Public Assessment Report

Transcription

1 Public Assessment Report Sodium Chloride 1 mmol/ml Oral Solution (sodium chloride) UK Licence No: PL 20346/0008 Viridian Pharma Ltd

2 LAY SUMMARY Sodium Chloride 1 mmol/ml Oral Solution (sodium chloride) This is a summary of the Public Assessment Report (PAR) for Sodium Chloride 1 mmol/ml Oral Solution (PL 20346/0008). It explains how Sodium Chloride 1 mmol/ml Oral Solution was assessed and its authorisation recommended, as well as its conditions of use. It is not intended to provide practical advice on how to use Sodium Chloride 1 mmol/ml Oral Solution. For practical information about using Sodium Chloride 1 mmol/ml Oral Solution, patients should read the package leaflet or contact their doctor or pharmacist. What is Sodium Chloride 1 mmol/ml Oral Solution and what is it used for? Sodium Chloride 1 mmol/ml Oral Solution is a medicine with well-established use. This means that the medicinal use of the active substance of Sodium Chloride 1 mmol/ml Oral Solution has been in wellestablished use in the European Union (EU) for at least ten years, with recognised efficacy and an acceptable level of safety. Sodium Chloride 1 mmol/ml Oral Solution is a source of sodium chloride used to correct hyponatraemia (low blood sodium levels) in infants. Sodium chloride is found widely in the body, and is important to normal body functions. How does Sodium Chloride 1 mmol/ml Oral Solution work? Sodium Chloride 1 mmol/ml Oral Solution contains the active ingredient sodium chloride. This helps to maintain sodium levels in the blood. How is Sodium Chloride 1 mmol/ml Oral Solution used? Sodium Chloride 1 mmol/ml Oral Solution is taken by mouth. The solution must be diluted and the bottle should be shaken before use. Patients should ensure that the product is added and thoroughly mixed into a drink, breast milk or formula feed immediately before administration. The patient s doctor will calculate the dose based on body weight in kilograms. This can vary according to patient requirements. The recommended dose in infants is 3-5 mmol/kg (3 to 5 ml of Sodium Chloride 1 mmol/ml Oral Solution per kg) daily in divided doses. Sodium Chloride 1 mmol/ml Oral Solution can only be obtained on prescription from a doctor. For further information on how Sodium Chloride 1 mmol/ml Oral Solution is used, please refer to the Summary of Product Characteristics and the Patient Information Leaflet available on the MHRA website. What benefits of Sodium Chloride 1 mmol/ml Oral Solution have been shown in studies? As sodium chloride is a well-known substance, and its use in the correction of hyponatraemia (low blood sodium levels) in infants is well-established, the applicant presented data from the scientific literature. The literature provided confirmed the efficacy and safety of sodium chloride in the correction of hyponatraemia (low blood sodium levels) in infants. In addition, the company (Viridian Pharma Ltd) supplied their own observational data (clinical case series) to support this application. 2

3 What are the possible side effects of Sodium Chloride 1 mmol/ml Oral Solution? Like all medicines, this medicine can cause side effects, although not everybody gets them. For information about side effects that may occur with taking Sodium Chloride 1 mmol/ml Oral Solution, please refer to the package leaflet or the Summary of Product Characteristics available on the MHRA website. Why is Sodium Chloride 1 mmol/ml Oral Solution approved? The use of Sodium Chloride 1 mmol/ml Oral Solution for the approved indication is well-established. Literature data as well as company own observational data have been submitted to support this application. No new or unexpected safety concerns arose from this application. It was, therefore, considered that the benefits of Sodium Chloride 1 mmol/ml Oral Solution outweigh the risks and the grant of a Marketing Authorisation was recommended. What measures are being taken to ensure the safe and effective use of Sodium Chloride 1 mmol/ml Oral Solution? A Risk Management Plan has been developed to ensure that Sodium Chloride 1 mmol/ml Oral Solution is used as safely as possible. Based on this plan, safety information has been included in the Summary of Product Characteristics and the package leaflet for Sodium Chloride 1 mmol/ml Oral Solution, including the appropriate precautions to be followed by healthcare professionals and patients. Known side effects are continuously monitored. Furthermore new safety signals reported by patients/healthcare professionals will be monitored/reviewed continuously. Other information about Sodium Chloride 1 mmol/ml Oral Solution A Marketing Authorisation was granted in the UK on 30 th July The full PAR for Sodium Chloride 1 mmol/ml Oral Solution follows this summary. For more information about treatment with Sodium Chloride 1 mmol/ml Oral Solution, read the Patient Information Leaflet (PIL), or contact your doctor or pharmacist. This summary was last updated in September

4 TABLE OF CONTENTS I Introduction Page 5 II Quality aspects Page 6 III Non-clinical aspects Page 7 IV Clinical aspects Page 7 V User consultation Page 8 VI Overall conclusion, benefit/risk assessment and Page 9 Recommendation Table of content of the PAR update Page 11 4

5 I INTRODUCTION Based on the review of the data on quality, safety and efficacy, the Medicines and Healthcare products Regulatory Agency (MHRA) granted Viridian Pharma Ltd a Marketing Authorisation for the medicinal product Sodium Chloride 1 mmol/ml Oral Solution (PL 20346/0008) on 30 th July The product is a prescription-only medicine (POM) indicated for correction of mild to moderate hyponatraemia in infants. The application was submitted under Article 10a of Directive 2001/83/EC, as amended, claiming to be an application for a product containing an active substance of well-established use. During assessment of this national abridged application major objections with respect to the efficacy and safety of the product were raised. The application was considered by the Commission on Human Medicines (CHM) at the meeting in October In response to the CHM advice, the applicant has provided new bibliographic efficacy and safety data from appropriate sources to support the requested indication and posology. The information provided was adequate and the issues were resolved. The procedure was positively concluded on 30 th July The active ingredient, sodium chloride, maintains the osmotic tension of the blood and tissues. With the exception of the clinical case series, no new non-clinical or clinical studies were conducted for this application, which is acceptable given that this is a bibliographic application for a product containing an active ingredient of well-established use. Bioequivalence studies are not necessary to support this application. The MHRA has been assured that acceptable standards of Good Manufacturing Practice (GMP) are in place for this product type at all sites responsible for the manufacturing and assembly of this product. Evidence of compliance with GMP has been provided for the named manufacturing and assembly sites. A summary of the pharmacovigilance system and a detailed risk management plan have been provided with this application and these are satisfactory. 5

6 II QUALITY ASPECTS II.1 Introduction This product is a non-sterile aqueous solution for oral administration containing 1 mmol (58.44 mg) of sodium chloride per ml, as an active ingredient. The excipients present in this product are potassium sorbate (E202), citric acid (E330) and purified water. All excipients comply with their respective European Pharmacopoeia monographs. Satisfactory Certificates of Analysis have been provided for these excipients. The finished product is packaged in an amber glass bottle with polypropylene screw cap and low density polyethylene (LDPE) liner containing 100 ml. The bottle is packed in a cardboard carton containing a 5 ml oral syringe with an adaptor together with the patient information leaflet. Satisfactory specifications and Certificates of Analysis have been provided for all packaging components. All primary packaging complies with the current European regulations concerning materials in contact with food. II.2 Drug Substance INN: Sodium chloride PhEur name: Sodium chloride Chemical name(s): Sodium chloride Molecular formula: NaCl Molecular weight: g/mol Appearance: White or almost white, crystalline powder or colourless crystals or white or almost white pearls. Solubility: Freely soluble in water and very slightly soluble in ethanol. Sodium chloride is the subject of the European Pharmacopoeia monograph. All aspects of the manufacture and control of the active substance, sodium chloride, are covered by a European Directorate for the Quality of Medicines and Healthcare (EDQM) Certificate of Suitability. II.3 Medicinal Product Pharmaceutical Development The objective of the development programme was to formulate a safe, efficacious and stable oral solution containing 1 mmol/ml of sodium chloride. Manufacture of the product A satisfactory batch formula has been provided for the manufacture of the product, along with an appropriate account of the manufacturing process. The manufacturing process has been validated using the minimum commercial scale batch sizes and has shown satisfactory results. The applicant has committed to perform further process validation on full scale commercial batches. Finished Product Specification The finished product specification is satisfactory. The test methods have been described and have been adequately validated. Batch data have been provided that comply with the release specifications. Certificates of Analysis have been provided for any working standards used. Stability of the product Finished product stability studies have been conducted in accordance with current guidelines and in the packaging proposed for marketing. 6

7 Based on the results, a shelf-life of 2 years with a storage condition Keep bottle in outer carton has been set. After first opening the bottle the product may be used for up to 1 month. These are satisfactory. II.4 Discussion on chemical, pharmaceutical and biological aspects The grant of a Marketing Authorisation is recommended. III NON-CLINICAL ASPECTS III.1 Introduction As sodium chloride is a widely used, well-known active substance, the applicant has not provided any additional studies and none are required. An overview based on a literature review is appropriate. The non-clinical overview has been written by an appropriately qualified person and is a suitable summary of the non-clinical aspects of the dossier. III.2 Pharmacology Not applicable for this product type. Refer to section III.1; Introduction detailed above. III.3 Pharmacokinetics Not applicable for this product type. Refer to section III.1; Introduction detailed above. III.4 Toxicology Not applicable for this product type. Refer to section III.1; Introduction detailed above. III.5 Ecotoxicity/environmental risk assessment (ERA) The Marketing Authorisation holder has provided adequate justification for not submitting an Environmental Risk Assessment. This is acceptable as sodium chloride is an electrolyte and is exempt from the requirement to conduct an ERA. III.6 Discussion on the non-clinical aspects No new non-clinical studies were conducted, which is acceptable given that this is a bibliographic application for a product containing an active ingredient of well-established use. There are no objections to the approval of this product from a non-clinical point of view. IV CLINICAL ASPECTS IV.1 Introduction In addition to the submission of published clinical references the applicant has also provided a case series of treatment with oral sodium chloride. With the exception of the case series, no new efficacy or safety studies have been provided and none are required for this type of application. A comprehensive review of the published literature has been provided by the applicant, citing the well-established clinical pharmacology, efficacy and safety of sodium chloride. The applicant s clinical overview has been written by an appropriately qualified person and is considered acceptable. IV.2 Pharmacokinetics No new pharmacokinetic data were submitted and none were required for an application of this type. IV.3 Pharmacodynamics No new pharmacodynamic data were submitted and none were required for an application of this type. 7

8 IV.4 Clinical efficacy The clinical efficacy of sodium chloride is well-established. This was supported by the review of the bibliographic data and the clinical case series. IV.5 Clinical safety No new safety data were submitted and none were required for this bibliographic application. Safety is adequately reviewed in the clinical overview. The safety profile of sodium chloride is well-known. IV.6 Risk Management Plan (RMP) The Marketing Authorisation Holder (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 Sodium Chloride 1 mmol/ml Oral Solution. A summary of safety concerns and planned risk minimisation activities, as approved in the RMP, is listed below: IV.7 Discussion on the clinical aspects The clinical overview has been written by an appropriately qualified physician and is a suitable summary of the clinical aspects of the dossier. The publicly available bibliographic data does support the claim of well-established use for the sought indication in the target population. The applicant has also provided a clinical case series to support this application. The grant of a Marketing Authorisation is recommended. V USER CONSULTATION The package leaflet 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 language used for the purpose of user testing the PIL was English. The results show that the package leaflet meets 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. 8

9 VI OVERALL CONCLUSION, BENEFIT-RISK ASSESSMENT AND RECOMMENDATION QUALITY The quality of the product is acceptable and no new non-clinical or clinical concerns have been identified. Extensive clinical experience with sodium chloride is considered to have demonstrated the therapeutic value of the compound. The benefit risk is, therefore, considered to be positive. Summary of Product Characteristics (SmPC), Patient Information Leaflet (PIL) and labelling In accordance with Directive 2010/84/EU the Summaries of Product Characteristics (SmPCs) and Patient Information Leaflets (PILs) for products that are granted Marketing Authorisations at a national level are available on the MHRA website. Labelling 9

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11 Table of content of the PAR update Steps taken after the initial procedure with an influence on the Public Assessment Report (Type II variations, PSURs, commitments) Date submitted Application type Scope Outcome 11