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Why do Pharmaceutical Glass Containers Break The
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Macroscopic located on the inner surface along with syringe Figure 6 Upon microscopic. fracture patterns a contamination trace as can be seen examination the fracture origin could. Figure 2 are the in Figure 5 The identification of the not be definitively found having been. crack and crack fracture origin on the inner surface along blurred or made indistinct Figure 7 Due. branching patterns with an observed contamination trace to the repeatable positions of the cracks. visible by eye or with combined with information from the. low magnification,which develop due,to the momentary. mechanical stress,Figure 2 state e g due to,M a c r o s c o p i c flexural loading. crack branching vertical loading,pattern on a torsional loading. tubular glass vial,internal pressure,thermal stress. Microscopic fracture patterns Figure,1 bottom are characteristic surface.
markings left behind on the fracture, surface from the breakage event that Figure 4 Macroscopic fracture pattern of. confirm location s of breakage initiation a cracked cartridge red arrows indicate. direction of breakage e g outer to inner the breakage propagation directions. surface vice versa instantaneous or,delayed breakage crack propagation. interrupted or stepwise approximate,applied mechanical load only possible if. particular fracture surface markings are,well developed blunt or sharp geometry. of impacting object and slow subcritical,crack growth that leads to time delayed.
catastrophic failure Figure 6 Macroscopic fracture patterns. at two locations on a glass syringe, Fractography Example Manufacturing top close to the syringe cone shoulder. or Processing Root Cause section bottom close to the syringe. The power of fractography is best flange section,shown by example SCHOTT pharma. services was contracted by a glass,Figure 5 Close up view onto the fracture. converter to identify the root cause of their odd appearance no evidence for. origin vicinity of the cracked cartridge, failure for a cracked cartridge that was impact Wallner lines3 4 indicating a. from Figures 3 and 4 the position of, found after filling with drug product general direction for the fracture origin.
the fracture origin coincides with a, at a pharmaceutical company The but not being able to observe it and. contamination trace on the inner surface, pharmaceutical company had filed a knowledge of the syringe manufacturing. of the cartridge red arrows indicate the, complaint with the glass converter for process the root cause was determined. approximate breakage propagation, compensation for delivered pieces The and confirmed to be due to fused cracks. directions, cartridge is shown in Figure 3 with formed from thermal stress during the.
cracking observed near the shoulder manufacturing of the syringe flange and. of the cartridge Figure 4 displays glass manufacturer and pharmaceutical cone regions The result was a justified. the macroscopic run of the crack The company on contact materials to that complaint and a replacement of the. fracture origin was determined to be inner surface region resulted in the syringes by the container manufacturer. determination and confirmation that the, root cause was due to contact with a Glass Strength Misperceptions and. washing siliconisation or filling needle Facts, during processing at the pharmaceutical To understand the breakage behaviour of. company Thus fractography helped to glass it is essential to understand some. objectively prove the true circumstances basic concepts of brittle failure every. for failure of the cartridge and resulted disturbance of the three dimensional. in the pharmaceutical company structure of the glass e g pores. withdrawing the complaint A second inclusions cracks or any kind of surface. example came from a customer faced defects can appear as a concentrator. with odd appearance of cracks with no for mechanical loads that may occur or. apparent beginning in the barrel section are applied to the glass container e g. Figure 3 Glass cartridge with cracked of many glass syringes from a syringe mechanical loads generated by an impact. tip shoulder section lot at two repeatable positions on the during glass to glass contact bending. www ipimedia com INTERNATIONAL PHARMACEUTICAL INDUSTRY 89. IPI March2016 indd 89 19 04 2016 19 39 29, projection of its surface quality defined may arise resulting in undesirable. by the criticality of disturbances within consequences such as quarantine of. its structure It is then easy to understand batches production line shutdown root. that a high surface quality results in a cause and corrective action reporting to. high strength because according to the the FDA It is an undeniable fact that glass. equation above a low criticality allows containers normally have much more than. a high amount of applied mechanical sufficient strength for pharmaceutical. loads until the load multiplication reaches packaging applications This is proven. the toughness limit On the other hand billions of time per year yet while the. a low surface quality equal to flaws or de risking mantra of requiring zero. defects of high criticality results in a low container breakage is a worthy goal the. strength because a high criticality allows fracture statistics can help to reduce the. only a low amount of applied mechanical gap to reality A good risk management. loads until the load multiplication strategy thus would be to regularly test. reaches the toughness limit In this these strength distributions to determine. context it has to be admitted that every the risk of breakage for each production. glass surface contains flaws Or in other batch to keep the risk as low as possible. words a perfect glass surface without of low strength containers reaching the. any flaws does not exist Each handling market The determination of the statistical. or processing step may introduce strength distribution of a particular batch. further surface flaws or may enlarge of glass containers is the main purpose. pre existing ones which can result in a of such strength investigations There. reduction of the overall strength of the are myriad challenges confronting. glass Furthermore as each individual pharmaceutical companies when they. Figure 7 Microscopic fracture patterns glass object exhibits a unique surface need to investigate glass strength as part. of two cracked glass syringes cf Figure flaw structure its resulting strength is also of a breakage investigation They quickly. 6 represented by an individual value As find out glass container strength is not. a consequence a collection of strength normally part of the specification glass. thermal shock internal or external values results in a statistical distribution strength data per manufactured lot is not. pressure vertical load during capping It is the shape of this statistical distribution provided by the glass manufacturer and. The magnitude of this load multiplication which finally can be considered as the strength specification for processing. significantly depends on the position size a representative quantification of the transportation and usage is not known. and the shape of the disturbance as well strength of a collection of tested samples by the pharmaceutical company or. as on the magnitude of the mechanical So as another important fact contract filler Adding to the challenge. load There may be disturbances which is the variety of strength testing methods. act as weak multiplier of applied stresses THE STRENGTH OF A POPULATION available and needed to appropriately. Such disturbances can be considered OF GLASS CONTAINERS CAN BE determine the strength of a given lot of. as rather uncritical On the other hand CONSIDERED AS A PROJECTION OF ITS glass. there may be also disturbances which SURFACE QUALITY AND WHICH HAS. act as strong multipliers which then have TO BE DESCRIBED BY A STATISTICAL An important factor for the right test. to be considered as critical Now if the DISTRIBUTION method is to mimic the mechanical stress. combination of applied mechanical load under the application conditions as. and criticality of the disturbance reaches Such a strength distribution cannot realistically as possible Burst pressure. or exceeds a particular limit glass be regarded as being stable as there testing is appropriate for assessing. breakage will occur originating from this are numerous incidences during the container strength during lyophilisation. location This limit is a material constant lifetime of glass containers which can and as a general smart method to find the. and can be thought of as a measure of affect the surface quality of the glass weakest point on the interior or exterior. the toughness against breakage it is For instance for a running production surface of a container Axial compression. actually called fracture toughness 7 of pharmaceutical products many testing is appropriate for assessing. Thus glass breakage can be expressed as process steps are conducted which lower container strength during stoppering. the simple equation the strength of the primary packaging shipping and storage Side compression. material due to known or unknown testing is appropriate for assessing. GLASS BREAKAGE OCCURS WHEN and uncontrolled damages Typical container strength during processing. LOAD x CRITICALITY TOUGHNESS candidates are static glass to glass Bending testing is appropriate for. contacts in accumulation tables dynamic assessing the syringe cone during. If none or only one of the two conditions glass to glass contacts due to sudden needle attachment tip cap removal and. are present i e existence of a critical stops impacts at the end of conveying injection Impact testing is appropriate for. disturbance but no mechanical load belts glass to metal contacts with parts assessing container resistance to impact. or mechanical load at positions without unintentionally protruding into the damage All these destructive tests are. disturbances glass will not break As a conveying path of containers Without designed to determine the location of the. consequence of this fundamental equation any knowledge of the strength batches fracture origin i e the weakest point. of brittle failure the strength property of low quality might enter the field and of the container for a particular load. of glass is not constant but rather a complaints about broken containers situation Therefore strength testing with. 90 INTERNATIONAL PHARMACEUTICAL INDUSTRY Spring 2016 Volume 8 Issue 1. IPI March2016 indd 90 19 04 2016 19 39 32, subsequent fractographic investigation both incidences The following examples forming process shipping conditions. to determine the location of the fracture show the usefulness of strength testing to and or the process at the pharmaceutical. origin is a very powerful combination to determine the strength of glass containers company When compared to the control. determine the strength of a given sample and answer a variety of questions vials which have not yet experienced the. set the location of the fracture origin and process at the pharmaceutical company. assess if the observed strength is normal SCHOTT pharma services was Figure 9 there was a significant. or lowered due to a discontinuity or contracted by a client who was filling reduction in strength demonstrating. non conformity While some industrial a product for clinical trial into vials the effect of glass strength reduction as. standards are established for testing the and during post fill inspection found a function of processing regardless of. strength of glass containers primarily approximately 20 of the lot had chatter. coming from the food beverage marks scuffs of varying size which. industries 8 10 a few ISO standards have were detected by visual inspection after. recently been released for prefilled glass processing According to the PDA TR 43. syringes11 but none are in force from the cosmetic defect manual15 a scuff defect is. major pharmacopeia regulatory bodies Minor or N A The pharmaceutical. USP12 EP13 JP14 company was concerned about risk of. breakage at the clinic and contracted, Due to these complexities and the low strength testing to be done to assess Figure 9 Cumulative failure probability.
overall incident rate of glass breakage the strength criticality of the scuffs and i e total probability of failure for the. the strategy of the pharmaceutical whether or not the scuffed containers could batch in dependence on the burst. industry today is to forgo strength testing be safely used or if new material would pressure for glass vials with rejected. and to assess the criticality of surface have to be made Burst pressure testing without accepted and controls. flaws non conformities i e risk of was done on 100 samples featuring unprocessed. glass breakage by using optical visual scuffs 92 samples without scuffs and. inspection with defect manuals Industry 43 control samples vials processed. standard defect manuals are available but taken out after depyrogenisation whether visual defects were observed or. for instance from the PDA15 Edito Cantor As shown in Figure 8 a graph of not. Verlag16 and the glass manufacturers17 breaking pressure on the y axis versus Strength testing is also invaluable for. There are numerous non conformities the number of samples broken on the determining or selecting appropriate. scuffs bruises checks cracks etc x axis showed quite similar distributions containers and or drive springs for. which classify the criticality with respect with even a little higher strength for the auto injection devices SCHOTT pharma. to strength and integrity by their visual vials featuring scuffs compared to vials services was contracted to perform. appearance mostly by the largest lateral without scuffs This difference in strength flange strength testing on glass syringes. dimension length diameter The danger by a client who wanted to determine and. in this approach is that defect manuals compare the device failure probability. are designed for cosmetic assessment when using two different drive springs. of containers and the categorisation of on three different lots of glass syringes. non conformities disturbances just by Figure 10, their lateral dimensions cannot provide While performing. an assessment to the criticality with flange strength. respect to container strength because flange support experiments with. optical and visual inspection cannot genuine part a slow constant. provide the full information required load rate as a. to assess the criticality of a disturbance destructive lifetime. in terms of strength e g depth shape dF dt,test all syringes. three dimensional geometry So judging exhibited breakage. Figure 8 Histograms of breaking strength, the criticality of disturbances in terms syringe in a range of forces. data of glass vials with rejected left and, of strength solely from their optical far above the range. without accepted right scuffs, appearance can lead to misinterpretation of the application.
with disastrous consequences forces To get, Disturbances of small lateral dimensions was mathematically determined to be k109z6 an impression. might get classified as uncritical but due statistically significant Additionally a. to their shape they can turn out to be fractographic examination on every. critical and might lead to breakage in the broken sample from the rejected lot. field On the other hand disturbances revealed that not a single fracture origin. of large lateral dimensions might get coincided with a scuff This means that. classified as critical but because of while scuffs indeed represent a cosmetic. their shape are uncritical Such batches defect in this particular case they were. might then erroneously get rejected proven not to decrease the container. or even be destroyed unnecessarily strength compared to containers without. Figure 10 Scheme of flange strength, Appropriate strength testing strategies scuffs The higher strength of the rejected. testing setup top and spring force time, routinely implemented into production containers was supposed to result from. profiles bottom, processes can help to lower the risk of normal variations of the container hot. www ipimedia com INTERNATIONAL PHARMACEUTICAL INDUSTRY 91. IPI March2016 indd 91 19 04 2016 19 39 35, about the failure probability under real be aware of these methods and be.
conditions i e under the fast complex able to employ them to address glass. force time profile of the drive springs breakage events in a cost effective and. Figure 10 above a suitable continuous timely manner. statistical distribution function was fitted,References. to the strength data as a first step In a 1 SCHOTT pharma services two day on site fractography. second step the mechanical loads of training courses http www us schott com pharma. services english accessed October 30 2015, the true force time profiles of the two 2 SCHOTT pharma services two day training courses at. drive springs were transformed to single laboratory centers http www us schott com pharma. services english accessed October 30 2015, equivalent force values which can be 3 Fr chette V D Failure Analysis of Brittle Materials. Advances in Ceramics Volume 28 1990, compared to the data of the strength 4 Quinn G D Fractography of Ceramics and Glasses NIST. experiments An estimation of the failure Figure 12 Histograms of breaking Special Publication 960 16 2007. probability of the syringes under the load strength data for glass syringes before 5 Varner J D Fractography of Glasses and Ceramics VI. Ceramic Transactions 230 2012, of the two different drive springs then is left and after right process step solid 6 Bradt R C Fractography of Glass Plenum Press 1994.
achieved by an extrapolation of the fitted lines represent statistical distribution 7 Lawn B L Fracture of Brittle Solids Second Edition. Cambridge University Press 1993, continuous statistical distribution function functions fitted to the data 8 DIN EN ISO 7458 Glass containers Internal pressure. resistance Test methods May 2004,9 DIN EN ISO 8113 Glass containers Resistance to. processing step indicating the creation vertical load Test method May 2004. of additional surface flaws as well as a 10 DIN 52295 Testing of glass Pendulum impact on. containers Testing by attributes and by variables, second large population in the shoulder March 2010. 11 ISO 11040 4 Prefilled syringes Part 4 Glass barrels. region in the lower strength regime as for injectables and sterilized subassembled syringes ready. was found in the samples before the for filling April 2015. 12 United States Pharmacopeia 39 National Formulary 34. step So the combination of systematic November 2 2015. strength testing in combination with 13 European Pharmacopeia 8 8 January 1 2016. 14 Japanese Pharmacopeia 24 March 24 2011, fractographic examination was able to 15 PDA Technical Report 43 Identification and. Figure 11 Weibull plot i e total reveal damage mechanisms on the outer Classification of Nonconformities in Molded and Tubular. Glass Containers for Pharmaceutical Manufacturing, probability of failure for the batch versus surface in the flange and the shoulder Covering Ampoules Bottles Cartridges Syringes and.
Vials Revised 2013, flange strength for three lots of glass section of the syringes With this type 16 Defect List for Containers made out of Tubular Glass Edito. syringes the failure probability of each of insight into processes appropriate Cantor Verlag 2009. 17 SCHOTT pharmaceutical systems glass vial and glass. of the three lots under the mechanical corrective and preventive actions were syringe defect manuals available upon request. load of the two different drive springs suggested to be applied to eliminate. can be estimated by extrapolation of severe damage mechanisms and thus. the statistical distribution functions fitted Dr Dan Haines. to the data solid straight lines to the Scientific Advisor for SCHOTT pharma. equivalent forces Feq determined for the services earned his doctorate in. Inorganic Chemistry at the University of, two drive springs vertical lines Chicago He joined SCHOTT in 2001. with a focus on developing glass coatings,to control drug formulation interactions. to the two equivalent force values of the with glass surfaces Since 2010 he is. responsible for SCHOTT pharma services in North,drive springs Figure 11. America providing analytical support of packaging, A last example demonstrates the material for pharmaceutical companies.
effectiveness of root cause analysis and E Mail daniel haines us schott com. corrective action when combining strength, testing with systematic fractographic Dr Florian Maurer Senior Scientist for. analysis SCHOTT pharma services Figure 13 Axial fracture origin position Strength and Fractography at SCHOTT. was contracted to perform syringe y y 0 mm measured from top of the. Inc earned his doctorate in Materials,Science and Engineering at Darmstadt. strength testing on samples before and flange vs burst pressure data of glass University of Technology Germany He. after a particular processing step that syringes before filled circles and after has been with SCHOTT for over nine. was introducing sporadically observed years with his focus on strength reliability. filled squares process step and fracture analysis of primary. surface flaws The client wanted to know packaging containers used in the pharmaceutical. the extent of strength decrease and industry His expertise is requested worldwide for on. successively improve the strength of the site trainings consulting services and contributions to. whether or not the observed defects were,product publications. responsible for the strength decrease E Mail florian maurer schott com. Conclusion,Burst pressure testing of the syringe was. Strength testing methods in combination,conducted Figure 12 on samples drawn.
with fractographic investigations and Dr Uwe Rothhaar. before and after the suspicious process Director of SCHOTT pharma services. appropriate evaluation procedures are, step showing a statistically significant earned his doctorate in Physics at the. available to provide the pharmaceutical University of Kaiserslautern in Germany. decrease in strength in the samples after, industry the methodology for determining He joined SCHOTT in 2000 and focused. the processing step as well as a narrowing his activities on analytical support around. the root cause and help in identifying, of the strength distribution Assessment glass and glass surfaces Over the last. effective corrective actions for glass years he is responsible for SCHOTT. of each syringe after breakage for the pharma services providing analytical support of. breakage events during processing, location of the fracture origin Figure 13 packaging material for pharmaceutical companies. filling shipping or during administration, found an enlarged population of fracture E Mail uwe rothhaar schott com.
Every pharmaceutical company should,origins in the flange region after the. 92 INTERNATIONAL PHARMACEUTICAL INDUSTRY Spring 2016 Volume 8 Issue 1.

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