Angelini Acraf - Ancona

The plant

Angelini ACRAF S.p.A. carried out production at the Ancona plant, the capital of the Marche region in central Italy, situated 7 km from one of the most important ports in the Adriatic Sea, 5 km from the exit of the A14 motorway south of Ancona and about 20 Km from "Raffaello Sanzio" airport.  The Ancona plant is EU-GMP authorized, regularly inspected by the Italian Medicines Agency (AIFA) and produces medicinal products that are exported to over 40 countries in different continents.  Also manufactured are some types of highly active products such as hormones and antibiotics not beta-lactams/cephalosporins. The Ministry of Health has also authorized the production of biocides, cosmetics, medical devices and the use of narcotic and psychotropic substances for the manufacture of drug products.

The production site is certified by TUV South of Munich for the ISO regulations:

Size and people
The plant covers a property area of ​​177,000 square meters which is used as follows:
  • 15.540 mq production departments,
  • 660 mq experimental drugs production department
  • 2.340 mq chemical and microbiological laboratories,
  • 5.000 mq warehouse for components (raw materials and packaging materials),
  • 21.700 mq distribution warehouse,
  • 21.650 mq offices and facilities.

The manufacturing plant in Ancona, active for over 40 years, has over time been subjected to several renovations and reorganizations, and, to date, has about 523 employees, 57% of which  work in the &quotManufacturing and Warehouses&quot area, 13% in the &quotQuality&quot Area, 15% in the Engineering Maintenance and Industrialization departments , and the remaining 15% as Staff. The average age of employees is relatively low - 55% of the workforce, in fact, is less than 40 years old - and there is a high percentage of high school graduates (74%) and university graduates (23%).  Excluding the working population, university graduates reach 47%.

Technological Asset  
In the period 2000-2013 approximately €100 million have been invested in the plant, both in technologies and facilities, in order to adapt it to the increased production and quality requirements.  The production site has a hightechnological asset with processing and packaging machines with cutting-edge modern automatic control systems, high level of computerization with various software fully validated for warehouse management, weighing, quality control and Batch Record. The production of non-sterile pharmaceutical forms in product exposed rooms designed in Class-D, primary packaging separate from secondary packaging with its own HVAC system, contribute to making Ancona a site of technological excellence and maximum application of GMP.

The production capacity currently exploited is approximately 96.000.000 units per year, about 50% of which solids, 33%  liquid, 15% semi-solid and 2% sterile.

Contract Manufacturing
The maximum production capacity of the plant is impressive and is around 150 million units per year of the major pharmaceutical forms of which only 64% is currently being exploited.  As evident by these figures, a large amount of production capacity appears to be free which is potentially available to possible partners, in particular for liquid, semi-solid and sterile pharmaceutical forms both for medicinal products for human use and for experimental drugs.  Also available for third party activities, is a qualified analytical laboratory authorized for control and release of batches inside EC/EEA area, also of medicinal products manufactured in non-European countries without mutual recognition agreements and manufacturing compliance  facilities able to prepare and maintain form 3 of the CTD.  The logistically favorable location of the plant near the port, airport, railway and highway, the high technological level of the production facilities, the quality system, safety and environment certifications, the reliability of company management, guarantee products with a high quality/price ratio.

For Contract Manufacturing contact:
Phone: +39 071 809339

The warehouses are very impressive and have a storage capacity of approximately 7,500 pallet spaces for components and 19,300 pallet positions for the finished product fully managed by the SAP computer system.  Withdrawal movements are managed with bar codes and radio frequency systems that allow an unambiguous identification of the goods and the quality conditions of the material.  Inside the components warehouse is also installed a sampling box, with its own HVAC system, dust extraction hood and NIRS analytical instrumentation for performing real-time identification tests on the individual containers of raw materials. The distribution warehouse is also equipped with a refrigerator for storing medicines at a temperature below 8°C and is authorized to sell narcotic drugs and psychotropic substances.

Material Handling

The first phase of the production is carried out at the Weighing Centre. All stages of weighing are administered inside  boxes equipped with HVAC systems, dust suppression hoods, and modern scales connected to dedicated validated software (PMX DISY), which manages all operations and guides the operators. Another box is dedicated to weighing particularly active raw materials such as hormones, beta-lactam antibiotics/cephalosporin drugs. This box is also equipped for carrying out sampling and chemical analysis, thus avoiding the possibility of cross contamination.



Medicine for human use
The production of solids is the core business of the Ancona plant. Two granulation poles, one of which is moisture reduced, two direct mixing poles, various tablet presses and drum mixers, four automatic lines for packaging blisters, two automatic sachet packaging lines where it is possible to produce powders, effervescent granules and tablets, tablets, film coated and sugar coated tablets.

The departments producing non-sterile liquids are equally sophisticated. Several preparation reactors from 500 to 10.000 liters storage vessels, an automatic drops packaging line, an automatic syrups and mouthwash packaging line, an automatic ready for use douches packaging line, an automatic sprays packaging line, a automatic micro-enemas packaging line, an automatic single-use vials packaging line, a bottles packaging line.

The semisolid production departments also represent a strong point of the plant. This is testified by the 100,000,000 suppositories produced each year and two turbo-automatic packaging lines, as well as the creams department with cutting edge preparation equipment which includes CIP systems and an automatic packaging line for single-dose tubes and creams for vaginal administration.

The department for vials sterilized in the final container is equipped with a system for producing WFI water fed by PW water, equipped with two storage receptacles and a distribution ring maintained at 80°C in perennial recirculation, several reactors of various capacities up to a maximum of 500 liters, sterilizing filtration systems, storage vessels, product transport lines and power supply fully cleaned and sterilized in place (CIP and SIP), two closed tip vial fillers, a double door depyrogenation oven, a double door sterilization autoclave, an automatic inspecting machine, an automatic line for packaging vials in dumpsters.

Experimental drugs
The Ancona plant is also authorized by AIFA to produce investigational medicinal products (IMP) for all pharmaceutical forms manufactured industrially.  For this purpose a modern department has been setup where lots intended for clinical trial for non-sterile liquid and solid pharmaceutical forms can be produced, from step 1 onwards. The sterile pharmaceutical forms can be made directly in the production department as well as large lots for all other pharmaceutical forms authorized.  The department has highly qualified staff able to prepare all documentation required by recent laws (Product Specification File, IMPD, etc..) and follow the product from the preparation phase to masking, packaging, labeling, control, release and shipment to the test center.  This department has been built to support the development of new business products and can also be made ​​available to partners who wish to entrust us with their new products for clinical trials and subsequent industrial production.


Quality area

Quality control
The entire activity of the Quality Control analytical laboratories are handled through the software validated LIMS QUALITY+. Barcodes trace the entire history of the samples and analytical certificates. 

The laboratories are equipped with the latest generation of analytical instrumentation: gas chromatography, HPLC, UV-VIS spectrophotometers, IR, FT-IR spectrometer in issuance for determining heavy metals, NIRS (qualitative and quantitative), titrator, pH meters, density meters , polarimeters, dissolution test, LAL test equipment, test disaggregation, room and hood to test for sterility, equipment for biochemical identification of microorganisms. A dedicated laboratory performs ongoing ICH stability tests.

The facilities for the quality control laboratories is sufficient to absorb all analytical activities related to normal industrial production, the production of experimental products and can also be made ​​available to partners who want to entrust control activities for their products to a qualified laboratory approved for control and batch release within the EMEA also for medicinal products manufactured in non-European countries without mutual recognition agreements.

Quality Assurance
The Quality Assurance is modernly organized to meet the demands of the EU-GMP. 
Qualified personnel regularly carries out the following activities:
  • Validation of processes, cleaning activities, holding times, computerized systems
  • Product Quality Review, Change Control and Standard Operating Procedure (SOP)
  • Internal and External Audits (including manufacturers of APIs); CAPA system (corrective and preventive action) for failure and complaints management
  • Staff Training
  • Batch Record Review

The Batch Record Review is managed by PMX EBR validated software. All products have methods of preparation and an electronic packaging that guide production operators in the proper execution of all the individual stages of production and process controls. The batch release is performed by a Qualified Person with electronic signature.

Manufacturing compliance
The Quality facilities area is complemented by an organizational unit that continuously checks that manufacturing and control methods correspond to the authorizing requirements of the various national health authorities.  These facilities also handles all Quality Agreements for products manufactured in the Ancona plant and is able to manage, with all partners, the preparation and ongoing regulatory maintenance of form 3 of the Common Technical Document (CTD) by setting all the relevant changes to the standards enforced in the various countries.