Legal Framework
For the purpose of implementing Law of Ukraine No. 2469-IX of 28 July 2022, “On Medicinal Products” the State Service of Ukraine on Medicines and Drugs Control, in cooperation with the Ministry of Health of Ukraine, has developed a draft order of the Ministry of Health “On Approval of the Procedure for Confirming the Compliance of Medicines Manufacturing Facilities Located Outside Ukraine with the Requirements of Good Manufacturing Practice Established in Ukraine” (hereinafter referred to as the “Procedure”).
The Procedure was drafted based on the procedure for the verification of good manufacturing practice, approved by Order No. 1130 of the Ministry of Health of Ukraine dated 27 December 2012, which had previously been harmonized with the provisions of European Union legislation, in particular Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001, on the Community Code relating to medicinal products for human use, the European Commission’s guidance document “Community Procedures on Inspections and Exchange of Information” (EMA/572454/2014), and the guidelines of the Pharmaceutical Inspection
Co-operation Scheme (PIC/S) on the classification of GMP violations
(PI 040-1).
The new Procedure ensures the continued implementation of European approaches to good manufacturing practices and is aimed at improving the process for verifying compliance with the conditions for medicines manufacturing.
Who concerns
This procedure applies exclusively to foreign manufacturers of medicines. It establishes the procedure for:
- recognition of official documents confirming compliance of manufacturing conditions with GMP requirements, issued by authorized bodies of countries with strict regulatory authorities (SRAs), followed by the issuance of a Conclusion;
- inspection of manufacturing facilities that do not have such documents, followed by the issuance of a Certificate.
Main novelties (compared to the current GMP procedure)
The list of documents to be submitted for the purpose of obtaining a Certificate or Conclusion has been shortened. At the same time, for obtaining a GMP Conclusion, the list of documents will be determined depending on the location of the place of activity of the production of medicines.
The following are required for producers carrying out all stages of production in SRAs:
- Licence for medicines manufacturing;
- GMP certificate issued by the competent authority of the SRAs (which is recognised);
- General list of product nomenclature;
- Letter of guarantee;
- Certificate of medicines for international trade;
- Power of attorney.
If any stage of manufacturing is carried out outside the country of SRAs, the following shall be added:
- manufacturing site dossier;
- the inspection report of the SRAs’ competent authority, issued after the last inspection;
- registration certificates issued by the competent authority of the EU country or SRAs.
The reasonable time limits for the consideration of applications under the Law of Ukraine "On Administrative Procedure" have been established. The consideration of applications will take place within a period of no more than 30 calendar days.
The State Control Authority shall consider the application and the documents thereto within 3 working days from the date of receipt of the relevant application. If deficiencies are found, such an application shall be left without action, with a deadline for their elimination, while the State Control Authority may provide an additional deadline for the elimination of the identified deficiencies.
If the identified deficiencies are eliminated within the time limit set by the state control authority, the relevant application shall be deemed to have been submitted on the date of its initial submission. In this case, the time limit for examining such an application shall be extended by the period of time during which it was left without action.
Based on the documents submitted with the application for the issuance of the Conclusion, the state control authority will make a decision on the issuance or refusal to issue the Conclusion; with the application for the issuance of the Certificate – it will conduct an inspection, based on the results of which it will make a decision on the issuance or refusal to issue the Certificate.
The Certificate shall be issued within 90 calendar days after the inspection, provided that there are no critical non-conformities and less than 6 significant non-conformities and a corrective and preventive action plan approved (acceptable) to address the identified non-conformities.
The possibility to extend the Certificate for a period of up to 6 months has been introduced, provided that a new application is submitted no later than 3 months before the expiry of the Certificate.
Continuation shall not be permitted in the following cases:
- the existence of orders for a complete ban on circulation and/or decisions of the state supervision (control) authorities regarding the withdrawal from circulation of medicines of three batches of non-sterile medicines or one batch - for sterile and aseptically manufactured medicines, which were manufactured in this section, if the quality defect of the medicine can be associated with the manufacturing technology and/or methods of its control, and/or storage and transport conditions;
- failure to provide documentary evidence of the corrective actions taken within the time limits set by the manufacturer in accordance with the CAPA plan and/or failure to implement them within the time limits set;
- technical re-equipment of manufacturing with replacement of equipment units, substantial modernisation or reconstruction of a manufacturing unit, including systems for providing manufacturing with technological environments;
- relocation of the manufacturing site to other areas or buildings.
Limited monopoly and ensured proper competition between applicants - business entities. Provided for the possibility of adopting the SARA plan in cases where the manufacturing site has already been inspected by the authorized body of Ukraine, but the documentary evidence of elimination of the identified violations by the applicant is not provided in full. This applies, in particular, if the declared medicines were not subject to previous inspection or the application was submitted by another applicant. At the same time, documentary evidence of elimination of violations established during the previous inspection may be submitted by another applicant in the presence of a relevant order.
How to get involved
The draft order is available for public discussion on the website of the Ministry of Health of Ukraine in the section “Public discussion”. Proposals or comments can be sent to the e-mail address of Tetiana Zadorozhna, Deputy Head of Division on Medicines Manufacture Certification (Zadorozhna_TA@dls.gov.ua).