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PART 11U.K.Pharmacovigilance

Periodic Safety Update ReportsU.K.

Obligation on holder to submit periodic safety update reports: general requirementsU.K.

191.—(1) The holder must submit reports known as periodic safety update reports (“PSURs”) in relation to the product to the EMA [F1and the licensing authority or, in the case of a holder of a UKMA(GB), to the licensing authority only,] in accordance with this regulation, or in a case where paragraph (2) applies, in accordance with regulation 192.

(2) This paragraph applies to—

(a)a [F2UK] marketing authorisation granted pursuant to regulations 51 (applications for UK marketing authorisations relating to generic medicinal products) or 54 (application relating to products in well-established medicinal use); or

(b)a traditional herbal registration.

(3) In the following paragraphs of this regulation—

“authorisation” means a UK marketing authorisation or an Article 126a authorisation;

“the holder” means the holder of a UK marketing authorisation or an Article 126a authorisation; and

“product” means a product to which a UK marketing authorisation or Article 126a authorisation relates.

(4) Each PSUR must contain—

(a)summaries of data relevant to the benefits and risks of the product, including results of all studies, with a consideration of their potential impact on the authorisation for the product;

(b)a scientific evaluation of the risk-benefit balance of the product; and

(c)all data relating to the volume of sales of the product and any data the holder has relating to the volume of prescriptions, including an estimate of the population exposed to the product.

[F3(4A) A PSUR in relation to a product authorised under a UKMA(GB) must also include the content, and be submitted in the format, specified in Part 8 of Schedule 12A.]

(5) For the purposes of paragraph (4)(b), the scientific evaluation must be based on all available data, including data from clinical trials conducted outside the terms of the authorisation for the product.

(6) Each PSUR must be submitted electronically.

(7) PSURs must be submitted to the EMA [F4and the licensing authority or, in the case of a holder of a UKMA(GB), to the licensing authority only,] with the frequency and on the dates as set out in paragraphs (8) to (10).

(8) In the case of an authorisation granted on or after 21st July 2012, the holder must submit PSURs with the frequency as specified in the authorisation for the product, with the dates of submission being calculated from the date of authorisation.

[F5(8A) In the case of a conditional marketing authorisation in relation to a product authorised under a UKMA(GB), the holder must submit PSURs immediately upon the request of the licensing authority and at least every six months beginning with the date on which the authorisation for the medicinal product is granted or renewed by the licensing authority.]

(9) In the case of an authorisation granted before 21st July 2012 which specifies the frequency and dates of submission of PSURs, the holder must submit PSURs with the frequency and on the dates as specified in the authorisation for the product.

(10) In the case of an authorisation granted before 21st July 2012 which does not specify the frequency and dates of submission of PSURs, the holder must submit a PSUR—

(a)immediately upon the request of the licensing authority;

[F6(b)where—

(i)in relation to a product authorised under a UKMA(NI) or UKMA(UK), the product has not yet been placed on the market within the EEA or Northern Ireland, at least every six months following authorisation until the placing on the market within the EEA or Northern Ireland, or

(ii)in relation to a product authorised under a UKMA(GB), the product has not yet been placed on the market in Great Britain, at least every six months following authorisation until the placing on the market within Great Britain; and]

[F7(c)where—

(i)in relation to a product authorised under a UKMA(NI) or UKMA(UK), the product has been placed on the market within the EEA or Northern Ireland—

(aa)at least every six months during the first two years following the initial placing on the market,

(bb)once a year for the following two years, and

(cc)every three years after that;

(ii)in relation to a product authorised under a UKMA(GB), the product has been placed on the market in Great Britain—

(aa)at least every six months during the first two years following the initial placing on the market,

(bb)once a year for the following two years, and

(cc)every three years after that.]

F8(11) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Textual Amendments

[F9Obligation on holder of a parallel import licence to submit periodic safety update reportsU.K.

191A.—(1) The holder of a parallel import licence must submit reports known as periodic safety update reports (“PSURs”) to the licensing authority if notified to do so by the licensing authority.

(2) Each PSUR must contain—

(a)summaries of data relevant to the benefits and risks of the product, including results of all studies, with a consideration of their potential impact on the licence for the product;

(b)a scientific evaluation of the risk-benefit balance of the product; and

(c)all data relating to the volume of sales of the product and any data the holder of the licence has relating to the volume of prescriptions, including an estimate of the population exposed to the product.

(3) For the purposes of paragraph (2)(b), the scientific evaluation must be based on all available data, including data from clinical trials conducted outside the terms of the authorisation for the product.

(4) Each PSUR must be submitted electronically.

(5) The PSUR must be submitted to the licensing authority within the period specified by that authority.]

Textual Amendments

Obligation on holder to submit periodic safety update reports: derogation from general requirementsU.K.

192.—(1) This regulation applies in relation to medicinal products granted—

(a)a [F10UK] marketing authorisation pursuant to regulations 51 (applications for UK marketing authorisations relating to generic medicinal products) or 54 (application relating to products in well-established medicinal use); or

(b)a traditional herbal registration.

(2) In the following paragraphs of this regulation—

“authorisation or registration” means a marketing authorisation to which paragraph (1)(a) applies or a traditional herbal registration;

“the holder” means the holder of a marketing authorisation to which paragraph (1)(a) applies or of a traditional herbal registration; and

“product” means a product to which a marketing authorisation referred to in paragraph (1)(a) or a traditional herbal registration relates.

(3) The holder must submit PSURs in relation to the product to the EMA [F11and the licensing authority or, in the case of a holder of a UKMA(GB), to the licensing authority only,] in accordance with paragraph (5)—

(a)where requested to do so by the licensing authority in accordance with paragraph (4); or

(b)in the case of a product to which paragraph (1)(a) applies, where it is a condition to which the marketing authorisation for the product is subject by virtue of regulations 59 (conditions of UK marketing authorisation: general) or 60 (conditions of UK marketing authorisation: exceptional circumstances) to do so.

(4) The licensing authority may request the holder to submit PSURs where—

(a)it has concerns relating to the product's pharmacovigilance data; or

(b)it considers there is a lack of PSUR data relating to an active substance of the product after the authorisation or registration is granted.

(5) The submission of PSURs under paragraph (3) must be in accordance with—

(a)where the PSUR is submitted pursuant to a request under paragraph (3)(a), the terms of the request; and

(b)where the PSUR is submitted pursuant to a condition under paragraph (3)(b), the terms of the condition.

(6) Each PSUR must contain—

(a)summaries of data relevant to the benefits and risks of the product, including results of all studies, with a consideration of their potential impact on the authorisation or registration for the product;

(b)a scientific evaluation of the risk-benefit balance of the product; and

(c)all data relating to the volume of sales of the product and any data the holder has relating to the volume of prescriptions, including an estimate of the population exposed to the product.

(7) For the purposes of paragraph (6)(b), the scientific evaluation must be based on all available data, including data from clinical trials conducted outside the terms of the authorisation or registration for the product.

(8) Each PSUR must be submitted electronically.

(9) Where the licensing authority requests submission of PSURs under paragraph (3)(a) [F12from the holder of a UKMA(UK), UKMA(NI), THR(UK), THR(NI) or Article 126a authorisation], it must communicate a PSUR assessment report to the EMA as soon as is reasonably practicable after each report is received.

(10) In this regulation “PSUR assessment report” means a report which evaluates the information provided in a PSUR.

(11) This regulation is subject to regulation 212 (transitional arrangements).

Textual Amendments

Harmonisation of PSUR frequency or date of submissionU.K.

193.—[F13(1) Where products that are subject to different authorisations or registrations contain the same active substance or the same combination of active substances, the frequency and dates of submission may be amended and harmonised in accordance with—

(a)Article 107c(4) of the 2001 Directive, where—

(i)any of the authorisations or registrations is a UKMA(NI), UKMA(UK), THR(NI), THR(UK) or Article 126a authorisation; and

(ii)none of the authorisations or registrations is a UKMA(GB) or THR(GB); or

(b)paragraphs (2A), (3) and (4A), where—

(i)any of the authorisations or registrations is a UKMA(GB) or THR(GB); and

(ii)none of the authorisations or registrations is a UKMA(NI), UKMA(UK), THR(NI), THR(UK) or Article 126a authorisation.]

(2) The holder [F14of a UKMA(NI), UKMA(UK), THR(NI), THR(UK) or Article 126a authorisation] may, where one or more of the grounds in paragraph (3) is met, submit a request in relation to the product to the EMA—

(a)to determine an EU reference date; or

(b)to change the frequency of submission of the PSUR.

[F15(2A ) Where one or more of the grounds in paragraph (3) is met, the holder of a UKMA(GB) or THR(GB) may submit a request in writing to the licensing authority, or the licensing authority may in any event decide, to—

(a)determine a UK reference date from which submission dates are calculated in respect of products that fall under paragraph (1); or

(b)change the frequency and date of submission of the PSUR.]

(3) The grounds in this paragraph are—

(a)reasons relating to public health;

(b)in order to avoid duplication of the assessment; or

(c)in order to achieve international harmonisation.

(4) The second paragraph of Article 107c(6) of the 2001 Directive has effect in relation to the submission and determination of a request under paragraph (2).

[F16(4A) Where the licensing authority makes a decision under paragraph (2) following a written request from a holder of a UKMA(GB) or THR(GB), it must notify that holder in writing of its decision to approve or refuse the request.]

(5) Where the frequency or dates of submission of a PSUR are changed in accordance with Article 107c(4) or Article 107c(6) of the 2001 Directive [F17or paragraph (2A) (as the case may be)], the holder must apply to vary the product's authorisation or registration to reflect the new frequency or date of submission before the end of the period of six months beginning on the day after the change is made public by the EMA [F18or licensing authority (as the case may be)].

(6) In this regulation, “EU reference date” in relation to a product means—

(a)the date of the first marketing authorisation in the EEA of a medicinal product containing the same active substance or the same combination of active substances as that product; or

(b)if the date referred to in point (a) cannot be ascertained, the earliest of the known dates of the marketing authorisations in the EEA for a medicinal product containing the same active substance or the same combination of active substances as that product.

[F19(6A) Subject to paragraph (6B), in this regulation, “UK reference date” means a date determined by the licensing authority under paragraph (2)(a) in respect of medicinal products containing the same active substance or the same combination of active substances.

(6B) Until the licensing authority makes a decision under paragraph (2), any—

(a)Union reference date in respect of medicinal products containing the same active substance or the same combination of active substances; or

(b)date of submission and frequency of periodic safety reports in respect of such products,

published by the EMA under Article 107c(7) of the 2001 Directive, is deemed to be the UK reference date or, as the case may be, the required date or frequency of PSUR submission, in respect of those medicinal products.]

[F20(7) The licensing authority must publish a list of—

(a)UK reference dates it determines under paragraph (2); and

(b)the required date of submission and frequency for PSURs in respect of medicinal products containing the same active substance or the same combination of active substances.

(8) Any change to the date of submission and frequency of PSURs as a result of the application of this regulation is to take effect after a 6 month period, such period beginning with the day after the licensing authority publishes that change under paragraph (7).]

Textual Amendments

Responding to a single assessment of PSUR under Article 107e of the 2001 DirectiveU.K.

194.—(1) This regulation applies where PSURs relating to a medicinal product [F21authorised under a UKMA(NI), UKMA(UK), THR(NI), THR(UK) or Article 126a authorisation] have been assessed under the EU single assessment procedure.

(2) The licensing authority must implement—

(a)the necessary measures that are consequent upon any agreement reached under Article 107g(2) of the 2001 Directive as part of the EU single assessment process, in accordance with the implementation timetable determined in the agreement; or

(b)any decision adopted under Article 107g(4)(a) of the 2001 Directive before the end of the period of 30 days beginning on the day after the day on which the licensing authority received notification of the decision.

(3) Paragraph (4) applies where—

(a)an agreement reached under Article 107g(2) of the 2001 Directive requires a variation to be made to an authorisation or registration; and

(b)the terms of the agreement are known to the holder of that authorisation or registration.

(4) A holder of an authorisation or registration referred to in paragraph (3)(a) must submit to the licensing authority in accordance with the implementation timetable determined in the agreement an appropriate application for a variation, including—

(a)an updated summary of the product characteristics; and

(b)an updated package leaflet.

(5) In this regulation, “EU single assessment procedure” means the single assessment procedure laid down in Article 107e of the 2001 Directive, which covers—

(a)medicinal products that are authorised in more than one member State; and

(b)medicinal products that contain the same active substance or the same combination of active substances and for which a harmonised EU reference date and frequency of submission of PSURs have been established under Article 107c of the 2001 Directive.

Textual Amendments

Obligation on licensing authority to assess PSURs F22...U.K.

195.— [F23(A1) This regulation applies in the circumstances specified in paragraphs (1) and (1A).]

(1) This regulation applies where PSURs relating to a medicinal product [F24authorised for sale or supply authorised under a UKMA(NI), UKMA(UK), THR(NI), THR(UK) or Article 126a authorisation] have not been assessed under the EU single assessment procedure because—

[F25(a)the medicinal product to which the PSUR relates—

(i)has not been authorised to be placed on the market in accordance with the 2001 Directive in an EEA State F26...; and

(ii)a harmonised EU reference date and frequency of submission of PSURs have not been established for that product under Article 107c of the 2001 Directive; or

(b)the medicinal product is one that is imported into the UK under a parallel import licence.]

[F27(1A) This regulation applies where PSURs relating to a medicinal product authorised for sale or supply under a UKMA(GB) or THR(GB) have been submitted to the licensing authority under regulations 191 to 192.]

(2) The licensing authority must assess the PSURs to determine whether there are any relevant changes.

(3) Where the licensing authority has assessed a PSUR under paragraph (2) it must—

(a)consider whether any action concerning the authorisation or registration of the product to which the PSUR relates is necessary; and

(b)vary, suspend, or revoke the authorisation or registration as appropriate.

[F28(3A) If the licensing authority considers under paragraph (3)(b) that an authorisation or registration needs to be varied, it may require the holder to submit to the licensing authority, within a time period that the licensing authority specifies, an application for a variation, including—

(a)an updated summary of the product characteristics; and

(b)an updated package leaflet.]

(4) In this regulation—

“EU reference date” has the meaning given in regulation 193(6);

“EU single assessment procedure” has the meaning given in regulation 194(5); and

“relevant changes” in relation to a medicinal product means—

(a)

new risks,

(b)

risks that have changed, or

(c)

changes to the risk-benefit balance.

Textual Amendments

F25Reg. 195(1)(a)(b) substituted (E.W.S.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.I. 2014/1878), regs. 1, 21 and reg. 195(1)(a)(b) substituted (N.I.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.R. 2014/324), regs. 1(1), 21