Ancona Plant Quality and Innovation 100% MANUFAC TURING SOLUTIONS

Transcription

1 HIGH Ancona Plant Quality and Innovation 100% MANUFAC TURING SOLUTIONS TECHNOLOGY

2 THE PLANT WHERE A.C.R.A.F. S.p.A. performs the manufacturing activities in the plant of Ancona, capital of the region of Marche in the central Italy. The manufacturing site is 7 km from one of the most important seaports of the Adriatic Sea, 5 km from the toll gate Ancona Sud of the motorway A14 and about 20 km from the airport Raffaello Sanzio. The manufacturing plant of Ancona is EU-GMP authorised and periodically submitted to the inspections of Italian Agency of Medicinal products (AIFA). The drug products here manufactured are marketed in more than 40 countries among all the continents. The manufacturing site can produce some kinds of high potency drug products like hormones and non-beta-lactamic/ cephalosporin antibiotics. The Health Authority has also authorised the production of biocides, cosmetics, medical devices and the use of narcotic and psychotropic substances for the manufacture of drug products. CERTIFICATIONS The manufacturing plant is certified by TUV South of Munich for the ISO regulations: ISO 9001:2008, ISO 13485:2003, ISO 14001:2004 for the environment, OHSAS 18001:2007 for the safety. ENVIRONMENTAL COMMITMENT Special attention is focused on the environmental issues. A complete cycle of waste handling is applied with activities of recycling and recovery. The consumed electric power is almost completely produced by a modern co-generation system which, together with the solar energy produced by the kw photovoltaic system, allows to save about tons of CO2 per year. 3

3 DIMENSIONS The manufacturing site is placed on a proprietary area of sm, which are divided: sm for the manufacturing departments, 660 sm for the manufacturing department of the investigational drug products, sm for the chemical and microbiological laboratories, sm for the warehouse of the starting materials (ingredients and packaging), sm for the supply warehouse, sm for offices and facilities. The manufacturing plant of Ancona, working for more than 40 years, has been repetitively renewed and re-organized over the time and at present it counts 523 people, whose the 57% works in the Manufacturing and Warehouses area, the 13% in the Quality area, the 15% in the Engineering, Maintenance and Technology Transfer departments and the remaining 15% as staff. The average age is quite young the 55% of the personnel actually is under 40 years and there is an high percentage of people which have obtained a diploma (73%) and a degree (23%). Without considering the workers of the factory, the graduated reach the 47%. TECHNOLOGICAL ASSET During the period about have been invested both in technologies and in facilities to adapt the plant to the increased market demand and to the highest qualitative standards. The manufacturing site has a high technological asset with advanced manufacturing and packaging equipments provided of modern automated control systems and a high level of computerization by means of fully validated softwares for the management of the warehouse, dispensing, the quality control and the batch record. The manufacturing of non-sterile pharmaceutical forms in the class D-designed rooms for exposed product and the primary packaging separated from the secondary packaging and provided of own HVAC system, help to make the Ancona plant an excellent site for technologies and full GMP application. MANUFACTURING CAPACITY The currently used manufacturing capacity is about pieces per year whose approximately the solids represent the 50%, the liquids the 33%, the semisolids the 15% and the sterile forms the 2%. CONTRACT MANUFACTURING The full manufacturing capacity of the plant is significant and is about pieces per year of the main pharmaceutical forms, actually only for 64% used. As these numbers suggest, at present a wide quantity of manufacturing capacity is still free and available for potential partners, in particular for non sterile - sterile liquids and semisolids, both for human use medicinal products and for investigational medicinal products. The highly qualified analytical laboratories are also available for partners, authorized for control and release of batches inside EC/ EEA area, also of medicinal products manufactured in extra-ec countries without mutual recognition agreement. As a completion a Manufacturing Compliance structure is available, in order to ensure module 3 CTD life cycle. The logistically optimum plant positioning, close to airport, railways and highway, the high technological standards, the quality safety environment certifications, the reliability of company management assure product with high quality / price ratio. CONTRACT MANUFACTURING CONTACT: acrafcmfg@angelini.it Phone:

4 WAREHOUSES The warehouses dimensions are very important, the storage capacity is about pallet boxes for the components and pallet boxes for the finished products, completely managed by the SAP system. The picking operations are managed by bar codes and radiofrequency-systems which allow the unambiguous identification of the products and of the qualitative status of the materials. The components warehouse is also equipped of a sampling box, provided of own HVAC system, down cross hood and NIRS analytical instruments to perform real time identification test of the raw materials in each single container. The finished products warehouse is also provided of refrigerating room to store drug products at temperature below 8 C and is authorized to market narcotic and psychotropic substances. MATERIAL HANDLING The first manufacturing step is performed in the dispensing area. All the weighing operations are managed inside boxes provided of HVAC systems, down cross hood and modern balances connected to a specific validated software (PMX DISY) which controls all the operations and drive the operators. A specific box is dedicated to high potency drug substances like hormones, non-beta-lactamic/cephalosporin antibiotics and narcotic substances. This box is also equipped to perform sampling activities and chemical analysis in order to avoid cross contamination risk. HUMAN USE PHARMACEUTICAL PRODUCTS SOLIDS The production of oral solids is the core business of the Ancona plant. Two granulation areas, whose one is at reduced humidity, two areas for direct powders mixing, several high-speed tabletting machines and coating machines for film/ sugar coating, four automated packaging lines for blisters, two automated packaging lines for sachets, where it s possible to produce powders, granules, effervescent tablets and granules, tablets, film coated and sugar coated tablets. NON STERILE LIQUIDS Manufacturing departments for non-sterile liquids are well-equipped too. Several dissolution tanks and storage tanks from 500 to l, an automated packaging line for oral drops, an automated packaging line for syrups and mouthwashes, an automated packaging line for vaginal solutions, an automated packaging line for oral sprays, an automated packaging line for micro-enemas, an automated packaging line for single dose bottles and an automated packaging line for multi-dose bottles. SEMISOLIDS Also the manufacture of semisolids is a strong point of the plant suppositories and pessaries per year are currently manufactured, two turbo-emulsifiers and two automated packaging lines are available. Also the creams department is provided of advanced manufacturing equipment, which has also CIP system and an automated packaging line for tubes and vaginal creams for single dose administration. TERMINALLY STERILIZED AMPOULES The terminally sterilized ampoules sector is provided of a Water for Injections (WFI) production system, fed with purified water (PW), with two storage tanks and distribution loop maintained at 80 C in continuous recycle, several tanks of various capacity up to a maximum of 500 l, sterilizing-filtering systems, storage tanks, carrying lines which may be completely cleaned and sterilized in situ (CIP and SIP), two filling machines for closed top ampoules, a double-door dehydrogenization oven, a double-door autoclave for steam sterilisation, an automatic electronic testing machine for ampoules visual inspection and an automated packaging line for ampoules into trays. 6 7

5 INVESTIGATIONAL MEDICINAL PRODUCTS The plant of Ancona is also authorized by AIFA to manufacture investigational medicinal products (IMP) concerning all the authorized pharmaceutical forms manufactured on industrial scale. For this aim a modern department has been built where clinical studies batches may be produced for non-sterile liquids and solids starting from phase I and subsequent ones. The sterile pharmaceutical forms may be directly produced in the specific manufacturing department such as the industrial scale batches for all the other authorized pharmaceutical forms. The department is provided of highly qualified personnel which is trained to prepare all the required documentation according to the current laws and guidelines (Product Specification File, IMPD and so on) and to follow the product from the manufacture to the blinding, packaging, labeling, control, release and shipment step to the experimental centers. This department has been built to support the development of the new products of the company and may be available for potential partners interested to outsource their investigational drug products and the subsequent industrial production. QUALITY QUALITY CONTROL All analytical operations in Quality Control is managed by a LIMS validated software QUALITY +. Bar codes monitor the whole life of samples and analytical certificates. The laboratories are provided of new generation analytical instruments: gas-chromatographs, high pressure liquid-chromatographs, UV-VIS, IR, FT-IR spectrophotometers, atomic emission spectrometry for heavy metals determination, qualitative and quantitative NIRS (near infrared spectrometry), titrators, phmeters, densimeters, polarimeters, automatic equipment for dissolution test and for disintegration test, LAL test equipment, specific room and fan for sterility tests, equipment for biochemical identification of microorganisms. A specific laboratory performs ICH and on-going stability studies. The organization of CQ laboratories is such to fulfill all the analytical activities linked to the standard industrial production and investigational medicinal production and may be also made available for partners interested to outsource the control of their products to a qualified laboratory authorized to control and release within EC/EEA area also drug products manufactured in extra EU countries without Mutual Recognition Agreement. 8 9

6 FORMS & FORMATS QUALITY ASSURANCE The Quality Assurance has a modern organization to fulfill the EU-GMP requirements. Qualified personnel punctually performs the following activities: Validation of the manufacturing processes, cleaning activities, holding times, softwares Product Quality Review, Change Control and Standard Operating Procedures management (SOP) Internal and external Audit (including API manufacturers); CAPA system (preventive and corrective actions) for failure and complaint management Training of the personnel Batch Record Review MANUFACTURING COMPLIANCE The organization of the Quality Department is completed by a functional unit which constantly verifies the compliance of the manufacturing and control methods with the authorized requirements of the various international Health Authorities. This unit manages also all the Quality Agreements for the products manufactured in the plant of Ancona and organizes the continuous regulatory compliance of Module 3 of the Common Technical Document (CTD) with all the partners preparing all the relevant Marketing Authorization variations according to the standards in force in the involved countries. The Batch Record Review is managed by the validated software PMX EBR. All the products have electronic manufacturing and packaging methods which drive the personnel to the right performance of any single manufacturing step and relevant in-process controls. The Qualified Person batch release is performed through electronic signature. 10

7 LIQUIDS MOUTHWASHES & SYRUPS FORMAT BATCH SIZE [l] PIECES/MIN BOTTLE Material CAPSULE Type MEASURING CUP & SYRINGE SEMISOLIDS CREAMS, GELS, PASTES IN TUBES FORMAT MAX BATCH SIZE [Kg] PIECES/MIN TUBE Material & Closures APPLICATOR Material MINI-CARTON n of Applicators 120 ml Amber or Transparent Glass or Plastic PET 200 ml Amber Glass or Plastic HDPE 240 ml Transparent Glass 250 ml Plastic PET Child Proof or Tamper Evident Cup: 10 ml - 20 ml - 45 ml Syringe: 5 ml 15 g Plastic LDPE 2 Applicators 30 g Aluminium tube closed by folding & plastic cap Plastic PP 6 Applicatrors 50 g Not Applicable Not Applicable 75 ml HDPE/PE/ALU/PE/HDPE Laminate tube closed by heat-sealing & plastic cap Not Applicable Not Applicable 500 ml Plastic PET Plastic HDPE 100 g Aluminium tube closed by folding & plastic cap Not Applicable Not Applicable DROPS FORMAT BATCH SIZE [l] PIECES/MIN BOTTLE Material CAPSULE Type DROPPER 12,5 ml SUPPOSITORIES IN PLASTIC SHELL FORMAT ALVEOLUS VOLUME MAX BATCH SIZE [Kg] ALVEOLI/H ALVEOLI PER STRIP - STRIPS PER CARTON 15 ml 20 ml 30 ml Amber Glass Child Proof Lucas Dropper or Tige Glass Pipette Dropper 0.7 ml , 4 or 5 alveoli per strip 1 or 2 strips per carton 0.93 ml ml ml ( if 1 strip per carton) 3, 4 or 5 alveoli per strip 1 or 2 strips per carton VAGINAL DOUCHE FORMAT BATCH SIZE [l] PIECES/MIN BOTTLE Material PIPE Type & Material CUP Material SUPPOSITORIES IN ALUMINIUM SHELL 140 ml Plastic LDPE Special design Plastic LDPE Plastic PP FORMAT ALVEOLUS VOLUME MAX BATCH SIZE [Kg] ALVEOLI/H ALVEOLI PER STRIP - STRIPS PER CARTON FLACONS FORMAT BATCH SIZE [l] PIECES/MIN BOTTLE Material CAPSULE Type 1.3 ml ml alveoli per strip - 2 strips per carton 5 ml 10 ml Amber Glass PP hood + Alu seal + PE gasket PESSARIES IN PLASTIC SHELL FORMAT ALVEOLUS VOLUME MAX BATCH SIZE [Kg] ALVEOLI/H ALVEOLI PER STRIP - STRIPS PER CARTON OROMUCOSAL SPRAY FORMAT BATCH SIZE [l] PIECES/MIN BOTTLE Material CAPSULE Type 15 ml max Spray vol: 0.17 or 0.20 ml 120 Plastic HDPE 30 ml max Spray vol: 0.17 ml 1.9 ml alveoli per strip - 3 strips per carton alveoli per strip - 2 strips per carton alveoli per strip - 1 strips per carton alveoli per strip - 2 strips per carton STERILE LIQUIDS MICRO ENEMAS FORMAT MAX BATCH SIZE [Kg] PIECES/MIN BOTTLE Material APPLICATOR Material CAP Material AMPOULES - Closed Ampoules "Marzocchi" type FORMAT BATCH SIZE (Ampoules) AMPOULES/ MIN BOTTLE Material 3 g 9 g Plastic PE-EVA 6 alveoli per strip - 3 strips per carton 6 alveoli per strip - 2 strips per carton Plastic LDPE 1 ml / ml / ml / ml / ml Amber or Transparent Glass GELS IN BOTTLE FORMAT MAX BATCH SIZE [Kg] PIECES/MIN BOTTLE Material CAP Material 80 ml Plastic PVC Plastic PP 100 ml 12 13

8 SOLIDS CIRCULAR TABLETS FORMAT BATCH SIZE [tablets] BLISTER: n Tablets per blister CARTONS/MIN diam. 8 mm tab 120 (50 tab) diam. 8 mm tab 70 (30 tab) 6 tab 180 (6 tab) diam. 10 mm tab 372 (12 tab) 204 (24 tab) 136 (36 tab) diam. 11,5 mm tab 70 (20 tab) 25 (60 tab) 15 tab 70 (30 tab) 6 tab 180 (6 tab) diam. 12,5 mm tab 372 (12 tab) 204 (24 tab) diam. 12,5 mm tab 372 (10 tab) 204 (20 tab) 136 (30 tab) diam. 25 mm effervescent tab 30 (12 tab) 30 (12 tab) 4 tab 30 (20 tab) OBLONG TABLETS SACHETS FORMAT BATCH SIZE [tablets] BLISTER n tablets per blister CARTONS/MIN 12 x 4 mm tab 70 (30 tab) 14 x 6 mm tab 70 (10 tab) 70 (20 tab) 25 (60 tab) 15 tab 70 (30 tab) 20 tab 240 (20 tab) 17,46 x 7,93 mm tab 80 (14 tab) 17,46 x 7,93 mm tab 126 (16 tab) 19 x 8 mm tab 240 (1-5 tab) 5 tab 120 (10 tab) 19,05 x 6,6 mm tab 70 (7 tab) STRIP DIMENSION BATCH SIZE [Kg] CARTONS/MIN 64 x 95 mm Single sachet 104 x 105 mm 4 sachets 105 x 105 mm 2 sachets 105 x 105 mm 3 sachets 105 x 125 mm 2 sachets (10 strips/carton) (5 strips/carton) (3 strips/carton) (5 strips/carton) (10 strips/carton) (2 strips/carton) (10 strips/carton) 70 (14 tab) 35 (28 tab) 10 tab 70 (10 tab) 70 (20 tab) 47 (30 tab) 19,05 x 6,95 mm tab 70 (14 tab) 35 (28 tab) 10 tab 70 (10 tab) 70 (20 tab) 47 (30 tab) 22 x 9 mm tab 240 (4 tab) 8 tab 204 (8 tab) 126 (16 tab) 14

9 A.C.R.A.F. S.p.A. Manufacturing plant and administrative office: Via Vecchia del Pinocchio, Ancona - Italy T CONTRACT MANUFACTURING acrafcmfg@angelini.it T