HMR

Question 1

Tell me about the HMR

Answer 1

Human medicine regulation is made up of 17 Parts followed by 35 Schedules

They set out a comprehensive regime for the authorisation of products; for the manufacture, import, distribution, sale and supply of those products; for their labelling and advertising; and for pharmacovigilance.

Question 2

What parts make up the HMR?

Answer 2

Part 1 (general) - including the definition of the licensing authority as the body responsible for regulating products. Part 1 also provides for interpretation, and for special provisions concerning the applicability of the Regulations to a number of activities by pharmacists and others
Part 2 (administration) - Medicines commission, British pharmacopeia commission, Expert advisory groups appointment
Part 3 (manufacturing and wholesale dealing) - governs the manufacture and importation of, and wholesale dealing in, products. Incl, importation, QP and RP requirements
Part 4 (requirement for authorisation) - establishes that products must not be sold, supplied, or offered for sale or supply in the United Kingdom unless authorised, either by the United Kingdom licensing authority under the Regulations, or by the European Medicines Agency
Parts 5 (marketing authorisations) - application, conditions, post marketing commitments, renewals, variation, withdrawal
Parts 6 to 8 (certification of homoeopathic medicinal products, traditional herbal registrations and Article 126a authorisations) - provide for the procedures for authorisation by the United Kingdom licensing authority of medicinal products in various categories
Part 9 (borderline products)
Part 10 (exceptions)
Part 11 (pharmacovigilance)
Part 12 (dealings with medicinal products)
Part 13 (packaging and leaflets) - 18 requirements for packaging information, 7 for immediate packaging. Incl. Braille
Part 14 (advertising)
Part 15 (British Pharmacopoeia)
Parts 16 (enforcement) - right of entry and powers of inspection and Part 17 (miscellaneous and general)

Question 3

Name some of the schedules in the HMR that are important to the QP

Answer 3

3. SCHEDULE 3
   Applications for licences under Part 3
4. SCHEDULE 7
   Qualified persons - qualification, education and obligations
5. SCHEDULE 8
   Material to accompany an application for a UK marketing authorisation - general information and summary of product characteristics
6. SCHEDULE 9
   Undertakings by non-EEA manufacturers
7. SCHEDULE 24
   Packaging information requirements
8. SCHEDULE 25
   Packaging requirements: specific provisions
9. SCHEDULE 26
   Packaging requirements: special provisions
10. SCHEDULE 27
    Package leaflets

Question 4

What are the schedules of the HMR

Answer 4

1. SCHEDULE 1
   Further provisions for classification of medicinal products
2. SCHEDULE 2
   Supplementary provision relating to advisory bodies and expert advisory groups
3. SCHEDULE 3
   Applications for licences under Part 3
4. SCHEDULE 4
   Standard provisions of licences under Part 3
5. SCHEDULE 5
   Review upon oral representations
6. SCHEDULE 6
   Manufacturer’s and wholesale dealer’s licences for exempt advanced therapy medicinal products
7. SCHEDULE 7
   Qualified persons - qualification, education and obligations
8. SCHEDULE 8
   Material to accompany an application for a UK marketing authorisation - general information and summary of product characteristics
9. SCHEDULE 9
   Undertakings by non-EEA manufacturers
10. SCHEDULE 10
    National homoeopathic products
11. SCHEDULE 11
    Advice and representations
12. SCHEDULE 12
    Material to accompany an application for a traditional herbal registration
13. SCHEDULE 13
    Prescription only medicines for which community practitioner nurse prescribers are appropriate practitioners
14. SCHEDULE 14
    Prescription etc by supplementary prescribers: particulars of clinical management plan
15. SCHEDULE 15
    Requirements for specific products subject to general sale
16. SCHEDULE 16
    Patient group directions
17. SCHEDULE 17
    Exemption for sale, supply or administration by certain persons
18. SCHEDULE 18
    Substances that may not be sold or supplied by a pharmacist without a prescription in reliance on regulation 225
19. SCHEDULE 19
    Medicinal products for parenteral administration in an emergency
20. SCHEDULE 20
    Herbal medicinal products specified for the purposes of regulation 241
21. SCHEDULE 21
    Medicinal products at high dilutions
22. SCHEDULE 22
    Classes of person for the purposes of regulation 249
23. SCHEDULE 23
    Particulars in pharmacy records
24. SCHEDULE 24
    Packaging information requirements
25. SCHEDULE 25
    Packaging requirements: specific provisions
26. SCHEDULE 26
    Packaging requirements: special provisions
27. SCHEDULE 27
    Package leaflets
28. SCHEDULE 28
    Labelling requirements for registrable homoeopathic medicinal products
29. SCHEDULE 29
    Labelling of traditional herbal medicinal products
30. SCHEDULE 30
    Particulars for advertisements to persons qualified to prescribe or supply
31. SCHEDULE 31
    Sampling
32. SCHEDULE 32
    Transitional provisions and savings
33. SCHEDULE 33
    Transitional arrangements: pharmacovigilance
34. SCHEDULE 34
    Amendments to existing law
35. SCHEDULE 35
    Repeals and revocations

Question 5

Tell me about the HMR 2012:1916 revision

Answer 5

Revision of Human Medicines legislation
On 25 November 2020 the European Commission published a pharmaceutical strategy document,
which they said was the first step in a “complete overhaul” of the medicines legislative framework for
human medicines to be proposed in about two years’ time. C

The draft legislation was eventually published, after several delays, on 26 April 2023. The objectives
of the proposed changes are given as the following:

General objectives:
* Guarantee a high level of public health by ensuring the quality, safety and efficacy of medicinal products for EU patients
* Harmonise the internal market.
It had been generally expected that the revised legislation would be issued as a Regulation, as had already been done with the Directives for clinical trials, veterinary medicines and medical devices.

However, the proposed revision of the pharmaceutical legislation consists of two legislative proposals:
* A new Directive, repealing Directives 2001/83/EC and 2009/35/EC and incorporating and amending relevant parts of the paediatric Regulation (EC) 1901/2006
* A new Regulation, repealing Regulations (EC) No 726/2004, 141/2000 (orphan medicines) and 1901/2006 (paediatric use) and incorporating and amending Regulations 1394/2007 (ATMPs) and 536/2014 (CTs).

There are also links with other EU regulatory frameworks for health products. EU legislation on blood, tissues and cells is relevant as some substances of human origin are starting materials for medicines.

The EU regulatory framework for medical devices is also relevant as there are products that combine medicines and medical devices.

The following are amongst the changes contained in the proposed new human medicines Directive:

1. Decentralised manufacture and testing
   The draft proposes a hub and spoke model, very similar to the 2021 UK proposals for pointof‐
   care manufacture, where there is a central, ‘hub’ site that takes responsibility for
   decentralised manufacture and testing sites. The central site will hold an MIA, with a QP, and
   be responsible for managing decentralised sites that will not be required to hold a MIA. The
   central MIA holder will register the decentralised sites with the relevant competent authority.
   The decentralised manufacturing and testing sites will be supervised by the QP(s) of the
   central site, as illustrated below:
2. Qualified Person Qualifications and Duties
   The list of qualifications and experience that will permit someone to act as a QP is largely
   unchanged and the detail is given in Annex III of the Directive.
   There is a new legal duty for “The MA holder and the QP to ensure that the practical
   experience acquired is appropriate to the types of products to be certified”.
   The legal duties of the QP are unchanged except that a new section has been added to cover
   the duties of the QP at the central site when point‐of‐care, decentralised manufacturing
   operations are adopted. The additional legal duties for QPs at central sites who are
   responsible for decentralised manufacturing and testing are as follows:
   a) Supervise that the manufacturing or testing activities carried out at the decentralised
   sites comply with principles of relevant GMP and conform to the marketing
   authorisation,
   b) Provide a written confirmation of GMP compliance,
   c) Notify to the competent authority of the Member State where the decentralised site
   is established, an inventory of the changes that have taken place as regards the
   information provided in the required registration form for each decentralised site.
   Any changes that may have an impact on the quality or safety of the medicinal products that
   are manufactured or tested at the decentralised site must be notified immediately.
3. Cyprus, Ireland, Malta and Northern Ireland
   There is a whole new Chapter providing specific provisions concerning Cyprus, Ireland, Malta
   and the United Kingdom in respect of Northern Ireland. This reproduces the provisions that
   are in Directive 2022‐642 that was implemented in April 2022.
   However, these provisions will have to be changed in the final version to reflect the provisions
   in the June 2023 Regulation 2023/1182 that implements the ‘Windsor framework’ in EU law.
4. Excipients
   A new definition of a ‘functional excipient’ has been added:
   “… an excipient that contributes to or enhances the performance of a medicinal product or
   performs an action ancillary to that of the active substance but does not have a therapeutic
   contribution on its own.”
   The proposed Directive clarifies that competent authorities are empowered to inspect
   excipient suppliers and will do so where there are grounds for suspecting non‐compliance with
   GMP or GDP.
5. SoHO‐derived Medicinal Product
   With regard to medicines where the starting material is derived from substances of human
   origin (SoHO) there is an interface with the proposed EU SoHO regulation and there is a new
   definition of a SoHO‐derived medicinal product:
   ‘SoHO‐derived medicinal product other than ATMPs’ means any medicinal product containing,
   consisting of or deriving from a substance of human origin (SoHO), as defined in Regulation
   [SoHO Regulation], other than tissues and cells, that is of standardised consistency and is
   prepared by:
   (a) a method involving an industrial process which includes pooling of donations; or
   (b) a process that extracts an active ingredient from the substance of human origin or
   transforms the substance of human origin by changing its inherent properties.

The following are amongst the changes contained in the proposed new human medicines Regulation:
1. Changes to EMA Committees
The proposal is to just have two human medicines committees: the Committee on Medicinal
Products for Human Use (CHMP) and the Pharmacovigilance Risk Assessment Committee
(PRAC).
The expertise of the other four scientific committees would be retained and organised into
working parties and a “pool of experts” that would give input to the CHMP, the PRAC and the
EU Heads of Medicines Agencies’ Co‐ordination group for mutual recognition and
decentralized procedures – human (CMDh). The four committees that would be discontinued
are the CAT (advanced therapies), the COMP (orphan medicines), the PDCO (paediatric
medicines) and the HMPC (herbal medicinal products).

2. Changes to EMA Role
   An inspectorate will be established within EMA to reinforce Member States’ capacities, in
   particular for inspections in third countries to build efficiency in surveillance and support
   marketing authorisation procedures.
   The mandate of the EMA and its Executive Steering Group on Shortages and Safety of
   Medicinal Products, as established by Regulation 2022/123, will be extended with respect to
   the management of critical shortages and the security of supply of critical medicines.
3. Marketing Authorisation (MA) Changes
   The requirement for MAs to be renewed after 5 years is dropped and MAs will be granted for
   an unlimited period.
   The sunset clause that requires companies to place a product on the market in at least one EU
   member state within three years of an MA being granted, is also to be scrapped.
   The regulatory review time for centralised MA applications to be reduced from 210 days to
   180 days. The time for the Commission to make the decision on MAs is also reduced from 67
   days to 46 days.
   A new temporary emergency marketing authorisation for future health crisis‐related
   medicines.
4. Shortage Prevention
   MA holders to be required to have in place and keep up to date a shortage prevention plan,
   for any medicinal product placed on the market. The details of what to include in this plan are
   given in Part V of Annex IV.
   In order to be approved, these proposals will need to be scrutinised by the European Parliament (EP)
   and the Council of the EU. It is expected that substantial amendments will be made as a result of this
   scrutiny. How long this review will take is difficult to determine but it will not be helped by the fact
   that there are fresh elections to the EP in 2024.
   The speculation is that it could up to 3 years before the final legislation is agreed and this likely to be
   followed by an implementation period that could add several more years before the changes become
   effective.