Medicines PART 1 General Citation and commencement 1 These Regulations may be cited as the Medicines (Products for Human Use-Fees) Regulations 2008 and shall come into force on 1st April 2008. Interpretation 2 1 In these Regulations, unless the context requires otherwise— “the 2001 Directive” means Directive 2001/83/EC of the European Parliament and of the Council on the Community code relating to medicinal products for human use ; “the 1994 Regulations” means the Medicines for Human Use (Marketing Authorisations Etc) Regulations 1994 ; “the Act” means the Medicines Act 1968 and, except as provided below, expressions used in these Regulations have the same meaning as in the Act; “ API manufacturer ” means a person, other than the holder of a manufacturer’s licence, engaged in the manufacture or assembly of active substances used as starting materials in the manufacture of medicinal products; “ application ”, in relation to a clinical trial authorisation, means a request for authorisation to conduct a clinical trial made in accordance with regulation 17 (request for authorisation to conduct a clinical trial) of the Clinical Trials Regulations, and “ applicant ”, in relation to such authorisation, means the person making the request; “ authorised medicinal product ” means a medicinal product in respect of which a marketing authorization has been granted; “ blood product ” means any medicinal product derived from human blood or human plasma and includes albumin, coagulating factor and immunoglobulin of human origin; “ capital fee ” means any fee, other than a periodic fee, payable under the provisions of these Regulations; “ change of ownership application ” means an application— for— a marketing authorization for a medicinal product in respect of which another person holds a marketing authorization, a manufacturing authorisation for activities in respect of which another person holds a manufacturing authorisation, a traditional herbal registration for a medicinal product in respect of which another person holds a traditional herbal registration, a manufacturer’s licence for activities in respect of which another person holds a manufacturer’s licence, or a wholesale dealer’s licence for activities in respect of which another person holds a wholesale dealer’s licence; which refers to particulars which are in all material respects identical to the particulars of the marketing authorization, manufacturing authorisation, traditional herbal registration, manufacturer’s licence, or wholesale dealer’s licence which is held by that other person; and which includes a statement to the effect that that other person intends to cease the activities to which his marketing authorization, manufacturing authorisation, traditional herbal registration or licence relates and has consented in writing to the making of the application, and in this definition particulars do not include particulars relating to the name and address of the applicant, the labelling of any medicinal product or the content of any leaflet relating to such a product; “ clinical trial ” means any investigation in human subjects, other than a non-interventional trial, intended— to discover or verify the clinical, pharmacological or other pharmacodynamic effects of one or more medicinal products; to identify any adverse reactions to one or more such products; or to study absorption, distribution, metabolism and excretion of one or more such products, with the object of ascertaining the safety or efficacy of those products; “ clinical trial authorisation ” means authorisation of the conduct of a clinical trial— by the licensing authority in accordance with regulation 18 (authorisation procedure for clinical trials involving general medicinal products), 19 (authorisation procedure for clinical trials involving general medicinal products for gene therapy etc.) or 20 (authorisation procedure for clinical trials involving general medicinal products with special characteristics) of the Clinical Trials Regulations; or which is treated as having been given by the licensing authority by virtue of Schedule 12 to those Regulations; “Clinical Trials Regulations” means the Medicines for Human Use (Clinical Trials) Regulations 2004 ; “ Commission Regulation (EC) No. 1084/2003 ” means Commission Regulation (EC) No. 1084/2003 concerning the examination of variations to the terms of a marketing authorisation for medicinal products for human use and veterinary medicinal products granted by a competent authority of a Member State ; “Community marketing authorization” means a marketing authorization granted by the European Commission under Council Regulation (EEC) No. 2309/93 or Regulation (EC) No. 726/2004 ; “ concerned member State ” means an EEA State, the competent authorities of which receive an application to obtain recognition, according to the procedure laid down in Title III, Chapter 4 of the 2001 Directive, of a United Kingdom marketing authorization; “ conditions and principles of good clinical practice ” means the conditions and principles specified in Schedule 1(conditions and principles of good clinical practice and for the protection of clinical trial subjects) to the Clinical Trials Regulations; “ contract laboratory ” means a laboratory carrying out the examinations and tests referred to in— paragraph 5A(2) of Schedule 2 (standard provisions for manufacturer’s licences and manufacturer’s licences of right) to the Medicines (Standard Provisions for Licences and Certificates) Regulations 1971 ; and Article 11(1) of Directive 2003/94/EC, on behalf of the holder of a manufacturing authorisation, manufacturer’s licence or wholesale dealer’s licence, pursuant to Article 11(2) of that Directive and Article 20(b) of the 2001 Directive; “ Council Regulation (EEC) No. 2309/93 ” means Council Regulation (EEC) No 2309/93 laying down Community procedures for the authorization and supervision of medicinal products for human and veterinary use and establishing a European Agency for the Evaluation of Medicinal Products ; “Directive 75/319/EEC” means Council Directive 75/319/EEC on the approximation of provisions laid down by law, regulation or administrative action relating to medicinal products ; “Directive 2003/94/EC” means Commission Directive 2003/94/EC laying down the principles and guidelines of good manufacturing practice in respect of medicinal products for human use and investigational medicinal products for human use ; “EEA State” means a member State, Norway, Iceland or Liechtenstein; “ exempt imported product ” means a medicinal product, as defined in Article 1(2) of the 2001 Directive, to which paragraph 1 of Schedule 1 (exemptions and exceptions from the provisions of regulation 3) to the 1994 Regulations applies, which was not manufactured in the United Kingdom and in relation to which no marketing authorization has been granted; “ fee period ” means the period beginning with the first day of April in any year and ending with the last day of March in the following year; “Herbal Regulations” means the Medicines (Traditional Herbal Medicinal Products for Human Use) Regulations 2005 ; “ herbal substances ” has the meaning given by Article 1(31) of the 2001 Directive; “ holder ”, in relation to a clinical trial authorisation, means— in the case of an authorisation treated as having been given by the licensing authority by virtue of Schedule 12 (transitional provisions) to the Clinical Trials Regulations, the person acting as sponsor of the clinical trial for the purposes of those Regulations; or in any other case, the person who made the request for that authorisation; “ homoeopathic medicinal product ” means any medicinal product (which may contain a number of principles) prepared from substances called homoeopathic stocks in accordance with a homoeopathic manufacturing procedure described by the European Pharmacopoeia or, in the absence thereof, by any pharmacopoeia used officially in a member State; “ immunological product ” means any medicinal product which is a vaccine, toxin, serum or allergen product; “ manufacturer’s licence ” means a manufacturer’s licence which relates wholly or partly to medicinal products for human use; “ manufacturing authorisation ” means a manufacturing authorisation granted for the purposes of regulation 36 (requirement for authorisation to manufacture or import investigational medicinal products) of the Clinical Trials Regulations; “ marketing authorization ” means, except in regulation 3— a United Kingdom marketing authorization granted by the licensing authority under the 1994 Regulations; a Community marketing authorization; or a product licence, including one which is a licence of right or one which has effect as a marketing authorization by virtue of paragraph 1 of Schedule 6 (transitional provisions) to the 1994 Regulations, which relates to a medicinal product for human use; “ medicinal product ” includes any medicinal product for human use to which the 2001 Directive applies and any substance or article specified in any order for the time being in force made under section 104 (application of the Act to certain articles and substances) or 105(1)(a) (application of the Act to certain other substances which are not medicinal products) of the Act which directs that Part II of the Act or the Clinical Trials Regulations shall have effect in relation to such substance or article; “ national homoeopathic product ” means a homoeopathic medicinal product which – does not satisfy the conditions set out in article 14(1) of the 2001 Directive; and is indicated for the relief or treatment of minor symptoms or minor conditions in humans; “ operator ”, in relation to a contract laboratory, means the person having control of the contract laboratory; “ orphan medicinal product ” has the meaning given in article 2(b) of Regulation (EC) No. 141/2000 of the European Parliament and of the Council of 16th December 1999 on orphan medicinal products ; “ parallel import licence ” means a United Kingdom marketing authorisation granted by the licensing authority under the 1994 Regulations in respect of a relevant medicinal product which is imported into the United Kingdom from another EEA State in accordance with the rules of Community law relating to parallel imports; “ penalty fee ” means a fee payable under regulation 41; “ periodic fee ” means the fee payable under regulation 31 or 32 by the holder of a marketing authorization (other than a Community marketing authorization), a traditional herbal registration, a manufacturing authorisation, a manufacturer’s licence, a wholesale dealer’s licence or a clinical trial authorisation for the holding of the authorization, registration, authorisation or licence; “ Periodic Safety Update Report ” means a report prepared to meet the requirements of the 2001 Directive; “ product licence of right ” means a product licence within the meaning of section 7 (general provisions as to dealing with medicinal products) of the Act which is a licence of right within the meaning of section 25(4) (entitlement to licence of right) of the Act; “Regulation (EC) No. 726/2004 ” means Regulation (EC) No. 726/2004 of the European Parliament and of the Council laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency ; “ relevant fee period ” means any fee period during any part of which a marketing authorization, a traditional herbal registration, a clinical trial authorisation, manufacturing authorisation or licence in respect of which a periodic fee is payable is in force; “ relevant medicinal product ” means a medicinal product for human use to which the provisions of the 2001 Directive apply other than– a traditional herbal medicinal product, or a homoeopathic medicinal product that fulfils the conditions laid down in Article 14(1) of the 2001 Directive; “ special import notice ” means a written notice given to the licensing authority in accordance with paragraph 7(2) of Schedule 2 (standard provisions which may be incorporated in a manufacturer’s licence relating to the import of relevant medicinal products from a third country) to, or paragraph 3(2) of Schedule 4 (standard provisions which may be incorporated in a wholesale dealer’s licence) to, the Medicines for Human Use (Manufacturing, Wholesale Dealing and Miscellaneous Amendments) Regulations 2005 ; “ traditional herbal medicinal product ” has the meaning given by Article 1(29) of the 2001 Directive; “ traditional herbal registration ” means a registration granted by the licensing authority under the Herbal Regulations; “ United Kingdom marketing authorization ” means a marketing authorization granted by the licensing authority under the 1994 Regulations; “variation”— in relation to— a United Kingdom marketing authorization, or a product licence which has effect as such a marketing authorization by virtue of paragraph 1 of Schedule 6 (transitional provisions) to those Regulations, means “ variation to the terms of a marketing authorization ” as defined in Article 3(1) of Commission Regulation (EC) No. 1084/2003 ; in relation to a traditional herbal registration, means a variation of the provisions of a traditional herbal registration; “ wholesale dealer’s licence ” means a wholesale dealer’s licence which relates wholly or partly to medicinal products for human use; and Part 1 of Schedule 1 shall have effect for the purpose of interpreting that Schedule. 2 For the purposes of these Regulations, a clinical trial authorisation is in force unless the licensing authority has— a received notification of the conclusion of the clinical trial to which the authorisation relates, in accordance with regulation 27 (conclusion of clinical trial) of the Clinical Trials Regulations; or b suspended or terminated the trial at all sites at which that clinical trial was conducted, in accordance with regulation 31 (suspension or termination of clinical trial) of those Regulations . 3 In these Regulations any reference to an application for the variation of a marketing authorization includes a reference to a notification of such a variation and any reference to an applicant for a variation to a marketing authorization includes a reference to a person who submits such a notification. PART 2 Capital Fees for Pre-Application Meetings Interpretation of Part 2 3 In this Part— “ clinical development ” means the conduct of studies of a medicinal product in human subjects in order to— discover or verify the effects of such a product; identify any adverse reaction to such a product; or study absorption, distribution, metabolism and excretion of such a product, with the object of ascertaining the safety or efficacy of that product, in accordance with section 5 of Part 1 of Annex 1 to the 2001 Directive; “ EC marketing authorization ” means— a United Kingdom marketing authorization granted by the licensing authority under the 1994 Regulations; a marketing authorization granted by the competent authority of an EEA State other than the United Kingdom in accordance with the 2001 Directive; or a Community marketing authorization; “ pharmacovigilance advice ” means advice, other than scientific advice, which falls within one or more of the descriptions specified in paragraphs (a) and (b)— the advice is in connection with an application for an EC marketing authorization, or is given with a view to a person making such an application, and relates to— the obligations that would relate to the holder of such an authorization by virtue of Title IX of the 2001 Directive or Chapter 3 of the Title II of Regulation (EC) No. 726/2004 , the pharmacovigilance and risk-management systems that the applicant would be required to introduce in accordance with Article 8(3)(ia) of the 2001 Directive, or a post-authorization safety study protocol; the advice is given to the holder of a United Kingdom marketing authorization or a Community marketing authorization and relates to— compliance with the obligations that relate to him by virtue of Title IX of the 2001 Directive or Chapter 3 of Title II of Regulation (EC) No. 726/2004 , the pharmacovigilance and risk-management systems that he has introduced in accordance with Article 8(3)(ia) of the 2001 Directive, or a post-authorization safety study protocol; “ post-authorization safety study protocol ” means a document that describes the objectives, design, methodology, statistical considerations and organisation of a post-authorization safety study; “ product range ” means one or more medicinal products containing the same active substance in relation to which the same person holds more than one EC marketing authorization; “ quality development ” means the chemical, pharmaceutical and biological testing necessary to demonstrate the quality of a relevant medicinal product, in accordance with section 3 of Part 1 of Annex 1 to the 2001 Directive; “ regulatory advice ” means advice, other than scientific advice, in relation to the requirements of the 2001 Directive or Regulation (EC) No. 726/2004 and which falls within one or more of the descriptions specified in paragraphs (a) to (c)— the advice is in connection with a change to the dates for renewal of one or more EC marketing authorizations relating to a product range pursuant to Article 24 of the 2001 Directive; the advice is in connection with— a referral pursuant to Article 30, 31 or 36 of the 2001 Directive, or the procedure referred to in Article 35(2) of the 2001 Directive, in relation to a product range; or the advice is given to a person with a view to him making— an application for the variation or renewal of one or more EC marketing authorizations, or an application to amend the time periods for submitting Periodic Safety Update Reports under Article 104(6) of the 2001 Directive, in relation to a product range; “ scientific advice ” means advice in connection with the quality, safety or clinical development for a relevant medicinal product; “ relevant medicinal product ” means a medicinal product for human use to which the provisions of the 2001 Directive apply; and “ safety development ” means the toxicological and pharmacological testing necessary to demonstrate the safety of a relevant medicinal product, in accordance with section 4 of Part 1 of Annex 1 to the 2001 Directive. Fee for scientific advice: application for or variation to EC marketing authorization 4 Unless regulation 5 or 44 apply, the fee payable by a person with whom the licensing authority holds a meeting in order to provide scientific advice with a view to that person making an application for an EC marketing authorization or an application for the variation of a marketing authorization, is— a £2,227, if the advice provided at that meeting consists of advice in connection with— i quality development only, or ii safety development only; b £2,797, if the advice provided at that meeting consists only of advice in connection with clinical development; c £3,099, if the advice provided at that meeting consists only of advice in connection with quality and safety development; d £3,669, if the advice provided at that meeting consists of advice in connection with— i quality and clinical development, or ii safety and clinical development; e £4,542, if the advice provided at that meeting consists of advice in connection with quality, safety and clinical development. Fee for scientific advice: classification of a medicinal product 5 1 Unless regulation 44 applies, the fee payable by a person with whom the licensing authority holds a meeting to provide scientific advice in connection with the classification of a relevant medicinal product, is — a £2,797, if the advice relates to a product which if reclassified will be available on general sale; and b £3,699, if the advice relates to a product which if reclassified will be available without a prescription from a pharmacy. 2 For the purposes of this regulation a product is on general sale if it is a medicinal product of a description, or falling within a class specified in an order made under section 51 (general sale lists) of the Act . Fee for advertising advice 6 Unless regulation 44 applies, the fee payable by the holder of a marketing authorization with whom the licensing authority holds a meeting in order to provide advice before the publication of advertising of a medicinal product by his undertaking on whether that advertising conforms to the requirements of Title VIII of the 2001 Directive, is £2,227. Fee for pharmacovigilance advice 7 1 Unless regulation 44 applies, the fee payable by a person with whom the licensing authority holds a meeting in order to provide pharmacovigilance advice is — a £3,699, in a case where the time taken by the licensing authority to prepare for and attend the meeting is more than six hours; b £3,099, in any other case. 2 The time taken by the licensing authority for the purposes of paragraph (1) shall be the aggregate of times spent by each individual engaged in preparing for or attending the meeting on behalf of the authority. Fee for advice on labelling or leaflets 8 Unless regulation 44 applies, the fee payable by the holder of one or more marketing authorizations with whom the licensing authority holds a meeting in order to provide advice on proposed changes to the labelling or the package leaflets of the medicinal products to which those authorizations relate, is £2,227. Fee for regulatory advice 9 Unless regulation 44 applies, the fee payable by the holder of a marketing authorization with whom the licensing authority holds a meeting in order to provide regulatory advice to that person, is £2,797. Fee for advice for other purposes 10 1 Unless regulation 44 applies, the fee payable by a person specified in paragraph (2) with whom the licensing authority holds a meeting for a purpose specified in paragraph (3) is £4,579. 2 A person who— a is or is to be a sponsor of a clinical trial; b manufactures medicinal products; c is or is to be responsible for placing medicinal products on the market; or d acts on behalf of, or provides advice or assistance to, a person referred to in sub-paragraphs (a) to (c), is a specified person for the purpose of paragraph (1). 3 A meeting referred to in paragraph (1) is for a specified purpose if it is held to provide advice in relation to— a scientific or regulatory issues relating to the development of a medicinal product or a type of medicinal product; b the design of pharmaceutical or pre-clinical tests, or clinical trials, for a medicinal product or a type of medicinal product; c the management of risk in relation to a medicinal product or a type of medicinal product which is under development, or is being marketed in the European Community; or d other scientific or regulatory issues relating to a medicinal product or a type of medicinal product after an EC marketing authorization has been granted for that product or a product of that type. 4 This regulation does not apply to a meeting for the purpose of providing only any advice specified in regulations 4 to 9. 5 In this regulation— “ medical device ” has the same meaning as in Article 1(2)(a) of Directive 93/42/EEC ; “ Directive 93/42/EEC ” means Council Directive 93/42/EEC concerning medical devices ; “ medicinal product ” includes a substance incorporated in a medical device which, if used separately, may be considered to be a medicinal product as defined in Article 1(2) of the 2001 Directive; “ regulatory issues ” means issues relating to the application of any Community instrument relating to EC marketing authorizations or to medical devices, or any enactment which implements such an instrument; “ risks ” means any risk relating to the quality, safety or efficacy of a medicinal product as regards patients’ health or public health, or any risk of undesirable effects on the environment; “ sponsor ” shall be construed in accordance with regulation 3 (sponsor of a clinical trial) of the Clinical Trials Regulations ; and a reference to the development of a medicinal product or a type of medicinal product is a reference to development for the purposes of— a obtaining an EC marketing authorization, or making a variation to an EC marketing authorization, for that product or a product of that type, or b obtaining an EC design-examination certificate within the meaning of paragraph 4.3 of Annex II to Directive 93/42/EEC or an EC type-examination certificate within the meaning of paragraph 5 of Annex III to that Directive, for a medical device incorporating that product or a product of that type. Time for payment of fees under regulations 4 to 10 11 Unless regulation 44 applies, all sums payable by way of fees under regulations 4 to 10 must be paid within 14 days following written notice from the licensing authority requiring payment of those fees. PART 3 Capital Fees for Applications for Authorizations, Registrations, Licences, Certificates or Authorisations and for Associated Inspections Fees for applications for authorizations, licences or certificates, etc 12 1 Unless regulation 44, or 48 applies, the application fee for a marketing authorization (other than a Community marketing authorization), a traditional herbal registration, a manufacturer’s licence, a manufacturing authorisation, a wholesale dealer’s licence or a clinical trial authorisation is— a the fee prescribed for that application in Part 2 of Schedule 1; and b in respect of an inspection of a site made in connection with that application the fee payable in accordance with regulations 27 to 29. 2 Unless regulation 28 applies, the fee in paragraph (1) is payable by the applicant. Fee for applications for copy certificates of good manufacturing practice 13 The fee payable by an applicant for a certified copy of a certificate of good manufacturing practice issued pursuant to Article 111(5) of the 2001 Directive is £63. Fees for applications for certificates and copy certificates by exporters of medicinal products 14 1 The fee payable by an applicant for a certificate issued under section 50 (export certificates) of the Act , is — a £141, if the applicant requests the certificate to be issued within 24 hours of receipt of the application; and b £63 in any other case. 2 The fee in sub-paragraphs (a) and (b) is for three identical signed certificates. 3 The fee payable by the applicant for a copy of the certificate referred to in paragraph (1) is £31 for a certified copy of the certificate. PART 4 Capital Fees for Assistance in Obtaining Marketing Authorizations in Other EEA States Meaning of “set of applications” 15 For the purposes of this Part and Part 3 of Schedule 1, a “ set of applications ” means— a a number of applications to the licensing authority for regulatory assistance in connection with obtaining recognition according to the procedure laid down in Title III, Chapter 4 of the 2001 Directive of a single United Kingdom marketing authorization in other EEA States, but only if all the applications relate to applications for marketing authorizations in other EEA States that have the same 90 day assessment period for the purposes of Article 28.4 of the 2001 Directive; or b a number of applications to competent authorities of other EEA States for marketing authorizations relating to a single United Kingdom marketing authorization, but only if all the applications have the same 90 day assessment period for the purposes of Article 28.4 of the 2001 Directive. Fees for applications for regulatory assistance under the mutual recognition procedure 16 Unless regulation 44 applies, the fee payable by an applicant to the licensing authority for regulatory assistance in connection with obtaining recognition according to the procedure laid down in Title III, Chapter 4 of the 2001 Directive of a single United Kingdom marketing authorization in another EEA State or in other EEA States, is the fee prescribed in Part 3 of Schedule 1 in connection with the application or set of applications. Time for payment of fees under regulation 16 17 Unless regulation 39 or 44 applies, all sums payable by way of fees under regulation 16 must be paid at the time when, in connection with the application or set of applications for regulatory assistance, a request is made pursuant to the second sub-paragraph of Article 28.1 of the 2001 Directive for an assessment report to be prepared or updated. PART 5 Capital Fees for Applications for Variations of Authorizations, Registrations, Licences and Certificates and for Associated Inspections Fees for variations of authorizations, registrations, licences and authorisations 18 1 Unless regulations 44 or 48 applies, the fee for an application— a under regulation 4 (applications for the grant, renewal or variation of a United Kingdom marketing authorization) of the 1994 Regulations for the variation of a United Kingdom marketing authorization; b under regulation 6 (consideration and grant or refusal, of an application for, or for renewal or variation of, a traditional herbal registration) of the Herbal Regulations for the variation of a traditional herbal registration; c under section 30 (variation of licence on application of holder) of the Act for the variation of a product licence, a manufacturer’s licence or a wholesale dealer’s licence; or d under regulation 44 (variation of manufacturing authorisation) of the Clinical Trials Regulations for the variation of a manufacturing authorisation, is the fee mentioned in paragraph (2). 2 The fee referred to in paragraph (1) is— a the fee prescribed in Part 4 of Schedule 1 in connection with the application; and b in respect of an inspection of a site made in connection with the application, the fee payable in accordance with regulations 27 to 29. 3 Unless regulation 28 applies, the fee in paragraph (1) is payable by the applicant. Fees for amendments to clinical trial authorisations 19 1 A person who sends a valid notice of amendment under regulation 24 (amendments by the sponsor) of the Clinical Trial Regulations relating to amendment of the dossier accompanying a request for authorisation in accordance with paragraph 11 of Part 2 of Schedule 3 (request for authorisation) to those Regulations must pay the fees mentioned in paragraph (2). 2 The fees referred to in paragraph (1) are— a the fee prescribed in paragraph 23 of Part 4 of Schedule 1 in connection with that amendment; and b in respect of an inspection of a site made in connection with the application, the fee payable in accordance with regulations 27 to 29. Applications for multiple variations 20 1 Unless paragraph (2) applies, a separate fee is payable in respect of each variation of each provision of a marketing authorization, traditional herbal registration, manufacturing authorisation or licence applied for in any one application. 2 A separate fee is not payable for a variation which is wholly consequential upon another variation of a provision of a marketing authorization, traditional herbal registration, manufacturing authorisation or licence which is applied for in the same application. PART 6 Capital Fees for Assessment of Labels and Leaflets Meaning of “set of proposed changes” 21 For the purposes of this Part and Part 5 of Schedule 1, a “ set of proposed changes ” means a number of proposed changes to the labelling or package leaflet of a medicinal product, where— a if there is more than one version of the labelling or package leaflet for that product, those changes all relate to the same version; and b those changes are submitted to the licensing authority at the same time. Fees for assessment of a set of proposed changes to labels and leaflets 22 1 Unless paragraph (2) or regulation 44 apply, where— a a set of proposed changes to the labelling or the package leaflet of a medicinal product which is the subject of a United Kingdom marketing authorization (other than a parallel import licence) is submitted to the licensing authority in accordance with Article 61(3) of the 2001 Directive; or b a set of proposed changes to the labelling or the package leaflet of a medicinal product which is the subject of a parallel import licence is submitted to the licensing authority, the fee payable by the holder of that authorization or licence is the fee prescribed in Part 5 of Schedule 1 in connection with that change. 2 Paragraph (1) does not apply where a change to the labelling or package leaflet of a medicinal product is proposed in connection with an application for the variation of the marketing authorization for that product. Time for payment of fees under regulation 22 23 Unless regulation 44 applies, all sums payable by way of fees under regulation 22 (1) must be paid at the time when the proposed changes are submitted to the licensing authority. PART 7 Capital Fees for Applications for Renewals of Certain Manufacturer’s Licences and for Associated Inspections Fees for renewals of certain manufacturer’s licences 24 1 Unless regulation 44 applies, the fee payable by the applicant for an application to renew a manufacturer’s licence which falls within the description in paragraph (2) is £165. 2 The licence referred to in paragraph (1) is one— a which is solely for the manufacture of medicinal products the sale or supply of which does not require a marketing authorization or a product licence; and b to which article 2(2)(i)(e) (exemptions for certain special manufactured products) of the Medicines (Exemption from Licences) (Special and Transitional Cases) Order 1971 applies. 3 But if an inspection of a site is made in connection with the application an inspection fee of £273 is also payable by the applicant. Fees for renewals in terms which are not identical to the existing authorization, licence or certificate 25 Where an applicant applies for renewal of a marketing authorization (other than a Community marketing authorization), a traditional herbal registration, a manufacturer’s licence or a wholesale dealer’s licence so as to contain provisions which are not identical to those in the authorization, registration or licence as in force at the date of the application, the fee payable under this Part of these Regulations is increased by an amount equal to the fee which would have been payable under Part 5 of these Regulations had he made a separate application for variation of that authorization, registration or licence in respect of each provision which is not identical. PART 8 Capital Fees for Regulatory Assistance Given by the United Kingdom Acting as Reference Member State Relating to the Assessment of Applications for the Renewal of Specified Marketing Authorizations Fees for regulatory assistance for certain marketing authorizations 26 1 Unless regulation 44 applies, where— a an application is made to the licensing authority for the renewal of a United Kingdom marketing authorization for a medicinal product which has been subject to the procedures specified in paragraph (2); and b the United Kingdom is to provide regulatory assistance acting as reference member State in relation to that application, the fee payable by the applicant is the fee prescribed in Part 6 of Schedule 1 in connection with that regulatory assistance. 2 The procedures referred to in paragraph (1) are— a the procedures laid down in Articles 7 and 7a of Council Directive 65/65/EEC on the approximation of provisions laid down by law, regulation or administrative action relating to medicinal products and in Articles 17 and 18 of the 2001 Directive; b the procedures laid down in Article 9(4) of Directive 75/319/EEC and in Article 28 of the 2001 Directive; c the procedures laid down in Articles 10 to 14 of Directive 75/319/EEC and in Articles 29 to 34 of the 2001 Directive; d referral to the Committee for Propriety Medicinal Products in accordance with Council Directive 87/22/EEC on the approximation of national measures relating to the placing on the market of high-technology medicinal products, particularly those derived from biotechnology , if the opinion of the Committee in accordance with Article 4.1 of that Directive was given before 1st January 1995. 3 For the purposes of this regulation and Part 6 of Schedule 1, the United Kingdom provides regulatory assistance acting as reference member State if— a the licensing authority prepares or updates an assessment report in respect of the medicinal product to which the renewal application relates in order to make it available to the competent authorities of another EEA State; and b an application to renew the marketing authorization relating to that product has been made in that other EEA State. PART 9 Capital Fees for Inspections Fees for inspections 27 1 Unless regulation 44 or 48 applies, a fee in accordance with paragraphs 1 to 7 of Schedule 2 is payable for any inspection of a site made in connection with an application for, or during the currency of, a marketing authorization, a traditional herbal registration, a clinical trial authorisation, a manufacturing authorisation, a manufacturer’s licence or a wholesale dealer’s licence, except for an inspection for which a fee is payable under regulations 24 or 30. 2 Unless regulation 28 or 29 applies, the fee in paragraph (1) is payable by the holder of or applicant for, as the case may be, the authorization, registration, authorisation or licence in relation to which the inspection is made. Payer of inspection fee (contract laboratories and API manufacturing sites) 28 Where an inspection is made of a contract laboratory or a site used by an API manufacturer the fee is payable by the operator of that laboratory, or, as the case may be, that API manufacturer. Inspections in connection with multiple applications. 29 1 Where an inspection is made outside the United Kingdom at a site which is named as a possible site for the manufacture or assembly of a medicinal product, or for the preparation of a substance which is to be used in the manufacture of an immunological product or a blood product— a in more than one marketing authorization, clinical trial authorisation, traditional herbal registration; or b by more than one applicant for such an authorisation or licence, the fee for the inspection referred to in regulation 27(1) is payable in equal proportions by the holders of, or as the case may be, applicants for, the authorization, authorisation, licence or registration. 2 In paragraph (1), the reference to an applicant for a clinical trial authorisation is a reference to a person who sends a valid notice of amendment as mentioned in regulation 19(1). 3 Where an inspection is made in the United Kingdom at a site which is named as a possible site for the manufacture or assembly of a medicinal product, or the preparation of a substance which is to be used in the manufacture of an immunological product or a blood product— a in more than one manufacturer’s licence or manufacturing authorisation; or b by more than one applicant for such a licence or authorisation, the fee for the inspection referred to in regulation 27(1) is payable in equal proportions by each applicant. 4 But this regulation does not apply if the inspection is made of a contract laboratory or a site used by an API manufacturer. Fees for inspections relating to good clinical practice in clinical trials 30 Unless regulation 44 applies a fee in accordance with paragraphs 2 and 3 of Schedule 2 is payable by a person in respect of an inspection of one or more sites for the purpose of ascertaining whether that person— a is— i conducting, or has conducted, a clinical trial, or ii performing, or has performed, the functions of a sponsor of a clinical trial (whether that person is the sponsor or is acting under arrangements made with that sponsor), in accordance with the conditions and principles of good clinical practice, pursuant to regulation 28(1) (good clinical practice and protection of clinical trial subjects) of the Clinical Trials Regulations; or b has put and kept in place arrangements for the purpose of ensuring that with regard to a clinical trial the conditions and principles of good clinical practice are satisfied or adhered to, pursuant to regulation 28(2) of those Regulations. PART 10 Periodic Fees for Marketing Authorizations and Licences Periodic fees 31 1 Unless paragraphs (2), (4), (5) or (6) or regulation 44 or 48 applies, the periodic fee must be paid for each fee period during which the authorization, registration, authorisation or licence is in force, even if it is in force for only part of that fee period. 2 Marketing authorizations of a type referred to in Part 3 of Schedule 3 shall be treated for the purposes of paragraph (1) as if they were one marketing authorization and only one periodic fee in respect of each relevant fee period is payable in connection with the holding of such authorizations. 3 The periodic fee is the appropriate fee prescribed in Part 3 of Schedule 3 and, for the purposes of that Part, Parts 1 and 2 of that Schedule have effect. 4 No periodic fee is payable in respect of the fee period during which a marketing authorization or a traditional herbal registration is first granted unless the authorization or registration is granted pursuant to— a a change of ownership application; or b an application for a marketing authorization or traditional herbal registration which— i is for a product for which an authorization or registration has expired, ii will contain identical provisions to those contained in the expired authorization or registration, iii is made by the person who held the expired authorization or registration, and iv is made no later than three months after the expiry of the authorization or registration referred to in sub-paragraph (i), and, in each case, a periodic fee has not been paid in respect of that fee period in connection with the expired marketing authorization or a traditional herbal registration. 5 An authorization, registration, authorisation or licence which is in force is treated for the purposes of this regulation as not being in force during any part of a fee period if— a at least three months before the commencement of that fee period, the holder of that authorization, registration, authorisation or licence has given written notice to the licensing authority indicating that he wishes it to cease to have effect before the commencement of that period; and b no products are sold, supplied or manufactured pursuant to that authorization, registration authorisation or licence within that fee period. 6 No periodic fee is payable in respect of the fee period during which a manufacturing authorisation, a manufacturer’s or wholesale dealer’s licence is first granted unless— a that authorisation or licence is granted pursuant to a change of ownership application; and b a periodic fee has not been paid in respect of that fee period in connection with the manufacturing authorisation or manufacturer’s or wholesale dealer’s licence which is mentioned in that application in the statement of intention to cease activities. Periodic fees for clinical trial authorisations 32 1 Unless paragraph (3) or regulation 44 applies, the holder of a clinical trial authorisation must pay the periodic fee for each fee period during which the authorisation is in force, even if the authorisation is in force for only part of that fee period. 2 The periodic fee is the fee prescribed in paragraph 16 of Part 3 of Schedule 3. 3 No periodic fee is payable in respect of the fee period during which the clinical trial to which the authorisation relates was authorised by the licensing authority in accordance with regulation 18 (authorisation procedure for clinical trials involving general medicinal products), 19 (authorisation procedure for clinical trials involving medicinal products for gene therapy etc.) or 20 (authorisation procedure for clinical trials involving medicinal products with special characteristics) of the Clinical Trials Regulations . PART 11 Capital Fees For Application For Membership of Good Clinical Practice Accreditation Scheme and for Certificate of Membership Meaning of “good clinical practice accreditation” scheme 33 In this Part— “ good clinical practice accreditation scheme ” means the non-statutory voluntary scheme of accreditation operated by the licensing authority in relation to Phase 1 trials which participants may join following satisfactory completion of a good clinical practice inspection; and “Phase I trials” are clinical trials to study the pharmacology of a medicinal product when administered to humans, where the sponsor and investigator have no knowledge of any evidence that the product has effects likely to be beneficial to the subjects of the trial. Fees for applications for membership and certificate 34 1 The fee payable by an applicant for membership of the good clinical practice accreditation scheme is £120. 2 The fee payable by an applicant for a certificate of membership of the good clinical practice accreditation scheme is £63. PART 12 Capital Fees for Persons Appointed Hearing Fees for persons appointed hearing 35 1 The fee payable by an applicant or holder of an authorization who gives notice under paragraph 11 (right to be heard by a person appointed or to make further representations) or 16 (right to be heard by a person appointed) of Schedule 2 to the 1994 Regulations of his wish to appear before or be heard by a person appointed by the licensing authority is £10,000. 2 But the licensing authority will refund to that person— a 60% of that fee if the person withdraws the notice two weeks before the commencement of the hearing before the person appointed; b 100% of that fee if the decision notified by the licensing authority in accordance with sub-paragraph (10) of paragraph 17 (hearing before person appointed) of Schedule 2 to the 1994 Regulations is— i not to revoke, vary or suspend the authorization, or ii to grant or renew the authorization in accordance with the application submitted under regulation 4(1) (applications for the grant, renewal or variation of a UK marketing authorization) of the 1994 Regulations. Time for payment under regulation 35 36 The fee in regulation 35 is payable at the time the notice is given. PART 13 Administration Payment of fees to Ministers 37 Any sums which under the provisions of these Regulations become payable by way of, or on account of, fees must be paid to one of the Ministers. Time for payment of capital fees in connection with applications or inspections 38 1 Except where regulation 11, 17, 23 or 36 applies and subject to paragraph (2) and to regulations 39 and 44, all sums payable by way of capital fees under these Regulations in connection with any application must be paid at the time of the application. 2 All sums payable by way of fees in respect of inspections made either in connection with an application for, or during the currency of, an authorization, licence or certificate must be paid within 14 days following receipt of written notice from the licensing authority requiring payment of those fees. Time for payment of capital fees – applications made by small companies 39 1 Schedule 4 shall have effect with respect to the capital fee payable in connection with an application made by or on behalf of a small company. 2 For the purpose of these Regulations, a company is a small company if, for the financial year before that in which the application is made, the amount of its turnover for the financial year is not more than the amount for the time being specified under the heading “Small company” in section 247(3) (qualification of company as small or medium-sized) of the Companies Act 1985 ; and a its balance sheet total (as defined in section 247(5) of that Act) is not more than the amount for the time being specified under the heading “Small company” in section 247(3) of that Act; or b the average number of persons employed by the company in the financial year before that in which the application is made (determined on a weekly basis) does not exceed the number for the time being specified under the heading “Small company” in section 247(3) of that Act. Time for payment of periodic fees 40 All periodic fees must be paid on the first day of the fee period to which they relate. Penalty fees for late payment of periodic fees 41 1 Subject to paragraph (2), if a person has failed to pay a periodic fee at the time it should have been paid under regulation 40, a penalty fee is payable by that person. 2 A penalty fee is payable only if after 60 days following written notice from the licensing authority requiring payment of that fee, the fee remains unpaid. 3 Unless regulation 42 applies, the penalty fee is— a £100 where the total periodic fee unpaid by a person after 60 days following the notice referred to in paragraph (2) exceeds £200; or b £50 where the total periodic fee unpaid by a person after such period does not exceed £200. 4 In paragraph (3), the “ total periodic fee ” means the aggregate of all the periodic fees payable by a person in connection with all the authorizations, registrations, authorisations or licences held by that person. Daily penalty fees for late payment of periodic fees 42 If the periodic fee and penalty fee under regulation 41 (“the outstanding amount”) have not been paid within 90 days following the written notice from the licensing authority, the amount of penalty fee payable shall be the amount specified in regulation 41(3) plus £5 for each day of the period which— a begins with the day 90 days from the date of the written notice; and b ends with the day before that on which payment of the outstanding amount is actually made. Refund or waiver of fees under regulation 41 or 42 43 The licensing authority may refund or waive payment of the penalty fee, or reduce the amount payable, where it is satisfied that the holder of the authorization, registration, authorisation or licence was not responsible for the failure to pay the periodic fee within the period specified in regulation 41(2) or 42. Adjustment, waiver, reduction or refund of fees 44 1 If after a capital or periodic fee is paid it becomes apparent that— a a lesser fee should have been paid, the excess shall be refunded to the applicant or, as the case may be, the holder of the authorization, registration, authorisation or licence concerned; or b a higher fee should have been paid, the balance due shall be payable within 14 days following written notice from the licensing authority to the applicant or, as the case may be, the holder of the authorization, registration, authorisation or licence concerned requiring payment of that balance. 2 The licensing authority shall, to the extent provided in Schedule 5 in relation to capital fees or in Schedule 6 in relation to periodic fees— a adjust, waive payment of or reduce any fee or part of a fee otherwise payable under these Regulations; or b refund the whole or part of any fee already paid. Suspension of licences and certificates 45 Where any sum due by way of, or on account of, any fee or any part thereof payable under these Regulations remains unpaid by the holder of a product licence or a product licence of right, a manufacturer’s licence or a wholesale dealer’s licence, the licensing authority may serve a written notice on him requiring payment of the sum unpaid and, if after a period of one month from the date of service of such notice, or such longer period as the licensing authority may allow, the said sum remains unpaid, the licensing authority may forthwith suspend the licence until such sum has been paid. Civil proceedings to recover unpaid fees 46 All unpaid sums due by way of, or on account of, any fees payable under these Regulations shall be recoverable as debts due to the Crown. PART 14 Amendment of the Medicines (Homoeopathic Medicinal Products for Human Use) Regulations 1994 47 1 The Medicines (Homoeopathic Medicinal Products for Human Use) Regulations 1994 are amended as follows. 2 In regulation 14 (fees for variation of certificates)— a in paragraph (1)(a), for “£110” substitute “£127”; b in paragraph (1)(b)(i), for £110” substitute “£127”; c in paragraph (1)(b)(ii), for “£55” substitute “£63.50”; d in paragraph (2)(a), for “£237” substitute “£250”; e in paragraph (2)(b)(i), for “£237” substitute “£250”; f in paragraph (2)(b)(ii), for “”£237” substitute “£250”; g in paragraph 2(b)(iii), for “£120” substitute “£127”; and h in paragraph 2(b)(iv), for “£60”, substitute “£62.50”. 3 In regulation 15 (fees payable by holders of certificates), in paragraph (1), for “£19” substitute “£22”. 4 In the table in Schedule 2 (fees for applications for the grant of certificates of registration)— a in column (2) (fees for applications in respect of products prepared from not more than 5 homoeopathic stocks)— i for “£155” substitute “£164”, ii for “£466” substitute “£492”, iii for “£488” substitute “£516”, and iv for “£770” substitute “£813”. b in column (3) (fees for other applications)— i for “£383” substitute “£405”, ii for “£686” substitute “£725”, iii for “£622” substitute “£657”, and iv for “£1,007” substitute “£1,064”. 5 In Schedule 2A (fees for assistance in obtaining certificates of registration in other EEA States) , in paragraph 2— a in sub-paragraph (a), for “£279” substitute “£295”; and b in sub-paragraph (b), for “£365” substitute “£386”. PART 15 Revocationand Savings Revocation and savings 48 1 The Regulations listed in Schedule 7 are revoked to the extent specified in that Schedule. 2 But— a in relation to capital fees, the Medicines (Products for Human Use – Fees ) Regulations 1995 continue to apply as if they had not been revoked to any application or inspection made before the date on which these Regulations come into force; b the Medicines (Products for Human Use – Fees ) Regulations 1995 continue to apply as if they had not been revoked to any periodic fee payable in relation to a fee period ending before the date on which these Regulations come into force; c paragraph (1) does not affect any proceedings constituted under the revoked Regulations for the recovery of any fees due as debts to the Crown. 3 For the purpose of this regulation “ capital fee ” and “ periodic fee ” have the same meaning as is given in the Medicines (Products for Human Use – Fees ) Regulations 1995. Signed by authority of the Secretary of State for Health. Dawn Primarolo Minister for Health, Department of Health 27th February 2008 Michael McGimpsey Minister for Health, Social Services and Public Safety 27th February 2008 Michelle Gildernew Minister for Agriculture and Rural Development 28th February 2008 Alan Campbell Steve McCabe Two of the Lords Commissioners of Her Majesty’s Treasury 26th February 2008