Sterile operation scenarios at GSK-Parma

Transcription

1 Sterile operation scenarios at GSK-Parma R.Cassaniti, N.Trivelli, M.Bini - GSK manufacturing S.p.A. Dexterous Manipulation in hazardous areas workshop- Lyon 21/3/2013 Property of GlaxoSmithKline

2 GSK-Glaxo Smith Kline GlaxoSmithKline plc. ( is a British multinational pharmaceutical, biologics, vaccines, and consumer healthcare company headquartered in London, United Kingdom. It is the world s thirdlargest pharmaceutical company measured by revenues. GlaxoSmithKline plc. was formed in 2000 by the merger of GlaxoWellcome plc. (formed from the acquisition of Wellcome plc. by Glaxo plc.), and SmithKline Beecham plc. (from the merger of Beecham plc., and SmithKline Beckman Corporation). The company s stock is listed on the London stock exchange and ADRs are listed on the NYSE. GlaxoSmithKline plc. have a challenging and inspiring mission: to improve the quality of human life by enabling people to do more, feel better and live longer. GSK is a global organization with offices in over 100 countries and major research centres in the UK, USA, Spain, Belgium and China. GSK produces medicines that treat major disease areas such as asthma, antivirals, infections, mental health, diabetes, cardiovascular, and digestive conditions. In addition, GSK is a leader in the important area of vaccines and is developing new treatments for cancer. Property of GlaxoSmithKline

3 GSK-Glaxo Smith Kline Manufacturing S.p.A As part of the GlaxoSmithKline plc. network, GlaxoSmithKline Manufacturing S.p.A. (GSK) is the Italian local company responsible for the manufacturing operations. GSK is part of the Global Manufacturing & Supply division that includes 76 manufacturing sites in 32 countries. As part of GSK, the Parma manufacturing site is a centre of excellence for the introduction of new products and new technologies in sterile areas. With 450 employees it focuses on sterile and aseptic operations and it is specialized in high potent compound. The major production streams are ampoules aseptic filling, freeze dry operations, cytotoxic and high potent facility. The Parma site is leader in the company network on rapid test technology and the operations automation level is very high.

4 Why GSK in icub2work icub2work goal is to develop a humanoid platform with harsh environment capabilities and high manipulatory skills; This new class of robot could be successfully used in GSK laboratory and production sterile environment to replace/support humans. real operational scenarios needs to reduce at minimum human intervention to increase product safety (drug manufacturing is critical production);

5 Why GSK in icub2work human operators are subjected to high physical stress for the needed multiple protection to keep environment clean ; operational time and productivity is low (high preparation time for human intervention); sterile human intervention quality is low and failure rate on long shift is potentially high for reduced attention in stressed operation

6 Operational scenario #1: media preparation Operational conditions: CLASS A Operations: Open and close bottles (bottle cap always up ) Open and unstack capsules;

7 Operational scenario #1: media preparation apply label to capsule; dispense liquid and powder; close and stack up capsules. 200 capsules per day

8 Operational scenario #2: sterility procedure Open bag Assemble funnel on the manifold Open flip of cover vials and reverse ampoules

9 Operational scenario #2: sterility procedure Assemble syringe Aspirate liquid Reconstitute lyophilizated Open ampoules

10 Operational scenario #2: sterility procedure Dispense Disassemble funnel Pick filter with tweezers Cut filter with scissors

11 Operational scenario #2: sterility procedure Task execution trough glove box or insulator tent > 60 full runs (batches) carried out per week! (minimum 20 vials/ampoules processed per each batches)

12 Operational scenario #3: filling machine in production maintenance Vials filling needles are in CLASS A environment (open vials being filled with drug)

13 Operational scenario #3: filling machine in production maintenance Operations: Open locking knob; Remove filling needle; Remove locking ring and replace needle; Reassemble all in place! 5 intrusions per day in sterile area for in line maintenance

14 icub2work impact for GSK The use of a humanoid solution to perform the laboratory sterility test and maintenance in grade A will have the follow impact: Time available for test: availability will be extended to potentially 24hr/day allowing the execution of the tests without the continuous presence of the laboratory technician ( walk away ); Test reliability, the operation will be standardized and the variability associated to the analysis will be minimized and potential contamination from the human intervention significantly reduced; Quality of life of the human workers: currently the sterility test is performed within an isolator. The isolator by design is not comfortable. The execution of operations in the constrained environment thus requires short work cycles. Robot could eliminate or reduce the human intrusion in filling line during the aseptic process (40-50%) reducing the risk of contamination

15 icub2work impact for GSK In summary, the biggest impact related with the use of the icub 2W is the limitation of potential human errors eliminating activities in critical working conditions and henceforth reducing the chances of defect in a critical product dedicated to the human health As a follow up result, we can reuse the same robotic skills in other production/maintenance tasks widening the use in the GSK production of the icub 2W. Once validated these applications could become a company standard: sterility test as said is a common day by day activity in several production sites of GSK at large and maintenance/intervention on production machines in sterile condition is one of the most sensitive quality issue in every production plant for sterile drugs (also worldwide).

16 Thank-you for your attention R.Cassaniti, N.Trivelli, M.Bini - GSK Manufacturing S.p.A

17 Environmental definitions European guidelines to GMP (Manufacture of sterile medicinal products) The manufacture of sterile products should be carried out in clean areas, entry to which should be through air locks for personal and / or for equipment and materials. The various operations of component preparations, product preparation and filling should be carried out in separate areas within the clean area. Manufacturing operations are divided into two categories 1.Those where the product is terminally sterilized 2.Those which are conducted aseptically at some or all stages Each manufacturing operation for sterile products require an appropriate environmental cleanliness level in the operational stage in order to minimize the risk of particulate or microbial; contamination of the product. In order to meet IN OPERATION condition these areas should be designed to reach certain specified air- cleanliness level in the At Rest occupancy state. The AT REST state is the condition where the installation is complete with production equipment installed and operating but with no operating personnel present The in operation state is the condition where the installation is functioning in the defined operating mode with the specified number of personnel working. For the manufacture of sterile medicinal products normally 4 grades can be distinguished: GRADE A : The local zone for high risk operations eg. Filling zone, stopper bowls, open ampules and vials, making aseptic connections. Normally such conditions are provided by a laminar airflow workstation. Laminar airflow system should provide a homogenous air speed of 0.45 m/s ±2.0% (guidance value) at the working position. GRADE B : In case of aseptic preparation and filling, the background environment for grade A zone. GRADE C & D : Clean areas for carrying out less critical stages in the manufacture of sterile products. Maximum permitted number of particles /m 3 Grade At rest In n operation 0.5mm 5mm 0.5mm 5mm A B , C 350,000 2,000 3,500,000 20,000 D 3,500,000 20,000 Not defined Not defined

18 Property of GlaxoSmithKline