3.1. CMDh guidance documents
3.1.1. Request form for RMS in a DCP / SEThe CMDh discussed and agreed an update of the template for requests for RMS in a DCP for medicinal products for human use. Applicants are now also asked to provide the proposed indication(s) of the product to be applied for and to indicate if ASMF worksharing will be used in case of an ASMF. Further minor editorial changes have been included. The updated
document will be published on the CMDh website (Action: EMA).
3.1.2. Template for new agenda topic / EMA
The CMDh discussed and agreed an update of the template for new topics to be included in the CMDh agenda. MSs are now also asked to provide information on the MAH(s), the MRP/DCP procedure number, CMSs and the INN concerned by a topic, as applicable. The additional information will help MSs to prepare for the CMDh discussion and will further facilitate identifying potential conflicts of interests of participants.
It was noted that for topics on newly identified nitrosamines MSs should provide the CAS number. This will however not be included in the general topic template.
The updated template was adopted and will be made available in MMD (Action: EMA).
3.2. Variations
3.2.1. Requests for worksharing procedures on Variations
The MSs chosen by the CMDh, based on the recommendations of MAHs, agreed to be reference authorities for the procedures.
3.2.2. Requests for recommendations on unforeseen Variation under Art. 5 of Variation Regulation
None
3.2.3. Submission of parallel national variations / FI
The CMDh discussed the parallel submission of purely national variations .
3.3. GMP
None
3.4. GCP
None
3.5. COVID-19
The CMDh was informed that the addendum to the variation guidelines related to changes to the active substance of a vaccine against human coronavirus has been published.
The CMDh agreed to stop having COVID-19 as standing topic on the agenda and include it only when there is a specific topic to be discussed.
3.6. Medical Device Regulation / EMA
The EMA presented the final versions of the update of the Q&As and application forms (new MAA and variations) for the implementation of Medical Device and In Vitro Diagnostics Regulations (MDR/IVDR). The updates have been prepared in collaboration with the EC.
With regard to the consultation procedure for ancillary substances in medical devices, it was specified in the Q&As that the given guidance is only applicable to the EMA consultation. For NCA consultation, applicants should consult the national guidance or liaise with the NCA.
Other minor changes to the AFs, that have been agreed in the past (not related to the MDR), have been included in the update.
The updated Q&As were adopted by the CMDh. The document will be published shortly after the CMDh meeting. The AFs will be forwarded to the NtA for written adoption. They will then be converted into the eAF within 2-3 months, before release.
The EC informed the CMDh that a response to the CMDh question on Art. 117 with respect to MRP/RUP is being prepared. The related Q&A can be updated, as needed, once a feedback from the EC is received.
In preparation of the update of the eAFs, the rapporteurs of related CMDh guidance documents (e.g. RMS validation check list and the user guide for the eAF) were asked to review the documents and prepare an update as needed (Action: BE, FR).
3.7. PEG laxatives and interaction with starch-based thickeners / IE
The CMDh was informed of a discussed the reported interaction on /“liquefying-effect” of PEG (Macrogol) -based laxatives with starch-based thickeners and the potential for aspiration pneumonia with concomitant use in patients with dysphagia.
Patients with dysphagia often need to use starch-based food thickeners to enhance an appropriate intake and may therefore deviate from SmPC advice on mixing the PEG product.
As warnings have been recently approved for Section 4.4 and 4.5 of the SmPC in variation procedure SE/H/1799/01-07/II/195, it was therefore agreed that MAHs for Polyethylene Glycol (PEG) laxatives should review their current product information wording and submit a variation to update sections 4.4 and 4.5 of the SmPC and consequentially the package leaflet in line with wording agreed in procedure SE/H/1799/01-07/II/195, if necessary. This wording is included below for reference, and the applicant is recommended to align their product information promptly, for example by submitting a Type IB variation within 3 months:
The CMDh agreed a common wording to be implemented by MAHs of PEG-based laxatives, in case a similar wording is not already present:
Summary of Product Characteristics Section 4.4
In patients with swallowing problems, who need the addition of a thickener to solutions to enhance an appropriate intake, interactions should be considered, see section 4.5.
Section 4.5
[Product] may result in a potential interactive effect if used with starch-based food
thickeners. The macrogol ingredient counteracts the thickening effect of starch, effectively liquefying preparations that need to remain thick for people with swallowing problems.
Package leaflet
Section 2. What you need to know before you take [Product]
Other medicines and [Product]
If you need to thicken fluids in order to swallow them safely, [Product] may counteract the effect of the thickener.
3.8. Submission of changes to PMS not classified as a variation / DE, Chair
Information related to this section cannot be released at the present time as it is deemed to contain commercially confidential information.
3.9. Informed consent applications in eCTD / PL
The CMDh was informed that the Human Harmonisation Group (HHG) is currently working on an update of the Harmonised Technical Guidance for eCTD Submissions in the EU. As part of the update a new section concerning informed consent applications was prepared on the basis of the CMDh document “Recommendations on Informed Consent Applications in MRP/DCP”.
The CMDh was consulted if the information in the CMDh guidance document is still up to date.
The CMDh confirmed that the information in the CMDh guidance is correct. Module 1 always has to be submitted by the applicant including a letter of consent to modules 3-5, as
applicable. Modules 2- 5, if provided due to national requirements, must be identical with the reference product dossier. MSs that only require Module 1 accept the submission of Modules 1-5, in case other CMS in the procedure have this as national requirement. The CMDh further confirmed that after granting of the MA, the product authorised under informed consent can develop independently. However, all necessary data needs to be submitted for variations. The Rapporteur of the CMDh guidance document will review it to see if more information on the submission of variations after granting of the MA needs to be added (Action: DK).
The CMDh feedback will be further discussed in the HHG for the update of the eCTD technical guidance.
4. Generic/hybrid marketing authorisations
4.1. Acceptability of BE waiver for an oily parenteral (i.m.) solution / IT
Following the discussion in May, the CMDh agreed to send a question to CHMP (PKWP) on the requirements for a biowaiver for oily parenteral solutions. The question will be sent after the meeting (Action: EMA).
4.2. Reliability of software for calculation of the 90% CI of f2 / IT
Following the discussion in May, the CMDh was informed that PKWP is working on a Q&A on software to be used for calculation of the 90% CI of f2 by means of bootstrapping for the comparison of highly variable dissolution profiles. As the question raised in the May meeting will be addressed in this Q&A, the CMDh agreed that there was no need to send the proposed question to PKWP.
4.3. Court cases
4.3.1. Court judgement on applications for generics of Tecfidera (dimethylfumarate) / Chair, EMA
The CMDh discussed the Judgment of the General Court of 5 May 2021 in Case T-611/18, Pharmaceutical Works Polpharma v European Medicines Agency. Based on a reading of the Judgment, the CMDh agreed that Member States that have received marketing authorisation applications for generics of Tecfidera (dimethyl fumarate) can currently not validate such applications until the role of monoethyl fumarate salts within Fumaderm has been assessed by the Committee for Medicinal Products for Human Use. These applications will therefore be held in validation until this assessment is finalised.
4.3.2. Discontinuation of court case on dexmedetomidine / DK, EC
The CMDh was informed that the court case between Orion and DKMA on dexmedetomidine has been discontinued.
4.4. Collaboration between CMDh/RMS and EMA on generics and hybrids / EMA
The EMA proposed to simplify the communication on safety changes of centrally authorised reference medicinal products. Instead of the circulation of emails, it is proposed to only table the information in MMD on a monthly basis. The CMDh agreed with the proposed approach.
The EMA will be looking into updating the best practice guidance on the common principle for collaboration between CMDh/RMS and EMA on generics and hybrids, as needed (Action:
EMA).
4.5. Generics containing pirfenidone / DE
The CMDh discussed and agreed to send questions on the BE requirement for generics of pirfenidone to the CHMP (PKWP). The question will be sent after the CMDh meeting (Action:
EMA).
4.6. Non-acceptability of a US reference product for a BE study in case the same batch is marketed in the EU / ES
The CMDh discussed if a bioequivalence study using a RefMP authorised in the US can be accepted in a MAA for a generic in the EU, in case the product belongs to the same manufacturing batch of a medicinal product marketed in the EU.
It has previously been discussed that a US product cannot be used as RefMP in generic applications in the EU.
Reference was made to the user guide on the eAF and Chapter 1 of the NtA. The CMDh agreed that from a legal point of view the RefMP in the BE study has to be authorised in the EU/EEA and should be sourced from the EU/EEA. The CMDh will consider clarifying this situation in a future revision of the NtA.
4.7.
.Information related to this section cannot be released at the present time as it is deemed to contain commercially confidential information.