Pharmaserv on the newest conditions within the GMP adjusted range

As supplier with experience of many years within the GMP adjusted range the Pharmaserv supports GmbH & CO. Kg their customers of project engineering up to the qualification activities. The supplier provides concepts, plans and builds clean-spacefair a living and accomplishes the necessary qualification steps and the instrumentation proofs. A living are conceived from aluminum profile systems - after customer's requests - by the pure access protection up to complete TAV ranges (technology-based dispatching procedure).�The current annex 1 for good HerstellungspraxisDer current annex 1 of the EEC-GMP-manual describes the current requirements to the production of sterile drugs, also regarding the air circulation during the flanging of aseptisch filled Vials. The annex 1 is since March 2008 into force and the regulations had until March 2009 and/or. for the flanging from aseptisch filled up Vials to March 2010 to be converted. What changed to the old annex 1? Pure space classification routine monitoring Media Fill acceptance criteria Bioburden regulation flanges of Vials For the plant engineer, the structure of the racking plants, the air circulation and the Servicedienstleister thereby the points pure space classification, monitoring and flanging of Vials are the main points, there them the structure, which affect kind of the air circulation as well as a living and also control of not finished locked Vials (plug seat etc.). They have influence on the monitoring concepts both for automatic Monitoringsysteme with firm sensors and for routine measurements with mobile devices and on the execution of the qualification measurements in the pure areas. Constructionally changes had to be likewise accomplished and/or with new installations must one other innovative solutions compile by the new requirements with inventory plants. With the requirements naturally also the conversion comes: What has to be done with inventory plants, how one plans new plants? The pure space classification the pure space classification was approximated the ISO 14644. - The minimum number of the measuring points is to be determined according to ISO 14644. - The minimum measuring volumes are according to ISO 14644 to determine - with exception in but-calibrate, there is 1 m � for each measuring point to be measured. - The evaluation and evaluation are to be accomplished according to the ISO 14644 with the limit values annex of the 1. Maximally particle number per m permitted � (directly or more largely than those specified size of) [values in parentheses old values] 4pt; background color: transparent" > � State of rest Operating condition Class 0,5 �m 2pt; background color: transparent" > 5,0 �m 0,5 �m 5,0�m A 3.520 [3500] 20 [1] 3. 520 [3500] 20 [1] B 3.520 [3500] 29 [1] 352.000 [350. 000] 2.900 [2000] C 352.000 [350.000] 2.900 [2000] 3.520.000 [3.500. 000] 29.000 [20.000] D 3.520.000 [3.500.000] 29.000 [20. 000] not fixed not fixed The statistic evaluation and also the sample volumes are clearly defined thereby. For the Servicedienstleister is thus clearly fixed, as they must proceed with well-known pure class of area in principle. Routine monitoring for the routine monitoring the measuring points are to be determined over a risk analysis. In but oaks so the particle numbers must be gemonitort, so that brief events and degradations be recognized and alarm can be released. Within B-ranges any longer, it does not have to be compellingly continuously gemonitort is recommended however nevertheless and should over a risk analysis be evaluated. The danger of faulty measurements exists by particles with the enterprise the danger of the damage or pollution of the measuring instruments and/or, which are process conditionally set free, the particle monitoring can on the time of the preparation and to simulated operational sequence to be limited. The minimum sampling volume of 1m is likewise prescribed for no more � for the monitoring. It is to be supervised rather in such a way that changes are fast recognized. For aseptische Vials site conditions were defined going by exactly that they are only valid after the flanging as completely locked. Partiallocked Vials up to complete locking must be kept on class A conditions, i.e. from filling to locking and flanges the Vials may not leave the controlled range of the class A. Due to the possible particle release the flange station should be however separate with own air circulation. For the suppliers partially different approach and a higher constructional expenditure result from these changes in the annex 1 regarding the constructional solutions and regarding the proof of the adherence to the demanded clean-spacetechnical parameters. The protective effects can be achieved by Verschutzungen with TAV ranges, in order to achieve a kolbenf�rmige displacement current, up to insulator-like systems. Which represents those for the application technically and economically best solution, must be compiled over risk analyses, feasibility studies and costs considerations. Independently the defaults annex of the 1 must be fulfilled to the used solution. It is to be always made certain that possible contamination from the surrounding field or by the operator of the product is moved away. For the re-equipment and/or retrofit of plants for aseptische Vials before often studies were accomplished and evaluated. A main part of these studies were flow visualizations in differently operating conditions. From these then appropriate improvement steps could be derived. Flow visualization is also with new plants a main part of the tests and a criterion for further optimization measures. For the complete range of the Vialabf�llung up to locking extensive qualifying measures must be accomplished. Apart from the proofs of the contamination freedom with Medialfill, which were intensified, complex examinations must be accomplished for the proof of the environment parameters. At the plants and in the direct environment mikrobielle surface loads must be measured. In the spatial air the mikrobielle load must be determined. Even in the later enterprise must both in the B-surrounding field, as well as in but-calibrate the loads to be further gemonitort. Micro-biological limit values Recommended limit values for those micro-biological contamination (A) 1pt; background color: transparent" > Class Air sample KBE/m3 Sedimentation plates (Diameter 90 mm) KBE/4 hours of (B) Contact plates (Diameter 55 mm) KBE/Platte 15pt; background color: transparent" > Glove casting 5 fingers KBE/Handschuh A < 1 < 1 < 1 15pt; background color: transparent" > < 1 B 10 5 5 15pt; background color: transparent" > 5 C 100 50 25 15pt; background color: transparent" > - D 200 100 50 15pt; background color: transparent" > - Likewise in the plants stationary particle measuring points and automatic Monitoringsysteme are installed. These supervise the particles and flow rate at points of reference, carried in air. The temperature and the dampness of the spatial air can be supervised likewise. With the qualification examinations over extensive measurements the flow rate over the entire surface of the TAV range (TAV = with low turbulences displacement current) are determined. With mobile particle counters and air germ collecting tanks the adherence to the limit values is proven in peace and operating condition. For the proof flow visualization presents itself to the protective effect of the displacement current, and the direction of flow and possible compression phases as very good means. Shown during flow visualization, favourable-proves, with one almost documented isotherms fog the air flows in the range which can be protected and with pictures and films. Above all the video documentation is wished ever more frequently by AUDI gates, even if this is not explicitly in the Guidelines demanded. Apart from the instrumentation proofs specified above it is to be documented visually the best method the air flow in all operating conditions at the POINT OF use. Here it is naturally important that the selected technical execution is so designed that all measurements and examinations which can be accomplished can be accomplished. Particularly with examinations in the operating condition it may come to no changes for the measurement, which do not correspond to normal operation. Thus appropriate precautions are to be inserted, which make a measurement possible. A ever larger attention is directed toward the risk analysis and the risk evaluation. They offer the possibility dangers purposefully to recognize to evaluate and minimize. Over the risk analysis one has to compile naturally also the possibility possibly less cost-intensive possibilities. Customer-oriented and top up-to-date the area of the clean-room technology Pharmaserv extended the power spectrum of instrumentation services in accordance with the requirements of the market and the sets of rules. In addition the determination of the pure classes of area belongs according to ISO, VDI, GMP Guideline for airborne particles and germs. The execution and evaluation of a large range of qualification measurements are natural. Apart from the determination of the air category of purity, the recovery time and the spatial air change also the examinations of suspended matter filters become (in and exhaust air) as well as further spatial air measurements accomplished in the range temperature and dampness surely and efficiently. In the last years Pharmaserv authority in the area of the visualization of the flow conditions developed e.g. in insulators, within ranges of turbulence-poor displacement current or at executions in pure limitation of space surfaces. The service technicians of the Pharmaserv have large experience and extensive knowledge with the examination of micro-biological safety work benches of the classes 1 to 3 and barrier systems (Separative DEVICE) most diverse manufacturer. With larger projects (e.g. start-up) and maintenance stop Pharmaserv in the position is to react extremely flexibly. By the co-operation of the specialist areas an extension of resources is possible and thus technical and adequate completion in the timeframe wished by the customer.

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