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The Human Medicines Regulations 2012

Type Statutory-Instrument

Publication 2012-07-19

Last updated 2026-03-31

State In force

Department King's Printer of Acts of Parliament

Source legislation.gov.uk

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articles 4

Reform history JSON API

(b) in the other cases, within six months, beginning with the date on which the information referred to in paragraph 10(a) is sent to the holder,

and the licensing authority must notify the holder of the amended decision without delay.

(2) The statement indicating compliance with the agreed completed paediatric investigation plan provided for under regulation 58A(2)(a) must be included within the technical dossier of the UK marketing authorisation, and the licensing authority must confirm to the holder that it is so included when it notifies the holder under paragraph 10(a).

Implementation of variations

16

(1) Minor variations of type IA may be implemented any time before completion of the procedures laid down in paragraph 6.

(2) Where a notification concerning one or several minor variations of type IA is rejected, the holder must cease to apply the rejected variation immediately after receipt of the information referred to in paragraph 10(a).

(3) Minor variations of type IB may only be implemented after the licensing authority has informed the holder that it has accepted the notification pursuant to paragraph 7, or after the notification is deemed accepted pursuant to paragraph 7(2).

(4) Major variations of type II may only be implemented after the licensing authority has informed the holder that it has accepted the variation pursuant to paragraph 10.

(5) An extension may only be implemented after the licensing authority has amended the decision granting the marketing authorisation and notified the holder accordingly.

(6) Urgent safety restrictions, and variations which are related to safety issues, must be implemented within a time frame agreed by the holder and the licensing authority.

Continuous monitoring

17

Where requested to do so by the licensing authority, the holder must supply to the licensing authority without delay any information related to the implementation of a given variation.

PART 1A — Paediatric Decisions

Application of this Part

13A

This Part applies to a proposed decision by the licensing authority—

(a) to refuse to agree a paediatric investigation plan (including a waiver or deferral proposed to be included in that plan), or to agree such a plan otherwise than in accordance with the request for agreement;

(b) to refuse to agree a modification to a paediatric investigation plan (including a waiver or deferral which is, or is proposed to be, included in that plan), or to agree such a modification otherwise than in accordance with the request for the modification;

(c) to impose, revoke or refuse to grant a waiver of the obligation under regulation 50A(3) to provide to the licensing authority the results of all studies performed, and details of all information collected, in compliance with an agreed paediatric investigation plan; or

(d) to revoke a waiver which was agreed as part of an agreed paediatric investigation plan.

Opportunity to make representations

13B

(1) If the licensing authority proposes to make a decision to which this Part applies, the licensing authority must notify the person to whom the proposed decision would be addressed (“the applicant”).

(2) The applicant may, by notice in writing to the licensing authority, request the opportunity to make written or oral representations to the appropriate committee.

(3) The applicant must make the request before the end of the period of 28 days beginning with the day on which the notification is given or such longer period as the licensing authority may allow.

(4) The licensing authority must inform the appropriate committee of the applicant's request.

Written representations

13C

(1) If the applicant requests the opportunity to make written representations, the applicant must provide the appropriate committee with those representations and any documents on which the applicant wishes to rely in support of them—

(a) before the end of the period of 28 days beginning with the date of the request; or

(b) before the end of such shorter period as the licensing authority may specify in the notification under paragraph 13B.

(2) The appropriate committee may at the request of the applicant extend the period mentioned in sub-paragraph (1) up to a maximum of 56 days beginning with the date of the request under paragraph 13B.

(3) The applicant may submit additional representations or documents after the end of the period for doing so only with the permission of the appropriate committee.

(4) The appropriate committee must—

(a) take the representations made under this paragraph into account; and

(b) report its findings and advice to the licensing authority together with the reasons for that advice.

Oral representations

13D

(1) If the applicant requests the opportunity to make oral representations, the applicant must provide the appropriate committee with a written summary of those representations and any documents on which the applicant wishes to rely in support of them—

(a) before the end of the period of 28 days beginning with the date of the request; or

(b) before the end of such shorter period as the licensing authority may specify in the notification under paragraph 13B.

(2) The appropriate committee may, at the request of the applicant, extend the period mentioned in sub-paragraph (1) up to a maximum of 56 days beginning with the date of the request under paragraph 13B.

(3) The applicant may submit additional representations or documents after the end of the period for doing so only with the permission of the appropriate committee.

(4) After receiving the summary and any other documents provided under this paragraph, the appropriate committee must arrange for the applicant to make oral representations at a hearing before the committee.

(5) The appropriate committee must—

(a) take the representations made under this paragraph into account; and

(b) report its findings and advice to the licensing authority together with the reasons for that advice.

Other decisions of the appropriate committee

13E

(1) This paragraph applies if the applicant—

(a) requests the opportunity to make written representations, but fails to make those representations within the period for doing so; or

(b) requests the opportunity to make oral representations, but—

(i) fails to provide a summary of those representations or the documents in support of them within the period for doing so, or

(ii) fails to make oral representations at a hearing before the appropriate committee.

(2) The appropriate committee must notify the licensing authority of that fact.

Decision of licensing authority

13F

(1) The licensing authority must decide whether to proceed with its proposed decision—

(a) if the applicant requested the opportunity to make written or oral representations, after receiving the appropriate committee's report under paragraph 13C or 13D or notification under paragraph 13E; or

(b) if the applicant did not request the opportunity to make written or oral representations, after the expiry of the period of time for notifying a request for that opportunity.

(2) If the appropriate committee gives a report under paragraph 13C or 13D, the licensing authority must take that into account in making its decision.

(3) The licensing authority must notify the applicant of—

(a) its decision; and

(b) any advice given to it by the appropriate committee and the reasons for that advice.

Right to review after paragraph 13F notification

13G

(1) This paragraph applies if the licensing authority notifies the applicant of its decision under paragraph 13F.

(2) The applicant may notify the licensing authority in writing that the applicant wishes the licensing authority to submit the decision to review upon oral representations.

(3) The applicant must give the notification before the end of the period of 28 days beginning with the day on which the notification is given to the applicant under paragraph 13F or such longer period as the licensing authority may allow.

(4) The review must be conducted in accordance with Schedule 5.

(5) This paragraph does not apply if the applicant has not made any representations in accordance with paragraph 13C or 13D.

21

For medicinal products included on the list referred to in Article 23 of Regulation (EC) No 726/2004 or regulation 202A, as the case may be, the symbol and statement “▼ This medicinal product is subject to additional monitoring”.

22

The name of the medicinal product followed by its strength and pharmaceutical form.

23

The qualitative and quantitative composition, using the usual common name or chemical description, of the medicinal product in terms of—

(a) the active substances; and

(b) those excipients of which knowledge is essential for proper administration of the medicinal product.

24

The pharmaceutical form of the medicinal product.

25

The pharmacological properties of the medicinal product, covering—

(a) pharmacodynamic properties;

(b) pharmacokinetic properties; and

26

Pharmaceutical particulars of the medicinal product, covering—

(a) a list of excipients;

(b) major incompatibilities;

(c) shelf life after reconstitution of the medicinal product or when the immediate packaging is opened for the first time (as appropriate);

(d) special precautions for storage;

(e) nature and contents of the container; and

(f) special precautions for disposal of the used medicinal product or waste materials derived from the medicinal product (as appropriate).

27

The holder of the traditional herbal registration.

28

The number of the traditional herbal registration.

29

The date of the first traditional herbal registration or, where the traditional herbal registration has been renewed, the date of the last renewal.

30

The date of any revisions of the text of the summary of the product characteristics.

SCHEDULE 12A — Further provision as to the performance of pharmacovigilance activities

PART 1 — Pharmacovigilance system master file

Structure of the pharmacovigilance system master file

1

(1) The information in the pharmacovigilance system master file must be accurate and reflect the pharmacovigilance system in place.

(2) The holder may, where appropriate, use separate pharmacovigilance systems for different categories of medicinal products and if it does so, each such system must be described in a separate pharmacovigilance system master file.

(3) All medicinal products for which the holder obtained a UKMA(GB) or a UKMA(UK)(Category 1) in accordance with these Regulations must be covered by a pharmacovigilance system master file.

Content of the pharmacovigilance system master file

2

The pharmacovigilance system master file must, as a minimum, contain—

(a) the following information relating to the qualified person responsible for pharmacovigilance—

(i) a description of the responsibilities demonstrating that the qualified person for pharmacovigilance has sufficient authority over the pharmacovigilance system in order to promote, maintain and improve compliance with pharmacovigilance tasks and responsibilities,

(ii) a summary curriculum vitae of the qualified person responsible for pharmacovigilance,

(iii) contact details of the qualified person for pharmacovigilance,

(iv) details of back-up arrangements to apply in the absence of the qualified person responsible for pharmacovigilance, and

(v) responsibilities and contact details of the nominated person (where a person is nominated under regulation 182(2A));

(b) a description of the organisational structure of the holder, including the list of each site where one or more of the following pharmacovigilance activities are undertaken—

(i) individual case safety report collection and evaluation,

(ii) safety database case entry,

(iii) periodic safety update report production,

(iv) signal detection and analysis,

(v) risk management plan management,

(vi) pre and post-authorisation study management, and

(vii) management of safety variations to the terms of a UK marketing authorisation;

(c) a description of the location of, functionality of and operational responsibility for computerised systems and databases used to receive, collate, record and report safety information, and an assessment of their fitness for purpose;

(d) a description of data handling and recording and of the process used for each of the following pharmacovigilance activities—

(i) the continuous monitoring of the risk-benefit balance of each medicinal product, the result of that monitoring and the decision-making process for taking appropriate measures,

(ii) operation of each risk management system and of the monitoring of the outcome of risk minimisation measures,

(iii) collection, assessment and reporting of individual case safety reports,

(iv) drafting and submission of periodic safety update reports, and

(v) procedures for communicating safety concerns and safety variations to the summary of product characteristics and package leaflet to healthcare professionals and the general public;

(e) a description of the quality system for the performance of pharmacovigilance activities, including—

(i) a description of—

(aa) the organisational structure for the performance of pharmacovigilance activities,

(bb) a summary description of the training concept, including a reference to the location of training files and qualifications records, and

(cc) instructions on critical processes,

(ii) a description of the record management system referred to in paragraph 12, including the location of the documents used for pharmacovigilance activities,

(iii) a description of the system for monitoring the performance of the pharmacovigilance system; and

(f) where applicable, a description of the activities or services subcontracted by the holder.

Content of the Annex to the pharmacovigilance system master file

3

The pharmacovigilance system master file must have an Annex containing the following documents—

(a) a list of medicinal products covered by the pharmacovigilance system master file, including the name of each medicinal product, the international non-proprietary name (INN) of each active substance and the countries other than the United Kingdom in which the products covered are authorised to be marketed;

(b) a list of written policies and procedures for the purpose of complying with Part 11 of these Regulations;

(d) a list of the tasks that have been delegated by the qualified person for pharmacovigilance;

(e) a list of all scheduled and completed audits;

(f) where applicable, a list of the performance indicators that support the quality system for pharmacovigilance specified in paragraph 2(e);

(g) where applicable, a list of other pharmacovigilance system master files held by the same holder; and

(h) a logbook containing a record of any alteration of the content of the pharmacovigilance system master file made within the preceding 5 year period, except any alteration of the content that is specified in of paragraph 2(a)(ii) to (iv) or this paragraph.

Maintenance of the pharmacovigilance system master file

4

(1) The holder must keep the pharmacovigilance system master file up to date and, where necessary, revise it to take account of experience gained, and of technical and scientific progress.

(2) The pharmacovigilance system master file and its Annex must be subject to version control and, in particular, must indicate the date when it was last updated by the holder.

(3) Any deviations from the pharmacovigilance procedures, their impact and their management must be documented in the pharmacovigilance system master file until resolved.

Form of the documents contained in the pharmacovigilance system master file

5

(1) The pharmacovigilance system master file documents must be complete and legible.

(2) Subject to sub-paragraph (1), in the pharmacovigilance system master file—

(a) where appropriate, information may be provided in the form of charts or flow diagrams;

(b) all documents must be indexed and archived so as to ensure their accurate and ready retrieval throughout the period for record-keeping; and

(c) the particulars and documents may be presented in modules in accordance with the system delineated in detail in the guidance on good pharmacovigilance practices which applies by virtue of regulation 205B.

(3) The pharmacovigilance system master file may be stored in electronic form provided that the media used for storage remain readable over time, and a clearly arranged printed copy can be made available for audits and inspections.

Subcontracting

6

(1) The holder may subcontract certain activities of the pharmacovigilance system to third parties, but if it does so it must nevertheless retain full responsibility for the completeness and accuracy of the pharmacovigilance system master file.

(2) The holder must draw up a list of the existing subcontracts between it and the third parties referred to in sub-paragraph (1), specifying each product and each country concerned.

Availability and location of the pharmacovigilance system master file

7

(2) The holder must ensure that the qualified person and nominated person (where a person is nominated under regulation 182(2A)) for pharmacovigilance have permanent access to the pharmacovigilance system master file.

(3) For the purposes of regulation 182(2)(b), the licensing authority may limit its request to specific parts or modules of the pharmacovigilance system master file and the holder is to bear the costs of submitting the copy of the pharmacovigilance system master file.

(4) The licensing authority may request the holder to submit a copy of the logbook referred to in paragraph 3(h) at regular intervals.

PART 2 — Minimum requirements for the quality systems for the performance of pharmacovigilance activities by the licensing authority and holders

Quality system

8

(1) Any holder, and the licensing authority, must establish and use a quality system that is adequate and effective for the performance of their pharmacovigilance activities.

(2) The quality system must cover organisational structure, responsibilities, procedures, processes and resources, appropriate resource management, compliance management and record management.

(3) The quality system must be based on all of the following activities—

(a) quality planning: establishing structures and planning integrated and consistent processes;

(b) quality adherence, namely carrying out tasks and responsibilities in accordance with quality requirements;

(c) quality control and assurance, namely monitoring and evaluating how effectively the structures and processes have been established and how effectively the processes are being carried out; and

(d) quality improvements, namely correcting and improving the structures and processes where necessary.

(4) All elements, requirements and provisions adopted for the quality system must be documented in a systematic and orderly manner in the form of written policies and procedures, such as quality plans, quality manuals and quality records.

(5) All persons involved in the procedures and processes of the quality systems established by the licensing authority for the performance of pharmacovigilance activities shall be responsible for the good functioning of those quality systems, and must ensure a systematic approach towards quality and towards the implementation and maintenance of the quality system.

Performance indicators

9

(1) The holder and the licensing authority may use performance indicators to continuously monitor the good performance of pharmacovigilance activities.

(2) The licensing authority may publish a list of performance indicators.

PART 3 — Minimum requirements for the quality systems for the performance of pharmacovigilance activities by holders

Management of human resources

10

(1) The holder must have sufficient competent and appropriately qualified and trained personnel available for the performance of pharmacovigilance activities.

(2) For the purposes of sub-paragraph (1), the holder must—

(a) ensure that the qualified person responsible for pharmacovigilance has acquired adequate theoretical and practical knowledge for the performance of pharmacovigilance activities; and

(b) where the qualified person has not completed basic medical training in accordance with Article 24 of Directive 2005/36/EC of the European Parliament and of the Council of 7 September 2005 on the recognition of professional qualifications, ensure that the qualified person responsible for pharmacovigilance is assisted by a medically trained person, with such assistance being duly documented.

(3) The duties of the managerial and supervisory staff, including the qualified person responsible for pharmacovigilance, must be defined in job descriptions and their hierarchical relationships must be defined in an organisational chart.

(4) The holder must ensure that the qualified person responsible for pharmacovigilance has sufficient authority to influence the performance of the quality system and the pharmacovigilance activities of the holder.

(5) All personnel involved in the performance of pharmacovigilance activities must receive initial and continued training in relation to their role and responsibilities, and the holder must keep training plans and records for documenting, maintaining and developing the competences of personnel and make them available for audit or inspection.

(6) The holder must provide appropriate instructions on the processes to be used in case of urgency, including business continuity.

Compliance management

11

(1) Specific quality system procedures and processes must be in place in order to ensure the following—

(a) the continuous monitoring of pharmacovigilance data, the examination of options for risk minimisation and prevention and that appropriate measures are taken by the holder;

(b) the scientific evaluation by the holder of all information on the risks of medicinal products, as referred to in regulation 182(4)(a);

(c) the submission of accurate and verifiable data on serious and non-serious adverse reactions to the licensing authority within the time limits provided for in regulation 188(1)(a) or (b);

(d) the quality, integrity and completeness of the information submitted on the risks of medicinal products, including processes to avoid duplicate submissions;

(e) effective communication by the holder with the licensing authority, including communication on—

(i) new risks or changed risks,

(ii) the pharmacovigilance system master file,

(iii) risk management systems,

(iv) risk minimisation measures,

(v) periodic safety update reports,

(vi) corrective and preventive actions, and

(vii) post-authorisation studies;

(f) the update of product information by the holder in the light of scientific knowledge, including the assessments and recommendations made public via the UK web-portal, and on the basis of a continuous monitoring by the holder of information published on that web-portal; and

(g) appropriate communication by the holder of relevant safety information to healthcare professionals and patients.

(2) Where a holder has subcontracted some of its pharmacovigilance tasks, it must retain responsibility for ensuring that an effective quality system is applied in relation to those tasks.

Record management and data retention

12

(1) A holder must record all pharmacovigilance information and ensure that it is handled and stored so as to allow for accurate reporting, interpretation and verification of that information.

(2) A holder must put in place a record management system for all documents used for pharmacovigilance activities that ensures—

(a) the retrievability of those documents; and

(b) the traceability of the measures taken to investigate safety concerns, of the timelines for those investigations and of decisions on safety concerns, including their date and the decision-making process.

(3) A holder must establish mechanisms enabling the traceability and follow-up of adverse reaction reports.

(4) A holder must arrange for the elements referred to in sub-paragraph (2) to be kept for at least five years, beginning with the day after the system as described in the pharmacovigilance system master file has been formally terminated by the holder.

(5) Pharmacovigilance data and documents relating to individual authorised medicinal products must be retained as long as the product is authorised and for at least 10 years, beginning with the date on which the UKMA(GB) or the UKMA(UK)(Category 1), as the case may be, ceased to exist.

Audit

13

(1) Risk-based audits of the quality system must be performed at regular intervals to ensure that the quality system complies with the quality system requirements set out in paragraphs 8, 10, 11 and 12, and to determine its effectiveness.

(2) The audits referred to in sub-paragraph (1) must be conducted by individuals who have no direct involvement in or responsibility for the matters or processes being audited.

(3) Following a risk-based audit—

(a) any corrective action, including a follow-up audit of deficiencies, must be taken where necessary;

(b) a report on the results of the audit must be drawn up for each audit and follow-up audit;

(d) the dates and results of audits and follow-up audits must be documented in accordance with regulation 184(1)(b).

PART 4 — Minimum requirements for the quality systems for the performance of pharmacovigilance activities by the licensing authority

Management of human resources

14

(1) The licensing authority must have sufficient competent and appropriately qualified and trained personnel available for the performance of pharmacovigilance activities: the organisational structures and the distribution of tasks and responsibilities must be clear and, to the extent necessary, accessible.

(2) Named contact points in the licensing authority for pharmacovigilance activities must be established.

(3) The licensing authority must ensure that—

(a) all of its personnel involved in the performance of pharmacovigilance activities receive initial and continued training;

(b) it keeps training plans and records for documenting, maintaining and developing the competences of personnel; and

(4) The licensing authority must ensure that it provides to its personnel performing pharmacovigilance activities appropriate instructions on the processes to be used in case of urgency, including business continuity.

Compliance management

15

The licensing authority must establish specific procedures and processes in order to achieve the following objectives—

(a) ensuring the evaluation of the quality, including completeness, of pharmacovigilance data submitted;

(b) ensuring the assessment of pharmacovigilance data and its processing within the timelines provided for in Part 11 of these Regulations;

(d) ensuring effective communication among regulatory bodies in countries other than the United Kingdom who have the same or similar functions as the licensing authority, as well as with patients, healthcare professionals, marketing authorisation holders and the general public; and

(e) conducting inspections, including pre-authorisation inspections.

Record management and data retention

16

(1) The licensing authority must—

(a) record all pharmacovigilance information, and ensure that it is handled and stored so as to allow for accurate reporting, interpretation and verification of that information; and

(b) put in place a record management system for all documents used for pharmacovigilance activities that ensures—

(i) the retrievability of those documents, and

(ii) the traceability of the measures taken to investigate safety concerns, of the timelines for those investigations and of decisions on safety concerns, including their date and the decision-making process.

(2) The licensing authority must arrange for the essential documents describing their pharmacovigilance system to be kept for at least five years, such period beginning with the day after the system has been formally terminated.

(3) Pharmacovigilance data and documents relating to individual authorised medicinal products must be retained by the licensing authority for as long as the product is authorised and for at least 10 years, such period beginning with the day after the UKMA(GB) or the UKMA(UK)(Category 1), as the case may be, has expired.

Audit

17

(1) Risk-based audits of the quality system must be performed by the licensing authority at regular intervals to ensure that the quality system complies with the requirements set out in paragraphs 8, 14, 15 and 16, and to ensure its effectiveness.

(2) Following a risk-based audit—

(a) any corrective action, including a follow-up audit of deficiencies, must be taken where necessary;

(b) a report on the results of the audit must be drawn up for each audit and follow-up audit;

(d) the dates and results of audits and follow-up audits must be documented.

PART 5 — Use of terminology, formats and standards

Use of internationally agreed terminology, formats and standards

18

The licensing authority may publish a list of which of the internationally agreed—

(a) terminology; and

(b) formats and standards,

are to be used for the description, classification, retrieval, presentation, risk-benefit evaluation and assessment, electronic exchange and communication of pharmacovigilance and medicinal product information.

PART 6 — Transmission of reports of suspected adverse reactions

Individual case safety reports

19

Individual case safety reports must be used for reporting to the licensing authority suspected adverse reactions to a medicinal product that occur in a single patient at a specific point in time.

Content of the individual case safety report

20

(1) Holders must—

(a) ensure that individual case safety reports are as complete as possible; and

(b) communicate the updates of those reports to the licensing authority in an accurate and reliable manner.

(2) In the case of expedited reporting, the individual case safety report must include at least an identifiable reporter, an identifiable patient, one suspected adverse reaction and any medicinal product concerned.

(3) Holders and the licensing authority must record the details necessary for obtaining follow-up information on individual case safety reports and such reports must be adequately documented.

(4) When reporting suspected adverse reactions, holders must provide all available information on each individual case, including—

(a) administrative information, namely—

(i) report type, date and a worldwide unique case identification number as well as unique sender identification and sender type,

(ii) the date on which the report was first received from the source and the date of receipt of the most recent information, using a precise date, and

(iii) other case identifiers and their sources, as well as references to additional available documents held by the sender of the individual case safety report, where applicable;

(b) literature reference in accordance with the ‘Vancouver style’ as developed by the International Committee of Medical Journal Editors for adverse reactions reported in the worldwide literature, including a comprehensive English summary of the article;

(c) study type, study name and the sponsor's study number or study registration number for reports from studies not covered by the Clinical Trials Regulations;

(d) information on any primary source, namely information identifying the reporter, including country of residence and professional qualifications;

(e) information identifying the patient (and parent in the case of a parent-child report), including age at the time of the onset of the first reaction, age group, gestation period when reaction or event was observed in the foetus, weight, height or gender, last menstrual date and, where relevant, gestation period at time of exposure;

(f) relevant medical history and concurrent conditions;

(g) the name of any medicinal product suspected to be related to the occurrence of the adverse reaction, including interacting medicinal products or, where the name is not known, any active substance and any other characteristics that allow for the identification of a medicinal product, including—

(i) the name of the holder, UK marketing authorisation number, pharmaceutical form and each (parent) route of administration,

(ii) any indication for use in the case, dose administered, start date and end date of administration,

(iii) actions taken with any medicinal product, and

(iv) effect of the dechallenge and rechallenge for suspect medicinal products;

(h) for a biological medicinal product, the batch number;

(i) concomitant medicinal products, identified in accordance with paragraph (g), which are not suspected to be related to the occurrence of the adverse reaction and past-medical drug therapy for the patient (and for the parent), where applicable;

(j) information on any suspected adverse reaction, including—

(i) start date and end date of any suspected adverse reaction or duration,

(ii) seriousness,

(iii) outcome of any suspected adverse reaction at the time of last observation,

(iv) time intervals between suspect medicinal product administration and start of any adverse reaction,

(v) the original reporter's words or short phrases used to describe any reaction, and

(vi) country of occurrence of the suspected adverse reaction;

(k) results of tests and procedures relevant to the investigation of the patient;

(l) in the event of death of the patient, date and reported cause of death, including autopsy-determined causes;

(m) a case narrative, where possible, providing all relevant information for individual cases with the exception of non-serious adverse reactions; and

(n) reasons for nullifying or amending an individual case safety report.

(5) For the purposes of—

(a) sub-paragraph (4)(b), upon request of the licensing authority, the holder that transmitted the initial report must provide a copy of the relevant article taking into account copyright restrictions, and a full translation of that article into English;

(b) sub-paragraph (4)(h), a follow-up procedure must be in place to obtain the batch number where it is not indicated in the initial report;

(c) sub-paragraph (4)(m), the information must be presented in a logical time sequence, in the chronology of the patient's experience including clinical course, therapeutic measures, outcome and follow-up information obtained: any relevant autopsy or post-mortem findings must also be summarised in the narrative.

(6) Suspected adverse reactions must be reported in English.

Format of electronic transmission of suspected adverse reactions

21

Holders must use the formats and terminology specified in the list published under paragraph 18 for the electronic transmission of suspected adverse reactions, if the licensing authority has published a list under that paragraph.

PART 7 — Risk management plans

Content of the risk management plan

22

(1) The risk management plan established by the holder must contain the following elements—

(a) an identification or characterisation of the safety profile of the medicinal product concerned;

(b) an indication of how to characterise further the safety profile of the medicinal product(s) concerned;

(c) a documentation of measures to prevent or minimise the risks associated with the medicinal product, including an assessment of the effectiveness of those measures; and

(d) a documentation of post-authorisation obligations that have been imposed as a condition of the UKMA(GB) or the UKMA(UK)(Category 1).

(2) Medicinal products may, where appropriate be subject to the same risk management plan if they—

(a) contain the same active substance; and

(b) belong to the same holder.

(3) Where a risk management plan refers to post-authorisation studies—

(a) it must indicate whether those studies are initiated, managed or financed by the holder voluntarily, or pursuant to obligations imposed by the licensing authority or an equivalent authority to the licensing authority in another country; and

(b) all post-authorisation obligations must be listed in the summary of the risk management plan referred to in paragraph 23, together with a timeframe for meeting those obligations.

Summary of the risk management plan

23

(1) The summary of the risk management plan to be made publicly available in accordance with regulation 203(2)(d) (obligations on licensing authority in relation to national medicines web-portal) must include key elements of the risk management plan with a specific focus on risk minimisation activities and, with regard to the safety specification of the medicinal product concerned, important information on potential and identified risks as well as missing information.

(2) Where a risk management plan concerns more than one medicinal product, a separate summary of the risk management plan must be provided by holders for each medicinal product.

Updates of the risk management plan

24

(1) Subject to sub-paragraph (2), where the holder updates a risk management plan, it must submit the updated risk management plan to the licensing authority.

(2) If the licensing authority agrees, the holder may submit only the modules concerned by the update.

(3) If necessary, the holder must provide the licensing authority with an updated summary of the risk management plan.

(4) Each submission of the risk management plan must—

(a) have a distinct version number; and

(b) be dated.

Format of the risk management plan

25

The risk management plan must be in the following format—

(a) Part I: product overview;

(b) Part II: safety specification consisting of—

(i) Module SI: epidemiology of each indication and each target population,

(ii) Module SII: non-clinical part of the safety specification,

(iii) Module SIII: clinical trial exposure,

(iv) Module SIV: populations not studied in clinical trials,

(v) Module SV: post-authorisation experience,

(vi) Module SVI: additional EU requirements for the safety specification,

(vii) Module SVII: identified and potential risks, and

(viii) Module SVIII: summary of the safety concerns;

(d) Part IV: plans for post-authorisation efficacy studies;

(e) Part V: risk minimisation measures, including evaluation of the effectiveness of risk minimisation activities;

(f) Part VI: summary of the risk management plan; and

(g) Part VII: annexes.

PART 8 — Periodic safety update reports

Content of periodic safety update reports

26

(1) The periodic safety update report (“PSUR” ) must—

(a) be based on all available data; and

(b) focus on new information which has emerged since the data lock point of the last PSUR.

(2) The PSUR must provide an accurate estimate of the population exposed to the medicinal product, including all data relating to the volume of sales and volume of prescriptions.

(3) The estimate of exposure referred to in sub-paragraph (2) must be accompanied by a qualitative and quantitative analysis of actual use, which must indicate, where appropriate, how actual use differs from the indicated use based on all data available to the holder, including the results of observational or drug utilisation studies.

(4) The PSUR must contain the results of assessments of the effectiveness of risk minimisation activities relevant to the risk–benefit assessment.

(5) Where any conditions are imposed under regulation 59(4A) (conditions in relation to UK marketing authorisations to which paediatric specific provisions apply) or 59(4D) (conditions in relation to UK marketing authorisations for advanced therapy medicinal products), the PSUR must also include an assessment of the effectiveness of any risk management system, and the results of any studies performed, in order to comply with those conditions.

(6) Subject to sub-paragraph (7), holders are not required to include systematically detailed listings of individual cases, including case narratives, in the PSUR.

(7) Holders must provide case narratives in the relevant risk evaluation section of the PSUR where integral to the scientific analysis of a signal or safety concern in the relevant risk evaluation section.

(8) Based on the evaluation of the cumulative safety data and the risk-benefit analysis, the holder must draw conclusions in the PSUR as to the need for changes or actions, including implications for the approved summary of product characteristics for each product for which the PSUR is submitted.

(9) Unless otherwise agreed with the licensing authority, a single PSUR must be prepared for all medicinal products which—

(a) contain the same active substance; and

(b) are authorised for the same holder,

and sub-paragraph (10) applies to that single PSUR.

(10) Where this sub-paragraph applies—

(a) the PSUR must cover all indications, routes of administration, dosage forms and dosing regimens, irrespective of whether authorised under different names and through separate procedures; and

(b) where relevant, data relating to a particular indication, dosage form, route of administration or dosing regimen must be presented in a separate section of the PSUR, with any safety concerns addressed accordingly.

(11) Unless otherwise agreed with the licensing authority, if the substance that is the subject of the PSUR is also authorised as a component of a fixed combination medicinal product, the holder must either—

(a) submit a separate PSUR for the combination of active substances authorised for the same holder, with cross-references to each relevant single-substance PSUR; or

(b) provide the combination data within one of the single-substance PSURs.

Format of periodic safety update reports

27

(1) Electronic PSURs must be submitted in the following format—

(a) Part I: title page including signature;

(b) Part II: executive summary; and

(i) introduction,

(ii) worldwide marketing authorisation status,

(iii) actions taken in the reporting interval for safety reasons,

(iv) changes to reference safety information,

(v) estimated exposure and use patterns—

(aa) cumulative subject exposure in clinical trials,

(bb) cumulative and interval patient exposure from marketing experience,

(vi) data in summary tabulations—

(aa) reference information,

(bb) cumulative summary tabulations of serious adverse events in clinical trials,

(cc) cumulative and interval summary tabulations from post-marketing data sources,

(vii) summaries of significant findings from clinical trials during the reporting interval—

(aa) completed clinical trials,

(bb) ongoing clinical trials,

(cc) long-term follow-up,

(dd) other therapeutic use of medicinal product,

(ee) new safety data related to fixed combination therapies,

(viii) findings from non-interventional studies,

(ix) information from other clinical trials and sources,

(x) non-clinical data,

(xi) literature,

(xii) other periodic reports,

(xiii) lack of efficacy in controlled clinical trials,

(xiv) late-breaking information,

(xv) overview on signals: new, ongoing or closed,

(xvi) signal and risk evaluation—

(aa) summaries of safety concerns,

(bb) signal evaluation,

(cc) evaluation of risks and new information,

(dd) characterisation of risks, and

(ee) effectiveness of risk minimisation (if applicable),

(xvii) benefit evaluation—

(aa) important baseline efficacy and effectiveness information,

(bb) newly identified information on efficacy and effectiveness, and

(cc) characterisation of benefits,

(xviii) integrated benefit-risk analysis for authorised indications—

(aa) benefit-risk context: medical need and important alternatives, and

(bb) benefit-risk analysis evaluation,

(xix) conclusions and actions, and

(xx) appendices to the PSUR.

(2) In this paragraph, “signal evaluation” means the process of further evaluating a validated signal taking into account all available evidence, to determine whether there are new risks causally associated with the active substance or medicinal product, or whether known risks have changed, and that process—

(a) may include non-clinical and clinical data; and

(b) must be as comprehensive as possible regarding the sources of information used for that process.

PART 9 — Post-authorisation safety studies

Scope and interpretation

28

(1) This Part applies to non-interventional post-authorisation safety studies initiated, managed or financed by a holder under obligations imposed under regulation 59 or 61 (conditions of UK marketing authorisation).

(2) In this Part—

“start of data collection” means the date on which information on the first study subject is first recorded in the study dataset or, in the case of the secondary use of data, the date on which the data extraction starts; and

“end of data collection” means the date on which the analytical dataset is completely available.

Obligations as to post-authorisation safety studies

29

(1) The holder must submit in English—

(a) the study protocol; and

(b) the abstract of the final study report and the final study report.

(2) The holder must ensure that—

(a) all study information is handled and stored so as to allow for accurate reporting, interpretation and verification of that information;

(b) the confidentiality of the records of the study subjects remains protected; and

(c) the analytical dataset and statistical programmes used for generating the data included in the final study report are kept in electronic format and are available for auditing and inspection.

(3) The licensing authority may publish appropriate templates for the protocol, abstract and final study report.

Format of the study protocol

30

The study protocol for a non-interventional post-authorisation safety studies must be submitted in the following format—

(a) title: informative title including a commonly used term indicating the study design and the medicinal product, substance or drug class concerned, and a sub-title with a version identifier and the date of the last version;

(b) name of holder;

(d) abstract, which must consist of a stand-alone summary of the study protocol, including the following subsections—

(i) title with subtitles including version and date of the protocol and name and affiliation of the main author,

(ii) rationale and background,

(iii) research question and objectives,

(iv) study design,

(v) population,

(vi) variables,

(vii) data sources,

(viii) study size,

(ix) data analysis, and

(x) milestones;

(e) amendments and updates, namely any substantial amendment and update to the study protocol after the start of data collection, including a justification for the amendment or update, the date of the change, and a reference to the section of the protocol where the change has been made.

(f) milestones, namely a table with planned dates for the following milestones—

(i) start of data collection,

(ii) end of data collection,

(iii) any study progress report as referred to in regulation 198(2),

(iv) any interim report of study results, if applicable, and

(v) final report of study results;

(g) rationale and background, namely a description of any safety hazard, the safety profile or the risk management measures that led to the study being imposed as an obligation for a UKMA(GB) or a UKMA(UK)(Category 1);

(h) research question and objectives in accordance with the decision of the licensing authority in imposing the study as an obligation;

(i) research methods, namely a description of the research methods, including—

(i) study design,

(ii) setting, namely the study population defined in terms of persons, place, time period, and selection criteria, including the rationale for any inclusion and exclusion criteria: where any sampling from a source population is undertaken, a description of the source population and details of sampling methods must be provided and where the study design is a systematic review or a meta-analysis, the criteria for the selection and eligibility of studies must be explained,

(iii) variables,

(iv) data sources, namely strategies and data sources for determining exposures, outcomes and all other variables relevant to the study objectives: where the study will use an existing data source, such as electronic health records, any information on the validity of the recording and coding of the data must be reported and in the case of a systematic review or meta-analysis, the search strategy and processes and any methods for confirming data from investigators must be described,

(v) study size, namely any projected study size, precision sought for study estimates and any calculation of the study size that can minimally detect a pre-specified risk with a pre-specified interpretative power,

(vi) data management,

(vii) data analysis,

(viii) quality control, and

(ix) limitations of the research methods;

(j) protection of human subjects, namely safeguards in order to comply with national requirements for ensuring the well-being and rights of participants in non-interventional post-authorisation safety studies;

(k) management and reporting of adverse events or adverse reactions and other medically important events while the study is being conducted;

(l) plans for disseminating and communicating study results; and

(m) references.

Format of the abstract of the final study report

31

The abstract of the final study report for a non-interventional post-authorisation safety studies must be submitted in the following format—

(a) title, with subtitles including date of the abstract and name and affiliation of main author;

(b) keywords (not more than five keywords indicating the main study characteristics);

(d) research question and objectives;

(e) study design;

(f) setting;

(g) subjects and study size, including dropouts;

(h) variables and data sources;

(i) results;

(j) discussion (including, where relevant, an evaluation of the impact of study results on the risk–benefit balance of the product);

(k) name of holder; and

(l) names and affiliations of principal investigators.

Format of the final study report

32

The final study report for a non-interventional post-authorisation safety studies must be submitted in the following format—

(a) title, including a commonly used term indicating the study design; sub-titles with date of final report and name and affiliation of the main author;

(b) abstract, namely a stand-alone summary referred to in paragraph 31;

(d) investigators, namely the names, titles, degrees, addresses and affiliations of the principal investigator and all co-investigators, and list of all collaborating primary institutions and other relevant study sites;

(e) milestones, namely the dates for the following milestones—

(i) start of data collection (planned and actual dates),

(ii) end of data collection (planned and actual dates),

(iii) study progress reports,

(iv) interim reports of study results, where applicable,

(v) final report of study results (planned and actual date), and

(vi) any other important milestone applicable to the study, including date of study registration in the electronic study register

(f) rationale and background, namely a description of the safety concerns that led to the study being initiated, and critical review of relevant published and unpublished data evaluating pertinent information and gaps in knowledge that the study is intended to fill;

(g) research question and objectives;

(h) amendments and updates to the protocol, namely a list of any substantial amendments and updates to the initial study protocol after the start of data collection, including a justification for each amendment or update;

(i) research methods, namely—

(i) study design: key elements of the study design and rationale for this choice,

(ii) setting: setting, locations, and relevant dates for the study, including periods of recruitment, follow-up, and data collection: in the case of a systematic review or meta-analysis, study characteristics used as criteria for eligibility, with rationale,

(iii) subjects: any source population and eligibility criteria for study subjects. Sources and methods for selection of participants shall be provided, including, where relevant, methods for case ascertainment, as well as number of and reasons for dropouts,

(iv) variables: all outcomes, exposures, predictors, potential confounders, and effect modifiers, including operational definitions: diagnostic criteria shall be provided, where applicable,

(v) data sources and measurement: for each variable of interest, sources of data and details of methods of assessment and measurement; if the study has used an existing data source, such as electronic health records, any information on the validity of the recording and coding of the data must be reported and in the case of a systematic review or meta-analysis, description of all information sources, search strategy, methods for selecting studies, methods of data extraction and any processes for obtaining or confirming data from investigators,

(vi) bias,

(vii) study size: study size, rationale for any study size calculation and any method for attaining projected study size,

(viii) data transformation: transformations, calculations or operations on the data, including how quantitative data were handled in the analyses and which groupings were chosen and why,

(ix) statistical methods: description of the following items—

(aa) main summary measures,

(bb) all statistical methods applied to the study,

(cc) any methods used to examine subgroups and interactions,

(dd) how missing data were addressed,

(ee) any sensitivity analyses, and

(ff) any amendment to the plan of data analysis included in the study protocol, with rationale for the change, and

(x) quality control: mechanisms to ensure data quality and integrity;

(j) results: comprising the following subsections—

(i) participants, namely numbers of study subjects at each stage of study: in the case of a systematic review or meta-analysis, number of studies screened, assessed for eligibility and included in the review with reasons for exclusion at each stage,

(ii) descriptive data: characteristics of study participants, information on exposures and potential confounders and number of participants with missing data. In the case of a systematic review or meta-analysis, characteristics of each study from which data were extracted,

(iii) outcome data: numbers of study subjects across categories of main outcomes,

(iv) main result: unadjusted estimates and, if applicable, confounder-adjusted estimates and their precision and where relevant, estimates of relative risk must be translated into absolute risk for a meaningful time period,

(v) other analyses, and

(vi) adverse events and adverse reactions;

(k) discussion which must include—

(i) key results with reference to the study objectives, prior research in support of and conflicting with the findings of the completed post-authorisation safety study, and, where relevant, the impact of the results on the risk–benefit balance of the product,

(ii) limitations of the study taking into account circumstances that may have affected the quality or integrity of the data, limitations of the study approach and methods used to address them, sources of potential bias and imprecision, and validation of the events; both the direction and magnitude of potential biases must be discussed,

(iii) interpretation of results, considering objectives, limitations, multiplicity of analyses, results from similar studies and other relevant evidence, and

(iv) generalisability; and

(l) references.

PART 4 — Outer and immediate packaging: advanced therapy medicinal products ...

34

The name of the advanced therapy medicinal product which is the international non-proprietary name, or if none, the common name.

35

Where appropriate, whether the product is intended for babies, children or adults.

36

The expiry date in clear terms including the year and month and, if applicable, day.

37

A description of the active substance, expressed qualitatively and quantitatively.

38

Where the product contains tissues and cells of human or animal origin—

(a) a statement that the product contains such cells or tissues; and

(b) a short description of the cells or tissues and of their specific origin, including the species of animal in cases on non-human origin.

39

The pharmaceutical form and the contents by weight, volume or number of doses of the product.

40

A list of excipients, including preservative systems.

41

The method of use, application, administration or implantation and, if appropriate, the route of administration, with space provided for the prescribed dose to be indicated.

42

A special warning that the product is to be stored out of the sight and reach and children.

43

Any special warning necessary for the particular product.

44

Any special storage precautions.

45

Specific precautions relating to the disposal of the unused product or of waste derived from the product and, where appropriate, reference to any appropriate collection system.

46

The name and address of the holder of the UK marketing authorisation and, where applicable, the name of the representative appointed by the holder to represent him.

47

The UK marketing authorisation number.

48

The manufacturer's batch number.

49

The unique donation code assigned by a tissue establishment pursuant to—

(a) paragraph 1 of Schedule 3A to the Human Fertilisation and Embryology Act 1990, as regards human gametes and embryos; and

(b) paragraph 1 of Schedule 2 to the Human Tissue (Quality and Safety for Human Application) Regulations 2007, as regards other human tissues and cells.

50

Where the exempt advanced therapy medicinal product is for autologous use, the unique patient identifier and the words “for autologous use only”.

PART 5 — Immediate packaging: blister packs and small packaging (advanced therapy medicinal products ...)

51

The information specified in Part 2.

52

The unique donation code assigned by a tissue establishment pursuant to—

(a) paragraph 1 of Schedule 3A to the Human Fertilisation and Embryology Act 1990, as regards human gametes and embryos; and

(b) paragraph 1 of Schedule 2 to the Human Tissue (Quality and Safety for Human Application) Regulations 2007, as regards other human tissues and cells.

53

Where the exempt advanced therapy medicinal product is for autologous use, the unique patient identifier and the words “for autologous use only”.

Part 3 — Advanced therapy medicinal products ...

18

The name of the advanced therapy medicinal product.

19

Where appropriate, whether the product is intended for babies, children or adults.

20

The common name of the advanced therapy medicinal product.

21

The therapeutic group, or type of activity, of the product, in terms easily comprehensible for the patient.

22

Where the product contains cells or tissues, a description of those cells or tissues and of their specific origin, including the species of animal in cases of non-human origin.

23

Where the product contains medical devices or active implantable medical devices, a description of those devices and their specific origin.

24

The product's therapeutic indications.

25

A list of information which is necessary before the medicinal product is taken or used, including—

(a) contra-indications;

(b) appropriate precautions for use;

(d) interactions with other substances, including alcohol, tobacco and foodstuffs which may affect the action of the product;

(e) special warnings; if any, relating to the product.

26

The list mentioned in paragraph 25 must—

(a) take into account the special requirements of particular categories of users (including, in particular, children, pregnant or breastfeeding women, the elderly and persons with specific pathological conditions);

(b) mention, if appropriate, possible effects on the ability to drive vehicles or operate machinery; and

(i) if knowledge of the excipients is important for the safe and effective use of the product; and

(ii) the excipients are included in the guidance published under regulation 257D.

27

Instructions for proper use of the product including in particular—

(a) the dosage;

(b) the method of use, application, administration or implantation and, if necessary, the route of administration;

(c) the frequency of administration (including, if necessary, specifying the times at which the product may or must be administered);

(d) the duration of treatment if this is to be time limited;

(e) symptoms of an overdose and the action, if any, to be taken in the case of an overdose;

(f) what to do if one or more doses have not been taken;

(g) a specific recommendation to consult a doctor or pharmacist, as appropriate, for further explanation of the use of the product.

28

A description of the adverse reactions which may occur in normal use of the medicinal product and, if necessary, the action to be taken in such a case.

29

A reference to the expiry date printed on the packaging of the product with—

(a) a warning against using the product after that date;

(b) if appropriate, details of special storage precautions to be taken;

(d) the full qualitative and quantitative composition;

(e) the name and address of the UK marketing authorisation holder and, if applicable, the name of the holder's appointed representative; and

(f) the name and address of the manufacturer.

30

The date on which the package leaflet was last revised.

2A

In relation to an advertisement in Great Britain (other than an advertisement falling within the exception in regulation 296) where the medicinal product concerned is authorised under a UKMA(GB), a statement that the product concerned is authorised under a UKMA(GB).

SCHEDULE 33A — Transitional provision in relation to EU Exit

PART 1 — Interpretation

1

In this Schedule—

“the COMP” means the Committee for Orphan Medicinal Products of the EMA, established under Article 4 of the Orphan Regulation;

“converted EU marketing authorisation” has the meaning given in paragraph 6(1) and (2);

“the Paediatric Regulation” means Regulation (EC) No 1901/2006 of the European Parliament and of the Council of 12 December 2006 on medicinal products for paediatric use and amending Regulation (EEC) No 1768/92, Directive 2001/20/EC, Directive 2001/83/EC and Regulation (EC) No 726/2004, as it has effect in EU law;

“the Paediatric Committee” means the committee of the EMA established under Article 3 of the Paediatric Regulation;

“the Pharmacovigilance Risk Assessment Committee” means the Committee of the EMA established by Article 56(1)(aa) of Regulation (EC) No 726/2004; and

“Regulation (EC) No 507/2006” means Commission Regulation (EC) No 507/2006 on the conditional marketing authorisation for medicinal products for human use falling within the scope of Regulation (EC) No 726/2004 of the European Parliament and of the Council, as it has effect in EU law.

PART 2 — Manufacturing, wholesale dealing and brokering

Wholesale dealer's licence used to distribute a medicinal product imported from an EEA State before IP completion day

2

(1) Subject to sub-paragraphs (2) and (3), a person (“P”) who is the holder of a wholesale dealer's licence which—

(a) was granted before IP completion day by the licensing authority;

(b) was in force immediately before IP completion day and remains in force on IP completion day (whether or not it is suspended); and

(c) was used by P to distribute a medicinal product, which was imported from an EEA State, by way of wholesale dealing, or to possess a medicinal product imported from an EEA State for such a purpose,

is deemed on and after IP completion day to hold a wholesale dealing licence granted under Part 3 (manufacture and distribution of medicinal products and active substances) that permits the operation of importing medicinal products from an approved country for import for the purposes specified in paragraph (c).

(2) After the end of the period of 6 months beginning with IP completion day, P is deemed to continue hold a wholesale dealer's licence that permits the operation of importing medicinal products from an approved country for import by virtue of sub-paragraph (1) only if, before the end of that period, P has notified the licensing authority in writing of—

(a) P's intention to continue to import medicinal products from an approved country for import; and

(b) either—

(i) P's intention to appoint a responsible person (import) who will carry out the functions under regulation 45AA(4) (requirement as to responsible persons where licence holder imports from an approved country for import) in respect of the licence, or

(ii) that P will only import medicinal products from an approved country for import to which an exemption in regulation 45AA(2) applies.

(3) Unless P has notified the licensing authority as provided for in sub-paragraph (2)(b)(ii), after the end of the period of 2 years beginning with IP completion day, P is deemed to continue to hold a wholesale dealer's licence that permits the operation of importing medicinal products from an approved country for import by virtue of sub-paragraph (1) only if, before the end of that period, P has notified the licensing authority in writing of the name, address and qualifications of a person who—

(a) is included in the register under regulation 45AB(1); and

(b) will carry out the functions under regulation 45AA(4) in respect of the licence.

(4) From IP completion day, until the date on which P notifies the licensing authority of the information specified in sub-paragraph (3), the responsible person in respect of that licence under regulation 45 must carry out the functions under regulation 45AA(4).

(5) As soon as reasonably practicable after receipt of the information specified in paragraph (3), the licensing authority must provide P with written notice that the responsible person (import) is named on the licence.

(6) Where P has notified the licensing authority as provided for in sub-paragraph (2)(b)(ii), the licensing authority must, as soon as reasonably practicable, notify P in writing that the wholesale dealer's licence includes import of a medicinal product from an approved country for import limited to medicinal products to which an exemption in regulation 45AA(2) applies.

Approved country for import list on IP completion day (regulation 18A)

3

(1) For the purposes of regulation 18A(1) (approved country for import), during the transitional period, the licensing authority must publish an approved country for import list that includes each EEA State in it.

(2) The licensing authority must not, before the end of the transitional period, exercise its power under regulation 18A(3) to remove an EEA State from the approved country for import list.

(3) In this paragraph, “the transitional period” is the period of two years beginning with IP completion day.

Qualified persons and approved country for batch testing list on IP completion day (Schedule 7)

4

(1) Sub-paragraph (2) applies to a person who—

(a) is acting as a qualified person immediately before IP completion day; and

(b) satisfies the requirements of Part 1 of Schedule 7 (qualification requirements for qualified persons) immediately before IP completion day as they had effect at that time.

(2) The person is to be treated on and after IP completion day as continuing to satisfy the requirements of Part 1 of Schedule 7 if the person would otherwise fail to do so as a result of amendments made to that Part by the EU Exit Regulations.

(3) For the purposes of paragraph 14(1)(b) of Schedule 7 (obligations of qualified person), for the transitional period, the licensing authority is deemed to have made appropriate arrangements with—

(a) each EEA State;

(b) Australia;

(d) Israel;

(e) Japan;

(f) New Zealand;

(g) Switzerland; and

(h) the United States of America,

and the licensing authority must, on IP completion day, publish a list that includes those countries under paragraph 14(3) of Schedule 7.

(4) The licensing authority may, in respect of any country specified in sub-paragraph (3)(b) to (h), include that country in the list subject to a condition or restriction as provided for in paragraph 14(4) of Schedule 7, insofar as that condition or restriction was reflected in the appropriate arrangements that existed immediately before IP completion day under Article 51(2) of the 2001 Directive.

(5) The licensing authority must not, before the end of the transitional period, exercise its powers under paragraph 14(6) of Schedule 7 to remove an EEA State from the list it publishes.

(6) In this regulation, “the transitional period” is the period of two years beginning with IP completion day.

List of countries with equivalent regulatory standards as to the manufacturing of active substances on IP completion day (regulation 45O(6) to (9))

5

(1) For the purposes of regulation 45O(6) (requirements for registration as an importer, manufacturer or distributor of active substances), for the transitional period, the licensing authority must publish a list that includes the following countries—

(a) each EEA State;

(b) Australia;

(d) Israel;

(e) Japan;

(ea) Republic of Korea;

(f) Switzerland; and

(g) the United States of America.

(2) The licensing authority must not, before the end of the transitional period, exercise its power under regulation 45O(9) to remove an EEA State from the list it publishes.

(3) In this paragraph, “the transitional period” is the period of two years beginning with IP completion day.

PART 3 — Transitional provision in respect of conversion of EU marketing authorisations in force immediately before IP completion day

Conversion of EU marketing authorisations in force before IP completion day

6

(1) This paragraph applies in relation to an EU marketing authorisation which was in force immediately before IP completion day.

(2) An EU marketing authorisation to which this paragraph applies—

(a) insofar as it authorises sale or supply of a medicinal product in Great Britain, has effect on and after IP completion day as a UKMA(GB) granted under regulation 49(1) of these Regulations (but, insofar as it authorises sale or supply of a medicinal product in Northern Ireland, continues to operate in Northern Ireland as an EU marketing authorisation); and

(b) is referred to in this Part as a “converted EU marketing authorisation”.

(3) If the holder of an EU marketing authorisation to which this paragraph applies notifies the licensing authority in writing before the end of the period of 21 days beginning with IP completion day that it does not wish to be the holder of a converted EU marketing authorisation, the licensing authority must revoke the converted EU marketing authorisation with effect from the date of receipt of the notification.

(4) A converted EU marketing authorisation—

(a) is treated as if it had been granted by the licensing authority under regulation 49(1) on the same terms as those on which the EU marketing authorisation was granted, including any conditions or restrictions subject to which the EU marketing authorisation was granted and which remain in force immediately before IP completion day;

(b) is treated, for the purposes of regulations 65 or 65B (validity of UK marketing authorisation), as if it had been granted by the licensing authority on the date that the EU marketing authorisation took effect;

(c) is treated for the purposes of regulation 67(1) (failure to place on the market) as if it had been granted on IP completion day, and the period of three years referred to in regulation 67(2) is treated as having started on IP completion day;

(d) is treated for the purposes of determining the relevant fee period for the purposes of Schedule 4 to the Fees Regulations (periodic fees for marketing authorisations) as if it had been granted by the licensing authority on the date that the EU marketing authorisation took effect;

(e) is treated, for the purposes of the reference to the date of grant in regulation 27A(a) of the Fees Regulations (fees for renewals of a marketing authorisation) as if it had been granted on the date that the EU marketing authorisation took effect;

(f) retains, for the purposes of regulation 51A(1) and (6), the benefit of any remaining periods of data or marketing exclusivity (if any) from which the holder benefitted immediately before IP completion day;

(g) retains the benefit of any decision by the EMA to exempt the holder from Articles 14(4) or (5) of Regulation (EC) No 726/2004 (failure to place on the market), and that decision is treated as if it had been made by the licensing authority under regulation 67(3); and

(h) remains subject to—

(i) any suspension of the EU marketing authorisation that is in force immediately before IP completion day,

(ii) any post-authorisation obligations imposed after it was granted, and which remain in force immediately before IP completion day, and

(iii) any variation to its terms which were granted or accepted before IP completion day.

(5) For the purposes of this paragraph, an EU marketing authorisation is in force, even if that authorisation is suspended immediately before IP completion day.

(6) A converted EU marketing authorisation to which this paragraph applies which—

(a) was granted as a conditional marketing authorisation within the meaning of Article 1 of Regulation (EC) No 507/2006; and

(b) remains such a conditional marketing authorisation immediately before IP completion day,

has effect on and after IP completion day as a UK marketing authorisation granted under regulation 58F.

(7) A converted EU marketing authorisation to which this paragraph applies which relates to a medicinal product which—

(a) was designated as an orphan medicinal product by the European Commission pursuant to Article 5 of the Orphan Regulation; and

(b) remains in the Community register of Orphan Medicinal Products as referred to in that Article immediately before IP completion day,

has effect on and after IP completion day as a UK marketing authorisation granted under regulation 58C and retains, for the purposes of regulation 58D, the benefit of any period of marketing exclusivity from which the holder benefitted immediately before IP completion day under Article 8 of the Orphan Regulation.

Classification of converted EU marketing authorisations

7

For the purposes of regulation 62 (classification of UK marketing authorisation), it is a term of a converted EU marketing authorisation that the product to which the authorisation relates is to be available—

(a) in a case where the product was classified in its EU marketing authorisation immediately before IP completion day as a prescription only medicine, the product is to be available only on prescription;

(b) in a case where the product was not so classified and the licensing authority has determined that the product should be available on general sale, the product is to be available on general sale; or

Obligations of licensing authority in connection with converted EU marketing authorisations

8

(1) The licensing authority must, before the end of the period of 7 days beginning with IP completion day, notify the holders of converted EU marketing authorisations—

(a) that the EU marketing authorisation is converted to a UK marketing authorisation; and

(b) that the holder may notify the licensing authority in accordance with paragraph 6(3) that it does not wish to be the holder of a UK marketing authorisation.

(2) The licensing authority must, as soon as reasonably practicable after the end of the period referred to in paragraph 6(3), publish a list of converted EU marketing authorisations.

(3) The list mentioned in sub-paragraph (2) must specify which converted EU marketing authorisations have been revoked in accordance with paragraph 6(3).

Obligations of holders of converted EU marketing authorisations

9

(1) A holder of a converted EU marketing authorisation must submit to the licensing authority, before the end of the period of one year beginning with IP completion day, the information described in sub-paragraph (3).

(2) The obligation in sub-paragraph (1) is subject to any requirement imposed by the licensing authority to provide that information before the end of a shorter period specified by the licensing authority under paragraph 10(1).

(3) The information which must be submitted in accordance with sub-paragraph (1) (referred to in this paragraph as the “baseline data”) is—

(a) such information concerning the product to which the converted EU marketing authorisation relates as may be specified in writing for this purpose and published by the licensing authority on or before IP completion day;

(b) notification of whether or not the product to which the converted EU marketing authorisation relates—

(i) is on the market in the United Kingdom at the time the notification is given, or

(ii) if not, whether the product has been on the market in the United Kingdom at any time on or after IP completion day and if so, the date on which it was withdrawn from the United Kingdom market.

(4) In this Part, the date on which the holder of a converted EU marketing authorisation complies with the obligation in sub-paragraph (1), or with any requirement imposed by the licensing authority under paragraph 10(1) to provide all of the baseline data before the end of a period shorter than the period of one year beginning with IP completion day, is referred to as “the data submission date”.

Powers of licensing authority in connection with provision of information

10

(1) If the licensing authority requests a holder of a converted EU marketing authorisation to submit all or part of the baseline data at any time before the expiry of the period of one year beginning with IP completion day, the holder must supply the information within the time period specified by the licensing authority in its request.

(2) If the licensing authority requests a holder of a converted EU marketing authorisation to provide any other information relating to the EU marketing authorisation, the holder must supply the information within the time period specified by the licensing authority in its request.

Variations of converted EU marketing authorisations notified or applied for before IP completion day

11

(1) This paragraph applies where, before IP completion day—

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