par herbal cold flu sachets, thr 12063 0010 · · 2010-05-101 galpharm herbal cold and flu...

MHRA PAR; HERBAL COLD AND FLU SACHETS, THR 12063/0010

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GALPHARM HERBAL COLD AND FLU SACHETS

ASDA HERBAL COLD AND FLU SACHETS TESCO HERBAL COLD AND FLU SACHETS

MORRISONS HERBAL COLD AND FLU SACHETS SUPERDRUG HERBAL COLD AND FLU SACHETS

WILKO HERBAL COLD AND FLU SACHETS BOOTS HERBAL FLU RELIEF SACHETS

HERBALSTORE HERBAL COLD AND FLU SACHETS SAINSBURY’S HERBAL COLD AND FLU SACHETS

THR 12063/0010

UKPAR

TABLE OF CONTENTS

Lay summary

Page 2

Scientific discussion

Page 3

Steps taken for assessment

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Summary of product characteristics

Page 15

Product information leaflet

Page 20

Labelling Page 23


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GALPHARM HERBAL COLD AND FLU SACHETS,

ASDA HERBAL COLD AND FLU SACHETS TESCO HERBAL COLD AND FLU SACHETS

MORRISONS HERBAL COLD AND FLU SACHETS SUPERDRUG HERBAL COLD AND FLU SACHETS

WILKO HERBAL COLD AND FLU SACHETS BOOTS HERBAL FLU RELIEF SACHETS

HERBALSTORE HERBAL COLD AND FLU SACHETS SAINSBURY’S HERBAL COLD AND FLU SACHETS

THR 12063/0010

LAY SUMMARY

The Medicines and Healthcare products Regulatory Agency (MHRA) granted Wrafton Laboratories Limited, a Traditional Herbal Registration Certificate for the traditional herbal medicinal product Galpharm Herbal Cold and Flu Sachets, Asda Herbal Cold and Flu Sachets, Tesco Herbal Cold and Flu Sachets, Morrisons Herbal Cold and Flu Sachets, Superdrug Herbal Cold and Flu Sachets, Wilko Herbal Cold and Flu Sachets, Boots Herbal Flu Relief Sachets, Herbalstore Herbal Cold and Flu Sachets and Sainsbury's Herbal Cold and Flu Sachets (Herbal Registration number: THR 12063/0010). This product will be referred to as Herbal Cold and Flu Sachets throughout the remainder of this report. Herbal Cold and Flu Sachets are available without prescription and can be bought from pharmacies and other outlets.

This product contains Echinacea purpurea root extract as the active ingredient. It also contains vitamin C and zinc. This product is a traditional herbal medicine used to relieve the symptoms of the common cold and flu type infections based on traditional use only. This registration is based exclusively upon the longstanding use of Echinacea purpurea root as a traditional herbal medicine and not upon data generated from clinical trials. There is no requirement under the Traditional Herbal Registration scheme to prove scientifically that a 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.


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HERBAL COLD AND FLU SACHETS.

THR 12063/0010

SCIENTIFIC DISCUSSION

TABLE OF CONTENTS

Introduction

Page 4

Pharmaceutical assessment

Page 5

Non-clinical assessment

Page 10

Clinical assessment

Page 11

Overall conclusions and risk assessment Page 13


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INTRODUCTION

The MHRA granted a Traditional Herbal Registration Certificate for the traditional herbal remedy Herbal Cold and Flu Sachets on 23 March 2010. This product is on the general sales list (GSL). This application was submitted according to Article 16.c of Directive 2001/83 EC, as amended, as part of the Traditional Herbal Medicines Registration Scheme. Each sachet of this product contains 71.5 mg extract (dry extract) from Echinacea purpurea root (6-7:1) (equivalent to 429-500 mg of Echinacea purpurea (L.) Moench, root), zinc (as 13.73 mg sulphate monohydrate) and ascorbic acid (vitamin C). The product is indicated as a traditional herbal medicinal product used to relieve the symptoms of the common cold and influenza type infections based on traditional use only. The data supplied by the Applicant demonstrate 30 years of traditional use of Echinacea purpurea root in the European Community. A satisfactory review of the available safety data on Echinacea purpurea root has also been provided, together with an Expert Safety Report supporting the proposed product.


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PHARMACEUTICAL ASSESSMENT

HERBAL SUBSTANCE: ECHINACEA

Name: Echinacea purpurea (L) Moench Family: Asteraceae/Compositae Common name: Echinaceae Parts of the plant used: Root Description of the plant/herbal substance: Echinacea purpurea is a perennial plant of 60-100 cm tall (cultivated, up to 150 cm). The leaves, which have more or less serrated edges, are broad and oval, with an intense green upper side and rather coarsely hirsute on both sides. The inflorescence is a single flower head terminating stem comprised of approximately 20 radial collar like flowers, of a purplish violet colour, which first remain vertical and then horizontal, and have numerous cone-shaped flowers in the central part, in the shape of a wide brimmed hat or hedgehog, of about 3 cm in height by 3-5 cm wide. Manufacture The plant is cultivated in Europe and harvested during winter. The roots are stored in a cool dry place. The supplier of the Echinacea purpurea has provided confirmation that the herbal substance is cultivated under GACP controlled conditions. The lowest effective doses of herbicides and pesticides are used. The manufacturing process is clearly defined and the controls necessary are carried out to verify correct manufacture of the herbal substance. Control of Herbal Substance An appropriate specification based on the Ph Eur monograph is applied and is acceptable. The specification is supported by batch data provided. Container Closure System Satisfactory details of the container closure system are provided and confirmation has been given that all components of the container closure system comply with Directive 2002/72/EC relating to plastic materials and articles intended to come into contact with foodstuffs. Stability Confirmation is given that the herbal substance will be tested prior to being used to make the herbal preparation. A shelf-life for the herbal substance is not appropriate because it is only a precursor of the active substance, the herbal preparation. The actual guideline requires stability testing data for the herbal preparation and the herbal product in the application documents and not for the herbal substance. HERBAL PREPARATION General information


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Herbal preparation: Dry quantificated extract of Echinacea at 4-6% in phenolic acids derived from dihydroxycinnamic acid, expressed as caffeic acid, chicoric acid, chlorogenic acid and caftaric acid. Manufacture Manufacture of the extract is a standard procedure. A satisfactory description of the manufacturing process of the herbal substance and flow diagram has been provided. There are no critical steps identified as the manufacture of the herbal preparation is considered a standard procedure. Certificates of analysis for all materials used in the manufacture of the herbal preparation have been provided. Control of Herbal Preparation A satisfactory specification, with appropriate tests and limits has been provided for the herbal preparation. Satisfactory analytical procedures are used to control the quality of the herbal preparation. Analytical procedures have been validated as appropriate. Container Closure System The container closure system used to store the dry extract complies with Directive 2002/72/EC. Stability Batches were packed in the final container closure system and stored under ICH real time, intermediate and accelerated conditions. The data support the storage conditions used. ANCILLIARY VITAMIN (ascorbic acid) General information White or almost white, crystalline powder or colourless crystals, becomes discoloured on exposure to air and moisture. Freely soluble in water and soluble in alcohol, practically insoluble in ether. Manufacture The process of manufacture of the ascorbic acid active materials is compliant as it is controlled by an appropriate Certificate of Suitability. Control of Ancillary Vitamin A satisfactory specification, with appropriate tests and limits has been provided for the ascorbic acid. Satisfactory analytical procedures are used to control the quality of the ascorbic acid. Analytical procedures have been validated as appropriate. Satisfactory certificates of Analysis have been provided. Container Closure System The container closure system used to store the ascorbic acid complies with Directive


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2002/72/EC. Stability Batches were packed in the final container closure system and stored under ICH real time, intermediate and accelerated conditions. The data support the storage conditions used. ANCILLIARY MINERAL (zinc sulphate monohydrate) General information White or almost white, crystalline powder or colourless crystals, becomes discoloured on exposure to air and moisture. Freely soluble in water and soluble in alcohol, practically insoluble in ether. Manufacture Zinc sulphate monohydrate is an inorganic material therefore this section is not relevant. Control of Ancillary Mineral A satisfactory specification, with appropriate tests and limits has been provided for the zinc sulphate monohydrate. Satisfactory analytical procedures are used to control the quality of the zinc sulphate monohydrate. Analytical procedures have been validated as appropriate. Satisfactory certificates of analysis have been provided. Container Closure System The container closure system used to store the zinc sulphate monohydrate complies with Directive 2002/72/EC. Stability Zinc sulphate monohydrate is an inorganic material therefore this section is not relevant. HERBAL PRODUCT Description and Composition of the Herbal Product The product is a sachet containing an off-white free flowing powder designed to be reconstituted into a hot drink intended for oral administration. The sachets are packed into a paper/foil laminate with either five or ten sachets in a cardboard carton. Qualitative composition of Herbal Cold and Flu Sachets; Name of Ingredient Function Reference to

standards

Active ingredient:

Echinacea purpurea powder extract 7-8:1equivalent to 500mg Echinacea active ingredient HSE

Ascorbic acid active ingredient Ph Eur


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Zinc sulphate monohydrate active ingredient Ph Eur

Excipients:

Maltodextrin Sodium citrate Citric acid Aspartame Acesulfame K Lemon Flavour F/29088 Lemon Flavour F/29089 Lemon Flavour F/28151 Lemon Flavour 501.476.AP05.04 Quinoline Yellow

Diluent Flavour Flavour Sweetener Sweetener Flavour Flavour Flavour Flavour Colour

Ph. Eur Ph. Eur Ph. Eur Ph. Eur Ph. Eur HSE HSE HSE HSE HSE

Manufacture A copy of the manufacturing licence is provided. The site complies with GMP standards. A flow diagram summarising the manufacturing process and in-process controls has been provided. A number of in-process control tests are performed during manufacture. All are considered adequate. Control of Excipients All excipients, apart from Lemon Flavour F/29088, Lemon Flavour F/29089, Lemon Flavour F/28151, Lemon Flavour 501.476/AP05.04 and quinoline yellow, are described in the European Pharmacopoeia. There are no excipients of human or animal origin used in the manufacture of the product. Certificates of Analysis have been provided from all excipients. The flavouring ingredients all comply with Directive 88/388/EEC which covers flavourings for use in food stuffs and source materials for their production. The colour, quinoline yellow (E104) conforms to the Food Regulations Commission Directive 95/45/EC which lays down specific purity criteria concerning colours for use in food stuffs. The declaration is provided on the Certificate of Analysis. Control of Herbal Product The finished product specifications for release and end of shelf life are detailed and the tests and limits used were found to be satisfactory for a product of this nature. Satisfactory details have been provided on all analytical procedures and these analytical procedures are valid. Satisfactory batch data have been provided to support the specifications. Reference Standards or Materials Certificates of analysis have been provided for all reference standards used for the active substances.


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Container Closure System The finished product is packed in paper/foil laminate sachets in a standard grade cardboard carton in packs of five or ten sachets. Specifications and certificates are provided from the manufacturers and the applicant has confirmed that all components of the final container closure system comply with Directive 2002/72/EC relating to plastic materials and articles intended to come into contact with foodstuffs. Stability Data is provided for production scale batches. Batches were packed in the final packaging and tested under ICH conditions of real, intermediate and accelerated time. Based on the data provided, a shelf life of 36 months with no additional storage conditions is acceptable. ASSESSOR’S COMMENTS ON THE SUMMARY OF PRODUCT CHARACTERISTICS, LABEL AND PATIENT INFORMATION LEAFLET Summary of Product Characteristics (SPC). The SPC for this product is satisfactory. Patient Information Leaflet (PIL) The PILs for this product is satisfactory. The package leaflets were submitted to the MHRA along with results of consultations with target patient groups ("user testing"), in accordance with Article 59 of Council Directive 2001/83/EC. The results indicate that the package leaflets are well-structured and organised, easy to understand and written in a comprehensive manner. The test shows that the patients/users are able to act upon the information that they contain. Labelling All labelling is satisfactory. ADMINISTRATIVE Comment on the Quality Overall Summary The Quality Overall Summary has been written by a pharmacist with suitable pharmaceutical and experience and is satisfactory. ASSESSOR’S OVERALL CONCLUSIONS ON QUALITY This product is satisfactory and a Traditional Herbal Registration can be granted.


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NON-CLINICAL ASSESSMENT Non-clinical aspects The Safety Expert Report submitted by the applicant lists relevant references to published work studying the toxicology of Echinacea purpurea. Non-clinical overview The applicant has submitted an adequate literature review with this application. An Expert Safety Report was also provided, which included reviews of some non-clinical data. The overview submitted in support of this application is satisfactory. Due to a shortage of published data on Echinacea purpurea it is not possible to assess if the safety package for the phytochemical constituents of Echinacea purpurea is acceptable to the standards of today’s GLP and safety testing requirements. However, the information supplied demonstrating traditional use is acceptable and thus the lack of provision of a complete standard safety package may be acceptable and in compliance with guideline EMEA/HMPC/32116/05. In view of the absence of results of genotoxicity testing, the applicant has provided assurance that results will be provided before the renewal of the registration. Summary of product characteristics The Summary of Product Characteristics for this product is satisfactory. Environmental risk assessment An environmental risk assessment is not required for herbal medicinal products according to guidance CPMP/SWP/4447/00. Conclusion The information supplied demonstrating traditional use of Echinacea purpurea. is acceptable. An adequate literature review for Echinacea purpurea. has been carried out by the applicant and no new nonclinical data were submitted for assessment with this application. Granting of a THR is acceptable.


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CLINICAL ASSESSMENT LEGAL STATUS Echinacea purpurea is currently on Schedule 1 of the General Sales List for internal use. PROPOSED INDICATION The applicant has proposed the following: ‘A traditional herbal medicinal product used to relieve the symptoms of the common cold and influenza type infections based on traditional use only’. This indication is appropriate. POSOLOGY AND METHOD OF ADMINISTRATION The applicant has submitted the following: ‘Adults, the elderly and children over 12 years: 1 sachet 3 times a day. For oral administration after dissolution in water. Pour the contents of one sachet into a mug. Fill it with hot, not boiling, water and stir until dissolved and drink’. This is acceptable. EFFICACY No clinical efficacy data is required for registration of Traditional Herbal Medicinal Products (THMP). EVIDENCE OF TRADITIONAL USE Article 16 c 1 (c) requires the Applicant to provide bibliographic or expert evidence showing that the medicinal product in question, or a corresponding product, has been in medicinal use throughout a period of at least 30 years, including at least 15 years within the European Community. The Applicant has provided a bibliographic review as evidence of the use of Echinacea purpurea within the EU for a period exceeding 30 years. The information provided is considered to satisfy the requirement to demonstrate use for at least 30 years of which at least 15 years have been in an EU Member State. The requirements of the Directive are therefore addressed for this aspect. SAFETY REVIEW Article 16 c 1 (d) requires the Applicant to provide a bibliographic review of the safety data together with a safety expert report. A safety review has been provided as well as an expert report written by a suitably qualified professional who is a pharmacologist and medical herbalist. The Safety Review and expert report are satisfactory. ANCILLARY VITAMINS AND MINERALS IN THMP Information has been provided on the product and the ancillary vitamin and mineral components are justified on the basis of their RDA.


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SUMMARY OF PRODUCT CHARACTERISTICS The SPC for this product is satisfactory. PATIENT INFORMATION LEAFLET The PILs for this product is satisfactory. LABELLING All labelling is satisfactory. DISCUSSION This is an application for registration under the Traditional Herbal Medicinal Products Directive. The data supplied by the Applicant are sufficient to demonstrate 30 years’ of traditional use within the European Community of corresponding products and satisfactory safety data have been provided supporting the proposed product. RECOMMENDATIONS A Traditional Registration may be granted.


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OVERALL CONCLUSION AND RISK ASSESSMENT QUALITY The quality data submitted with this application are satisfactory. PRECLINICAL No new preclinical data were submitted and none are required for an application of this type. EFFICACY AND SAFETY No clinical efficacy data are required for registration of Traditional Herbal Medicinal Products (THMP). The Applicant has provided a bibliographic review which shows ample evidence for the use of Echinacea purpurea within the EU for a period exceeding 30 years. A satisfactory review of the safety data has been provided. The SPC, PIL and labelling are satisfactory. RISK ASSESSMENT The quality of the product is acceptable and no new preclinical or clinical safety concerns have been identified.


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HERBAL COLD AND FLU SACHETS

THR 12063/0010

STEPS TAKEN FOR ASSESSMENT

1 The MHRA received the Traditional Herbal Registration application on 25 March 2008

2 Following standard checks and communication with the applicant the MHRA considered the application valid on 18 April 2008

3 Following assessment of the application the MHRA requested further information relating to the quality and clinical dossier on 23 June 2008, 30 September 2008, 29 April 2009, 30 June 2009 and 26 October 2009.

4 The applicant responded to the MHRA’s requests, providing further information on the dossier on 06 April 2009, 30 June 2009, 01 September 2009 and 20 January 2010

5 A THR was granted on 23 March 2010.


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SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT Galpharm Herbal Cold and Flu Sachets

Sainsbury’s Herbal Cold and Flu Sachets

Asda Herbal Cold and Flu Sachets

Tesco Herbal Cold and Flu Sachets

Morrisons Herbal Cold and Flu Sachets

Superdrug Herbal Cold and Flu Sachets

Wilko Herbal Cold and Flu Sachets

Boots Herbal Flu Relief Sachets

Herbalstore Herbal Cold and Flu Sachets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION Each sachet contains:

71.5 mg extract (dry extract) from Echinacea purpurea root (6-7:1)

(equivalent to 429 – 500 mg of Echinacea purpurea (L.) Moench, root)

Extraction solvent: Ethanol 30% v/v

Ancilliary vitamins / minerals

Zinc 5 mg

(as 13.73 mg sulphate monohydrate)

Ascorbic Acid 60 mg

Excipients:

Each sachet contains 45 mg aspartame and 104 mg sodium.

For full list of excipients, see 6.1

3 PHARMACEUTICAL FORM Powder for oral solution.

Off white powder.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications A traditional herbal medicinal product used to relieve the symptoms of the common cold and influenza type infections based on traditional use only.


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4.2 Posology and method of administration Adults, the elderly and children over 12 years: 1 sachet 3 times a day.

For oral administration after dissolution in water. Pour the contents of one sachet into a mug. Fill it with hot, not boiling, water and stir until dissolved and drink.

Start at first sign of common cold or influenza type infection. Do not use the medicinal product for more than 10 days.

If symptoms worsen during the use of the product or persist for more than 10 days, a physician or a qualified healthcare practitioner should be consulted.

Not recommended for children under 12 years of age (see section 4.4 ‘Special warnings and precautions for use’.

4.3 Contraindications Hypersensitivity to Echinacea, zinc or ascorbic acid or to the plants of the Asteraceae (Compositae) family.

Because of its immunostimulating activity, Echinacea must not be used in cases of progressive systemic disorders (tuberculosis, sarcoidosis), autoimmune diseases (e.g.: collagenoses, multiple sclerosis), immunodeficiencies (e.g.:HIV infection; AIDS), immunosuppression (e.g.: oncological cytostatic therapy; history of organ or bone marrow transplant), diseases of the white blood cell system (e.g.: agranulocytosis, leukemias) and allergic diathesis (e.g.: urticaria, atopic dermatitis, asthma).

Children under 12 years of age.

4.4 Special warnings and precautions for use Do not exceed the stated dose.

If the condition worsens or high fever occurs during the use of the product or if symptoms persist for more than 10 days, consult a doctor or qualified healthcare practitioner.

This formulation is not suitable for children under 12 years.

There is a possible risk of anaphylactic reactions in atopic patients. Atopic patients should consult their doctor before using Echinacea.

Contains aspartame (E951) a source of phenylalanine. May be harmful for people with phenylketonuria. See section 2.

Contains sodium. To be taken into consideration by patients on a controlled sodium diet. See section 2.

4.5 Interaction with other medicinal products and other forms of interaction Not to be used concomitantly with immunosuppressant medications such as ciclosporin and methotrexate.


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4.6 Pregnancy and lactation In the absence of sufficient data the use in pregnancy and lactation is not recommended.

Limited data (several hundreds of exposed pregnancies) indicate no adverse effects of Echinacea on pregnancy or on the health of the foetus/newborn child. Data concerning the immune system of the newborn child are not available. To date, no other relevant epidemiological data are available. The potential risk for humans is unknown.

4.7 Effects on ability to drive and use machines No studies on the effects on the ability to drive and use machines have been performed.

4.8 Undesirable effects Hypersensitivity reactions (rash, urticaria, Stevens-Johnson Syndrome, angioedema of the skin, Quincke edema, bronchospasm with obstruction, asthma and anaphylactic shock) may occur. Echinacea can trigger allergic reactions in atopic patients. Association with autoimmune diseases (encephalitis disseminata, erythema nodosum, immunothrombocytopenia, Evans Syndrome, Sjögren syndrome with renal tubular dysfunction) has been reported.

Leucopenia may occur in long-term use (more than 8 weeks).

The frequency is not known.

If other adverse reactions not mentioned above occur, a doctor or qualified healthcare practitioner should be consulted.

4.9 Overdose Symptomatic and supportive measures should be taken as appropriate.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties Not required as per Article 16c(1)(a)(iii) of Directive 2001/83/EC as amended.

5.2 Pharmacokinetic properties Not required as per Article 16c(1)(a)(iii) of Directive 2001/83/EC as amended.

5.3 Preclinical safety data Tests on reproductive toxicity, genotoxicity and on carcinogenicity have not been performed with Echinacea purpurea root.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients Excipients of the herbal preparation;


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Maltodextrin

Silica, colloidal anhydrous

Other excipients;

Maltodextrin

Sodium Citrate

Citric Acid

Acesulflame K

Aspartame (E951)

Quinoline Yellow (E104)

Lemon Flavour F/29088



Lemon Flavour 501.476/AP05.04

6.2 Incompatibilities None applicable.

6.3 Shelf life Shelf life of product as packaged for sale

36 months.

6.4 Special precautions for storage This medicinal product does not require any special storage conditions.

6.5 Nature and contents of container Paper/foil laminate sachets consisting of:

Bleached MG paper outer – 40 g/m2

LD Polyethylene – 12 g/m2

Aluminium foil 12 – 15 microns

Surlyn 25 g/m2

Five or ten sachets are contained in a boxboard carton.

6.6 Special precautions for disposal None.

7 MARKETING AUTHORISATION HOLDER Wrafton Laboratories Limited

Braunton

Devon

EX33 2DL


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8 MARKETING AUTHORISATION NUMBER(S) THR 12063/0010

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

23/03/2010 10 DATE OF REVISION OF THE TEXT

23/03/2010


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par herbal cold flu sachets, thr 12063 0010 · · 2010-05-101 galpharm herbal cold and flu...

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