Product Information and Validation Pack

Transcription

1 Product Information and Validation Pack Altimed SA 900/60 PUMP Validation Document Issue 1 Page i

2 Index Advantages of Platinum addition cured silicone...1 Altimed SA 900/60 Pump Biological testing...2 Altimed Batch definition...16 Altimed SA 900/60 PUMP Biological, Analytical and Summary Reports...25 Altimed SA 900/60 PUMP Registration...17 Biological Monitoring...22 Certificates of Conformance/Analysis...23 Chemical Resistance...4 Clean Room Extruded Tubing - Quality Information...12 Clean Room Particulate Inclusion Reference Chart...13 Cleaning Tubing Manufactured in Altimed SA 900/60 PUMP...21 European Pharmacopoeia 7 th edition, Section Example Certificate of Conformance...24 Example of the laser record...10 Hemolysis ISO In house testing...4 Introduction...1 ISO 13485: ISO 9001: Manufacture and Control of Altimed SA 900/60 PUMP Profiles...9 Manufacture of Altimed SA 900/60 PUMP profiles Extrusion Process...6 Manufacture of Altimed SA 900/60 PUMP profiles Post Cure Process (Loading)...7 Manufacture of Altimed SA 900/60 PUMP profiles Post Cure Process (Unloading)...8 Manufacture of Altimed SA 900/60 PUMP profiles - Raw material approval...5 Manufacturing Environment...4 Notes on Pumping Applications...20 Packing...12 Physical Properties of Altimed SA 900/60 PUMP...15 Platinum V Peroxide Cured Silicones...3 Post cure Control and Monitoring...14 Principle contacts at Silicone Altimex...28 Pump Life of Altimed SA 900/60 PUMP Grade Tubing...20 Sterilisation of SA 900/60 PUMP Products...21 Storage and Shelf Life of Altimed SA 900/60 PUMP Materials...23 Tolerances on cut length...12 Why use Silicone...1 Altimed SA 900/60 PUMP Validation Document Issue 1 Page ii

3 Altimed SA 900/60 PUMP Validation Document Issue 1 Page iii

4 Introduction Silicone Altimex was founded in 1976 and was one of the first silicone processing companies to introduce in house compounding of materials. In 1979 Silicone Altimex introduced a FED 209E class clean room facility for the manufacture of medical products. Silicone Altimex now has three class ISO Class 7 clean room facilities, one for the production of peroxide cured materials and a fully dedicated unit purely designed for the manufacture of Platinum addition cured silicone material. Silicone Altimex recently completed qualification of a brand new state of the art pharmaceutical assembly cleanroom facility. This unit is has a microprocessor controlled environment and is used purely for the manufacture of pharmaceutical assemblies and associated components. Why use Silicone. Silicone has the following advantages over organic rubbers:- Transparent. Chemically inert. Stable over a wide temperature range. Can be sterilised by ethylene oxide, gamma radiation or steam autoclave. Advantages of Platinum addition cured SA900/60 Pump Tubing Platinum addition cured silicone (Altimed SA 900/60 PUMP) offer the following benefits over peroxide cured materials Extremely long pump life None yellowing Free from cross linker by-products Free from PCB s (Poly Chlorinated Biphenyls) Very tight surface cure No impairment of odour or taste Dry and non-sticky surface finish Altimed SA 900/60 PUMP Validation Document Issue 1 Page 1

5 Altimed SA 900/60 Pump Biological testing A number a biological and analytical tests have been carried out on the base materials used in the manufacture of Altimed SA 900/60 Pump these are detailed below. Meets or exceeds European pharmacopoeia 7 th Ed. Section Silicone Elastomers for Closures and Tubing ISO The material did not release any leachable substance with haemolytic activity Silicone Altimex are constantly evaluating test requirements and will perform additional tests in line with changes and requirements of the medical and pharmaceutical industries. Customer specific tests can be carried out on request. Altimed SA 900/60 PUMP Validation Document Issue 1 Page 2

6 Platinum V Peroxide Cured Silicones The main difference between the physical and chemical properties of Platinum Addition Cured Silicone rubber Altimed SA 900/60 Pump and those of traditional Organic Peroxide Cured systems arise from the crosslinking process. This is the point at which a viscous soft material is transformed into a solid elastomeric one. Platinum catalysed addition curing is much faster the peroxide curing, because unlike peroxide curing, it involves just a single reaction: the addition of Si-H across the double bonds of the vinyl groups. Curing takes place rapidly and is controlled by the concentration of catalyst and inhibitor, with the Platinum catalyst acting also to reduce the activation energy of the reaction. Given enough time the reaction will take place at room temperature, but at elevated temperatures it is extremely fast. The specific advantage of this type of crosslinking is that no undesirable by-products are formed. The peroxide reaction, on the other hand, comprises of several partial reactions. In the first, an unstable molecule (organic peroxide) undergoes bond cleavage to obtain the highly reactive free-radicals that are required to induce the crosslinking reaction in the second. The free radicals add across the vinyl double bonds. This in turn produces a new free radical, triggering a chain reaction that terminates when cross linking has occurred at all the double bonds. A free radical reaction of this type, once initiated is a very aggressive reaction that is very quick and non selective producing many variant side reactions, giving rise to a whole host of undesirable by-products. Typical by-products that have been detected in peroxide cured silicone tubing using 2,4 diclorobenzoyl peroxide as the catalyst include: 2,4 diclorobenzoic acid Dichclorobenzoic acid Dichclorobenzoid acid, methyl ester Dichlorobenzoyl chloride Dichclorobenzaldehyde Trichlorobenzene Chlorinated aliphatics Polychlorinated biphenyls Phenol Benzyl alcohol Dichlorobenzene Dichlorophenol Because of the possibility that some or all of the above chemicals could be present on the surface of peroxide cured tubes it is necessary to wash the tube with pure water (WFI) before use. However the above by-products continue to leach from the silicone rubber matrix to the surface on a continual basis rendering the washing process invalid after time. Altimed SA 900/60 PUMP Platinum cured silicone tubing is manufactured in a dedicated platinum facility using dedicated equipment and is completely free of peroxide decomposition derivatives. Altimed SA 900/60 PUMP Platinum Cured Silicone Tubing is particularly suited for pump and fluid carrying applications where leaching of chemicals from the tube may be of concern, e.g. the manufacture of parenteral drugs. Altimed SA 900/60 PUMP Validation Document Issue 1 Page 3

7 Chemical Resistance Altimed SA 900/60 PUMP Platinum cured silicone tubing is very resistant to weak acids, alkalis or salts. Dilute acids and alkalis can be used at temperatures of 70 to 80ºC to clean tubing for use in the food industry for example. Acids with higher concentrations having strong oxidising properties (e.g. Sulphuric or Nitric acid) will destroy silicone rubber. Polar liquids such as short chain alcohols or low molecular weight ketones, cause hardly any swelling of silicone rubber. Non polar liquids such as linear or cyclic hydrocarbons, cause severe swelling and should be avoided except to a very limited extent. In house testing. Silicone Altimex has an extensively equipped laboratory allowing testing of every batch of compounded material ensuring product quality is not compromised. Biological monitoring of both our clean rooms is also carried out on a monthly basis including Bio-burden testing of Platinum cured tubing produced using Altimed SA 900/60 PUMP. During production of Altimed SA 900/60 PUMP profiles non contact laser micrometers monitor the profile dimensions to ensure compliance with the required specification. We can also perform pump and pressure tests on any tubing profile. Manufacturing Environment. All Silicone Altimex products are manufactured to stringent and highly controlled quality standards and in accordance with BS EN ISO 13485:2003 and BS EN ISO 9001/2000 requirements. All products manufactured in Altimed SA 900/60 PUMP are done so in an ISO Class 7 dedicated Platinum facility. This ensures the materials are not contaminated with any contaminants that can be found in peroxide cured silicone materials. Silicone Altimex also have a dedicated assembly cleanroom facility recently manufactured to the very latest cleanroom specifications. This cleanroom is constantly electronically monitored to ensure the environment is never compromised. Altimed SA 900/60 PUMP Validation Document Issue 1 Page 4

8 Manufacture of Altimed SA 900/60 PUMP profiles - Raw material approval Start Confirm supplier testing on CofA Does the material conform to supplier specification? Y/N Control of Nonconforming product Perform Silicone Altimex physical property testing Does the material meet SA material specification? Y/N Label product Accepted and release to production? Stop Altimed SA 900/60 PUMP Validation Document Issue 1 Page 5

9 Manufacture of Altimed SA 900/60 PUMP profiles Extrusion Process Start Select required die/pin setup as defined on Process Document Set cure system parameters as Process Document Extrude profile & check Does the profile meet the part specification? Adjust machine and reset meters counter Y/N Reject out of spec material Run coil length as Process Document Does the profile meet the part specification? Y/N Has the required quantity been extruded? Y/N Stop Altimed SA 900/60 PUMP Validation Document Issue 1 Page 6

10 Manufacture of Altimed SA 900/60 PUMP profiles Post Cure Process (Loading) Start Check the oven load capacity and work out the load on average coil weight Complete the post cure log Is the load weight close to the maximum oven load? Ensure no temperature probes are disturbed during loading Y/N Load Trays into the oven Calculate predicted load using the maximum coil weight Visually check no material is in contact with oven side or back wall Set post cure parameters as per PI Stop Altimed SA 900/60 PUMP Validation Document Issue 1 Page 7

11 Manufacture of Altimed SA 900/60 PUMP profiles Post Cure Process (Unloading) Check the post cure logging report Has any over temp alert been triggered? Do not proceed, contact Quality or Dev Manager Y/N Has the minimum post cure temp been achieved? Y/N Re post cure material Has the post cure period been achieved? Y/N Sign post cure log and unload material STOP Altimed SA 900/60 PUMP Validation Document Issue 1 Page 8

12 Manufacture and Control of Altimed SA 900/60 PUMP Profiles Silicone Altimex utilise high resolution Laser Micrometers to inspect the tubing profile. The non-contact method of inspection allowed by the laser micrometer remove inherent faults found in optical inspection methods, such as poor edge definition operator eye accuracy etc. The laser micrometers employed for inspection of tubing profiles have a resolution of mm ensuring high accuracy of measurement. Silicone Altimex also have several extrusion lines which have in line loop control systems. These systems can constantly monitor the profile outer diameter and adjust the extrusion accordingly. This ensures very precise tolerances can be maintained. All the information recorded by the laser micrometers is recorded and attached to our product batch records. In some cases they can be sent as additional information with customer certificates of conformity or analysis. A typical set of records is shown on the following pages showing the stability of our extrusion process. Bespoke laser systems ensure highly accurate inspection of profiles Altimed SA 900/60 PUMP Validation Document Issue 1 Page 9

13 Example of the laser record Altimed SA 900/60 PUMP Validation Document Issue 1 Page 10

14 Part Reference 5.2 x 1.8 Nom inal Tolerance (+/-) Part Description Silicone Tubing Inspection Method Laser Micrometer Quantity Inspected 47 Customer Characteristic Inspected Inner Diam eter Date 19-Feb-2002 Actual size Inner Diameter Sample No Range chart Mean USL LSL UWL LWL Component Information MEAN SD SD CP CPK MEDIAN R BAR Skew ness Mean + 3sd Mean - 3sd Samples O/Size 0 Samples U/Size 0 Within Tolerance 49 Min dimension Max dimension COMMENTS: 10 8 Frequency Statistical analysis can be performed on profiles and inspection results to determine workable tolerances etc. Altimed SA 900/60 PUMP Validation Document Issue 1 Page 11

15 Clean Room Extruded Tubing - Quality Information. The following information is based upon our standard quality inspection criteria for all of our tubing products, the details of which are outlined below. If you have any concerns regarding the following please contact the Silicone Altimex with the details, and we will be happy to discuss your requirements. Typical tolerances applied to clean room extruded tubing Inner Diameter Tolerance Wall Tolerance / / / / / / / / /-0.30 > / / /-0.80 > /-3% The typical coil length is twenty five meter however in cases where particulate contamination is evident we may cut the coil. We allow a maximum of two cuts per coil down to a minimum length of five metres. It is a natural process in silicone tubing for the material to tack slightly during post cure; this may result in faint lines on the surface of the material. These are not detrimental to the performance of the tube. Particles and Gel will be present in silicone tubing as a natural by-product of the process. Every precaution is taken to screen out particles during the production process and final inspection of the tubing endeavours to prevent tubing having particles greater than 0.1mm² being released. Particles of up to 0.5mm² are deemed acceptable provided they are not excessive in number, i.e. no more than one per metre. No metal particles are permitted. If cut lengths of extruded material is required we will apply tolerances as BS 3734 L3 unless specific tolerances are requested. All coils will be double bagged in 50µ HDPE bags. Bags are then packed into strong outer cartons. Altimed SA 900/60 PUMP Validation Document Issue 1 Page 12

16 Clean Room Particulate Inclusion Reference Chart 1 Small inclusions of this size or smaller are acceptable as long as they are not found in clusters or number more than 5 per metre. 2 Small inclusions of this size are acceptable as long as they are not found in clusters or number more than 3 per metre, particles of this size are not acceptable in very thin walled tubing. 3 Large particles of this size are only acceptable in large walled tubing (greater than 3.0mm) and there must be no more than 1 per metre. 4 Only acceptable in very large wall tubing (greater than 4.0mm). There must be no more than 1 particle per metre. 5 Only acceptable in commercial grade material. 1 Acceptable in all material provided they are not found in clusters or number more than 10 per metre. 1 Acceptable in all material provided they are not found in clusters or number more than 5 per metre. 1 Acceptable in all but very thin walled tubing provided that they do not appear in clusters or number more than 5 per metre. 4 Acceptable in medium and large walled tubing provided they do not exceed more than 2 per metre 5 Acceptable in medium and large walled tubing provided they do not exceed more than 1 per metre 6 Only acceptable in large walled tubing and not in quantities greater than 1 every 2 metres Acceptable particles must not distort the wall or bore of the tubing in any instance. Lines and scratch marks pay particular attention to sections of coils which have tacked together. Rippling on the surface of the product. Barium stripe is not distorting surface or contains air bubbles (where applicable). Fingerprints on the material surface. Change cleaning cloths regularly to prevent small particles of cloth from adhering to the tube surface, and change cleaning medium when it starts to become dirty. Altimed SA 900/60 PUMP Validation Document Issue 1 Page 13

17 Post cure Control and Monitoring Post cure is an important part of silicone processing. As well as maintaining a consistent temperature adequate air flow must be present to ensure the effective removal of any by products. Silicone Altimex perform regular air flow checks on our post cure ovens and adjust the load weights accordingly. The ovens are constantly monitored to ensure compliance with the post cure temperatures throughout the post cure cycle. The Dedicated Platinum ovens have 6 constantly located temperature probes which download the oven environment to bespoke software. The software starts logging the post cure information once the minimum post cure temperature has been achieved and continues monitoring until the post cure is complete. Any over temperature period exceeded 5 minutes results in the post cure oven shutting down to prevent any damage to the material Each post cure record has to be reviewed and signed off before the material can be unloaded and moved into the next process. Altimed SA 900/60 PUMP Validation Document Issue 1 Page 14

18 Physical Properties of Altimed SA 900/60 PUMP At silicone Altimex we have a comprehensively equipped laboratory where we batch test all our compounds, including platinum grades, to a selection of tests ensuring the physical properties of the material are to specification. The tests we carry out routinely are:- Hardness (Shore A) Specific Gravity (g/cm 3 ) Tensile Strength (N/mm 2 ) Elongation (%) Tear Strength (Kn/m) Our testing laboratory can also test the compression set of the material a long with pump life and burst pressure. The physical property specification for Altimed SA 900/60 PUMP is identified below*. All material batches are tested to this specification to ensure compliance. Cure Conditions Shore A ASTM D g/cm³ Electronic analysis 8.0 minimum N/mm² BS ISO 37: minimum % BS ISO 37: minimum Kn/m BS ISO 34-1: up to 200 C TBA % BS 903/A6 Translucent Physical properties are measured using a 2.5mm test sheet (6.0mm for hardness), cured under the following conditions: - 5 minutes press 165+/-5C 4 hours post 200+/-5C *Material specification correct at time of printing. Altimed SA 900/60 PUMP Validation Document Issue 1 Page 15

19 Altimed Batch definition Silicone Altimex define a batch as a manufactured quantity from a single raw material input grade batch or lot number. Any changes in the raw material input grades result in a new batch number. The batch number is Silicone Altimex s unique number, all the manufacturing details can be identified if the batch number is quoted during any correspondence. Altimed SA 900/60 PUMP Validation Document Issue 1 Page 16

20 Altimed SA 900/60 PUMP Registration BS EN ISO 9001/2008 BS EN ISO 13485:2003 Altimed SA 900/60 PUMP Validation Document Issue 1 Page 17

21 ISO 9001:2008 Altimed SA 900/60 PUMP Validation Document Issue 1 Page 18

22 ISO 13485:2003 Altimed SA 900/60 PUMP Validation Document Issue 1 Page 19

23 Pump Life of Altimed SA 900/60 PUMP Grade Tubing The pump life of Silicone Altimex tubing manufactured using Altimed SA 900/60 PUMP typically exceeds 500 hours. 600 Typical Pump Life (6.0mm ID x 2.0 Wall) Hours Peroxide Platinum SA 900/60 Pump Notes on Pumping Applications Great care should be taken to avoid over occlusive roller settings. Roller settings should always allow blood cells to pass through the tubing with out damage. Over-occlusive settings may cause excessive and premature wear and damage particularly to the inner bore. This can in some instances result in the result of small particles of silicone (spalls) being released from the tubing wall. Filtration in the return line to the patient is therefore recommended. Care should be taken when handling the tubing to prevent tears or nicks. Do not lubricate the tubing with silicone fluids or greases as these can cause swelling and weaken the tubing. Repeated use of silicone tubing in pump applications is not recommended. Pump application is specifically intended for single use and the user should validate the tubing for the predicted lifetime of the required delivery system. Tubing clamps both on the pump and elsewhere should be carefully used where they are unavoidable so as to not damage the surface of the tubing. Care must be taken to ensure the tubing is loaded into the pump head correctly. Altimed SA 900/60 PUMP Validation Document Issue 1 Page 20

24 Cleaning Tubing Manufactured in Altimed SA 900/60 PUMP All of our tubing is manufactured in an ISO Class 7 cleanroom facility and supplied double bagged so cleaning should not be necessary. However if the user requires the tubing to be cleaned for any reason then distilled water with a mild soap solution may be used (do not use synthetic detergents or oil based soaps). Rinse the tubing thoroughly in warm water followed by distilled water. Sterilisation of SA 900/60 PUMP Products Any of the following methods can be used to sterilise Altimed SA 900/60 PUMP profiles. Ethylene Oxide When sterilisation by Ethylene Oxide is carried out subsequent to delivery, the user should be satisfied that full sterilisation has been effective by carrying out bacteriological tests, and ensure that degassing is complete. Gamma Irradiation Radiation sterilisation of typically 25 KGrays has a negligible effect on Altimed SA 900/60 Pump material. Higher does will: Increase hardness Reduce Elongation Repeat cycles of 5 x 25 KGrays have shown to reduce elongation by approximately 65% and increase hardness by around 5º Shore A. Autoclave Typical autoclave cycles of ºC, ºC and 3 134ºC can be carried out. If repeated autoclaving is to take place the user should ensure the usability of the material after each cycle as the material will deteriorate slightly with each repeat cycle. Users should ensure that the chosen sterilisation method chosen should be carried out under controlled conditions following a validated process and that any parts used in assemblies for instance can also withstand the required sterilisation method. Altimed SA 900/60 PUMP Validation Document Issue 1 Page 21

25 Biological Monitoring Silicone Altimex performs regular biological monitoring of all the cleanroom facilities. This includes monthly settle and contact plates along with bio burden testing of tubing. All our cleanrooms are tested to BS EN ISO and meet a Class 7 environment. In addition to this our Platinum assembly facility is routinely monitored each week. Typical manned particle counts found in our Platinum assembly area are shown below. Platinum Extrusion 0.5u At Rest 400 Zone 1 Zone 6 Zone 11 Thousands Zone 2 Zone 3 Zone 4 Zone 5 Zone 7 Zone 8 Zone 9 Zone 10 Zone 12 Zone 13 Zone 14 Limit 0 28/01/ /02/ /03/ /04/ /05/ /06/ /07/ /08/ /09/ /10/ /11/ /12/2011 Period Platinum Extrusion 5.0u At Rest Zone 1 Zone 6 zone /01/ /02/ /03/ /04/ /05/ /06/ /07/ /08/ /09/ /10/ /11/ /12/2011 Thousands Zone 2 Zone 3 Zone 4 Zone 5 Zone 7 Zone 8 Zone 9 Zone 10 zone 12 Zone 13 Zone 14 Limit Period Specific customer testing can be performed if required. Silicone Altimex currently regularly perform bio burden testing of batch product before release. Altimed SA 900/60 PUMP Validation Document Issue 1 Page 22

26 Actual Settle Plate results for the 12 month period of 2011 are shown below: 60 Platinum Settle Plates (01/11-12/11) Total cfu P L S 2 P L S 3 P L S 4 P L S 5 P L S 6 P L S 7 W a rn i n g A c tio n / 0 1 / / 0 2 / / 0 3 / / 0 4 / / 0 5 / / 0 6 / / 0 7 / / 0 8 / / 0 9 / / 1 0 / / 1 1 / Storage and Shelf Life of Altimed SA 900/60 PUMP Materials Silicone Altimex certify that the material will meet the sales specification from five years from the date of despatch provided the goods are stored in the original unopened container and stored in such a way that damage to the container and its contents is avoided. Sterile products will typically be given a 2 year shelf life but this is dependant on the product and any component shelf life used within assemblies. Certificates of Conformance/Analysis A typical certificate of conformity is shown overleaf. Certificates can be of a bespoke designed and cover any elements from material test results, biological test results or a combination of these. Specific testing can also take place on parts and the results included on the certificates. Altimed SA 900/60 PUMP Validation Document Issue 1 Page 23

27 Example Certificate of Conformance Altimed SA 900/60 PUMP Validation Document Issue 1 Page 24

28 Altimed SA 900/60 PUMP Biological, Analytical and Summary Reports Altimed SA 900/60 PUMP Validation Document Issue 1 Page 25

29 European Pharmacopoeia 7 th edition, Section Altimed SA 900/60 PUMP Validation Document Issue 1 Page 26

30 Hemolysis ISO Altimed SA 900/60 PUMP Validation Document Issue 1 Page 27

31 Principle contacts at Silicone Altimex Managing director Chris Barker Technical director Glyn Ridgway Operations manager John Davis Quality manager Glyn Maltby European sales enquiries Biotech/pharma enquiries Robert Dijkstra Applied Critical Fluids GmbH Wolfgang Zimmernink Visit our website at 49 Pasture Road, Stapleford, Nottingham, NG9 8HR Tel: 44 (0) Fax: 44 (0) Altimed SA 900/60 PUMP Validation Document Issue 1 Page 28