79. Schedule 2 to the 2013 Regulations (manufacture of veterinary medicinal products) is amended in accordance with this Part.
80. For paragraph 1 (application) substitute—
1.—(1) No person may carry out any activity mentioned in sub-paragraph (2) otherwise than in accordance with an authorisation granted under this Schedule (a “manufacturing authorisation”).
(2) For the purposes of sub-paragraph (1) the activities are—
(a)the manufacture of veterinary medicinal products (whether for use in Great Britain or another country);
(b)the carrying out of any part of the manufacturing process or of bringing a veterinary medicinal product to its final state, including the processing, assembling, packaging or repackaging, labelling or relabelling, storing, sterilising or releasing for supply of a veterinary medicinal product;
(c)the importation of any veterinary medicinal product for use in Great Britain.”.
81. For paragraph 2 (time limits) substitute—
2.—(1) An application for a manufacturing authorisation must be submitted to the Secretary of State electronically and must include the matters mentioned in sub-paragraph (2).
(2) For the purposes of sub-paragraph (1) the matters are—
(a)the name of the person who will hold the manufacturing authorisation and that person’s address or registered place of business;
(b)the names and addresses of the sites (including any site where work is undertaken on behalf of the proposed holder under contract) where—
(i)each stage of the manufacturing process or of bringing a veterinary medicinal product to its final state, including processing, assembling, packaging or repackaging, labelling or relabelling, storing or sterilising, is carried out;
(ii)any imported products are held; or
(iii)any control or batch release is carried out;
(c)a description of the veterinary medicinal products or pharmaceutical forms proposed to be manufactured or imported under the authorisation;
(d)the name of the proposed qualified person (manufacture) for the purposes of paragraph 9;
(e)the name of the person proposed to have responsibility for quality control;
(f)the qualifications and a description of the relevant experience of the person proposed to have responsibility for quality control;
(g)the name of the person proposed to have responsibility for production;
(h)the qualifications and a description of the relevant experience of the person proposed to have responsibility for production;
(i)a declaration that the applicant complies with good manufacturing practice and any relevant legislation; and
(j)a declaration that any site mentioned in paragraph (b) is ready for inspection.”.
82. For paragraph 3 (granting the authorisation) substitute—
3.—(1) The Secretary of State must process an application mentioned in paragraph 2 within 90 days of validating the application.
(2) The Secretary of State must inspect the sites mentioned in paragraph 2(2)(b) within 90 days of validating the application.
(3) The Secretary of State must grant the manufacturing authorisation if satisfied, following the inspection mentioned in sub-paragraph (2), that—
(a)the sites are suitable for the intended purposes;
(b)the applicant has—
(i)suitable and sufficient staff, technical equipment and facilities for the proposed activities; and
(ii)a documented quality management system in place.
(4) Where the Secretary of State is not satisfied in relation to one or more of the matters mentioned in sub-paragraph (3), the Secretary of State may—
(a)reject the application; or
(b)grant a conditional manufacturing authorisation for a period specified by the Secretary of State until the deficiency has been addressed.
(5) The Secretary of State may extend the period for which a conditional manufacturing authorisation is granted under sub-paragraph (4)(b).
(6) Where a conditional manufacturing authorisation is granted under sub-paragraph (4)(b) and the deficiency is addressed within the specified period to the satisfaction of the Secretary of State, the authorisation continues to have effect without those conditions.”.
83. In paragraph 4(1) (authorisation)—
(a)in paragraph (a) after “be manufactured” insert “, controlled”;
(b)for paragraph (b) substitute—
“(b)the name and address of the site where the products are to be manufactured or controlled, or to which they are to be imported;”;
84. After paragraph 4 insert—
4A.—(1) The holder of a manufacturing authorisation must notify the Secretary of State, and apply for a variation of the authorisation, before—
(a)making a material alteration to the premises or facilities used under the authorisation, or to the operations for which they are used;
(b)changing the qualified person (manufacture), the person with responsibility for quality control or the person with responsibility for production.
(2) The Secretary of State must process an application under sub-paragraph (1) within 30 days of receiving it unless the Secretary of State notifies the applicant in writing that the time has been extended to 90 days.
(3) The Secretary of State must grant the application under sub-paragraph (1) if satisfied in respect of the matters in paragraph 3(3) as regards the proposed variation.
(4) The Secretary of State may inspect any site to which the manufacturing authorisation or proposed variation relates in connection with the application.
(5) Where the Secretary of State is not satisfied for the purposes of sub-paragraph (3), the Secretary of State may—
(a)reject the application; or
(b)grant a conditional variation to the manufacturing authorisation for a period specified by the Secretary of State until the deficiency has been addressed.
(6) The Secretary of State may extend the period for which a conditional variation to the marketing authorisation is granted under sub-paragraph (5)(b).
(7) Where a conditional variation to the manufacturing authorisation is granted under sub-paragraph (5)(b) and the deficiency is addressed within the specified period to the satisfaction of the Secretary of State, the authorisation continues to have effect as so varied without those conditions.”.
85. In paragraph 5 (suspension, variation or revocation of authorisation)—
(a)in sub-paragraph (1)—
(i)after paragraph (c) omit “or”;
(ii)at the end insert—
“(e)has failed to carry out the activity specified in the authorisation for a period of five years or more; or
(f)has not paid any fee required under these Regulations”;
(b)for sub-paragraph (2) substitute—
“(2) The Secretary of State may also suspend, vary or revoke the authorisation on being satisfied that the qualified person (manufacture), the person responsible for quality control or the person with responsibility for production is not fulfilling that person’s duties under these Regulations.
(3) In particular, the Secretary of State may—
(a)suspend the manufacture or import of veterinary medicinal products;
(b)suspend, revoke or vary the manufacturing authorisation for one or more pharmaceutical forms;
(c)suspend, revoke or vary the manufacturing authorisation for one or more activities in one or more manufacturing sites.”;
(c)in the heading for “Suspension, variation or revocation” substitute “Suspension, revocation etc”.
86. In paragraph 6 (inspection of premises)—
(a)in sub-paragraph (1)—
(i)for “premises” (in the first and the third place it appears) substitute “sites”;
(ii)for “registered” substitute “authorised”;
(iii)for “premises’ history” substitute “site’s history”;
(b)for sub-paragraph (2) substitute—
“(2) Within 90 days after an inspection, the Secretary of State must issue a certificate of good manufacturing practice to the manufacturer if the inspection establishes that the manufacturer has complied with the requirements of these Regulations in respect of the site to which the inspection relates.
(2A) Where the Secretary of State does not consider that compliance is established after inspection in accordance with sub-paragraph (2), the Secretary of State must enter that fact in the register mentioned in paragraph 12(a).
(2B) The Secretary of State may carry out an inspection on a site occupied by a manufacturer established in a country other than the United Kingdom notwithstanding any arrangements that may have been entered into between the United Kingdom and that country.
(2C) The importer of a veterinary medicinal product must ensure before importation that the manufacturer of that product has—
(a)a valid certificate of good manufacturing practice issued by the Secretary of State; or
(b)an equivalent certificate issued by a regulatory authority—
(i)with which the Secretary of State has an agreement or arrangement for such purposes; or
(ii)which the Secretary of State considers to have demonstrated equivalent standards to those in the United Kingdom.”;
(c)for the heading substitute “Good manufacturing practice certificates and inspection of sites”.
87. In paragraph 8 (duties on holder of manufacturing authorisation)—
(a)for sub-paragraph (2) substitute—
“(2) The holder must have permanently at the holder’s disposal the services of—
(a)staff complying with any legal requirements in relation to manufacture of veterinary medicinal products; and
(b)at least one qualified person (manufacture).
(2A) The holder must place at the disposal of any qualified person (manufacture) all necessary documents, premises and technical and other facilities in order to enable that person to discharge their duties as the qualified person.
(2B) Where any qualified person (manufacture) ceases to be available to provide services to the holder, the holder must give notice of the fact to the Secretary of State—
(a)at least 30 days in advance of the person’s ceasing to be so available; or
(b)where such notice is not possible, at the earliest opportunity.”;
(b)for sub-paragraph (3) substitute—
“(3) The holder must—
(a)comply with good manufacturing practice and have a valid certificate of good manufacturing practice;
(b)use as starting materials only active substances which have been manufactured in accordance with good manufacturing practice and distributed in accordance with good distribution practice for active substances;
(c)verify that each manufacturer, distributor or importer from whom the holder obtains active substances and to which paragraph 26 applies is registered with the Secretary of State under that paragraph;
(d)carry out audits based on a risk assessment in relation to the manufacturers, distributors and importers from which the holder obtains active substances;
(e)have in place a system of quality assurance and quality control; and
(f)give to the Secretary of State, on request, proof of any control test specified by the Secretary of State which has been carried out on the veterinary medicinal product or the constituents and intermediate products of the manufacturing process in accordance with the data submitted in support of the application for the marketing authorisation.
(3A) The holder of a manufacturing authorisation must inform the Secretary of State and the holder of any relevant marketing authorisation where the holder obtains information that veterinary medicinal products which fall within the scope of its manufacturing authorisation are falsified, or are suspected of being falsified, irrespective of whether those products were distributed within the legal supply chain or by illegal means.”;
(c)after sub-paragraph (5) insert—
“(6) A holder must keep detailed records of all veterinary medicinal products which the holder supplies.”.
88. After paragraph 8 insert—
8A.—(1) A holder of a manufacturing authorisation must ensure that the veterinary medicinal product is manufactured in accordance with this paragraph, whether the manufacturing is performed by the holder or another person.
(2) The manufacturing operations must be conducted in accordance with a written methodology, to be known as the “pharmaceutical quality system” or “PQS”.
(3) The PQS must be—
(a)clear;
(b)systematically reviewed from time to time in the light of experience; and
(c)capable of consistently manufacturing veterinary medicinal products which are of the required quality and which meet the requirements of the relevant marketing authorisation.
(4) The critical steps of the manufacturing process set out in the PQS must be validated.
(5) Any significant amendments to the PQS must be validated.
(6) The PQS must provide for—
(a)appropriately qualified and trained personnel;
(b)adequate premises and space;
(c)suitable equipment and access to services;
(d)suitable materials, containers and labelling;
(e)relevant procedures and instructions;
(f)suitable storage and transport;
(g)investigation into complaints and defects.
(7) The PQS must provide for any significant deviations from its provisions to be—
(a)fully recorded, and
(b)investigated, with appropriate corrective and preventative action implemented.
(8) The holder of a manufacturing authorisation must ensure that records of the manufacturing process, including distribution, are kept in a comprehensible and accessible form until the later of—
(a)the date which is five years after the date on which the veterinary medicinal product is placed on the market;
(b)the date which is one year after the expiry date of the batch of veterinary medicinal product.
(9) In this paragraph, a process (or part of a process) is “validated” if scientific evidence is assembled which demonstrates that it is capable of consistently delivering expected results.
8B.—(1) The holder of a manufacturing authorisation must comply with any requirement by the Secretary of State to recall a veterinary medicinal product and must record the details of the recall operation.
(2) The holder of a manufacturing authorisation must record any veterinary medicinal product which is—
(a)recalled (whether or not the holder physically receives the recalled product); or
(b)discovered to be counterfeit.
(3) Where any veterinary medicinal product is recalled and physically received, the qualified person (manufacture) must assess the recalled product in order to determine whether—
(a)the product has been stored (including during transport) in accordance with the summary of product characteristics;
(b)the product is a genuine product and not counterfeit.
(4) Where the qualified person (manufacture) determines that a recalled veterinary medicinal product does not satisfy sub-paragraph (3)(a) or (b), or where it is not possible for the qualified person (manufacture) to determine whether the product does so, the product may not be re-sold.
(5) The qualified person (manufacture) must record any assessment and determination made under sub-paragraphs (3) and (4).
(6) Any veterinary medicinal products which may not be re-sold must be identified, held separately and destroyed and the holder of a manufacturing authorisation must develop a suitable procedure to set out the steps to be taken in accordance with this sub-paragraph.
(7) The holder of a manufacturing authorisation must keep any information recorded under this paragraph for five years.”.
89. In paragraph 9 (qualified person for manufacture)—
(a)in sub-paragraph (1), after “any person” insert “(including the manufacturer of a veterinary medicinal product)”;
(b)after sub-paragraph (1) insert—
“(1A) For the purposes of sub-paragraph (1), a person has sufficient practical experience if they have been engaged in one or more of the activities mentioned in sub-paragraph (1B) for at least two years in the provision of services to the holder of a manufacturing authorisation.
(1B) For the purposes of sub-paragraph (1A) the activities are—
(a)quality assurance of medicinal products;
(b)qualitative analysis of medicinal products;
(c)quantitative analysis of active substances.
(1C) The Secretary of State may treat the reference in sub-paragraph (1A) to two years of practical experience as a reference to—
(a)one year, where the person’s formal course of study lasted for at least five years;
(b)six months, where the person’s formal course of study lasted for at least six years.”.
90. In paragraph 10 (refusal or revocation of appointment)—
(a)for “or revoke” substitute “, revoke, suspend or vary”;
(b)for the heading substitute—
91. In paragraph 13 (test sites)—
(a)in sub-paragraph (1) for “premises” substitute “a site”;
(b)in sub-paragraph (2) for “premises” substitute “site”;
(c)after sub-paragraph (2) insert—
“(2A) The site must be specified in an existing manufacturing authorisation.”;
(d)in sub-paragraph (3) for “Authorisation and inspection of the premises are” substitute “Inspection of the site is”.
92. For Parts 2 to 5 substitute—
14.—(1) The Secretary of State may authorise a person to—
(a)manufacture—
(i)autogenous vaccines; or
(ii)an unauthorised veterinary medicinal product for administration under the cascade;
(b)collect, store and supply blood in connection with the treatment of non-food animals;
(c)collect, store and supply blood constituents obtained by the physical separation of donor blood into different fractions within a closed bag system, for the treatment of non-food animals; or
(d)collect, process and store stem cells for use as an autologous treatment in non-food animals,
and may authorise sites for the purpose of carrying out those activities by that person.
(2) A single authorisation under sub-paragraph (1) may confer permission to carry out the activities mentioned in both paragraph (b) and (c) of that sub-paragraph.
(3) In this paragraph, a “closed bag system” means a system in which the blood pack assembly is manufactured under clean conditions, sealed to the external environment and sterilised.
15. No person may carry out any activity mentioned in paragraph 14 otherwise than—
(a)in accordance with an authorisation mentioned in that paragraph; or
(b)pursuant to paragraph 1(2) of Schedule 4 (administration under the cascade).
16. In order to be authorised the site mentioned in paragraph 14(1) must be under the supervision of a named person responsible for release (a “PRR”) who in the opinion of the Secretary of State has sufficient qualifications and experience to manufacture the product safely.
17.—(1) An applicant for authorisation under paragraph 14 must, at least two months before commencing an activity mentioned in that paragraph, submit the following to the Secretary of State—
(a)the name and address of the proposed holder of the authorisation;
(b)a description of the activity in which the applicant for authorisation proposes to be engaged;
(c)particulars (including the name and address) in relation to the site at which the relevant activity is to be carried out (whether in the occupation of the proposed holder or otherwise) and a description of the technical equipment on the site;
(d)particulars in relation to the qualifications and experience of the proposed PRR who will supervise the activities at the site.
(2) The application must include a declaration that the applicant will comply with the requirements of these Regulations and confirmation that the site is ready for inspection.
(3) Before granting an authorisation in relation to a site, the Secretary of State must be satisfied that the production process carried out there will produce a consistent, safe product and, in the case of a blood bank or a stem cell centre, that the welfare of the animals involved in the processes will be respected.
18.—(1) No person may collect blood for the purposes of a non-food animal blood bank other than a veterinary surgeon or a person acting under the responsibility of a veterinary surgeon.
(2) The holder of an authorisation to carry out an activity under paragraph 14(1)(b) or (c) may only supply blood or blood constituents to a veterinary surgeon.
(3) No person other than a veterinary surgeon or someone acting under a veterinary surgeon’s responsibility may administer blood to a non-food producing animal.
(4) No person may administer blood to a food-producing animal.
19.—(1) No person may collect stem cells for the purposes of treating animals other than a veterinary surgeon or a person acting under the responsibility of a veterinary surgeon.
(2) No person may collect stem cells from embryonic tissues.
(3) No person may administer any product grown from stem cells to a food-producing animal.
20.—(1) Subject to sub-paragraph (2), no person may manufacture a product for administration under the cascade that is the pharmaceutical equivalent of an authorised veterinary medicinal product.
(2) The Secretary of State may authorise the manufacture of a product notwithstanding sub-paragraph (1) where there is difficulty in relation to the supply of the authorised veterinary medicinal product.
(3) The holder of an authorisation under paragraph 14(1)(a)(ii) may not supply a product manufactured in accordance with that sub-paragraph other than to a veterinary surgeon who has prescribed the product under the cascade.
(4) The holder of an authorisation under paragraph 14(1)(a)(ii) must—
(a)provide a list of products manufactured in accordance with that sub-paragraph to the Secretary of State annually or at the request of the Secretary of State;
(b)provide sales data for products supplied under sub-paragraph (3) at the request of the Secretary of State.
(5) For the purposes of this paragraph, a product is the pharmaceutical equivalent of an authorised veterinary medicinal product if—
(a)it has the same qualitative and quantitative composition in active substances; and
(b)it has the same pharmaceutical form.
21. The Secretary of State may by notice suspend, vary or revoke an authorisation under paragraph 14 if the Secretary of State is satisfied that—
(a)the holder of the authorisation no longer uses fit and proper processes;
(b)the site at which the activity takes place is not suitable;
(c)the equipment is not suitable;
(d)the PRR has not carried out adequately the PRR’s responsibilities under these Regulations;
(e)in the case of a person authorised under paragraph 14(1), that person has manufactured a veterinary medicinal product pursuant to that authorisation that is not within its scope;
(f)the holder has not conducted an activity relating to the authorisation for five years or more;
(g)the holder has not paid any fee required under these Regulations; or
(h)the holder has not complied with any other provision in these Regulations.
22.—(1) The holder of an authorisation under paragraph 14 must ensure that every container used is labelled with—
(a)a precise description of the product;
(b)the date on which the product was produced;
(c)the name and address of the authorisation holder;
(d)the address of the site named under the authorisation and its authorisation number;
(e)the instructions for use;
(f)the expiry date;
(g)any necessary warnings;
(h)in the case of an autogenous vaccine or an unauthorised veterinary medicinal product for administration under the cascade, the name of the veterinary surgeon who ordered the product;
(i)in the case of blood or a stem cell product—
(i)the identification of the donor animal; and
(ii)the date of collection.
(2) In the case of blood or blood constituents there must be no specific therapeutic indication on the label or on any information related to the product.
(3) In the case of an unauthorised veterinary medicinal product for administration under the cascade the words “this veterinary medicinal product does not hold a marketing authorisation” must appear on the label.
23. The holder of an authorisation under paragraph 14 must, as soon as is reasonably practicable after the product is supplied, in addition to the expiry date of the product, record the following—
(a)in the case of an unauthorised veterinary medicinal product for administration under the cascade—
(i)the name and address of the veterinary surgeon who ordered the veterinary medicinal product;
(ii)a precise description of the product;
(iii)the date of production;
(iv)the date of supply to the veterinary surgeon;
(b)in the case of stem cells or blood—
(i)the identification of the source animal;
(ii)the name of the veterinary surgeon who collected the product (or under whose responsibility it was collected);
(iii)the date of collection of the product;
(iv)the date that the product was used or if the product was supplied to another veterinary surgeon, the name and address of that veterinary surgeon and the date the product was supplied;
(c)in the case of an autogenous vaccine—
(i)the name and address of the veterinary surgeon who ordered the vaccine;
(ii)the identification of the source animal;
(iii)the date of supply to the veterinary surgeon,
and must keep the records for at least five years.
24. The holder of an authorisation under paragraph 14 must notify the Secretary of State of any adverse event in relation to a product produced by that person under that authorisation within 30 days of learning of the event.
25. The Secretary of State must inspect any site authorised under paragraph 14, basing the frequency of the inspection on the risks associated with each site’s history and the nature of the products handled at the site.”.
93. After Part 2 (as substituted by the previous regulation) insert—
26.—(1) No person may manufacture, import or distribute an active substance unless the person is registered in the register maintained under sub-paragraph (2).
(2) The Secretary of State must establish and maintain a register of manufacturers, importers and distributors of active substances and the sites occupied by them for the purposes of manufacturing or holding active substances.
27.—(1) An applicant for registration under paragraph 26 must, at least two months before commencing an activity mentioned in paragraph 26(1) or, in the case of an existing manufacturer, within two months of the date on which this provision comes into force, submit the following to the Secretary of State—
(a)the name and address of the proposed registration holder;
(b)the name of the relevant active substance;
(c)a description of the activity proposed to be engaged in in relation to the relevant active substance; and
(d)particulars in relation to the site at which the relevant active substance is to be manufactured or held (as the case may be).
(2) Information may be submitted to the Secretary of State pursuant to sub-paragraph (1) prior to the date on which this provision comes into force, and in such a case—
(a)as regards an applicant for registration who is not an existing manufacturer, the relevant period of two months is to be treated as having started on the date of submission;
(b)as regards an applicant for registration who is an existing manufacturer, the information is to be treated as having been submitted within the relevant period of two months.
28. A manufacturer, importer or distributor of active substances must comply with good manufacturing practice or good distribution practice, as applicable.
29.—(1) A person registered under paragraph 26 must immediately inform the Secretary of State on receipt of any new information that might adversely affect the quality and safety of the active substance.
(2) A person registered under paragraph 26 must immediately inform the Secretary of State of any prohibition or restriction in relation to the active substance imposed by the competent authorities of any country other than the United Kingdom in which the active substance is authorised.
30. The Secretary of State may, from time to time, inspect sites registered under paragraph 26, basing the frequency of the inspections on the risks associated with each site’s history and the nature of the substances handled at the site.
31.—(1) After each inspection of a site for the purposes of this Part, the inspector must make a written report to the Secretary of State on whether the requirements in this Part are being complied with.
(2) The Secretary of State must inform the inspected registered person of the content of such reports.
32. It is an offence to fail to comply with—
(a)paragraph 1;
(b)paragraph 4(3);
(c)paragraph 8;
(d)paragraph 11;
(e)paragraph 15;
(f)paragraph 18;
(g)paragraph 19;
(h)paragraph 20(1), (3) or (4);
(i)paragraph 22;
(j)paragraph 23;
(k)paragraph 24;
(l)paragraph 26;
(m)paragraph 28;
(n)paragraph 29.”.