1. Recommendations to facilitate assessment of new application procedures
Initial
Submission
Assessment
Issues
Responses to
List of Questions
Legal framework
For Art 13 applications, ensure application form identifies a valid reference product.
To facilitate validation, careful selection of legal basis in application form for topically applied spot-on formulations & intra-mammary products for which systemic bioavailability cannot be demonstrated i.e.in accordance with Article 13.3 of Directive 2001/82/EC (see CMDv RfR July-Sept 2016).
DDPS
Submit a signed declaration form if the same version of the DDPS has been previously assessed and approved.
If the DDPS is a new version which has not been previously assessed, a variation application may be required to ensure all original CMS are aware of the implementation of the latest version of the DDPS, depending on the type of authorisation procedure.
Pictograms
Consider recent EMA guidance document on acceptability of pictograms.
Newly proposed pictograms should be endorsed within industry and then submitted to the CMDv and QRD secretariats for regulatory approval.
Hyperlink
Lengthy or bibliographic references should include a navigation facility/ index in the dossier.
Part II Quality
Ensure GMP certificates and declarations are valid and in-date.
For sterile products ensure selection of sterilisation method is justified in line with guideline.
Product specification limits should be supported by data.
Part III Safety
Pharmacokinetics
The applicant should identify which principle (section 7.1 of the current Guideline EMA/CVMP/016/00-REV.2) of the biowaiver is claimed.
User risk assessment
Check that the current version of applicable guidelines has been referred to.
Follow the GL recommendations regarding format and endpoints to determine MOE.
User safety warnings should be consistent with conclusion of URA.
Residues
Consider all components of the formulation:
Excipients - inclusion in Table 1 of Regulation 37/2010 or the official CVMP ‘out of scope’ list or a valid E number approved as additives in foodstuffs for human consumption.
Confirmation of use of final formulation in residue studies.
Vaccines: consider any potential residue issues arising from antibiotics used during manufacture.
Part IV Efficacy
Provide the study protocols including the pre-planned statistical analysis plan, and raw data of pivotal studies.
Confirmation of use of the final formulation in pivotal studies.
Mindful of GLP/GCP requirements.
Ensure that primary and secondary efficacy variables are well-defined with respect to the proposed claims.
Submission of response
Formatting of responses: submit responses in the same format as used in the list of questions document (font style, size, page margins, etc.)
Submission of large pdf files that are not book-marked impedes assessment of responses.
SPC & QRD text
The proposed text should be worded taking into account guidance within the latest QRD template (v.8.1).
Tracked change QRD text (as opposed to non-tracked change version) should be provided to facilitate review.
Clean and tracked change QRD text should be provided for circulation at the conclusion of the procedure.
Note that not all QRD template text examples may be relevant:
Disposal statements on package leaflet should be appropriate considering the method of sale and supply of the product.
Method of sale/supply
The harmonised labelling text should be relevant for all Member States.
National specific text should be handled during the national stage of the procedure in accordance with each Member State’s requirements.