5. EU Regulatory procedures for a marketing authorisation (MA)

Mandatory for human medicines containing a new active substance to treat:

• human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS);
• cancer;
• diabetes;
• neurodegenerative diseases;
• auto-immune and other immune dysfunctions;
• viral diseases.
• medicines derived from biotechnology processes, such as genetic engineering;
• advanced-therapy medicines, such as gene-therapy, somatic cell-therapy or tissue-engineered medicines;
• orphan medicines (medicines for rare diseases);

Optional for other human medicines:

• containing new active substances for indications other than those designated as mandatory;
• that are a significant therapeutic, scientific or technical innovation;whose authorisation would be in the interest of patients* at Union level
  • a new alternative to patients in treating, preventing or diagnosing a disease,
  • development based on or application of significant new scientific knowledge
  • a new technology or new application of technology for the development or manufacture.
• generic/hybrid applications of a centrally authorised product (automatic access to the CP under Article 3(3) of Reg. (EC) No 726/2004)

Months before submission

Pre-submission – Actions

18 to 7

7

7 to 6

3 to 2

Submission of eligibility request

Notify EMA of the intended submission date (letter of intent)

Pre-submission meetings (recommended)

Re-confirmation of submission date - before submission

Submission of the application – using the electronic common technical document (eCTD) format through the eSubmission gateway or web client

Technical validation of the application by EMA to ensure all essential regulatory elements required for scientific assessment are included in the application prior to the start of the procedure.

DAY

Evaluation Procedure – ACTIONS

1

Start of the procedure

1 to 120

Preparation of assessment reports

CHMP rapporteur’s and co-rapporteur’s teams assess the evidence provided on the medicine and independently prepare their assessment reports (AR)

Inspection (if recommended)

of the medicine’s manufacturing site

Assessment of risk management plan

rapporteur and co-rapporteur of EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) assess the company’s proposed risk management plan (RMP), This assessment is reviewed by all PRAC members.

List of questions

‘peer review’ meeting: discussion of comments from rapporteur and co-rapporteur teams, the other CHMP members, the PRAC members, and the CHMP peer reviewers, leading to a single AR and a list of concerns and objections.

CHMP plenary meeting: discussion and adoption of the single AR. The report includes a final list of questions to be addressed by the applicant.

120

*Clock stop 1
evaluation is paused

Applicant prepares responses to the CHMP’s questions and updates the RMP.

Time frame: generally, three to six months.

121

Restart of the clock
Submission of the responses, including revised SmPC labelling and PL texts in English.

121 to 180

Further assessment and list of outstanding issues

Rapporteur and co-rapporteur evaluate the information sent by the applicant in response to the list of questions and update the AR which is reviewed and commented by the CHMP and PRAC members.

The PRAC may at this stage request that the RMP include the conduct of safety studies after authorisation.

Comments are consolidated and integrated into an updated AR which is discussed and adopted at a plenary meeting of the CHMP. Most of the time, this report will include a new list of questions, called the list of outstanding issues (LoOI).

180

*Clock stop 2
evaluation paused if a list of outstanding issues is agreed, while the applicant prepares responses.

Time frame: one to three months.

181

Restart the clock

An oral explanation can be requested either by applicant or CHMP. If so, the applicant is asked to provide clarifications on the committee’s outstanding issues.

181 to 210

Further consultations

EMA may consult external experts, e.g., calling on an EMA working party for specific questions or on additional experts, including patients and healthcare professionals, through a scientific advisory group or ad-hoc expert group meeting

Final discussion and adoption of opinion

After discussion as before, adoption of CHMP Opinion + CHMP Assessment Report:

• recommendation on whether or not a medicine should be granted a marketing authorisation and, if so, under which conditions of use.
• agreement on the wording of the product information for healthcare professionals and patients (i.e., the SmPC, labelling and PL) (+ timetable for the provision of product information translations)
• agreement on any additional data that the company is required to provide after the medicine’s authorisation.

215 at the latest

Applicant provides the EMA with SmPC, labelling and PL in the official EU languages. EMA circulates draft translations to Member States for review.

232 at the latest

Applicant provides EMA with final translations of product information taking in account comments received from Member States by Day 229.

By 237

Transmission of Opinion and Annexes in all EU languages to applicant, Commission, and Members of the Standing Committee, and Liechtenstein, Norway and Iceland.

By 277

Within 67 days of receipt of CHMP opinion the European Commission either grants or refuses the marketing authorisation.

Commission decisions are published in the Community Register of medicinal products for human use. EMA publishes a European public assessment report (EPAR) (introduce footnote explaining the different meanings AR, EPAR, PAR) for each medicine.

When a new marketing authorisation application is refused, EMA publishes a refusal EPAR, including a question-and-answer document and an assessment report.