P.O.N. RICERCA E COMPETITIVITA' Azione II "Interventi di sostegno alla ricerca industriale"

Transcription

1 P.O.N. Ricerca & Competitività per le Regioni della convergenza Codice Progetto PON01_02464 cofinanziato a valere sull Asse I - Sostegno ai mutamenti strutturali; Obiettivo operativo Aree scientifico-tecnologiche generatrici di processi di trasformazione del sistema produttivo e creatrici di nuovi settori Azione II: Interventi di sostegno alla ricerca industriale ALLEGATO TECNICO Di seguito sarà descritto l oggetto e le caratteristiche complessive della fornitura con il dettaglio dei requisiti richiesti che il Fornitore aggiudicatario dovrà garantire. 1. CARATTERISTICHE TECNICHE DI FORNITURA FORNITURA DI UN PRODOTTO FARMACEUTICO PER SPERIMENTAZIONE CLINICA DI FASE I/IIa IN EUROPA DI UNA NUOVA ENTITA CHIMICA. FINAL PRODUCT 1. Required fill volume 0,2mL in 0,5 syringe; 2. Required tolerance on the fill volume: about 5%; 3. Required batch size (number of syringes): , depending on the minimum reservoir volume and dead volume; 1

2 4. Batches required: 1 batches filled with 20, 40 and 80mg/mL, respectively; 5. Syringes of 0.5 ml max capacity, mark sign at 0.100mL; 6. Needles: 30-31G, 8-12mm long; 7. Secondary packing: sterile envelope and box required; 8. CLINICAL OPEN LABEL labelling required; 9. Stability testing required; 10. Accelerated stability testing required. OTHER SERVICES 1. CDMO should supply all the components except the API; 2. Storage of finished drug product required; 3. CDMO should be responsible for organizing shipment in Europe of finished product; 4. CDMO should be responsible for managing the finished drug product testing; 5. Finished product requires Qualified Person release to clinic; 6. CDMO is responsible for Qualified Person release; 7. Support for part P of the IMPD. 2

3 ADDITIONAL INFORMATION API 1. Classification: Peptide; 2. Availability: ready to be used; 3. MSDS: available; 4. NOT derived from human or animal origin; 5. Exposure hazards: Undetermined; 6. Supplied sterile and UNCERTIFIED; 7. Supplied as POWDER; 8. Does not contain any live materials; 9. Does not contain any antibiotics; 10. Temperature storage conditions: 4 C; 11. UV chromophore present (λmax=257nm; ε=196.7 M -1 cm -1 ). Quantitation method should be set and validated for the drug product, alternatively HPLC-MS method should be developed and validated; 12. Analytical method validation reports are available for the API, not for the Drug Product; 13. Forced degradation studies are being conducted on the API using the currently available analytical methods; 14. Pre-formulation data NOT available (organic solvent, solubility, ph solubility, pka, Log P, physico-chemical properties, hygroscopicity); 15. No stability concerns with the current API; hydrolysis, oxidation, photo-stable or thermal instability. DRUG PRODUCT 1. Formulation details: Available; 2. No excipients required; 3

4 3. Pilot batches not required; 4. Intravitreal injection as dministration root; 5. The drug product has not been manufactured before and no method of manufacture are available; 6. Manufacturing process validation required; 7. The finished drug product appears colorless, clear, non-viscous solution; 8. There are no special manufacturing precautions/sensitivities, such as light, oxygen, viscosity, solubility, temperature; 9. No specific mixing required; um water compatible filter required; 11. N 2 gas used for filtration (not mandatory); 12. Autoclave sterilization required (to be confirmed); 13. Temperature storage conditions: advisable at 4 C; 14. Analytical test method and validation for drug product is currently unavailable; 15. Due to the simplicity of the formulation, the analytical methods for the current formulation should easily be developed starting from validated analytical methods of the API; 16. Analytical method protocol for the API may be transferred by the sponsor; 17. Analysis to perform for product release: 1) Sterility; 2) Endotoxins; 3) Pyrogens; 4) Visible particles; 5) Sub-visible particles; 6) Purity by HPLC; 7) Content by HPLC; 8) Uniformity of dosage by HPLC; 18. Reference substances: API provided by the sponsor; water, NaOH 1N and NaH 2 PO 4 H 2 O provided by the CDMO. CDMO should be in charge of testing and release of finished product: 1. Test method for finished product; 2. Analysis of finished product (including documentation); 3. Certificate of analysis for finished product; 4. Initial Stability Program; 5. Testing on going stability. 4

5 CDMO should be in charge of production and testing of raw materials: 1. Product specification; 2. Batch identification system; 3. Storage of active substances; 4. Sampling of active substances; 5. Retain reference samples of active substances for 5 years; 6. Procurement of inactive substances (including COA); 7. Storage of inactive substances; 8. Sampling of inactive substances; 9. Test method for inactive substances; 10. Analysis of inactive substances as required from the Contract acceptor relevant procedures; 11. Release of inactive substances; 12. Retain reference samples of inactive substances for 2 years; 13. Process Validation; 14. Cleaning validation; 15. Bill of Materials (BOM) for bulk manufacture; 16. Manufacturing Instructions (Production Operating Instructions - work sheet); 17. Production of bulk material (including batch documentation); 18. In-process control instructions; 19. In-process controls (including documentation); 20. Audit and written approval of the suppliers ( approved suppliers ) for active substance and packaging material; 21. Finished product specification; 22. Batch identification system for finished product; 23. Artwork and labelling text (blister, carton, leaflet, label, etc); 24. Labelling review and approval; 5

6 25. Specifications for packaging materials; 26. Test methods for packaging materials; 27. Procurement of packaging materials; 28. Analysis of packaging materials; 29. Release of packaging materials; 30. Retain samples of packaging materials in the packaging documentation of the batches; 31. Validation of packaging process; 32. Bill of Materials (BOM) for packaging; 33. In-process control instructions; 34. In-process controls during packaging (including documentation); 35. Finished product sampling plan; 36. Sampling of finished product; 37. Retain reference samples of finished product for 2 years after the product expiration; 38. Reconciliation of packaging materials; SPONSOR should be in charge of: 1. Procurement of active substances (including certificates of analysis, CoA); 2. Test method for active substances; 3. Analysis of active substances (including documentation, CoA); 4. Release of active substances. 6