Olanzapine 5,10,15mg Orodispersible Tablets - GOV.UK

1 UKPAR Olanzapine 5mg, 10mg and 15mg Orodispersible Tablets PL 33410/0024-6 & 0084-6. Olanzapine 5MG, 10MG AND 15mg Orodispersible Tablets . PL 33410/0024-6 & 0084-6. UKPAR. TABLE OF CONTENTS. Lay Summary Page 2. Scientific discussion Page 4. Steps taken for assessment Page 12. Steps taken after authorisation summary Page 13. Summary of Product Characteristics Page 14. Product Information Leaflet Page 53. Labelling Page 57. 1. UKPAR Olanzapine 5mg, 10mg and 15mg Orodispersible Tablets PL 33410/0024-6 & 0084-6. Olanzapine 5MG, 10MG AND 15mg Orodispersible Tablets . LAY SUMMARY. On 26th May 2011, the MHRA granted APSLA Limited Marketing Authorisations (licences). for Olanzapine 5mg, 10mg and 15mg Orodispersible Tablets . Olanzapine 5mg, 10mg and 15mg Orodispersible Tablets contain the active ingredient, Olanzapine .

2 Olanzapine belongs to a group of medicines called antipsychotics. Olanzapine 5mg, 10mg and 15mg Orodispersible Tablets are used to treat a condition with symptoms such as hearing, seeing or sensing things which are not there, mistaken beliefs, unusual suspiciousness and becoming withdrawn. People with this disease may also feel depressed, anxious or tense. They are also used to treat a condition with symptoms such as feeling "high", having excessive amounts of energy, needing much less sleep than usual, talking very quickly with racing ideas and sometimes severe irritability. Furthermore, it is also a mood stabiliser that prevents further occurrences of the disabling high and low (depressed) extremes of mood. No new or unexpected safety concerns arose from these applications and it was, therefore, judged that the benefits of taking Olanzapine 5mg, 10mg and 15mg Orodispersible Tablets outweigh the risks; hence Marketing Authorisations have been granted.

3 2. UKPAR Olanzapine 5mg, 10mg and 15mg Orodispersible Tablets PL 33410/0024-6 & 0084-6. Olanzapine 5MG, 10MG AND 15mg Orodispersible Tablets . PL 33410/0024-6 & 0084-6. SCIENTIFIC DISCUSSION. TABLE OF CONTENTS. Introduction Page 4. Pharmaceutical assessment Page 5. Non-clinical assessment Page 8. Clinical assessment (including statistical assessment) Page 9. Overall conclusions and risk benefit assessment Page 11. 3. UKPAR Olanzapine 5mg, 10mg and 15mg Orodispersible Tablets PL 33410/0024-6 & 0084-6. INTRODUCTION. The UK granted APSLA Limited Marketing Authorisations for the medicinal products Olanzapine 5mg, 10mg and 15mg Orodispersible Tablets (PL 33410/0024-6 and 0084-6) on 26th May 2011. Olanzapine 5mg, 10mg and 15mg Orodispersible Tablets are prescription only medicines (POM) and are indicated for: the treatment of schizophrenia.

4 Maintaining the clinical improvement during continuation therapy in patients who have shown an initial treatment response. the treatment of moderate to severe manic episode. the prevention of recurrence of manic episode in patients with bipolar disorder (in patients whose manic episode has responded to Olanzapine treatment). These applications for Olanzapine 5mg, 10mg and 15mg Orodispersible Tablets are submitted under Article of Directive 2001/83/EC, claiming to be generic medicinal products to Zyprexa 5mg, 10mg and 15mg Film-Coated Tablets , authorised via the centralised procedure to Eli Lilly Nederland on 27th September 1996. The UK reference products are Zyprexa Velotab 5mg, 10mg and 15mg Orodispersible Tablets authorised via the centralised procedure to Eli Lilly Nederland on 3rd February 2000.

5 Olanzapine is an antipsychotic, antimanic, and mood stabilising agent that demonstrates a broad pharmacologic profile across a number of receptor systems. The pharmacovigilance system as described by the applicant fulfils the requirements. It also provides adequate evidence that the applicant has the services of a qualified person responsible for pharmacovigilance and has the necessary means for the notification of any adverse reaction suspected of occurring. The Marketing Authorisation Holder did not submit a Risk Management Plan (RMP) and one is not required for this generic application. 4. UKPAR Olanzapine 5mg, 10mg and 15mg Orodispersible Tablets PL 33410/0024-6 & 0084-6. PHARMACEUTICAL ASSESSMENT. DRUG SUBSTANCE. INN: Olanzapine Chemical name: 2-methyl-4-(4-methyl-1-piperazinyl)-10-H -thieno[2,3-b][1,5] benzodiazepine.

6 Structure: Molecular formula: C17H2N4S. Molecular weight: Physical form: Yellow crystalline powder. Solubility: insoluble in water; sparingly soluble in acetonitrile, ethyl acetate and soluble in chloroform. Olanzapine complies with in-house specifications. Synthesis of the drug substance from the designated starting materials has been adequately described, and appropriate in-process controls and intermediate specifications are applied. Satisfactory specification tests are in place for all starting materials and reagents, and these are supported by relevant Certificates of Analysis. Appropriate proof of structure data has been supplied for the drug substance. All potential known impurities have been identified and characterised. An appropriate specification is provided for the drug substance, with suitable test methods and limits.

7 Analytical methods have been appropriately validated and are satisfactory for ensuring compliance with the relevant specifications. Batch analysis data are provided and comply with the proposed specification. Suitable Certificates of Analysis have been provided for all reference standards used. Satisfactory specifications and Certificates of Analysis have been provided for all aspects of the container-closure system. A declaration has been provided that the primary packaging complies with current regulations concerning contact with foodstuff. Appropriate stability data have been generated showing the drug substance to be a physically and chemically stable drug, and supporting an appropriate retest period. 5. UKPAR Olanzapine 5mg, 10mg and 15mg Orodispersible Tablets PL 33410/0024-6 & 0084-6.

8 DRUG PRODUCT. Other ingredients Other ingredients in the tablet core consist of pharmaceutical excipients lactose monohydrate, low substituted hydroxypropyl cellulose (L HPC LH-11) E463, purified water, sodium cyclamate E952, levomenthol and magnesium stearate. All the ingredients with the exception of low substituted hydroxypropyl cellulose (L HPC. LH-11) E463 comply with their relevant European Pharmacopoeia monographs. Low substituted hydroxypropyl cellulose (L HPC LH-11) E463 complies with the USP National Formulary which is considered to provide a satisfactory quality control. None of the excipients used contain material of human origin. A valid Transmissible Spongiform Encephalopathy (TSE) Certificate of Suitability has been provided from the supplier of the magnesium stearate.

9 The applicant has provided a declaration that milk used in the production of lactose monohydrate is sourced from healthy animals under the same conditions as those intended for human consumption. Product development The objective of the development programme was to produce Olanzapine containing products that could be considered generic medicinal products of Zyprexa Velotab 5mg, 10mg and 15mg Orodispersible Tablets . The applicant has provided a suitable product development section. Justifications for the use and amounts of each excipient have been provided and are valid. Comparative in vitro impurity and dissolution profiles have been provided for the proposed and reference products. Manufacture A description and flow-chart of the manufacturing method has been provided.

10 Satisfactory batch formulae have been provided for the manufacture of the products. In-process controls are satisfactory based on batch data and controls on the finished products. Process validation data on pilot-scale batches of each strength have been provided and are satisfactory. The applicant has committed to perform process validation on future commercial-scale batches of each strength. Finished product specification The finished product specifications are satisfactory. Test methods have been described and have been adequately validated, as appropriate. Batch data have been provided and comply with the release specifications. Certificates of Analysis for all working standards used have been provided and are satisfactory. Container-Closure System The products are packaged in push-through blister strips composed of 3-ply aluminium laminated film and plain aluminium foil and come in pack sizes of 28, 35, 56 or 70.