Rapporteur day 150 joint response assessment report
Quality, non-clinical and clinical – Overview assessment of the responses to the CHMP List of Questions
(Generic medicinal product)
<Invented Name>
<(Active Substance)>
EMEA/H/C/<xxx
Applicant:
CMHP Rapporteur: /PRAC Rapporteur:
EMA EPL:
EMA PM:
Start of the procedure:
Date of this report:
Deadline for comments:
Table of contents
1. Recommendation 7
2. Executive summary 7
2.1. Problem statement 7
2.2. About the product 7
2.3. The development programme/Compliance with CHMP Guidance/Scientific Advice 8
2.4. General comments on compliance with GMP, GLP, GCP 8
2.5. Type of application and other comments on the submitted dossier 8
3. Scientific overview and discussion 8
3.1. Quality aspects 8
3.1.1. Introduction 8
3.1.2. Active Substance 8
3.1.3. Finished Medicinal Product 8
3.1.4. Discussion on chemical, pharmaceutical and biological aspects 9
3.1.5. Conclusions on the chemical, pharmaceutical and biological aspects 9
3.2. <Non clinical aspects> 9
3.2.1. Ecotoxicity/environmental risk assessment 9
3.2.2. Discussion on non-clinical aspects 9
3.2.3. Conclusion on non-clinical aspects 9
3.3. Clinical aspects 9
3.3.1. Exemption 9
3.3.2. Pharmacokinetics 9
3.3.3. Pharmacokinetic conclusion 10
3.3.4. Pharmacodynamics 10
3.3.5. Additional data 10
3.3.6. Post marketing experience 10
3.3.7. Discussion on clinical aspects 10
3.3.8. Conclusions on clinical aspects 10
3.4. Risk management plan 10
3.5. Pharmacovigilance system 12
4. Benefit risk assessment 12
4.1. Conclusions 12
5. Assessment of the responses to the LOQ 12
5.1. Quality aspects 12
5.2. <Nonclinical aspects> 13
5.3. Clinical aspects 14
5.4. Overall summary and conclusions on the applicant’s responses 17
6. CHMP list of outstanding issues to be addressed in an oral explanation and/or in writing 17
6.1. Quality aspects 17
6.2. Non clinical aspects 17
6.3. Clinical aspects 17
7. Proposed conditions for marketing authorisation and product information 17
7.1. Proposed list of post-authorisation measures* 17
7.2. Other conditions 18
7.3. Summary of product characteristics (SmPC) 18
7.4. Labelling 18
7.5. Package leaflet (PL) 18
8. QRD CHECKLIST FOR THE REVIEW OF USER TESTING RESULTS 18
Administrative information
INN (or common name) of the active substance(s):
Active substance(s):
Applicant:
Applied Indication(s):
Pharmaco-therapeutic group
(ATC Code):
Pharmaceutical form(s) and strength(s):
Rapporteur contact person:
EMA Product Lead:
Procedure Manager: / Name:
Tel:
Fax:
Email:
Name:
Tel:
Fax:
Email:
Names of the Rapporteur assessors
(internal and external): / Quality:
Name(s)
Tel:
Fax:
Email:
Non-clinical:
Name(s)
Tel:
Fax:
Email:
Clinical :
Name(s)
Tel:
Fax:
Email:
Names of the PRAC Rapporteur assessors
(internal and external): / Name(s)
Tel:
Fax:
Email:
Declarations
The assessor confirms that proprietary information on, or reference to, third parties (e.g. ASMF holder) or products are not included in this assessment, unless there are previous contracts and/or agreements with the third party(ies).
The assessor confirms that reference to ongoing assessments or development plans for other products is not included in this assessment report.
Whenever the above box is un-ticked please indicate section and page where confidential information is located here:
List of abbreviations
1. Recommendation
Based on the review of the data and the Applicant’s response to the CHMP LoQ on quality, <safety>, <clinical> and <risk management plan>, the Rapporteur (s) consider(s) that the generic application for <product name> in the treatment of <claimed indication>,
<is approvable. The Rapporteur considers some points could be resolved after the marketing authorisation. See section 6.>
<A preliminary list of such post authorisation measures <and specific obligations> are in section 6 of this report>.
<could be approvable provided that satisfactory answers are given to the "other concerns" as detailed in the List of Questions. Failure to resolve other concerns may render the application not approvable
<In addition, the Rapporteur recommends conditions for marketing authorisation and product information. (see section 6).>
<However, the answers to the "other concerns" may affect the final product information and/or other conditions for the marketing authorisation.>
<is not approvable since "major objections" have been identified, which preclude a recommendation for marketing authorisation at the present time. The details of these major objections are provided in the List of Outstanding Issues (see section 5).>
<In addition, satisfactory answers must be given to the "other concerns" as detailed in the List of Outstanding Issues.>
<The major objections precluding a recommendation of marketing authorisation, pertain to the following principal deficiencies:>
<Deficiencies arising from concerns over the confidential (ASM - Active Substance Manufacturer restricted part) of the ASMF are mentioned in the appendix (this appendix is not supplied to the MAA). These concerns will be conveyed in confidence to the holder of the ASMF.>
Questions to be posed to additional experts
Inspection issues
2. Executive summary
2.1. Problem statement
2.2. About the product
<In the case o additional pack-sizes which contain more units than the pack sizes of the reference product, this should be reflected in the overview. Furthermore, it should be confirmed that all pack sizes are consistent with the dosage regimen and duration of use.
2.3. The development programme/Compliance with CHMP Guidance/Scientific Advice
2.4. General comments on compliance with GMP, GLP, GCP
2.5. Type of application and other comments on the submitted dossier
· Legal basis
3. Scientific overview and discussion
The structure of this AR is in accordance with the Day 120 LoQ and shall be updated at the different stages of the CHMP review (Day 180/CHMP AR/EPAR) so as to constitute a self standing document. See also the Day 80 Overview Guidance.
It should therefore be sufficiently detailed to eventually be used for the CHMP (Withdrawal)AR and (W)EPAR and give sufficient justifications for the LoQ/LoI as appropriate.
Tables and graphs to display results are encouraged.
3.1. Quality aspects
3.1.1. Introduction
3.1.2. Active Substance
General Information
Manufacture, characterisation and process controls
Specification
Stability
Comparability exercise for Active Substance
3.1.3. Finished Medicinal Product
Description of the product and Pharmaceutical Development
Manufacture of the product and process controls
Product specification
Stability of the product
Comparability exercise for Finished Medicinal Drug Product
Adventitious agents
3.1.4. Discussion on chemical, pharmaceutical and biological aspects
3.1.5. Conclusions on the chemical, pharmaceutical and biological aspects
3.2. <Non clinical aspects>
This template is aimed for generic applications. If, apart from bioequivalence studies, other (non)-clinical data have been submitted, the template should be supplemented with relevant headings from the general templates of assessment report for non-clinical and clinical data.
3.2.1. Ecotoxicity/environmental risk assessment
3.2.2. Discussion on non-clinical aspects
3.2.3. Conclusion on non-clinical aspects
3.3. Clinical aspects
This template is aimed for generic applications. If, apart from bioequivalence studies, other (non)-clinical data have been submitted, the template should be supplemented with relevant headings from the general templates of assessment report for non-clinical and clinical data.
3.3.1. Exemption
· Tabular overview of clinical studies
3.3.2. Pharmacokinetics
Methods
Study design
Test and reference products
Population(s) studied
Analytical methods
Pharmacokinetic Variables
Statistical methods
Results
Safety data
3.3.3. Pharmacokinetic conclusion
3.3.4. Pharmacodynamics
3.3.5. Additional data
3.3.6. Post marketing experience
3.3.7. Discussion on clinical aspects
3.3.8. Conclusions on clinical aspects
3.4. Risk management plan
Summary of the safety concerns [to be assessed by the CHMP rapporteur]
[Please copy table from RMP Part II Module SVIII]
The applicant identified the following safety concerns in the RMP:
Table XX: Summary of the Safety Concerns
Summary of safety concerns /Important identified risks / <List here>
Important potential risks / <List here>
Missing information / <List here>
[Please update the scientific discussion if any.]
<New safety specification that should be taken into account by the PRAC>
Pharmacovigilance Plan [to be assessed by the PRAC rapporteur]
[Please copy RMP table III.3 (only studies of categories 1-3)]
Table X: Ongoing and planned studies in the PhV development plan
Activity/Study title (type of activity, study title [if known] category 1-3)* / Objectives / Safety concerns addressed / Status Planned, started, / Date for submission of interim or final reports (planned or actual) /*Category 1 are imposed activities considered key to the benefit risk of the product.
Category 2 are specific obligations
Category 3 are required additional PhV activity (to address specific safety concerns or to measure effectiveness of risk minimisation measures)
[Please update the scientific discussion on pharmacovigilance activities if any, including PASS and PAES.]
Risk minimisation measures for <product name(s)> [to be assessed by the PRAC rapporteur]
[The RMP may cover more than one medicinal product. In some circumstances risk minimisation measures may be specified per product, or certain risks may not be relevant to all products.]
[Please copy table from RMP section V.3.]
Table XX: Summary table of additional Risk Minimisation Measures [only for safety concerns that require additional risk minimisation measures]
Safety concern / Routine risk minimisation measures / Additional risk minimisation measures /[Please update the scientific discussion on the additional risk minimisation measures if any.]
Public summary of the RMP [to be filled in by the PRAC rapporteur]
<The public summary of the RMP < may require<does not require> revision. >
<PRAC Outcome>
If applicable, the outcome of the PRAC plenary discussion should be added in that section, the above sections should be updated at the time of the circulation of the updated CHMP overview AR.
3.5. Pharmacovigilance system
<The (Co)Rapporteur considers that the pharmacovigilance system summary submitted by the applicant fulfils the requirements of Article 8(3) of Directive 2001/83/EC.>
<The (Co)Rapporteur, having considered the data submitted in the application was of the opinion that it was not appropriate to conclude on pharmacovigilance system at this time.<See list of outstanding issues>.
<The (Co)Rapporteur, having considered the data submitted in the application was of the opinion that a pre-authorisation pharmacovigilance inspection is required>.
4. Benefit risk assessment
(Update this section at Day 150/180. See Day 80 template/guidance for instructions)
Benefit-risk balance
Discussion on the benefit-risk assessment
4.1. Conclusions
The overall B/R of <name of products> <is> <positive> provided <general statement on conditions>; is <negative>.
5. Assessment of the responses to the LOQ
5.1. Quality aspects
Major objections
Drug substance [related to additional data provided by applicant only]
Question
Summary of the Applicant’s Response
Assessment of the Applicant’s response
Conclusion
Drug substance [related to additional data provided by ASMF holder]
Question
Summary of the Applicant’s Response
Assessment of the Applicant’s response
Conclusion
Drug Product
Question
Summary of the Applicant’s Response
Assessment of the Applicant’s response
Conclusion
Other concerns
Drug substance [related to additional data provided by applicant only]
Question
Summary of the Applicant’s Response
Assessment of the Applicant’s response
Conclusion
Drug substance [related to additional data provided by ASMF holder]
Question
Summary of the Applicant’s Response
Assessment of the Applicant’s response
Conclusion
Drug Product
Question
Summary of the Applicant’s Response
Assessment of the Applicant’s response
Conclusion
5.2. <Nonclinical aspects>
Major objections
Pharmacology
Question
Summary of the Applicant’s Response
Assessment of the Applicant’s Response
Conclusion
Pharmacokinetics
Question
Summary of the Applicant’s Response
Assessment of the Applicant’s Response
Conclusion
Toxicology
Question
Summary of the Applicant’s Response
Assessment of the Applicant’s Response
Conclusion
Other concerns
Pharmacology
Question
Summary of the Applicant’s Response
Assessment of the Applicant’s Response
Conclusion
Pharmacokinetics
Question
Summary of the Applicant’s Response
Assessment of the Applicant’s Response
Conclusion
Toxicology
Question
Summary of the Applicant’s Response
Assessment of the Applicant’s Response
Conclusion
5.3. Clinical aspects
Major objections
Pharmacokinetics
Question
Summary of the Applicant’s Response
Assessment of the Applicant’s Response
Conclusion
Pharmacodynamics
Question
Summary of the Applicant’s Response
Assessment of the Applicant’s Response
Conclusion
Clinical Efficacy
Question
Summary of the Applicant’s Response
Assessment of the Applicant’s Response
Conclusion
Clinical Safety
Question
Summary of the Applicant’s Response
Assessment of the Applicant’s Response
Risk Management plan
Question
Summary of the Applicant’s Response
Assessment of the Applicant’s Response
Conclusion
Pharmacovigilance system
Question
Summary of the Applicant’s Response
Assessment of the Applicant’s Response
Conclusion
Other concerns
Pharmacokinetics
Question
Summary of the Applicant’s Response
Assessment of the Applicant’s Response
Conclusion
Pharmacodynamics
Question
Summary of the Applicant’s Response
Assessment of the Applicant’s Response
Conclusion
Clinical Efficacy
Question
Summary of the Applicant’s Response
Assessment of the Applicant’s Response
Conclusion
Clinical Safety
Question
Summary of the Applicant’s Response
Assessment of the Applicant’s Response
Risk Management plan
Question
Summary of the Applicant’s Response
Assessment of the Applicant’s Response
Conclusion
Pharmacovigilance system
Question
Summary of the Applicant’s Response
Assessment of the Applicant’s Response
Conclusion
5.4. Overall summary and conclusions on the applicant’s responses
6. CHMP list of outstanding issues to be addressed in an oral explanation and/or in writing
6.1. Quality aspects
Note: In case the ASMF procedure is used the following should be stated in case potential serious risks to public health or other concerns are being raised on the restricted part of the ASMF:
“For <potential serious risks to public health> <and> <Other concerns> on the restricted part of the ASMF see separate LoOI on the ASMF”
6.2. Non clinical aspects
6.3. Clinical aspects
7. Proposed conditions for marketing authorisation and product information
7.1. Proposed list of post-authorisation measures*
[This table should be reserved to include conditions that are part of the marketing authorisation, such as specific obligations, Annex II conditions, or any additional studies that have arisen based on the assessment of the data]
Post-authorisation measure(s) / Motivation /Proposed post-authorisation measure 1 with proposed classification: / Motivation/Background information on measure, including due date:
1.
Proposed post-authorisation measure 2 with proposed classification: / Motivation/Background information on measure, including due date:
2.
Proposed post-authorisation measure 3 with proposed classification: / Motivation/Background information on measure, including due date:
3.
Proposed post-authorisation measure X with proposed classification: / Motivation/Background information on measure, including due date:
X.
* Classification: category 1= Annex II D condition; category 2= Annex II E specific obligations; category 3 = All other studies reflected only in the RMP (non-clinical, PK, PASS)
Proposed list of recommendations:
Description of post-authorisation measure(s) /1.
2.
7.2. Other conditions
[Please state in this section all additional risk minimisation measures.]
7.3. Summary of product characteristics (SmPC)
7.4. Labelling
7.5. Package leaflet (PL)
User consultation
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