potter’s pelargonium cold relief drops thr 33656/0079 ukpar · potter’s pelargonium cold relief...

MHRA PAR; POTTER’S PELARGONIUM COLD RELIEF DROPS, PL 33656/0079 1

Potter’s Pelargonium Cold Relief Drops

THR 33656/0079

UKPAR

TABLE OF CONTENTS

Lay summary

Page 2

Scientific discussion

Page 3

Steps taken for assessment

2

Summary of Product Characteristics

Page 13

Product Information Leaflet

Page 17

Labelling Page 19

POTTER’S PELARGONIUM COLD RELIEF DROPS

THR 33656/0079

LAY SUMMARY

The Medicines and Healthcare products Regulatory Agency (MHRA) granted Vifor Pharma UK Ltd (trading as Potters) a Traditional Herbal Registration Certificate for the traditional herbal medicinal product Potter’s Pelargonium Cold Relief Drops (Traditional Herbal Registration number: THR 33656/0079) on 06 February 2013. This product is available without prescription and can be bought from pharmacies and other outlets. Potter’s Pelargonium Cold Relief Drops are a traditional herbal medicinal product used to relieve the symptoms of upper respiratory tract infections including the common cold, based on traditional use only. The active ingredient in Potter’s Pelargonium Cold Relief Drops comes from the root of the Pelargonium plant, which is also known as Pelargonium sidoides DC. This registration is based exclusively upon evidence of the use of Pelargonium 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 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.



THR 33656/0079

SCIENTIFIC DISCUSSION

TABLE OF CONTENTS

Introduction

Page 4

Pharmaceutical assessment

Page 5

Non-clinical assessment

Page 8

Clinical assessment

Page 9

Overall conclusions and risk assessment Page 11


INTRODUCTION

The MHRA granted a Traditional Herbal Registration Certificate for the traditional herbal medicinal product Potter’s Pelargonium Cold Relief Drops (Traditional Herbal Registration number: THR 33656/0079) to Vifor Pharma UK Ltd on 06 February 2013. 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. The product is used to relieve the symptoms of upper respiratory tract infections including the common cold, based on traditional use only. The data supplied by the applicant demonstrate 30 years of traditional use of Pelargonium root in the European Community. A satisfactory review of the available safety data on Pelargonium root has also been provided, together with an Expert Safety Report supporting the proposed product.


PHARMACEUTICAL ASSESSMENT

HERBAL SUBSTANCE: PELARGONIUM ROOT

Latin name: Pelargonium sidoides DC (Geraniaceae) Common name: African geranium Family: Geraniaceae Manufacture of Herbal Substance The Pelargonium plants from which the herbal substance is obtained are cultivated in South Africa. The roots are harvested, cleaned, dried and packed into bags that are kept in cool, dry and dark conditions free from insects. Confirmation is given that the herbal substance is produced in accordance with the principles of Good Agricultural and Collection Practice (GACP) (EMEA/HMPC/246816/20050) and that the herbal substance is not treated with ethylene oxide or irradiation following harvesting. The plant may be treated with CO2 under pressure, as this treatment does not have a negative impact on the pharmaceutical quality of the dried plant, this is acceptable. Control of Herbal Substance An appropriate specification based on the Ph Eur monograph is applied and is acceptable. The specification is supported by the 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 current legislation relating to plastic materials and articles intended to come into contact with foodstuffs. Stability of Herbal Substance 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 necessary 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: PELARGONIUM ROOT TINCTURE

Ratio of herbal substance to Herbal preparation: 1:8-10 Extraction solvent: Ethanol 15% v/v.

Manufacture of Herbal Preparation A satisfactory description of the manufacturing process of the herbal preparation and flow diagram has been provided. The in-process controls are satisfactorily detailed. 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.

Certificates of Analysis have been provided for production batches of the herbal preparation, demonstrating satisfactory compliance with the proposed specification. Container Closure System The herbal preparation is not normally stored. However, if this is necessary then suitable containers are used. Stability of Herbal Preparation Stability studies have been performed in accordance with current guidelines. The proposed re-test period for the herbal preparation is acceptable. HERBAL PRODUCT: POTTER’S PELARGONIUM COLD RELIEF

DROPS

Description and Composition of Herbal Product The herbal product is a clear, light brown to reddish brown solution containing the herbal preparation (which includes the excipient ethanol) and glycerol. The compatibility of the herbal preparation with the excipients is demonstrated by the stability testing results. All excipients are controlled in line with their respective Ph Eur monograph. Satisfactory Certificates of Analysis are provided for all excipients.

The glycerol used in this product is of plant origin and, therefore, carries no TSE risk.

Manufacture of Herbal Product Flow diagrams outlining the various stages of the manufacturing process and the in-process controls are provided. The manufacturing method is a standard procedure. In-process controls are appropriate considering the nature of the product and the method of manufacture. Process validation has been carried out on product batches and the results are satisfactory. Control of Herbal Product The finished product specification is satisfactory. Acceptance limits have been justified with respect to conventional pharmaceutical requirements and, where appropriate, safety. Test methods have been described and have been adequately validated, as appropriate. Batch data have been provided and comply with the release specification.


Container Closure System

The oral drops are stored in hydrolytic Class III (PhEur.) brown glass bottles, incorporating a dropper insert (PE) and a white screw cap (PP) and are available in pack sizes of 20 ml, oral solution. Each bottle is inserted into a printed carton. Suitable specifications have been provided by the packaging suppliers and it has been confirmed that all primary packaging materials comply with current regulations.

Stability of Herbal Product Finished product stability studies have been conducted in accordance with current guidelines. Based on the results, a product shelf-life of 2 years is appropriate (unopened bottle) with the storage condition ‘Do not store above 30°C.’ Once the bottle is first opened, the product should be used within 3 months. Pharmaceutical Expert The Quality Overall Summary has been written by a professional with suitable experience.

Summary of Product Characteristics, product labels and Patient Information Leaflet All product literature is satisfactory. A package leaflet has been 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 leaflet is 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 it contains. Conclusion There are no objections to granting of a Traditional Herbal Registration from a quality point of view.


NON-CLINICAL ASSESSMENT

NON-CLINCIAL OVERVIEW An Expert Safety Report was provided, which included reviews of some non-clinical data. The Expert Safety Report was written by a suitably qualified professional. Due to a shortage of published data on Pelargonium root, it is not possible to assess if the safety package for the phytochemical constituents of pelargonium root 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 is acceptable and in compliance with guideline EMEA/HMPC/32116/05. The genotoxicity of the Pelargonium extract was tested in vitro in the Salmonella typhimurium reverse mutation assay and in the mouse lymphoma forward mutation assay. In addition, the extract was tested in vivo for potential genotoxic effects using the micronucleus test in bone marrow of the mouse by oral administration. All three tests did not reveal any mutagenic potential of the extract. The overview submitted in support of this application is satisfactory. SUMMARY OF PRODUCT CHARACTERISTICS (SmPC) The SmPC for this product is satisfactory from a non-clinical point of view. ENVIRONMENTAL RISK ASSESSMENT

An environmental risk assessment is not required for herbal medicinal products according to guidance CPMP/SWP/4447/00.

CONCLUSION There are no objections to granting of a Traditional Herbal Registration Certificate from a non-clinical point of view.


CLINICAL ASSESSMENT

PROPOSED INDICATION The applicant has proposed the following: “A traditional herbal medicinal product used to relieve the symptoms of upper respiratory tract infections including the common cold, based on traditional use only.” The indication is acceptable. POSOLOGY AND METHOD OF ADMINISTRATION The applicant has proposed the following: “For oral use. Adults, the elderly and children over 12 years: 30 drops three times per day. The use in children under 12 years of age is not recommended (see Section 4.4 Special warnings and precautions for use). The drops should be taken undiluted or with a small quantity of water, followed by a sufficient amount of liquid (preferably a glass of drinking water). 30 drops is equivalent to approximately 1.5 ml. Duration of use: After relief of symptoms, continuation of treatment for further 2 – 3 days is recommended in order to prevent a relapse, however treatment duration should not exceed 2 weeks. If the symptoms persist during the use of this product, a doctor or qualified healthcare practitioner should be consulted.” This is acceptable. EFFICACY No clinical efficacy data is required for registration of Traditional Herbal Medicinal Products. EVIDENCE OF TRADITIONAL USE Article 16 c 1 (c) requires the applicant to provide bibliographic or expert evidence to show 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 EU. The applicant has provided a report describing the traditional use of Pelargonium root within the EU for a period exceeding 30 years. 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 an Expert Safety Report. A satisfactory safety review has been provided as well as an Expert Safety Report written by a suitably qualified professional with experience in herbal medicines. The safety review is comprehensive and reveals the main safety issues associated with treatment with Pelargonium root. PRODUCT LITERATURE The product literature (Summary of Product Characteristics, Patient Information Leaflet and labelling) for this product is medically satisfactory. CONCLUSION There are no objections to granting of a Traditional Herbal Registration Certificate from a clinical point of view.


OVERALL CONCLUSION AND RISK ASSESSMENT

QUALITY The quality data submitted with this application are satisfactory.

NON-CLINICAL The results of genotoxicity testing were provided and the results were satisfactory. No other new non-clinical data were submitted with this application and none are needed.

EFFICACY AND SAFETY No clinical efficacy data are required for registration of Traditional Herbal Medicinal Products. The applicant has provided a bibliographic review which shows satisfactory evidence for the use of Pelargonium root within the EU for a period exceeding 30 years. No safety issues have been identified. The SmPC, PIL and labelling are satisfactory. RISK ASSESSMENT The quality of the product is acceptable and no new non-clinical or clinical safety concerns have been identified. The risk: benefit balance is acceptable and a Traditional Herbal Registration may be granted.



THR 33656/0079

STEPS TAKEN FOR ASSESSMENT

1 The MHRA received the Traditional Herbal Registration application on 08 January 2013

2 Following standard checks and communication with the applicant the MHRA considered the application valid on 28 January 2013

3 A THR was granted on 06 February 2013


SUMMARY OF PRODUCT CHARACTERISTICS 1 NAME OF THE MEDICINAL PRODUCT

Potter’s Pelargonium Cold Relief Drops 2 QUALITATIVE AND QUANTITATIVE COMPOSITION

10g (=9.75ml) of oral solution contains 8 g extract from Pelargonium root (Pelargonium sidoides DC) (1:8 – 10). Extraction solvent: Ethanol 15% (V/V). 1 ml (approximately 20 drops) of the product contains 93 mg ethanol (alcohol) equivalent to 2.4 ml of beer or 1.0 ml of wine. For a full list of Excipients see section 6.1

3 PHARMACEUTICAL FORM

Oral drops, solution. Clear, light brown to reddish brown solution.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

A traditional herbal medicinal product used to relieve the symptoms of upper respiratory tract infections including the common cold, based on traditional use only.

4.2 Posology and method of administration

For oral use. Adults, the elderly and children over 12 years: 30 drops three times per day. The use in children under 12 years of age is not recommended (see Section 4.4 Special warnings and precautions for use). The drops should be taken undiluted or with a small quantity of water,

followed by a sufficient amount of liquid (preferably a glass of drinking water).

30 drops is equivalent to approximately 1.5 ml. Duration of use: After relief of symptoms, continuation of treatment for further 2 – 3 days is recommended in order to prevent a relapse, however treatment duration should

not exceed 2 weeks. If the symptoms persist during the use of this product, a doctor or qualified healthcare practitioner should be consulted.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients. Patients with increased tendency to bleeding. Patients using coagulation-inhibiting drugs.


Patients with severe hepatic and renal diseases. 4.4 Special warnings and precautions for use

Do not exceed the stated dose. Medical advice should be sought if the symptoms persist for more than one week, or in cases of fever lasting for several days or in case of shortness of breath or bloody sputum. The product contains 12 % v/v ethanol (alcohol). This corresponds to: 139.5 mg alcohol equivalent to 3.6 ml beer or 1.5 ml wine per adults' single dose (30 drops). Harmful for those suffering from alcoholism. To be taken into account in children and high-risk groups such as patients with liver disease, or epilepsy. The use in children under 12 years of age is not recommended due to lack of adequate data.

4.5 Interaction with other medicinal products and other forms of interaction

Drug interactions have not been reported. However, due to the potential effect of the product on coagulation parameters, this product may enhance the effect of coagulation-inhibiting drugs such as warfarin and should not be taken concomitantly with these drugs (see section 4.3 Contraindications). Contains alcohol and should be avoided in patients taking other medicines known to interact with alcohol (e.g. metronidazole).

4.6 Fertility, pregnancy and lactation

Safety during pregnancy and lactation has not been established. In the absence of sufficient data, the use during pregnancy and lactation is not recommended. Studies on fertility have not been performed.

4.7 Effects on ability to drive and use machines

No studies on the effect on the ability to drive and use machines have been performed. This product contains alcohol and therefore may impair ability to drive or operate machines. If affected do not drive or operate machines (See Section 4.4 ‘Special warnings and precautions for use’.)

4.8 Undesirable effects The following adverse reactions have been reported. The frequency is not known.


Gastrointestinal complaints, such as stomach pain, heartburn, nausea or diarrhoea. Mild bleeding from the gingival or nose may occur. Hypersensitivity (e.g. oedemas, rash or pruritus on the skin or mucosa). Serious hypersensitivity reactions with swelling of the face, dyspnea and fall in blood pressure. In single cases, signs indicating disturbances of liver function have been reported after intake of Pelargonium; the causal relationship between this effect and the application of the product has not been demonstrated. If other adverse reactions not mentioned above occur, a doctor or a qualified health care practitioner should be consulted.

4.9 Overdose

No cases of overdose have been reported. Overdose of this product may result in alcohol intoxication: the amount of alcohol in a full bottle (1.86 g in 20 ml: equivalent to 1/10 glass of wine, respectively) may result in intoxication and should be treated accordingly.

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

Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity and toxicity to reproduction.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Glycerol Ethanol

6.2 Incompatibilities None known.

6.3 Shelf life

Unopened: 2 years. In use stability after first opening of the container: 3 months.

6.4 Special precautions for storage

Do not store above 30 °C.


6.5 Nature and contents of container A printed carton containing a hydrolytic Class III (PhEur.) brown glass bottle, incorporating a dropper insert (PE) and a white screw cap (PP), in pack sizes of 20 ml, oral solution.

6.6 Special precautions for disposal

There are no special precautions for disposal. 7 MARKETING AUTHORISATION HOLDER

Vifor Pharma UK Ltd 1 Botanic Court, Martland Park, Wigan, WN5 0JZ, UK. Trading as: Potters, Wigan WN5 0JZ

8 MARKETING AUTHORISATION NUMBER(S)

THR 33656/0079 9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION 06/02/2013 10 DATE OF REVISION OF THE TEXT

06/02/2013


PATIENT INFORMATION LEAFLET


LABELLING

Bottle label:



Carton:

potter’s pelargonium cold relief drops thr 33656/0079 ukpar · potter’s pelargonium cold relief...

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