Active substance / Generic: Meloxicam
This medicine is approved for use in the European Union
On 9 June 2011, the Committee for Medicinal Products for Veterinary Use (CVMP) adopted a positive opinion, recommending the granting of a marketing authorisation for the veterinary medicinal product Emdocam, a meloxicam 20 mg/ml solution for injection intended for use in cattle, pigs and horses. The applicant for this veterinary medicinal product is Emdoka bvba.
The active substance of Emdocam is meloxicam, an anti-inflammatory and anti-rheumatic product, non-steroids (oxicams) ATCvet code: QM01AC06.
The benefits of Emdocam are the alleviation of inflammation and relief of pain in the approved indications. The most common side effects are a slight transient swelling at the injection site following subcutaneous administration in cattle, and in horses a transient swelling at the injection site.
The approved indication is:
Cattle: For use in acute respiratory infection with appropriate antibiotic therapy to reduce clinical signs in cattle. For use in diarrhoea in combination with oral re-hydration therapy to reduce clinical signs in calves of over one week of age and young, non-lactating cattle. For adjunctive therapy in the treatment of acute mastitis, in combination with antibiotic therapy.
Pigs: For use in non-infectious locomotor disorders to reduce the symptoms of lameness and inflammation. For adjunctive therapy in the treatment of puerperal septicaemia and toxaemia (mastitis-metritis-agalactia syndrome) with appropriate antibiotic therapy.
Horses: For use in the alleviation of inflammation and relief of pain in both acute and chronic musculoskeletal disorders. For the relief of pain associated with equine colic.
Emdocam: Quality assessment
Emdocam is a generic medicinal product of a reference medicinal product previously authorised by the Community, Metacam 20 mg/ml solution for injection, for which the marketing authorisation holder (MAH) is Boehringer Ingelheim Vetmedica GmbH.
Emdocam, like the reference medicinal product Metacam, is an aqueous solution for injection and consists of the active substance meloxicam (20 mg/ml) and the excipients ethanol (preservative), poloxamer 188, meglumine, glycine, polyethylene glycol (macrogol) 300, sodium hydroxide, hydrochloric acid and water for injections.
The product is to be packaged in 50 ml, 100 ml and 250 ml clear Type I glass vials closed with bromobutyl bungs and aluminium caps.
Like the reference product, the generic product contains the active substance at a concentration of 20 mg/ml meloxicam. The excipient ethanol (anhydrous) is included in the formulation of the generic product as an antimicrobial preservative at a concentration of 150 mg/ml, which is in line qualitatively and quantitatively with the preservative in the reference product, for which the SPC is publicly available. Further information on the composition details of the reference product, Metacam 20 mg/ml solution for injection for cattle, pigs and horses, is drawn from publicly available information on its SPC. The applicant has developed a preparation which is identical to the reference product but which excludes disodium diaminoethane-tetraacetic acid (Na2-EDTA).
This generic product application was the subject of a CVMP Scientific Advice procedure (EMEA/V/SA/053/09/1) in which this difference in composition between the generic and reference product was considered. The applicant has investigated the influence of the omission of disodium EDTA from the generic product formulation in line with recommendations in Scientific Advice received from the CVMP. Furthermore the function of each of the chosen excipients is explained and justified with particular emphasis on those with a solubility function.
The suitability of terminal sterilisation was investigated during development studies and the product was found not to be heat labile. Arising from these studies, terminal sterilisation is the method of choice for the product as it affords the best sterility assurance.
No overages are included in this medicinal product.
Method of manufacture
The manufacturing formulae for batch sizes of the proposed range of batch sizes are presented. The manufacturing process is a simple conventional process involving the sequential addition and mixing of the excipients and active substance in water for injections followed by terminal sterilisation in its final container.
Process validation is presented for three batches which were then filled into all the proposed vial sizes.
Overall conclusion on quality
In general, Part Emdocam: Quality assessment of the dossier is of good quality and takes into account current rules and guidelines. Development pharmaceutics of the formulation is satisfactorily explained. The product is a simple aqueous solution for injection which utilises standard pharmaceutical excipients. The manufacturing process is described in detail and is suited to provide a finished product of constant quality. The active substance is the subject of a monograph in the Ph. Eur. The control tests of the finished product cover the relevant quality criteria and are suited to confirm adequate and constant product quality. Stability of both the active substance and the formulated product has been demonstrated. The shelf-life, in-use shelf-life and absence of specific storage precautions for the finished products have been justified.
Meloxicam: Efficacy assessment
Given that the proposed bioequivalence of the test and reference products was accepted, the CVMP agreed that there should be no difference between the two products in respect of their efficacy profiles, and that no efficacy data were therefore required for Emdocam 20 mg/ml solution for injection.
Emdocam: Benefit risk assessment
The application for Emdocam 20 mg/ml solution for injection for cattle, pigs and horses is a generic application and is submitted in accordance with Article 13.1 of Directive 2001/82/EC. The product was developed in such a way as to closely resemble the formulation of the originator product, Metacam 20 mg/ml solution for injection for use in cattle, pigs and horses.
It is considered that direct therapeutic benefits result from the claimed efficacy of the product in reducing clinical signs associated with:
• respiratory disease in cattle, diarrhoea in calves and young non-lactating cattle and acute mastitis in cattle
• non-infectious locomotor disorders in pigs and puerperal septicaemia and toxaemia in sows
• acute and chronic musculoskeletal disorders in horses
and consequently may be considered to benefit animal welfare and aid in the control of inflammatory symptoms associated with the disorders specified in section 4.2 of the SPC.
Indirect benefits may be considered to arise from the reduction in severity of illness in the above conditions which will consequently have a positive benefit in respect of improved herd productivity.
Given the nature of the active substance (meloxicam, an NSAID) it is considered that the following animals could be at risk of toxicity following administration of the product:
• foals less than 6 weeks of age and in diarrhoeic calves less than 1 week old
• animals suffering from impaired hepatic, cardiac or renal function and haemorrhagic disorders
• animals showing evidence of ulcerogenic gastrointestinal lesions
• animals with hypersensitivity to the product or to any of the excipients
• dehydrated, hypovolaemic or hypotensive animals.
Although use of the product in pregnant cows and sows is indicated, use of the product in pregnant mares is not.
Given the nature of the active substance (NSAID) it is considered that the following circumstances may result in an increased risk of toxicity following administration of the product:
• simultaneous use with another NSAID or a glucocorticoid
• simultaneous use with an anticoagulant.
The following potential risks to users have been identified:
• possible anaphylactoid-type reactions in people with hypersensitivity to the active substance meloxicam or any of the excipients
• accidental self-injection may give rise to pain.
The following target animal tolerance risks have been identified:
• transient local swelling at the injection site following subcutaneous administration of the product to cattle
• transient local swelling at the injection site following intravenous administration of the product to horses.
Risk management or mitigation measures
Appropriate information and warnings are included in the SPC and product information to minimise risks for the animals, the user and for the environment.
Evaluation of the benefit risk balance
In the opinion of CVMP, the information provided has demonstrated that the overall benefit/risk balance for this product is positive.
Conclusion on benefit risk balance
Given the nature of the application (a generic) and the fact that the formulation of both the test and reference products can be considered to be similar, the CVMP considered that the benefits and the risks for both Emdocam 20 mg/ml solution for injection and the reference product Metacam 20 mg/ml solution for injection should be the same.
In addition, the applicant has justified the omission of bioequivalence studies in accordance with section 4(b) of the CVMP bioequivalence guidelines.
Based on the CVMP review of the data on quality, safety and efficacy, the CVMP considers that the application for Emdocam is approvable.
Based on the original and complementary data presented, the Committee for Medicinal Products for Veterinary Use concluded that the quality, safety and efficacy of the product were considered to be in accordance with the requirements of Directive 2001/82/EC as amended.