UKPAR Goodnight THR 00904/0003. Goodnight THR 00904/0003 UKPAR TABLE OF CONTENTS. Lay Summary Page 2. Scientific discussion Page 3

Transcription

1 Goodnight THR 00904/0003 UKPAR TABLE OF CONTENTS Lay Summary Page 2 Scientific discussion Page 3 Steps taken for assessment Page 12 Steps taken after authorisation Page 13 Summary of Product Characteristics Page 14 Product Information Leaflets Page 18 Labelling Page 22 1

2 Goodnight THR 00904/0003 LAY SUMMARY On 16 th November 2010, the Medicines and Healthcare products Regulatory Agency (MHRA) granted Kerbina Limited (trading as Bio-Health) a Traditional Herbal Registration Certificate for the traditional herbal medicinal product, Goodnight (Traditional Herbal Registration number: THR 00904/0003). This is a medicine available on the General Sales List (GSL), and can be purchased at pharmacies and other retail outlets without the supervision of a pharmacist. Goodnight is a traditional herbal medicinal product used for the temporary relief of sleep disturbances based on traditional use only. Each tablet of Goodnight contains the stated quantities of the following active herbal ingredients (botanical names are given in brackets): 60mg Verbena herb (Verbena officinalis L.) 30mg Hops strobiles (Humulus lupulus L.) 36mg extract from Valerian root (Valeriana officinalis L) (5:1) 30mg extract from Passion flower herb (Passiflora incarnata L) (3:1) 18mg extract from Wild lettuce herb (Lactuca virosa L) (5:1) This registration is based exclusively upon evidence of the use of Verbena herb, Hops strobiles, Valerian root, Passion flower herb and Wild lettuce herb as traditional herbal medicines and not upon data generated from clinical trials. There is no requirement under the Traditional Herbal Registration scheme to prove scientifically that the product works. No new or unexpected safety concerns arose from this application and it was, therefore, decided that a Traditional Herbal Registration Certificate could be granted. 2

3 Goodnight THR 00904/0003 SCIENTIFIC DISCUSSION TABLE OF CONTENTS Introduction Page 4 Pharmaceutical assessment Page 5 Non-clinical assessment Page 9 Clinical assessment Page 10 Overall conclusion and risk assessment Page 11 3

4 INTRODUCTION The MHRA granted Kerbina Limited (trading as Bio-Health) a Traditional Herbal Registration Certificate for the traditional herbal medicinal product, Goodnight (Traditional Herbal Registration number: THR 00904/0003), on 16 th November This is a medicine available on the General Sales List (GSL). A product licence of right (PLR) was granted to Kerbina Limited (trading as Bio- Health) for this product (PL 00904/5060R) in The PLR was reviewed and a product licence was granted on 17 th March The PL 00904/5060 will be cancelled after the THR is granted. This THR application was made under Article 16.c of Directive 2001/83 EC in accordance with arrangements to transfer certain herbal products with a marketing authorisation (product licence) to a THR (according to MHRA Guidance dated January 2009). The application falls within the simplified THR application Category A as no changes have been made to the formulation of the product. No new data were submitted, nor was it necessary for this application, as the data are essentially identical to those of the existing product. Goodnight is a traditional herbal medicinal product used for the temporary relief of sleep disturbances based on traditional use only. The product contains 5 herbal ingredients. Each coated tablet contains: 60mg Verbena herb (Verbena officinalis L.) 30mg Hops strobiles (Humulus lupulus L.) 36mg of extract (as dry extract) from Valerian root (Valeriana officinalis L.) (5:1) Extraction solvent: Ethanol 60% v/v 30mg of extract (as dry extract) from Passion flower herb (Passiflora incarnata L.) (3:1) Extraction solvent: Ethanol 60% v/v 18mg of extract (as dry extract) from Wild Lettuce herb (Lactuca virosa L.) (5:1) Extraction solvent: Water 4

5 PHARMACEUTICAL ASSESSMENT HERBAL SUBSTANCE: VERBENA HERB Scientific name of the plant: Verbena officinalis L. Parts of the plant used: Whole or fragmented, dried aerial parts The herbal substance complies with its European Pharmacopoeia (Ph. Eur.) monograph; it is, therefore, acceptable. HERBAL SUBSTANCE: HOPS STROBILES Scientific name of the plant: Humulus lupulus L. Parts of the plant used: Dried, generally whole, female inflorescences The herbal substance complies with its European Pharmacopoeia (Ph. Eur.) monograph; it is, therefore, acceptable. HERBAL SUBSTANCE: VALERIAN ROOT Scientific name of the plant: Valeriana officinalis L. Family: Valerianaceae Synonyms of the herbal substance: Valerian Part of the plant used: root The herbal substance complies with its European Pharmacopoeia (Ph. Eur.) monograph; it is, therefore, acceptable. HERBAL PREPARATION: VALERIAN ROOT DRY EXTRACT (5:1) Herbal preparation: Valerian root dry extract (5:1) Extraction solvent: Ethanol 60% v/v The herbal preparation specification is in line with that applied to the herbal preparation used in the already licensed product. It is, therefore, acceptable. HERBAL SUBSTANCE: PASSION FLOWER HERB Scientific name of the plant: Passiflora incarnata L. Parts of the plant used: Fragmented or cut, dried aerial parts The herbal substance complies with satisfactory in-house specifications and is acceptable. 5

6 HERBAL PREPARATION: PASSION FLOWER HERB DRY EXTRACT (3:1) Herbal preparation: Passion flower herb dry extract (3:1) Extraction solvent: Ethanol 60% v/v The herbal preparation specification is in line with that applied to the herbal preparation used in the already licensed product. It is, therefore, acceptable. HERBAL SUBSTANCE: WILD LETTUCE HERB Scientific name of the plant: Lactuca virosa L. The herbal substance complies with satisfactory in-house specifications and is acceptable. HERBAL PREPARATION: WILD LETTUCE HERB DRY EXTRACT (5:1) Herbal preparation: Wild lettuce herb dry extract (5:1) Extraction solvent: water The herbal preparation specification is in line with that applied to the herbal preparation used in the already licensed product. It is, therefore, acceptable. 6

7 HERBAL PRODUCT: GOODNIGHT Description and Composition of the Herbal Product The medicinal product, Goodnight, is presented as grey, biconvex, sugar-coated tablets, each containing 60mg Verbena herb, 30mg Hops strobiles, 36mg of extract (as dry extract) from Valerian root (5:1), 30mg of extract (as dry extract) from Passion flower herb (3:1) and 18mg of extract (as dry extract) from Wild Lettuce herb (5:1). All excipients used comply with their respective European Pharmacopoeia monographs. Satisfactory Certificates of Analysis have been provided for all excipients. The formulation is identical to that of the already licensed product. It is, therefore, acceptable. The magnesium stearate has been confirmed as being of vegetable origin. The only excipient used that contains material of animal or human origin is lactose. The applicant has provided a declaration that milk used in the production of lactose is sourced from healthy animals under the same conditions as that for human consumption. None of the excipients are sourced from genetically modified organisms. Manufacture The manufacturing process is identical to that of the already licensed product and is satisfactory. Finished Product Specification The finished product specification is in line with that of the already licensed product and is satisfactory. Container Closure System The tablets are licensed for marketing in 100ml high-density polyethylene (HDPE) plastic containers with tamper-evident caps, in a pack size of 50 tablets. The HDPE containers are packaged with the Patient Information Leaflet (PIL) into cardboard outer cartons. This type of packaging has been used to store the already licensed product and is satisfactory. Stability The product shelf-life of 3 years was applied to the already licensed product and is appropriate. Storage instructions are Store below 25 C. Store in the original package. 7

8 Summary of Product Characteristics (SmPC), label and Patient Information Leaflet (PIL) All product literature is in line with that of the already licensed product, with some details amended in line with other valerian-containing products for sleep registered under the THR scheme. The Patient Information Leaflet (PIL) is in line with the SmPC and is satisfactory. The package leaflet for the existing product licence has been evaluated via a user consultation study in accordance with the requirements of Articles 59(3) and 61(1) of Directive 2001/83/EC, as amended. The results showed that the package leaflet met the criteria for readability as set out in the Guideline on the readability of the label and package leaflet of medicinal products for human use. The text, content and layout of the proposed leaflet are considered essentially identical to the approved leaflet for the existing product, and bridging of the PIL user testing to the existing product is therefore accepted. Assessor s Overall Conclusions on Quality The grant of a Traditional Herbal Registration is acceptable. 8

9 NON-CLINICAL ASSESSMENT No new non-clinical data have been supplied with this application and none are required for applications of this type. Tests on reproductive toxicity, genotoxicity and carcinogenicity have not been performed. The results of genotoxicity testing will be provided before the THR is renewed. All product literature is satisfactory from a non-clinical point of view. It is recommended that a Traditional Herbal Registration can be granted from a nonclinical perspective. 9

10 CLINICAL ASSESSMENT The clinical particulars for Goodnight are identical to those for the already licensed product. This is satisfactory. No new clinical data have been supplied with this application and none are required. All product literature is satisfactory from a clinical point of view. It is recommended that a Traditional Herbal Registration can be granted from a clinical perspective. 10

11 OVERALL CONCLUSION AND RISK ASSESSMENT QUALITY Goodnight is identical to an already licensed product. It is, therefore, pharmaceutically satisfactory. NON-CLINICAL No new non-clinical data were submitted and none are required for an application of this type. EFFICACY No clinical efficacy data are required for registration of Traditional Herbal Medicinal Products (THMP). SAFETY No new or unexpected safety concerns arose from this application. PRODUCT LITERATURE The approved Summary of Product Characteristics (SmPC) is satisfactory. PIL user testing has been accepted, based on a bridging statement provided by the applicant making reference to the successful user-testing of the PIL for the existing product licence. The bridging is accepted. Mock-ups of the labelling have been provided and are satisfactory. The approved labelling artwork complies with statutory requirements. In line with current legislation, the name of the product in Braille appears on the outer packaging. RISK BENEFIT ASSESSMENT The quality of the product is acceptable and no new non-clinical or clinical safety concerns have been identified. The proposed product is identical to the already licensed product. 11

12 Goodnight THR 00904/0003 STEPS TAKEN FOR ASSESSMENT 1 The MHRA received the Traditional Herbal Registration application on 25 th May Following standard checks and communication with the applicant the MHRA considered the application valid on 8 th June Following assessment of the application, a THR was granted on 16 th November

13 Goodnight THR 00904/0003 Not applicable STEPS TAKEN AFTER AUTHORISATION 13

14 SUMMARY OF PRODUCT CHARACTERISTICS 1 NAME OF THE MEDICINAL PRODUCT Goodnight 2 QUALITATIVE AND QUANTITATIVE COMPOSITION Each coated tablet contains: 60mg Verbena herb (Verbena officinalis L.). 30mg Hops strobiles (Humulus lupulus L.) 36mg of extract (as dry extract) from Valerian root (Valeriana officinalis L.) (5:1) Extraction solvent: Ethanol 60% v/v 30mg of extract (as dry extract) from Passion flower herb (Passiflora incarnata L.) (3:1) Extraction solvent: Ethanol 60% v/v 18mg of extract (as dry extract) from Wild Lettuce herb (Lactuca virosa L.) (5:1) Extraction solvent: Water Excipients: each coated tablet contains: 222mg of sucrose, 30mg lactose For full list of excipients see section PHARMACEUTICAL FORM Coated tablet. Grey, biconvex sugar coated tablet. 4 CLINICAL PARTICULARS 4.1 Therapeutic indications A traditional herbal medicinal product used for the temporary relief of sleep disturbances based on traditional use only. 4.2 Posology and method of administration For oral short term use only. Adults and the elderly. For the relief of sleep disturbances take two tablets 30 minutes before bedtime. As treatment effects may not be apparent immediately, GOODNIGHT should be taken for 2-4 weeks continuously. Duration of use:- If symptoms persist or worsen after 4 weeks of using the product, a doctor or qualified healthcare practitioner should be consulted. The use in children or adolescents under 18 years of age is not recommended (see Section 4.4. Special warnings and precautions for use). 4.3 Contraindications Hypersensitivity to the active substances Verbena, Hops, Valerian, Passion flower, Wild Lettuce or any of the excipients. 14

15 4.4 Special warnings and precautions for use Do not exceed stated dose The use of this product in children or adolescents under 18 years of age is not recommended because data are not sufficient and medical advice should be sought. This product contains sucrose and lactose. One coated tablet contains a maximum of 222mg of sucrose and a maximum of 30mg of lactose. Patients with rare hereditary problems of fructose intolerance, galactose intolerance, the Lapp lactase deficiency, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine. If symptoms persist or worsen after 4 weeks of using the product, a doctor or qualified healthcare practitioner should be consulted. 4.5 Interaction with other medicinal products and other forms of interaction Only limited data on pharmacological interactions with other medicinal products are available. Clinically relevant interactions with drugs metabolised by the CYP 2D6, CYP 3A4/5, CYP1A2 or CYP 2E1 pathway has not been observed. Additive effects with hypnotics and other sedatives cannot be excluded and therefore co-medication is not recommended as a general precaution. The effect of GOODNIGHT may be potentiated by alcohol. Excessive concomitant consumption of alcohol should therefore be avoided. 4.6 Pregnancy and lactation The safety of the product during pregnancy and lactation has not been established. In the absence of sufficient data, the use during pregnancy and lactation is not recommended. 4.7 Effects on ability to drive and use machines GOODNIGHT may impair ability to drive and use machines. Patients who are affected should not drive or operate machinery 4.8 Undesirable effects Gastrointestinal symptoms (eg nausea, abdominal cramps) may occur after ingestion of Valerian root preparations. The frequency is not known. One case of hypersensitivity (vasculitis) and one case of nausea and tachycardia have been reported with Passion flower. The frequency is not known. There are no known adverse reactions with the other active ingredients. If other adverse reactions not mentioned above occur, a doctor or qualified healthcare practitioner should be consulted. 4.9 Overdose Valerian root at a dose of approximately 20g (equivalent to 100 tablets) caused benign symptoms (fatigue, abdominal cramp, chest tightness, light headedness, hand tremor and mydriasis) which disappeared within 24 hours. If symptoms arise, treatment should be supportive. After intake of very high doses of Valerian root over several years (daily consumption corresponding to approximately 30 g of the drug) withdrawal symptoms (delirium) have been reported. 15

16 No cases of overdose have been reported for the other active ingredients. Symptomatic and supportive measures should be taken as appropriate. 5 PHARMACOLOGICAL PROPERTIES 5.1 Pharmacodynamic properties Not required as per Article 16 c (1) (a) (iii) of Directive 2001/83/EC as amended. 5.2 Pharmacokinetic properties Not required as per Article 16 c (1) (a) (iii) of Directive 2001/83/EC as amended. 5.3 Preclinical safety data Tests on reproductive toxicity, genotoxicity and carcinogenicity have not been performed. 6 PHARMACEUTICAL PARTICULARS 6.1 List of excipients Excipients of the herbal preparations: Calcium hydrogen phosphate, maltodextrin. Tablet core: Sucrose, lactose, sodium starch glycollate, magnesium stearate, talc. Tablet coating: Sucrose, talc, ferric oxide, titanium oxide 6.2 Incompatibilities Not applicable. 6.3 Shelf life 3 years 6.4 Special precautions for storage Store below 25 C. Store in the original package. 6.5 Nature and contents of container 100ml HDPE plastic container and tamper evident cap. Pack contains 50 tablets 6.6 Special precautions for disposal There are no special precautions for disposal. When the container is empty the label should be removed and the container placed in a recycling bin 7 MARKETING AUTHORISATION HOLDER Kerbina Limited T/A Bio-Health Culpeper Close Medway City Estate Rochester Kent ME2 4HU 8 MARKETING AUTHORISATION NUMBER(S) THR 00904/

17 9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 16/11/ DATE OF REVISION OF THE TEXT 16/11/

18 PRODUCT INFORMATION LEAFLET 18

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22 LABELLING Bottle label Braille 22

23 Carton 23