FZ LABORATORY SERVICES

Transcription

1 FZ LABORATORY SERVICES

2 For those working in biological product manufacturing/aseptic process filling: you can greatly benefit from support by Franz Ziel GmbH (FZ) with many years experience in scientific testing/residual studies and skills we have acquired while working with other clients. We are happy to adapt our extensive services to special wishes. Imprint AP-brochure, date of issue:

3 Content vh 2 Decontamination cycle end point residual studies...4 Gassing cycle development vh Performance Qualification (PQ) Support vh 2 cycles...8 Biological Indicator pre-use Qualification (BPQ) Smoke studies/cfd/lr...12 Environmental Monitoring (EM)...14 Training...16 Trends...18 NEW in 2018: Expanded Laboratory area...19 Page 3

4 vh 2 Decontamination cycle endpoint residual studies Vaporized Hydrogen Peroxide (vh 2 ) used for bio-decontamination is a potential oxidative risk to sensitive biological products and may impact efficacy and stability. Less than 50 ng/ml (50 ppb) H 2 residuals can cause significant protein oxidation. During project planning phases H 2 residual studies via Amplex Red assay (Limit of quantification 15 ppb) are used to define data based limits for H 2 end point concentration, to ensure that the residual level is below level of impact for the product as it quantifies the level of H 2 residuals absorbed by product containers/ surrogate after decontamination cycle. Another possibility is the test for H 2 transferred into loads during decontamination cycles. The acquired data can be used to choose the most suitable materials to minimize potential impact of H 2 on handled product or conducted tests. Most experiments can be carried out in our FZ analytical chemistry test laboratory equipped with a dedicated Isolator as pilot plant and a state of the art H 2 measurement devices for ppb concentrations (Picarro). You also have the option that one of our FZ laboratory experts will come to your site after qualification of the gassing cycle for residual end point qualification testing in operation on the installed Isolator line. Page 4

5 HO O OH H ² O ² HO O O N I C HRP N CH 3 II O Amplex Red Resorufin Conversion of Amplex Red into Resorufin Page 5

6 All documents supporting the GCD are GMP and FDA compliant

7 Gassing cycle development - vh 2 During gassing cycle development (GCD) the decontamination process of surfaces via vh 2 is characterized and robust parameters are determined. The iterative GCD study steps result in a decontamination cycle with proven and confirmed cycle efficacy and security. We offer GCD as a standard service for all our enclosures with vh 2 decontamination including all materials needed. This includes also the Factory testing GCD (FT-GCD) on FZ site. During FT-GCD and GCD the cycle is challenged with a microorganism known to be highly resistant to the effect of vh 2 which are inoculated on commercially available Biological Indicators (BIs). Our microbiology laboratory is just a few steps away from the workshops where barrier systems are manufactured thus enables a microbiological evaluation with short transport routes. Our enclosures with vh 2 decontamination are equipped with our own bio-decontamination system (FZ-BDS 12/60) which enables for in-process control of the decontamination cycle via cycle analysis using defined measuring points to achieve the shortest possible cycle times. Page 7

8 Performance Qualification (PQ) Support vh 2 cycles vh 2 PQ support is provided by team members of the FZ Aseptic Processing Technologies department. It is used to qualify the developed cycle for being repeatable and robust, including the defined security margin. Typically triplicate BI challenges in three cycle runs are used to verify cycle efficacy and repeatability. We offer PQ support on request. This includes support in GMP/FDA compliant documents, the execution of one PQ cycle and training and supervision of the other two cycles to prepare operators and QA for Requalification (RQ). Materials for PQ are provided on request. FZ recommend BIs used for PQ have independent (of manufacturer) pre-use qualification by our microbiology experts. This offer is also valid for BIs used for RQ. Page 8

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11 Biological Indicator pre-use Qualification (BPQ) Biological Indicators (BIs) based on Geobacillus stearothermophilus are standard efficacy challenges for qualification of the vh 2 bio-decontamination processes as they provide direct evidence of inactivation/kill. However, variances in the performance characteristics of BIs require careful analysis of each individual BI Lot. BIs can be subject to spore clumping in manufacture leading to false positive and variable efficacy because of BI quality issues. Also transport and storage conditions can influence the population and resistance of a BI Lot. It is highly recommended for users to check BI quality before use. FZ can offer the determination of population count (enumeration) in accordance with the requirements of DIN EN ISO and USP. BI lot qualification includes an important step of Scanning Electron Microscopy (SEM) study to check for out of characteristic spore clumping or spore inoculum adverse contamination that has a significant impact on efficacy studies. The D-value is describing the correlation of time and inactivation. Independently determining the D-value and hence the resistance of a BI Lot is recommended for users to ensure material quality. We offer System D-value determination for BIs via Survivor curve according to DIN EN ISO and USP (adapted according to Technical Report 51). For the BIs used during GCD the independent BI pre use qualification is a standard FZ procedure. Page 11

12 Smoke studies / CFD / LR According to the revised GMP Annex 1 Air flow patterns should be visualized in grade A/B areas. At the beginning of the project, the airflow can be visualized via CFD (Computational Fluid Dynamics) by our experts including the creation of detailed reports (demonstration, suggestions for improvement). Smoke studies using a smoke generator are performed to confirm unidirectional airflow everywhere inside the enclosure with defined acceptance criteria for airflow characteristics and velocity. They are also used to confirm the airflow along pressure cascades. By testing at lower limit parameters robustness of aseptic status can be confirmed. Page 12

13 The method for limitation of risk (LR-Method) provides reliable procedure for assessing potential microbiological risk of airborne contamination in clean zones in a systematic way. The LR-Method, which relies upon particle count analysis of particles in air movements, particle transfer testing and calculation of the Risk Factor presents an effective way for limitation of potential risks. It can be used for tracing the dispersion routes of airborne contamination risks, for identification of risk situations, for evaluating risks connected to single process steps, for immediate evaluation of changes, and for material transfer of potential risks. To support you in risk management and contamination control, we offer the performance of smoke studies on your site for all our enclosures in combination with the complex filling machines to meet the regulatory requirements. Page 13

14 Environmental Monitoring (EM) Risk based environmental classification and monitoring are requirements from FDA and GMP Annex 1 and this topic is increasing due to the revision of the Annex 1. The program should include particle counts and microbiological monitoring. The EM concept has to be considered in the early project phase (Design review) to avoid space limitations that make efficient risk based concepts impossible. We provide support in Risk assessments for Environmental control and EM sample location positioning considering current best practice with the preparation of rationales for Environmental classification according to cgmp/ ISO These documents are to support you in preparation of EM programs through Media fills, Routine production and end of batch surface sampling and setting Action and Alert levels and trend metrics. Any changes in the complex cleanroom environment can be an early indication of increasing risk for the inside of an enclosure. Therefore, we support and encourage the implementation of EM locations surrounding the Grade A area. Settle plate holder Cleanroom at Operator Isolator interface (outside Isolator) Page 14

15 Active Air Head und Particle counter Page 15

16 Training Regulatory requirements on using Barrier Separation technology and the usage of those technologies are increasing in the last years. Our training program delivers the required understanding of aseptic production, Barrier Separation technology, contamination control and prepares for Filling line operational readiness with operator hands-on training. It also provides understanding Barrier technology maintenance under the scope of GMP/cGMP Compliance. This training addresses those employees involved in barrier technology projects; engineering, validation and operation of these systems. Page 16

17 Training Expanding laboratory area Page 17

18 Trends Through our participation in national and international standardization committees, non-profit societies and as speakers at different exhibitions and conferences, we keep a finger on the pulse and use our knowledge to develop the actual state of the art technology. Page 18

19 NEW in 2018: Expanded Laboratory area To meet the increasing demand for FZ laboratory services we expanded our laboratory facilities to 150 m 2. The laboratory facility is equipped with the newest technology like HEPA filtered air handling and temperature and pressure control in all areas. The used FZ Isolator technology and Cleanbench for our microbiology services complete our high standards of quality. For the various service activities the laboratory area is sectioned in access controlled special designed areas for all needs such as the Microbiology or Chemical analysis laboratory. With our controlled and documented incoming goods and storage we comply across all workflows the requirements for all of our services. Page 19

20 Franz Ziel GmbH Raiffeisenstr Billerbeck Germany Franz Ziel USA Inc Southcross Boulevard Suite 100 Rock Hill, South Carolina USA +49 (02543) (02543) mail@ziel-gmbh.com ziel-gmbh.com +1 (803) (803) mail@ziel-usa.com ziel-usa.com