Public Assessment Report. Scientific discussion. True Test 24 Plaster for provocation test DK/H/0832/002/DC. 4 November 2015

Transcription

1 Public Assessment Report Scientific discussion True Test 24 Plaster for provocation test DK/H/0832/002/DC 4 November 2015 This module reflects the scientific discussion for the approval of True Test 24. The procedure was finalised on 18 November For information on changes after this date please refer to the module Update.

2 I. INTRODUCTION Based on the review of the quality, safety and efficacy data, the Member States have granted a marketing authorisation for True Test 24, plaster for provocation test, from SmartPractice Denmark ApS. The product is indicated for diagnosis of allergic contact dermatitis. A comprehensive description of the indications and posology is given in the SmPC. True Test 24 consists of two self-adhesive plasters for provocation test. True Test 24 is used for diagnosis of allergic contact dermatitis and contains 24 different allergens with 12 allergens incorporated into each of the two plasters. Traditionally diagnosis of contact dermatitis used the same allergens in petrolatum applied with the Finn Chamber technique. Comparative clinical trials have demonstrated that the sensitivity and specificity of the True Test 24 is comparable with the gold standard Finn Chambers method. A positive response to the patch test is a classical delayed hypersensitivity reaction (type IV), which can appear within 6-96 hours after exposure. The cell-mediated response involves the Langerhans' cell and T-lymphocytes, which interact and produce lymphokines. These lymphokines then form lymphocyte clones with trigger macrophages to cause a cutaneous inflammation. Clinical signs of a positive contact dermatitis reaction are: erythema, oedema papules, vesicles and a palpable dermal inflammatory infiltrate at the test area. This application for a marketing authorisation, via the decentralised procedure with Denmark as Reference Member State (RMS), concerns an extension application (new composition, new strength) of the existing marketing authorisation: True Test, plaster for provocation test (DK/H/0832/001). II. QUALITY ASPECTS II.1 Introduction True Test 24 is a plaster for provocation test. True Test 24 consists of 2 panels of surgical plaster each with 12 patches. Each patch is coated with a film containing the test substance. The test substances (active substances) are as follows: Active substance microgram/cm 2 microgram/patch Panel 1 1. Nickel sulphate Wool alcohols Neomycin sulphate Potassium dichromate Caine mix a) Fragrance mix b) Colophony Paraben mix c) Quinoline mix d) Balsam of Peru Ethylenediamine dihydrochloride Cobalt chloride 20 16

3 Panel p-tert Butylphenol formaldehyde resin Epoxy resin Carba mix e) Black rubber mix f) Cl+Me-Isothiazolinone Quaternium Mercaptobenzothiazole p-phenylenediamine Formaldehyde g) Mercapto mix h) Thiomersal Thiuram mix i) a) Five parts of benzocaine, one part of cinchocaine hydrochloride and tetracaine hydrochloride. b) Five parts of geraniol and oak moss, four parts of hydroxycitronellal and cinnamylalcohol, two parts of cinnamaldehyde and eugenol and one part of isoeugenol and α-amylcinnamaldehyde. c) Equal weights of methyl parahydroxybenzoate, ethyl parahydroxybenzoate propyl parahydroxybenzoate, butyl parahydroxybenzoate and benzyl parahydroxybenzoate. d) Equal weights of clioquinol and chlorquinaldol. e) Equal weights of diphenylguanidine, zincdiethyldithiocarbamate and zincdibutyldithiocarbamate. f) Two parts of N-isopropyl-N -phenyl paraphenylenediamine, five parts of N-cyclohexyl-N -phenyl paraphenylenediamine and five parts of N,N -diphenyl paraphenylenediamine. g) Actually contains N-hydroxymethyl succinimide. h) Equal weights of morpholinylmercaptobenzothiazole, N-cyclohexylbenzothiazylsulphenamide and dibenzothiazyl disulphide. i) Equal weights of disulfiram, dipentamethylenethiuram disulphide, tetramethylthiuram disulphide and tetramethylthiuram monosulphide. Besides the active substances, stated above, the test contains the following excipients: Plaster of cellulose acetate with acrylic adhesive; polyester patches; povidone 90; hydroxypropyl cellulose; methyl cellulose; ß-cyclodextrin; sodium carbonate; sodium bicarbonate; butylhydroxyanisole and butylhydroxytoluene. Each panel is covered by a protective sheet of silicone-treated polyethylene and then packed in airtight pouches of packaging laminate. For stabilization purposes, panel 2 contains a desiccant paper. True Test 24 is provided in a carton box with 1 test unit or 10 test units. 1 unit consists of one panel 1, one panel 2 and a reading template. The RMS has been assured that acceptable standards of GMP (see Directive 2003/94/EC) are in place for this product type at all sites responsible for the manufacturing of the active substance as well as for the manufacturing and assembly of this product prior to granting its national authorisation. II.2 Drug Substance In this extension application, no new information concerning the drug substances is provided. Reference is made to the procedure for True Test, DK/H/0832/001/DC. II.3 Medicinal Product The changes made to the formulation compared to the currently approved formulation for True Test (DK/H/0832/001/DC) has been acceptably described and justified by development studies. The proposed plaster for provocation test includes 24 patches, which include a total of 47 active substances. Seven of the twenty four patches have been changed compared to the currently approved patch True Test (DK/H/0832/001/DC). The changes consist of formulation changes, switch in the

4 position of patches and changes to the strengths and label claim (for analytical reasons and clinical reasons). Validation reports supporting the composition changes to the allergen patches are provided and acceptable justifications have been provided for the revised strengths. Acceptable stability data is presented to support the changes. A shelf-life of 2 years with the storage condition store in refrigerator (2ºC - 8ºC) has been justified. III. NON-CLINICAL ASPECTS III.1 Introduction No new nonclinical studies have been performed, and no literature references have been supplied in support of this line extension application. SmartPractice Denmark ApS has made the following justification for not submitting any non-clinical documentation in support of the application: The product is considered to be a product of well-established use and no new active substances are introduced with this extension application, which include changes (e.g. excipient, analytical method, strength) to certain already approved allergens. The excipients used in the product are well known substances in regard to patch testing and have been selected to enhance the dispersion of the allergen within the gel, its stability and the delivery of the allergen to the skin. In this application SmartPractice Denmark apply for a change of formulation for four allergens (neomycin sulphate, potassium dichromate, colophony and thiomersal). For all four allergens the gelforming agent is changed to povidone, which is a well-known excipient. Because the basic absorption and penetration mechanism for contact allergens is well understood, additional studies revealing the specific kinetics of the changed allergens applied for with this application were not considered necessary and no additional animal studies have been conducted for this application. Based on the argumentation above module 4 is not considered relevant for this extension application. The lack of any new non-clinical parts in the current line extension application is accepted, as the change sought for approval is to change the gel-forming agent for four allergens (listed above) to the wellknown excipient povidone. III.2 Ecotoxicity/environmental risk assessment (ERA) Since True Test 24 is intended to replace the current product of True Test, this will not lead to an increased exposure to the environment. An environmental risk assessment is therefore not deemed necessary. IV. CLINICAL ASPECTS IV.1 Introduction True Test is a well-known product used by dermatologists for diagnosis of allergic contact dermatitis.

5 True Test contains a number of common allergens known to be clinical relevant for eliciting contact allergy. With this application, the MAH seeks approval of a modified version of True Test optimizing the allergen strength of neomycin sulphate, potassium dichromate, colophony and thiomersal. Clinical testing of these modified new allergens have shown efficacy and safety comparable to existing allergens and may be approved. In addition a quality update has been performed for p-tert-butylphenol Formaldehyd Resin, black rubber mix, Thiuram mix and Cl+Me-Isothiazolinone. The quality changes is well founded and is not expected to change the responsiveness of these allergens and have therefore been approved. IV.2 Risk Management Plan The MAH has submitted a risk management plan, in accordance with the requirements of Directive 2001/83/EC as amended, describing the pharmacovigilance activities and interventions designed to identify, characterise, prevent or minimise risks relating to True Test 24. The following summary of safety concerns with no additional risk minimisation measures has been agreed: Table 1. Summary table of safety concerns as approved in RMP V. USER CONSULTATION A user consultation with target patient groups on the package information leaflet (PIL) has been performed on the basis of a bridging report making reference to True Test, DK/H/0/832/001/DC. The bridging report submitted by the applicant has been found acceptable. VI. OVERALL CONCLUSION, BENEFIT/RISK ASSESSMENT AND RECOMMENDATION True Test 24, plaster for provocation test has a proven chemical-pharmaceutical quality and is an extension of True Test. True Test is a well-known medicinal product with an established favourable efficacy and safety profile. The MAH has provided written confirmation that systems and services are in place to ensure compliance with their pharmacovigilance obligations. A Risk Management Plan has been presented.

6 Agreement between Member States was reached during a written procedure. There was no discussion in the CMD(h). The Concerned Member States, on the basis of the data submitted, considered that essential similarity has been demonstrated for True Test 24, plaster for provocation test with the reference product, and have therefore granted a marketing authorisation. The decentralised procedure was finalised on 18 November True Test 24 was authorised in Denmark on 18 December At present, no PSURs are required for this product. The date for the first renewal will be: 18 November There were no post-approval commitments made during the procedure.

7 Public Assessment Report Update True Test 24 Plaster for provocation test This module reflects the procedural steps and scientific information after the finalisation of the initial procedure.

8 Scope Procedure number Product Information affected Repeat use with CZ, DE, ES, FR, IT, NL, SK, UK Date of start of the procedure Date of end of procedure Approval/ non approval Assessment report attached DK/H/0832/002/E/001 N 11 February May 2016 Approval Y, Annex 1

9 ANNEX 1 Repeat use procedure (DK/H/0832/002/E/001) The repeat use procedure started on 11 February There was no discussion in the CMD(h). Agreement between member states was reached during a written procedure. The concerned member states CZ, DE, ES, FR, IT, NL, SK and UK on the basis of the data submitted, considered that sufficient documentation was provided, and therefore granted a marketing authorisation. The repeat use procedure was finalised on 11 May The MAH provided an updated dossier. No variations were filed prior to the repeat use procedure. The common renewal date is based on the date of End of Procedure, i.e. End of Procedure + 5 years for the First Use procedure, (18 November 2019). Commitments made during the repeat use procedure: Quality The applicant will submit a consolidated QOS (Quality Overall Summary) immediately after the end of the procedure, before the end of May Reference should be made to FUM case Id on submission. Clinical modules Update to include reaction index (RI) and positivity ratio (PR) data for each antigen in the dossier, including a discussion and integration of the conclusions into the overall benefit risk assessment in Module 2.5. Reference will be made to FUM case Id on submission. The Follow-Up Measure will be submitted no later than 3 months after EoP. Clinical, SmPC og RMP A marketing authorisation is recommended subject to a variation application being submitted no later than 3 months following the end of this MR procedure, to address the following: The applicant will submit following variations in order to update the SmPC, PIL, labelling and RMP as requested be the CMS during the RUP. A type II variation for update of SPC, PIL and labelling. For the RMP two variations will be submitted; Type II variation under category C.I.z (Changes to the product information resulting from comments of the new CMS during a repeat use procedure should be applied for in one single Type II variation under category C.I.z) Type II C.I.11 b) (New data will be included/specified in the RMP as requested) These variations will be submitted within 3 months after EoP.