- New Decree No 228/2008 Coll. on Marketing Authorisation (hereinafter referred to as the “Decree”) – request for submission of documentation in eCTD
- Non-intervention studies – new approach of SUKL, new guideline UST-35 NPS
- Price deregulation – manufacturer's notification duty – producer's price
- Guideline UST – 23, version 2
A brief introduction to the eCTD format (with regard to the questions and comments sent to SUKL it may be assumed that some of the representatives of pharmaceutical companies think that eCTD means a conversion of the paper format to electronic format); references to information regarding eCTD:eCTD description: http://en.wikipedia.org/wiki/ECTDTechnical specifications of eCTD by EMEA: http://estri.ich.org/eCTD/eCTD_Specification_v3_2.pdf
- eCTD – a uniform format which may be used for work (SUKL assessors), maintains the history of the document, any amendments to original dossier may be attached.
- eCTD applies to applications submitted after July 1 2008; decisions issued by SUKL after the coming into force of the Decree which are based upon a non-eCTD documentation may be challenged (decisions issued in an illegal manner, vulnerability for SUKL as well as for companies – competition); quotation of Section 3 of the Decree:
- The Decree allows for “special cases” where other arrangements may be “agreed” with the Institute. These cases shall be generally defined by Guideline REG-84 with respect to the availability of medicinal products, minimisation of administrative burden of the applicants, jeopardy to European procedures, etc. The cases shall be assessed individually for each application.
- eCTD shall not be required for pending applications submitted prior to the coming into force of the new Act on Pharmaceuticals, i.e. prior to December 30 2007.
- Applications with predetermined submission dates for this year, i.e. marketing authorisation procedures with the Czech Republic as the RMS (Mutual Recognition, Decentralised) shall be started as agreed; it is necessary to justify in the cover letter why it is not possible to submit in eCTD – a non-eCTD format has been agreed, cannot be reprocessed for time reasons, jeopardised EU procedure, availability of the medicinal product, etc.
- SUKL is able to identify the eCTD format on the validation level; applications which will not be considered special cases agreed with SUKL shall be suspended at the validation stage; at present SUKL prepares an enhancement of the data repository (the expected capacity of annual receipt of applications and documentation = 18 TB) and “tools” for the processing of eCTD.
- Discussion on the possibility to submit documentation in the eCTD format upon the last renewal – according to the position of the representatives of the associations this is not possible due to the fact that older documentation is not available even in the CTD version (original structuring into 4 modules); conversion is not possible.
- The representatives of the associations have mentioned previous agreements with SUKL on the process of implementing eCTD submissions in line with other EU Member States; these agreements are not fulfilled; it concerns outputs from regular meetings of SUKL and the representatives of the associations from previous years, when the preparation for the accession of the Czech Republic to the EU, processes for the commencement of EU procedures and harmonised procedure of SUKL and of other medicines agencies in areas requiring necessary cooperation were jointly discussed.
- The representatives of the associations have expressed their requirement for the possibility of a consultation prior to the submission of the application (pre-submission meetings); it is proposed that this information should be added to Guideline REG – 84.
- The proposal of the associations to organise a seminar for eCTD – each association will see whether their members would be interested and the requirement will be communicated to SUKL.
- Discussion on the sent comments and proposals for REG-84, handled as Q+A:
- Q: The Act on Pharmaceuticals (378/2007 Coll., on Pharmaceuticals) does not establish any form for submitting the application for marketing authorisation or variation thereto. The same Act does not include any authority for the Ministry of Health of the Czech Republic to establish the form of this application.
A: The authority is stipulated by Section 26, paragraph 7 of the Act on Pharmaceuticals: “The implementing legal regulation shall closely define the contents and form of data and documentation for the application.“
- Q: The Constitution of the Czech Republic, in its Article 2, paragraphs 3 and 4 stipulates:
„(3) State power serves all citizens and it may be applied only in those cases, limits and by those methods which are stipulated by the law. (4) Each citizen may do whatever is not forbidden by law, and nobody must be forced to do what the law does not impose. “ As the Act on Pharmaceuticals does not allow the Ministry of Health of the Czech Republic to establish, by means of a Decree, particulars of the form of the application, the Decree cannot do so and if it does, it imposes a duty which is not known to the law and would hence be in conflict with the Constitution.
A: See 1)
- Q: The Marketing Authorisation Decree does not contain any transitory provision which would define since when the above mentioned duty is imposed. A certain method of solution seems to be the use of the term “Special cases”: in such instance SUKL would, in REG-84, define all applications submitted from the coming into force of the Decree to (e.g.) December 31 2008 as special cases.
A: The duty is imposed as of the date of coming into force of the Decree, i.e. from July 1 2008. SUKL is not authorised to stipulate “transitory provisions”.
- Q: The draft guideline REG-84 does not clearly define what “eCTD” is – whether it should be understood only as an electronic format, whether SUKL wishes to use some form of XML documents, or whether DOC or PDF files are satisfactory?
A: See above – introduction to eCTD. Other formats are not acceptable.
- Q: The deadline for the completion of the implementation of all tools for the submission of documentation in “true” eCTD format into the European Agency is the end of 2009, with NRAs coordinating this timeline. As part of the harmonised procedure of the national medicines agencies and the European Agency, the amended text of the Decree of the Ministry of Health of the Czech Republic should reflect whatever is negotiated among individual state authorities on the European level.
A: SUKL would like to say that according to original plans of EU and EMEA, the harmonograme has been changed. EMEA http://www.emea.europa.eu/pdfs/human/regaffair/56336607en.pdf advise only electronic format of documentation since 1st January 2009 and recommend to use format eCTD since 1st July 2009. Because the EMEA define ultimate term of using eCTD, within the frame of harmonization, Czech republic establish the date of eCTD implementation since 1st July 2008, the Decree allows “special cases” , these cases shall be generally defined by Guideline REG-84.
- Q: A repeated requirement for the establishment of a transitory period and harmonisation with the dates published on the EMEA website; companies will not be able to obtain eCTD from their head offices.
A: SUKL is not authorised to introduce a transitory period; the issue may be resolved by means of the “special cases” and “agreement” during a limited period of time – see above.
- Q: The draft guideline has been published on the SUKL website for comments on July 4 2008 – retrospective effect of the guideline from July 1 2008 is not appropriate – the guideline should become effective only after its effective version is published.
A: Yes, that is true, but the Decree is effective, and the effective date of the guideline is not relevant.
- Q: The mentioned website does not provide application forms for all types of procedures (only new marketing authorisation, variation, and renewal), and the guideline for Module 1 in eCTD, which was published in May 2008, also assumes a 6-month transitory period. Furthermore, Section 3, paragraph 5 of the Decree states that the “completed application form in electronic format shall be submitted in the format specified by the relevant Institute in a manner allowing for remote access.” This is not covered by the draft guideline.
A: It does not as yet; it will be resolved in future with respect to the volume of data.
- Q: Although the guideline proposes a “transitory period”, within which it is possible, for the time being, to submit applications and documentation only on an electronic data carrier (CDs or DVDs), it does not specify how, in this case, application forms, cover letters and forms of proof of payment of administrative fees and reimbursement of costs which form an integral part of any submission and which so far had to be submitted in hard copies with the original signature of the authorised person, should be submitted.
A: The guideline does not define a “transitory period”, but special cases agreed with SUKL – see above. If the application is assessed as a “special case”, everything shall be submitted as has normally been done. (Please note that pursuant to the old Decree the application form was submitted electronically as well).
- Q: Although the drafted REG-84 covers the electronic version of marketing authorisation dossiers, it should also contain a reference to the previous guideline REG-76 (requirements governing the SPC, PIL, labelling…).
A: REG 76 was revoked as of may 1 2008.
- Q: Will this internet source (REG-84) be truly the only available one and will no other relevant form/guideline be published by SUKL?
A: Yes for the moment, SUKL plans to avail of the EU information sources as much as possible.
- Q: Do we really have to re-process all documents we have “in store” to the electronic version?
A: Yes, if these documents are to be submitted to SUKL, see above, except for those situations where in special cases other arrangements will be agreed with SUKL.
- Q: To be able to submit documentation in the eCTD format it will be necessary to have a special software/information system, which is associated with considerable investments. It might be useful to classify companies with respect to their turnover or the number of authorised products to those for whom it will be binding to submit in eCTD format as early as at present and those for whom a specific time schedule will be set up.
A: The legal regulation does not allow for any exemptions for companies with low turnover or low numbers of authorised medicinal products. It is possible to submit a proposed rationale why the company does not submit in eCTD, which will be assessed individually and the applicant will be notified, if the rationale is found unacceptable. In this respect we should note the harmonisation of the marketing authorisation procedure throughout the EU – due dates for the implementation of eCTD in the CP are given. MRPs/DCPs represent, for “successful” agencies, and hence applicants, a tool to ensure an effective utilisation of resources. Insisting on the “high costs of SW” position is only sticking to a substitute problem. Non-eCTD applications and documentation result in longer MA procedures, increased costs on the part of the applicant as well as the regulator, and complications in evidencing the procedures employed by both parties.
- Q: We as a company have “inherited” documentation from another company for products authorised in 1969, the documentation is in the NTA format. The products have been on the market continuously since, and their safety potential is, as suggested by the submitted PSURs, very favourable. Submission of e.g. variations for these products is, due to the existence of the NTA format, currently impossible, and for capacity reasons it is not feasible to quickly convert documentation to the eCTD format, also due to the fact that a number of clinical and preclinical chapters could not be completed due to the year of marketing authorisation of the products. It would be appropriate to have an exception for these cases. The regulation may be many times critical for these companies and the presence of certain generic products (as well as original ones) on the market could be hence jeopardised.
A: The documentation of authorised medicinal products has gone through so called “UPDATE” project before the accession to the EU, and companies had to submit updated documentation. Where a risk of a shortcut of important medicinal products on the market is involved it is possible to avail of the option to agree with SUKL a special case – see above – and to submit changes as before.
- Q: Products for which the last application for marketing authorisation renewal was lodged and accepted in the NTA format, incl. subsequent changes, should be classified as “special cases”.
A: SUKL will consider the acceptability of the proposal.
- Q: In the course of June, our marketing authorisation department has prepared a number of variations which they have planned to submit at the beginning of this month to the Institute; it involves a product authorised via the MRP, with Denmark as the RMS. Will they be accepted in non-electronic format?
A: Yes, for MRPs with the Czech Republic as the CMS, non-submission in eCTD is justified, it is necessary, though, to evidence the justification in the cover letter.
- Q: Will applications for renewal of marketing authorisation be accepted for products authorised in 1969 in the Czech Republic in non-eCTD form (with documentation in the NTA format)? The application for renewal has to be submitted early next year.
A: See above, it is necessary to evidence the justification.
- Q: I understand the draft guideline as follows: from now on, any documentation should be submitted to SUKL exclusively on CD-roms?
A: The issue of the carrier (CD,DVD) is not identical to that of the eCTD format – see introduction to eCTD in the initial part.
- Q: Should we expect any specifications of the requirements for eCTD on the part of SUKL? And in what timeline?
A: SUKL plans to update the draft guideline REG – 84 to reflect the received comments and ideas; it is also advisable to avail of the information provided on the EMEA and ICH websites; if interest is shown, we will organise a seminar/workshop (in line with the information from associations – see above).
- Q: I would like to ask whether we should continue to submit cover letters, proofs of payments of costs and administrative fees and application forms in hard copies, or whether SUKL will require everything only on CD-roms? 1 copy or 2 copies?
A: So far everything as before, if you have a certified electronic signature, electronic submission is possible.
- Q: Is the NEES format acceptable (it is currently acceptable in BE, UK, PT, ES, FR, NL, DK)? eCTD (with an xml backbone, etc.) requires preparation and adequate software tools.
A: The Decree does not allow for other formats than a full eCTD. Special cases may be considered – see above (e.g. relationship with EU procedures).
- Q: What will happen to documentation in the case of rejection?
A: Same as at present – archival in compliance with standard procedures.
A reminder of the new duty of marketing authorisation holders to inform SUKL in advance of the commencement and completion of all non-intervention studies (Section 92, paragraph 12 of the Act on Pharmaceuticals). A new guideline has been published - UST-35 NPS (published on the website). Information focuses not only on non-intervention post-marketing safety studies (NPSB) as has the case been up to now, but on all non-intervention post-marketing studies. A new form has been established for the provision of the required information and source materials to SUKL (interactive, available from the SUKL website). Definition of the type of study – in the form distinguishing safety studies (intended for pharmacovigilance activities) from other ones (intended for Surveillance in the area of advertising).The representatives of the associations have expressed their disapproval of the SUKL procedure concerning the publication of this guideline, as no option to submit comments has been provided and companies do have comments on the content of the form and terminology used (e.g. the term Investigator), specification is required. SUKL has offered the option to send comments as part of the comments procedure concerning these minutes of meeting.
The attendees have been reminded on the duty to notify producer prices – see information published on the SUKL website.
The representatives of the associations have drawn attention to repeated problems with the notification form – it has been recommended to forthwith inform SUKL about the errors (ALT+PrintScreen, insert to the data message using CTRL-V, send to the following e-mail address: tomas.melen@suklcz).
In relation to this item, the problem with payments via web interface has been discussed – when the form is completed and posted for the generation of the variable symbol, an error message comes up or different amounts are shown. SUKL has already identified and eliminated these errors, should the problem arise again, please inform SUKL immediately – see above.
This item has been included in the agenda additionally, upon request of ČAFF. For time reasons the guideline has not been discussed in much detail, the representatives of the associations have agreed that SUKL has not proceeded in compliance with the existing practice and has failed to provide the option to submit comments before publication. Companies can see space for specification. SUKL has invited the submission of comments – the guideline takes effect on August 1, comments may be processed in the course of July.
The attendees agree with the publication of the minutes of meeting on the SUKL website.Minutes taken by: Koblihová
Reviewed by: Tutterová, Melen