What Is CMDh? Role, Functions and Regulatory Significance in the EU Medicines System

Introduction

The Coordination Group for Mutual Recognition and Decentralised Procedures – Human, commonly abbreviated CMDh, is the European regulatory body responsible for coordinating questions concerning the marketing authorisation of human medicinal products in two or more European Union Member States under the mutual recognition procedure (MRP) and the decentralised procedure (DCP).

Its role is sometimes misunderstood because CMDh sits at the intersection of national medicines regulation and the European regulatory system.

CMDh is not a European marketing-authorisation committee equivalent to the Committee for Medicinal Products for Human Use (CHMP). It does not grant centrally authorised marketing authorisations. Nor is it a pharmacovigilance committee equivalent to the Pharmacovigilance Risk Assessment Committee (PRAC).

Its function is different.

CMDh provides a mechanism through which the Member States coordinate regulatory questions concerning nationally authorised human medicines within the MRP and DCP framework. It also has specific responsibilities for safety-related questions concerning nationally authorised medicines and participates in certain EU referral procedures.

Understanding CMDh therefore requires understanding where it sits within the architecture of EU medicines regulation.

A simplified relationship is:

National competent authorities
          |
          v
   RMS and CMSs
          |
          v
        CMDh
      /      \
     /        \
  MRP/DCP    Safety-related
  matters     procedures
                |
                v
               PRAC
                |
                v
              CMDh
                |
                v
          National implementation

The CMDh operates within the framework established by EU medicines legislation and is supported administratively by the European Medicines Agency (EMA).

1. What Does CMDh Stand For?

CMDh stands for:

Coordination Group for Mutual Recognition and Decentralised Procedures – Human

The final letter, h, distinguishes the human medicines group from the corresponding veterinary medicines coordination group, CMDv.

The group is concerned with human medicinal products.

Its principal regulatory context is the system of nationally authorised medicines that are authorised in more than one Member State through the MRP or DCP.

2. The Legal Basis of CMDh

The legal foundation of CMDh is found in Article 27 of Directive 2001/83/EC, the EU legal framework governing medicinal products for human use.

Article 27 establishes a coordination group for the examination of questions relating to the marketing authorisation of a medicinal product in two or more Member States under the procedures in the relevant chapter of the Directive.

The legislation provides that the Agency supplies the secretariat to the coordination group.

It also establishes the group's composition as one representative per Member State, with the possibility for members to be accompanied by experts. 1

The legal basis is important because CMDh is not simply an informal forum established by EMA.

It is a body established within the EU medicines legislation.

3. Why Was CMDh Established?

The MRP and DCP allow a medicinal product to obtain national marketing authorisations in several Member States through coordinated procedures.

This creates a regulatory problem that does not arise in exactly the same way when a medicine is authorised in only one country.

Several national competent authorities must reach compatible regulatory conclusions concerning the same medicinal product.

A mechanism is therefore required to coordinate questions that arise between those authorities.

CMDh provides that mechanism.

Its existence reflects a fundamental feature of the EU medicines system:

Marketing authorisation can remain national while the regulatory assessment and subsequent regulatory decisions are coordinated at European level.

CMDh is one of the principal institutional mechanisms that makes this system function.

4. CMDh and National Competent Authorities

CMDh is composed of representatives of the national competent authorities of the Member States.

This is important because CMDh should not be understood as a separate supranational medicines authority that replaces the national authorities.

The national competent authorities remain responsible for national marketing authorisations.

CMDh provides the European coordination structure through which those authorities address questions falling within its mandate.

This makes CMDh fundamentally different from the CHMP.

CHMP is a scientific committee of EMA.

CMDh is a coordination group representing the Member States in the national-authorisation system.

5. Composition of CMDh

Article 27 provides for one representative per Member State.

Members are appointed for a renewable period of three years.

Members may be accompanied by experts.

The group therefore combines national regulatory representation with access to specialist expertise where required. 2

The composition reflects CMDh's principal purpose: coordination between the national regulatory authorities responsible for the relevant medicinal products.

6. The Role of the European Medicines Agency

EMA provides the secretariat for CMDh.

This does not mean that CMDh is an EMA scientific committee.

The distinction is important.

EMA provides the organisational and administrative infrastructure that supports the group, including its secretariat.

The CMDh itself is the coordination group established under the EU medicines legislation.

EMA describes CMDh as one of the Agency's committees, working parties and other groups, and identifies its role as the examination and coordination of questions relating to marketing authorisation under the MRP and DCP. 3

7. What Is the Mutual Recognition Procedure?

To understand CMDh, it is necessary to understand the MRP.

The mutual recognition procedure applies where a medicinal product already has a marketing authorisation in one Member State and the marketing authorisation holder seeks recognition of that authorisation in one or more other Member States.

The Member State in which the existing authorisation was granted acts as the reference Member State (RMS).

The Member States in which recognition is sought are the concerned Member States (CMSs).

The assessment performed by the RMS provides the basis for recognition by the CMSs.

CMDh becomes relevant when questions arise within this coordinated national-authorisation framework.

8. What Is the Decentralised Procedure?

The decentralised procedure applies where a medicinal product has not yet received a national marketing authorisation in the participating Member States and the applicant seeks authorisation in several Member States simultaneously.

One Member State acts as the RMS.

The other participating Member States are CMSs.

The RMS prepares the assessment report and the participating Member States assess the application within the decentralised procedure.

Again, the fundamental structure is national authorisation with European coordination.

CMDh provides the coordination mechanism for questions arising within this system.

9. RMS and CMS: The Basic Relationship

The terminology can be summarised as follows:

The RMS and CMSs are national regulatory authorities.

CMDh provides the coordination structure through which specified questions involving those authorities are addressed.

10. The Core Function of CMDh

EMA describes CMDh as examining questions relating to the marketing authorisation of human medicines in two or more EU Member States in accordance with the MRP or DCP.

It also examines questions concerning variations to those marketing authorisations. 4

This gives two major areas of work:

1. Initial and procedural marketing-authorisation questions
2. Post-authorisation questions and variations

Its remit therefore extends beyond the original MRP or DCP.

11. CMDh and Variations

A medicinal product does not remain unchanged after authorisation.

Changes may be required to:

• the manufacturing process;
• specifications;
• pharmaceutical development;
• product information;
• safety information;
• other aspects of the marketing authorisation.

Where a nationally authorised medicinal product is subject to a variation involving several Member States, the applicable variation procedure operates within the European regulatory framework.

CMDh provides coordination for relevant questions arising from these procedures.

EMA explicitly identifies questions concerning variations of marketing authorisations among CMDh's responsibilities. 5

12. CMDh and Disagreement Between Member States

One of CMDh's most important functions becomes apparent when Member States disagree.

During an MRP or DCP, a CMS may consider that the available evidence does not support the proposed regulatory outcome.

In the specific circumstances defined by the legislation, disagreement based on a potential serious risk to public health is referred to the coordination group.

CMDh considers the matter and seeks to reach agreement.

EMA describes a 60-day period for CMDh to strive to reach agreement in such circumstances. 6

If agreement cannot be reached, the matter can proceed to the next stage of the statutory procedure.

13. CMDh Is Not the Final Arbiter of Every Disagreement

CMDh is designed first and foremost to coordinate.

It attempts to achieve agreement between the participating Member States.

Where agreement cannot be achieved in a disagreement falling under the relevant statutory provisions, the matter can proceed to CHMP.

EMA describes this as a referral to CHMP for arbitration when the CMDh cannot reach agreement on a potential serious risk to public health. 7

This creates a clear distinction:

CMDh
   |
   | attempt to reach agreement
   v
Agreement
   |
   | or
   v
No agreement
   |
   v
CHMP procedure

The precise legal route depends on the provision under which the disagreement arises.

14. CMDh and Potential Serious Risk to Public Health

The expression potential serious risk to public health has a specific place in the EU medicines legislation.

Article 29 of Directive 2001/83/EC provides the mechanism for a Member State to raise a disagreement on this ground during the relevant MRP/DCP process.

The Member State must provide a detailed explanation of its position.

The disagreement is then referred to the coordination group.

The CMDh therefore has a formal role in the resolution of these disagreements. 8

The term should not be interpreted as meaning that the risk has already been conclusively demonstrated.

The statutory threshold concerns a potential serious risk.

15. CMDh and Pharmacovigilance

CMDh also has an important role in pharmacovigilance concerning nationally authorised medicines.

EMA states that CMDh examines questions concerning the safety of non-centrally authorised medicines marketed in the EU where centrally authorised products are not affected.

This includes adopting a CMDh position on safety-related EU referral procedures while taking account of recommendations from the Pharmacovigilance Risk Assessment Committee, or PRAC. 9

This is one of the most important aspects of CMDh for pharmacovigilance professionals.

CMDh does not replace PRAC.

Rather, the two bodies have different functions.

16. PRAC and CMDh

PRAC is the EU committee responsible for assessing and monitoring safety issues associated with human medicines.

CMDh has a different role.

In relevant procedures involving nationally authorised medicines, PRAC performs the pharmacovigilance assessment and adopts its recommendation.

CMDh then considers that recommendation in the context of the nationally authorised medicines concerned.

The distinction can be represented as:

Safety issue
      |
      v
    PRAC
      |
      v

PRAC recommendation | v CMDh | v CMDh position | v National implementation or European Commission decision depending on the voting outcome and applicable procedure

EMA describes this relationship explicitly for safety-related EU referral procedures. 10

17. Why PRAC Does Not Simply Make the Final Decision for Nationally Authorised Medicines

PRAC is a scientific committee.

Its recommendation provides the pharmacovigilance assessment.

Where the products concerned are nationally authorised and the applicable legislation provides for CMDh involvement, CMDh considers the PRAC recommendation.

CMDh then adopts its position.

The subsequent legal pathway depends on whether the CMDh position is adopted by consensus or by majority.

This is why a pharmacovigilance referral involving nationally authorised products can contain both a PRAC recommendation and a CMDh position.

18. CMDh Consensus

Where CMDh reaches consensus, the position can be implemented by the Member States in accordance with the applicable procedure and timetable.

EMA explains that a consensus CMDh position is implemented by the Member States according to the timetable determined in the position. 11

Consensus is therefore an important feature of CMDh decision-making.

It allows the nationally authorised medicines concerned to proceed directly into national implementation without the same Commission decision route that applies following a majority position.

19. CMDh Majority Voting

Consensus is not the only possible outcome.

Where consensus cannot be reached, the applicable majority voting provisions can result in a CMDh position adopted by majority vote.

The legal framework provides that Member States represented within the coordination group use their best endeavours to reach a position by consensus.

Where consensus cannot be reached, the majority position prevails. 12

A majority position has different consequences from a consensus position.

EMA explains that where a CMDh position is adopted by majority vote in the relevant referral context, the Agency, MAHs and national competent authorities finalise the translations and the matter is sent to the European Commission for the decision-making process leading to a binding decision. 13

20. Why Consensus Versus Majority Matters

The distinction is not merely procedural.

It affects what happens after CMDh has adopted its position.

A simplified model is:

The distinction can be seen in actual regulatory procedures.

For example, EMA records that CMDh endorsed the 2013 recommendation concerning cyproterone acetate/ethinylestradiol-containing medicines by a majority of 26:1. 14

21. CMDh Positions

The term CMDh position is used because CMDh is a coordination group rather than the CHMP.

The regulatory document records the position reached by the group.

In safety-related referral procedures, the position can contain:

• the scientific conclusions;
• the reasoning supporting the position;
• the voting outcome;
• divergent views where applicable;
• the products and marketing authorisation holders concerned;
• required changes to product information;
• conditions or restrictions;
• implementation arrangements;
• communication measures where applicable. 15

The exact contents depend on the procedure.

22. Divergent Views

A CMDh position does not necessarily mean that every Member State agreed with every aspect of the scientific reasoning.

Where a position is adopted by majority rather than consensus, divergent views can be recorded.

EMA's guidance on the structure of CHMP opinions and CMDh positions identifies divergent views among the elements that may be included where adoption occurs by majority rather than consensus. 16

This is important when interpreting regulatory documents.

The existence of a CMDh position should not automatically be read as evidence of complete unanimity.

23. CMDh and Product Information

CMDh decisions can have direct consequences for the information supplied with a medicinal product.

Depending on the procedure, the relevant regulatory outcome may require changes to:

• the Summary of Product Characteristics;
• labelling;
• the package leaflet.

In safety-related procedures, EMA states that CMDh positions can include the wording to be incorporated into relevant sections of the product information for nationally authorised medicines. 17

Thus CMDh activity can have a direct effect on the information provided to healthcare professionals and patients.

24. CMDh and Risk Minimisation

Safety-related CMDh positions can also establish conditions or restrictions for the safe and effective use of medicinal products.

These can form part of the regulatory measures associated with a referral.

The CMDh document structure described by EMA includes conditions or restrictions imposed on marketing authorisations where applicable. 18

The exact measures depend on the scientific conclusions and the legal procedure.

25. CMDh and Direct Healthcare Professional Communications

In relevant safety procedures, a CMDh position can also include or be accompanied by a Direct Healthcare Professional Communication (DHPC) and communication plan.

EMA identifies the DHPC and communication plan among the possible elements of the final CHMP opinion or CMDh position. 19

This illustrates how a CMDh regulatory outcome can extend beyond the marketing authorisation itself to communication of safety information.

26. CMDh Is Not PRAC

The distinction can be summarised simply:

These functions overlap operationally but are not interchangeable.

27. CMDh Is Not CHMP

CHMP and CMDh are often mentioned together because both participate in EU medicines regulation.

Their legal and institutional functions are nevertheless different.

CHMP is a scientific committee of EMA.

CMDh is the coordination group representing Member States in the national-authorisation framework.

The simplest distinction is:

CHMP: scientific committee.

CMDh: Member State coordination group.

This distinction becomes particularly important when interpreting referral outcomes.

28. CMDh Is Not the European Commission

The European Commission has a different role.

Where a CMDh position is adopted by majority in a procedure requiring Commission action, the matter is sent through the European Commission decision-making process.

EMA describes this as leading to a binding decision. 20

The Commission therefore occupies a different legal position from CMDh.

29. CMDh and EMA

The relationship can be summarised as:

CMDh is the coordination group.

EMA provides its secretariat and supports its operation.

The Agency also provides scientific, regulatory and administrative infrastructure for many related EU medicines procedures.

CMDh should therefore not be described simply as "an EMA committee."

A more accurate description is:

CMDh is an EU coordination group established under the medicines legislation and supported by the European Medicines Agency.

EMA itself describes CMDh as a coordination group and provides its secretariat. 21

30. CMDh and the European Regulatory Network

CMDh illustrates the hybrid structure of European medicines regulation.

The EU system contains:

• national competent authorities;
• coordination groups;
• EMA scientific committees;
• the European Commission;
• European regulatory procedures.

These components are connected but retain distinct functions.

CMDh is one of the mechanisms that links national marketing-authorisation systems.

31. CMDh Meetings and Work

CMDh conducts its work through formal meetings and regulatory procedures.

Its activities include:

• examination of marketing-authorisation questions;
• coordination of MRP/DCP issues;
• consideration of variations;
• resolution of specified disagreements;
• consideration of safety matters involving nationally authorised medicines;
• adoption of positions in relevant procedures.

The work is therefore broader than a single referral mechanism.

32. CMDh and Routine Regulatory Work

Not every CMDh activity is a referral.

A substantial part of CMDh's role concerns the ordinary functioning of the MRP/DCP system.

The group can address questions concerning marketing authorisations in multiple Member States and variations to those authorisations. 22

This is an important corrective to the common perception that CMDh exists primarily to deal with major safety problems.

Safety referrals are important, but they represent only one part of the group's mandate.

33. CMDh and Major Safety Referrals

When a safety referral concerns nationally authorised medicines, CMDh can have a significant regulatory role.

The pathway may involve:

PRAC
  |
  v

PRAC recommendation | v CMDh | v CMDh position | +----------------------+ | | consensus majority | | v v Member State European implementation Commission decision

EMA describes this distinction in its pharmacovigilance referral guidance. 23

34. Example: Cyproterone/Ethinylestradiol Medicines

The 2013 referral concerning cyproterone acetate and ethinylestradiol-containing medicines provides a clear example of CMDh decision-making in a safety procedure.

PRAC assessed the safety issue and issued its recommendation.

CMDh subsequently endorsed the recommendation by a 26:1 majority.

The resulting measures concerned the conditions under which the medicines should be used and measures to minimise thromboembolic risk. 24

The example is useful because it demonstrates that:

• PRAC performs the pharmacovigilance assessment;
• CMDh considers the recommendation for nationally authorised products;
• CMDh can adopt a position by majority;
• the voting outcome is part of the regulatory record.

35. Example: Hydroxyethyl Starch

The hydroxyethyl starch procedure provides another example of the CMDh role.

Following a PRAC recommendation, CMDh considered the recommendation together with additional information and adopted its position.

EMA records that the CMDh position was adopted by majority vote and was therefore sent to the European Commission for an EU-wide legally binding decision. 25

This example illustrates the practical significance of the consensus-versus-majority distinction.

36. Example: Bromocriptine

In another safety-related procedure, CMDh endorsed recommendations concerning the use of bromocriptine-containing medicines to prevent or suppress lactation.

EMA records that CMDh endorsed the recommendations by majority.

The resulting regulatory position restricted routine use and introduced measures relating to the safety of the medicines. 26

Again, the example shows CMDh acting on nationally authorised medicines following a European safety assessment.

37. CMDh and the National Implementation of Safety Measures

The practical endpoint of a CMDh safety position is usually not a single European marketing authorisation.

Instead, the position affects nationally authorised medicinal products.

Where a consensus position is adopted, the Member States implement the position according to the applicable timetable.

Where a majority position triggers Commission decision-making, the binding Union decision determines the subsequent national regulatory implementation. 27

The distinction reflects the underlying legal status of the products concerned.

38. Why CMDh Matters to Pharmacovigilance

For pharmacovigilance professionals, CMDh matters because many important medicines in Europe are nationally authorised rather than centrally authorised.

A safety assessment may therefore produce different institutional pathways depending on the authorisation status of the products affected.

For a centrally authorised medicine, CHMP is the principal scientific committee involved in many regulatory safety decisions.

For nationally authorised medicines, PRAC recommendations can be considered by CMDh.

This distinction is fundamental to understanding the EU pharmacovigilance architecture.

39. Centrally Authorised Versus Nationally Authorised Medicines

The distinction can be summarised:

The exact procedure depends on the legal basis of the referral.

This is why the same pharmacovigilance issue can generate different regulatory documents depending on which products are affected.

40. CMDh and Article 31 Referrals

Article 31 pharmacovigilance referrals provide one important context in which CMDh participates.

Where a referral concerns nationally authorised medicines and centrally authorised products are not affected, PRAC assesses the safety issue and makes its recommendation.

CMDh then considers the recommendation.

EMA specifically identifies this as part of CMDh's role. 28

If the CMDh position is reached by consensus, it is implemented by the Member States according to the applicable timetable.

If the position is adopted by majority, the matter proceeds to the European Commission decision-making process where required.

41. CMDh and Article 29 Referrals

Article 29 is a different mechanism.

It concerns disagreement during the MRP or DCP where a Member State raises a potential serious risk to public health.

CMDh first attempts to resolve the disagreement.

If agreement cannot be reached, the matter can proceed to CHMP under the relevant statutory provisions.

Thus CMDh can appear in both:

• an Article 29 disagreement procedure; and
• a pharmacovigilance referral.

The presence of CMDh alone therefore does not identify the legal basis of a procedure.

42. CMDh and the Interpretation of Regulatory Documents

When reading an EU regulatory document, the following questions are useful:

1. What is the legal basis?
2. Is the product centrally or nationally authorised?
3. Is the procedure an MRP/DCP matter, a variation, or a referral?
4. Is PRAC involved?
5. Is CMDh adopting a position?
6. Was the position reached by consensus or majority?
7. Is a European Commission decision required?
8. What changes are required nationally?

These questions distinguish the institutional pathway from the scientific content.

43. The Structure of a CMDh Safety Position

In safety-related referral procedures, EMA describes a CMDh position as potentially containing several components.

These can include:

• the adopted position and voting outcome;
• the PRAC recommendation;
• the PRAC assessment report;
• the scientific grounds;
• explanations for differences from the PRAC recommendation;
• divergent views where applicable;
• the products and MAHs concerned;
• amendments to product information;
• conditions or restrictions;
• implementation timetable;
• DHPC and communication arrangements where applicable. 29

This structure allows the reader to reconstruct both the scientific basis and the regulatory consequence.

44. Reading a CMDh Position Correctly

A CMDh position should therefore be read in layers.

First layer: What procedure is this?

Identify the legal basis and procedure type.

Second layer: Which products are affected?

Determine whether the products are nationally authorised and identify the relevant active substances and marketing authorisation holders.

Third layer: What did PRAC conclude?

Read the pharmacovigilance recommendation and assessment.

Fourth layer: What did CMDh decide?

Determine whether CMDh agreed with the recommendation and whether it did so by consensus or majority.

Fifth layer: What changes?

Read the product-information amendments, restrictions and implementation provisions.

This sequence prevents the scientific recommendation from being confused with the final regulatory position.

45. CMDh and Divergence From PRAC

CMDh does not merely act as a mechanical transcription service for PRAC recommendations.

EMA's procedural guidance explicitly contemplates situations in which the CHMP or CMDh position differs from the PRAC recommendation.

Where this occurs, the scientific grounds for the difference are explained in the opinion or position. 30

The distinction is important because PRAC and CMDh perform different functions.

PRAC provides the pharmacovigilance assessment.

CMDh performs the regulatory coordination function assigned to it by the applicable legal framework.

46. CMDh and Scientific Versus Regulatory Roles

A useful conceptual distinction is:

PRAC asks: What does the pharmacovigilance evidence indicate?

CMDh asks: What regulatory position should be adopted for the nationally authorised medicines within the applicable legal procedure?

The two questions are closely related but not identical.

The CMDh position therefore incorporates the PRAC recommendation while operating within the broader regulatory framework.

47. CMDh and National Product Information

Where a safety position requires changes to nationally authorised products, the CMDh position can specify the wording to be incorporated into the relevant product information.

The changes can affect the SmPC, labelling and package leaflet.

This is one of the clearest ways in which CMDh activity translates European regulatory assessment into national product information.

48. CMDh and Implementation Timetables

A CMDh consensus position can include an implementation timetable.

The timetable specifies when the agreed regulatory changes are to be implemented by the Member States.

EMA identifies the implementation timetable as an element of the CMDh position in the relevant safety referral context. 31

The timetable therefore forms part of the regulatory outcome rather than being merely administrative background.

49. CMDh and the European Commission Decision

Where the applicable CMDh position is adopted by majority, the matter can proceed to the European Commission.

The Commission then undertakes the decision-making process leading to a binding decision.

EMA describes the process as involving finalisation of translations by EMA, the MAHs and national competent authorities, followed by transmission to the European Commission. 32

The resulting Commission decision provides the legally binding Union outcome.

50. CMDh in the Overall EU Regulatory Architecture

CMDh occupies a distinctive position between national and Union-level regulation.

A simplified architecture is:

European Commission
         |
         |
       EMA
         |
  +------+------+
  |             |
 PRAC          CHMP
  |             |
  +------?------+
         |
       CMDh
         |
  National authorities
         |
         v
  National MAs

This diagram should not be interpreted as an organisational hierarchy.

It represents functional relationships in different regulatory procedures.

CMDh is not subordinate to PRAC or CHMP.

Its role is defined by the legislation governing nationally authorised medicines.

51. CMDh and the National Nature of Marketing Authorisations

One of the most important concepts in understanding CMDh is that the underlying marketing authorisations remain national.

The MRP and DCP coordinate the authorisation process across Member States.

CMDh coordinates questions within that system.

The resulting national marketing authorisations remain subject to the competent authorities of the Member States.

This explains why CMDh decisions and positions frequently contain provisions that subsequently have to be implemented nationally.

52. CMDh Compared With CHMP

The table is a conceptual summary; the exact role of each body depends on the legal procedure involved.

53. CMDh Compared With PRAC

This distinction is particularly important when interpreting referral documentation.

54. CMDh Compared With a National Competent Authority

A national competent authority:

• grants and maintains national marketing authorisations;
• performs national regulatory functions;
• participates in MRP/DCP procedures;
• appoints or provides representatives to European coordination structures.

CMDh:

• coordinates specified questions between those national authorities;
• seeks agreement where the legislation provides for such coordination;
• adopts positions where its mandate requires it.

CMDh therefore does not replace national competent authorities.

55. What CMDh Actually Decides

The answer depends on the procedure.

In ordinary MRP/DCP matters, CMDh may facilitate agreement between Member States and address questions within its mandate.

In safety referral procedures, CMDh can adopt a position on the regulatory consequences of the PRAC recommendation for nationally authorised medicines.

Those consequences can include:

• maintenance;
• variation;
• suspension;
• revocation;
• restrictions or conditions;
• changes to product information.

EMA's pharmacovigilance referral guidance explicitly identifies these possible regulatory outcomes. 33

56. What CMDh Does Not Do

CMDh does not:

• replace national competent authorities;
• grant centrally authorised marketing authorisations;
• perform the pharmacovigilance risk assessment performed by PRAC;
• function as the European Commission;
• automatically become involved in every safety issue;
• automatically decide every MRP/DCP disagreement;
• constitute a general European marketing-authorisation authority.

Its role is specific to the statutory coordination framework.

57. Why the CMDh Name Matters

The name itself describes the group's principal function:

Coordination Group

for

Mutual Recognition

and

Decentralised Procedures

for

Human medicines.

The name is therefore more informative than it first appears.

It tells us that CMDh belongs primarily to the national-authorisation side of the EU medicines system.

58. A Practical Mental Model

A useful mental model is:

RMS and CMSs conduct the national-authority procedure.

CMDh coordinates the Member States when the legislation requires European coordination.

PRAC performs pharmacovigilance risk assessment.

CHMP performs scientific assessment in the procedures assigned to it.

The European Commission adopts binding Union decisions where the legislation requires it.

Keeping these functions separate prevents many common misunderstandings.

59. CMDh in One Regulatory Sequence

For a typical safety referral involving nationally authorised medicines, the sequence may be:

Safety concern
      |
      v
    PRAC
      |
      v

PRAC recommendation | v CMDh | v CMDh consensus or majority position | +-------------------+ | | consensus majority | | v v Member States European Commission implement decision | v Member States implement

The precise pathway depends on the legal basis of the procedure.

60. Why CMDh Is Important in EU Pharmacovigilance

The EU pharmacovigilance system operates across medicines with different authorisation routes.

A safety issue cannot be understood solely by looking at PRAC.

The regulatory consequence depends on:

• the legal basis of the procedure;
• whether the products are centrally or nationally authorised;
• the role assigned to CMDh;
• whether consensus is reached;
• whether a Commission decision is required.

CMDh is therefore an essential part of understanding how pharmacovigilance conclusions become regulatory action for nationally authorised medicines.

61. Key Takeaways

CMDh is the Coordination Group for Mutual Recognition and Decentralised Procedures – Human.

Its legal basis is Article 27 of Directive 2001/83/EC.

Its principal role is to examine and coordinate questions relating to human medicinal products authorised in two or more Member States through the MRP or DCP.

It also deals with relevant variations and specific safety questions concerning nationally authorised medicines.

CMDh is composed of one representative from each Member State, with experts able to support members where appropriate.

EMA provides the CMDh secretariat.

CMDh is not the same body as PRAC, CHMP or the European Commission.

In a safety-related EU referral involving nationally authorised medicines, PRAC provides the pharmacovigilance recommendation and CMDh considers it within its regulatory coordination role.

CMDh can adopt a position by consensus or, where consensus cannot be reached, by majority according to the applicable rules.

A consensus position can be implemented by Member States according to the applicable timetable.

A majority position can lead to European Commission decision-making where the applicable legal framework requires it.

CMDh positions can affect marketing authorisations, product information, restrictions, conditions and safety communications.

Most importantly, CMDh should be understood as part of the European coordination architecture for nationally authorised medicines, not as a general-purpose EU medicines authority.

References

1. European Parliament and Council. Directive 2001/83/EC on the Community code relating to medicinal products for human use, particularly Article 27 and the provisions governing mutual recognition and decentralised procedures. EUR-Lex. https://eur-lex.europa.eu/legal-content/EN/ALL/?uri=CELEX:32001L0083

2. European Medicines Agency. Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh). https://www.ema.europa.eu/en/committees/working-parties-other-groups/coordination-group-mutual-recognition-decentralised-procedures-human-cmdh

3. European Medicines Agency. Coordination Group for Mutual Recognition and Decentralised Procedures – Human: glossary entry. https://www.ema.europa.eu/en/glossary-terms/coordination-group-mutual-recognition-decentralised-procedures-human

4. European Medicines Agency. Questions and answers: Article 31 pharmacovigilance referrals. https://www.ema.europa.eu/en/human-regulatory-overview/post-authorisation/referral-procedures-human-medicines/questions-answers-article-31-pharmacovigilance-referrals

5. European Medicines Agency. Cyproterone- and ethinylestradiol-containing medicines – referral. https://www.ema.europa.eu/en/medicines/human/referrals/cyproterone-ethinylestradiol-containing-medicines

6. European Medicines Agency. Hydroxyethyl-starch solutions for infusion – CMDh safety procedure. https://www.ema.europa.eu/en/news/hydroxyethyl-starch-solutions-infusion-recommended-suspension-market

7. European Medicines Agency. CMDh endorses restricted use of bromocriptine for stopping breast milk production. https://www.ema.europa.eu/en/news/cmdh-endorses-restricted-use-bromocriptine-stopping-breast-milk-production

Regulatory note

This article describes the role and functions of CMDh within the EU medicines regulatory framework. It is intended as an educational reference and does not replace the current text of Directive 2001/83/EC, applicable implementing legislation, CMDh rules of procedure, EMA procedural guidance, European Commission decisions or national legislation.

The precise role of CMDh depends on the legal basis and type of procedure. MRP/DCP coordination, Article 29 disagreement procedures, pharmacovigilance referrals and other regulatory procedures should not be treated as interchangeable.

Where this article describes timelines, voting outcomes or procedural consequences, the applicable legislation and current EMA procedural guidance should be consulted for the specific procedure.

The examples included in this article illustrate CMDh activity in actual regulatory procedures. They are not intended to imply that every CMDh procedure follows the same pathway.