighted.
August. In order to observe the performance of this order, the Agency Medicines and Medical Devices will develop and approve within 30 days after its publication in the Official Gazette following documents:
1) Guide for excipients to be mentioned on the label and package drugs human use;
2) Guidance on readability, clarity and ease of use of the information on labeling and package leaflets of medicinal products;
3) Guidance on the application of legal provisions on writing in Braille format for labeling;
4) Guidelines on the application of post-authorization variations;
5) Guidelines on Summary of Product Characteristics (SPC);
6) Models of the prospectus, summary of product characteristics and labeling information for drugs.
September. Paragraphs 3 and 4 of Order No. 58 of 29.01.2015 "On amending Order no. 739 of 23/07/2012 is hereby repealed.
10. This order is published in the Official Gazette of the Republic of Moldova.
11. Control over execution of this order'm willing to take.
