United Kingdom Veterinary Medicines Directorate Woodham Lane New Haw Addlestone Surrey KT15 3LS DECENTRALISED PROCEDURE

Transcription

1 United Kingdom Veterinary Medicines Directorate Woodham Lane New Haw Addlestone Surrey KT15 3LS DECENTRALISED PROCEDURE PUBLICLY AVAILABLE ASSESSMENT REPORT FOR A VETERINARY MEDICINAL PRODUCT Forthyron 600 Microgram Tablets for Dogs 1/10

2 MODULE 1 PRODUCT SUMMARY EU Procedure number Name, strength and pharmaceutical form Applicant Active substance(s) ATC Vetcode Target species Indication for use Forthyron 600 Microgram Tablets for Dogs Handelsweg 25, 5531 AE Bladel The Netherlands Levothyroxine (as levothyroxine sodium) QH03AA01 Dogs For the treatment of hypothyroidism in dogs. 2/10

3 MODULE 2 The Summary of Product Characteristics (SPC) for this product is available on the Heads of Medicines Agencies (veterinary) (HMA(v)) website ( 3/10

4 MODULE 3 PUBLIC ASSESSMENT REPORT Legal basis of original application Date of completion of the original decentralised procedure Date product first authorised in the Reference Member State (MRP only) Concerned Member States for original procedure Application in accordance with Article 13 (3) of Directive 2001/82/EC as amended. 26 October 2011 N/A Austria Belgium Denmark France Germany Ireland Luxembourg The Netherlands Poland Sweden 4/10

5 I. SCIENTIFIC OVERVIEW These products are indicated for use in dogs for the treatment of hypothyroidism. These products contain levothyroxine (as levothyroxine sodium) as an active substance. The recommended starting dosage of levothyroxine sodium is 10 µg/kg bodyweight orally after 12 hours. The dosage may require alterations due to variability in absorption and metabolism before a complete clinical response is observed. The absorption of levothyroxine sodium may be affected by the presence of food in dogs. Therefore, the timing of treatment and its relation to feeding should be kept consistent from day to day. These applications were submitted in accordance with Article 13 (3) of Directive 2001/82/EC as amended hybrid products. The applicant cross-referred to Forthyron 200 µg tablets as the reference product. The reference product has been authorised in the EU since A product containing the active substance levothyroxine has been marketed by Eurovet Animal Health in The Netherlands since March Appropriate studies were performed in support of the bioequivalence claim. The products are produced and controlled using validated methods and tests, which ensure the consistency of the products released on the market. It has been shown that the products can be safely used in the target species; the slight reactions observed are indicated in the SPC 1. The products are safe for the user, and for the environment, when used as recommended. Suitable warnings and precautions are indicated in the SPC. The efficacy of each product was demonstrated according to the claims made in the SPC. II. QUALITY ASPECTS A. Composition Forthyron 600 Microgram Tablets for Dogs The product contains 600 microgram levothyroxine sodium per tablet equivalent to 583 microgram levothyroxine and calcium hydrogen phosphate dihydrate, microcrystalline cellulose, sodium starch glycolate (type A) and magnesium stearate as excipients. The product is supplied in cartons of 50 or 250 tablets presented in aluminium foil and a white opaque PVC/PE/PVDC foil blister each containing 10 tablets. The product contains 800 microgram levothyroxine sodium per tablet equivalent to 778 microgram levothyroxine and calcium hydrogen phosphate dihydrate, microcrystalline cellulose, sodium starch glycolate (type A) and magnesium stearate as excipients. The product is supplied in cartons of 50 or 250 tablets 1 Summary of product characteristics 5/10

6 presented in aluminium foil and a white opaque PVC/PE/PVDC foil blister each containing 10 tablets. The particulars of the containers and controls performed are provided and conform to the regulation. The choice of the formulation is justified. B. Method of Preparation of the Product The products are manufactured fully in accordance with the principles of good manufacturing practice from a licensed manufacturing site. Process validation data on the products have been presented in accordance with the relevant European guidelines. C. Control of Starting Materials The supporting data for levothyroxine have been provided in the form of EDQM 2 Certificates of Suitability (CEP). It is considered that the manufacturing process is adequately controlled and the active substance specifications have been suitably justified. There are four excipients used in the formulation and each has been used previously in veterinary medicines. All excipients have a monograph in the European Pharmacopoeia (Ph. Eur) and each complies with the requirements of the current edition of the Ph. Eur. D. Specific Measures concerning the Prevention of the Transmission of Animal Spongiform Encephalopathies There are no substances within the scope of the TSE Guideline present or used in the manufacture of this product. E. Control on intermediate products There are no intermediate products. F. Control Tests on the Finished Product The finished product specification controls the relevant parameters for the pharmaceutical form. The tests in the specification, and their limits, have been justified and are considered appropriate to adequately control the quality of the product. 2 The European Directorate for the Quality of Medicines & HealthCare. 6/10

7 Satisfactory validation data for the analytical methods have been provided. G. Stability Stability data on the active substances have been provided in accordance with applicable European guidelines, demonstrating the stability of the product throughout its shelf-life. The shelf-life of the veterinary medicinal product as packaged for sale is 2 years. H. Genetically Modified Organisms Not applicable. J. Other Information A shelf-life of 2 years and an in-use shelf life of 4 days is justified subject to the following storage precautions: Do not store above 25 C. Return any divided tablet to the opened blister and use within 4 days 7/10

8 III. SAFETY AND RESIDUES ASSESSMENT (PHARMACO- TOXICOLOGICAL) Since these are generic hybrid applications according to Article 13 (3), and bioequivalence with a reference product has been demonstrated, results of pharmacological and toxicological tests are not required. III.A Safety Testing Pharmacological Studies Since these are generic hybrid applications according to Article 13 (3), and bioequivalence with a reference product has been demonstrated, results of pharmacological tests are not required. Toxicological Studies Since these are generic hybrid applications according to Article 13 (3), and bioequivalence with a reference product has been demonstrated, results of toxicological tests are not required. User Safety A user risk assessment was provided. The following warnings and precautions as listed on the product literature are adequate to ensure safety to users of the product: Wash hands after administering the tablets. Pregnant women should handle the product with caution. In the case of accidental ingestion, seek medical advice immediately and show the package leaflet or the label to the physician. Note: this product contains a high concentration of L-thyroxine sodium and may present a risk to humans, in particular children, if ingested. Ecotoxicity The applicant provided a first phase environmental risk assessment in compliance with the relevant guideline which showed that no further assessment was required. The assessment concluded that no extensive exposure of the environment would occur due to use of the products, and this was acceptable Warnings and precautions as listed on the product literature are adequate to ensure safety to the environment when the product is used as directed. 8/10

9 IV CLINICAL ASSESSMENT (EFFICACY) As these are generic hybrid applications according to Article 13 (3), and bioequivalence with a reference product has been demonstrated, efficacy studies are not required. The efficacy claims for these products are equivalent to those of the reference products. Appropriate studies as indicated by the current bioequivalence guideline supported the claims for these products. These studies were acceptable for these applications. IV.A Pre-Clinical Studies Tolerance in the Target Species of Animals Since these are generic hybrid applications according to Article 13 (3), and bioequivalence with a reference product has been demonstrated, the applicant has not submitted any data on this section. This is considered acceptable. IV.B Clinical Studies Since these are generic hybrid applications according to Article 13 (3), and bioequivalence with a reference product has been demonstrated, the applicant has not submitted any data on this section. This is considered acceptable. V OVERALL CONCLUSION AND BENEFIT RISK ASSESSMENT The data submitted in the dossier demonstrate that when the product is used in accordance with the Summary of Product Characteristics, the benefit/risk profile for the target species is favourable and the quality and safety of the product for humans and the environment is acceptable. 9/10

10 MODULE 4 POST-AUTHORISATION ASSESSMENTS The SPC and package leaflet may be updated to include new information on the quality, safety and efficacy of the veterinary medicinal product. The current SPC is available on the Heads of Medicines Agencies (veterinary) (HMA(v)) website ( This section contains information on significant changes which have been made after the original procedure which are important for the quality, safety or efficacy of the product. None 10/10