ity-lab performance and overall customer satisfaction. These metrics can be submitted reporting on a quarterly basis.

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1 Pharma & Biotech Industrial Weighing & Product Inspection 22 News New FDA Quality Metrics: Burden or Potential? The latest quality metrics program developed by the FDA has led to lively discussions within the industry. Implementation seems to be a challenge, but better data analysis and improved understanding of process variability across production sites should shorten timeto-market and reduce costs. In 2009, the FDA was authorized to collect manufacturing quality data in lieu of or in advance of an inspection. A revised draft guidance published November 2016 announced a voluntary reporting phase running into 2018 to gain further experience with practical implementation. After this period is completed, regular submission of quality metrics will become mandatory. Data requirements The current draft guidance requires the submission of a reduced number of metrics (see Facts & Figures) that analyze manufacturing-process robustness, qual- ity-lab performance and overall customer satisfaction. These metrics can be submitted as product reporting or manufacturing-site reporting on a quarterly basis. Efforts and challenges The findings of a pilot program organized by the International Society of Pharmaceutical Engineering (ISPE) state that the effort to collect proposed data ranges from 20 to 30 hours for one period. The more complex a supply chain is, the more timeconsuming the data collection process becomes. Collecting data from multiple systems poses additional challenges because different definitions are often used.

2 Quality Metrics Digitizing processes Two aspects are critical to ensure consistent data collection and minimize time and effort involved: Equipment implemented in production, packaging or quality control labs should facilitate electronic data collection steps to more easily derive the described metrics. Software and processes which are used across manufacturing sites should be standardized to reduce time for staff training and education. Becoming a low-risk site Although it is not simple and takes effort, the appropriate quality metrics can be used to proactively implement more robust processes while providing transparency on improvements to employees, customers and regulatory authorities. Ideally, participation in the program and demonstrating consistently high quality will reduce the number of inspections at low-risk manufacturing sites. Quality Metrics Facts & Figures FDA Targets Develop risk-based inspection scheduling using submitted data Improve the ability to predict drug shortages Encourage implementation of quality management systems. Required Quality Metrics Lot acceptance rate - Measure for the robustness of the manufacturing process Invalidated Out-of-Specification Rate Indicator of the operation of a laboratory Product Quality Complaint Rate - Indicator of patient or customer feedback Timeline Revised draft guidance published in 2016 by the FDA Voluntary reporting phase until 2018 Mandatory reporting expected to start in 2018 Data Collection Efforts More than 40% of data reporting efforts are spent on guidance and coordination. (ISPE Quality Metrics Pilot Program) Guidance Data Collection Publisher / Production Mettler-Toledo GmbH Industrial Division Heuwinkelstrasse CH-8606 Nänikon Switzerland Subject to technical changes 09/2017 Mettler-Toledo GmbH New Industrial Weighing Catalog Find Your Required Solution with Our Full Product Portfolio 2 METTLER TOLEDO Pharma & Biotech News 22

3 Ensure Data Integrity 3 Key Functionalities In pharmaceutical manufacturing, all activities from lab to production and logistics must be recorded. Documentation must be accurate, traceable and secure. Automating all or a part of data-gathering for quality-critical processes using electronic solutions can help to ensure compliance. However, computerized systems need key functionalities to enable compliance with 21 CFR Part 11 or EU Annex 11. GMP regulations require that generated data must be analyzed and results and reports must be available for review processes or audits within a defined time period. For many of these processes, we offer compliant software solutions such as LabX, FreeWeigh.Net, FormWeigh.Net, ProdX and isense as well as aggregation and serialization software. We also provide the validation documentation and support you need to fulfill regulations. Secure Access and Storage Compliant software limits access to authorized users. It ensures uniqueness of user names and passwords and also safeguards against unauthorized use. Data must be stored safely, backed up and archived. Comprehensive Audit Trail The audit trail documents all record changes, indicating the change itself along with user information and date and time in full compliance with 21 CFR Part 11 and EU Annex 11. It ensures that all changes made to the data can be traced. Distinct Electronic Signatures Electronic records have to be signed electronically according to regulatory standards. The name of the user as well as the date and time of the signature is recorded in the signed record and audit trail. METTLER TOLEDO Pharma & Biotech News 22 3

4 Quality Management Streamline Your Quality Workflow Compliant Efficient Scalable Improve the control of your production quality from statistical monitoring of fill quantities to the documentation of tablet-testing data. FreeWeigh.Net statistical quality and process control ensures legal requirements are met and profitability potentials are realized. 4 METTLER TOLEDO Pharma & Biotech News 22

5 Full Quality Process Control Define, monitor and evaluate production quality from your workstation. Define quality tests and distribute test plans to all stations. Access measurement results and statistical data at any moment. Create customized reports and share quality data easily. Quick Deviation Response Immediately react to any deviations and minimize downtime. Receive immediate notifications on the line, on master stations, or via /sms. Benefit from trending functionality to detect tolerance violations in advance and minimize process interruptions. Integrate and Expand Easily Expand your quality control set-up at any time with little effort. Easily integrate third party devices, PLC or software solutions. Scale-up from a compact single station to a fully networked system. Add additional workplaces and functionalities when required. Full Regulatory Compliance Meet required regulations and benefit from comprehensive validation support. Rely on functionality for full FDA 21 CFR Part 11 and EU Annex 11 compliance, including user access management, electronic signatures and audit trail. Make use of comprehensive documentation and services for efficient software validation. Full Range of Quality Data Control a broad range of quality parameters for tablet and package testing. Tablet quality tests: including hardness, thickness, weight, friability, content uniformity, disintegration, color, odor and more. Package quality tests: including net-content, expiry date, label print quality, package insert included, batch ID and more. METTLER TOLEDO Pharma & Biotech News 22 5

6 Performance Verification Don t Gamble with Quality Implement Risk-Based Testing The performance of any measuring instrument will change over time. To ensure the equipment continues fulfilling the requirements for process tolerance, a monitoring strategy is needed and required by GMP. Implement a risk-based performance-verification approach to meet regulations and optimize resource allocation. Optimize Schedules and Procedures Implement Compliant SOPs GWP Verification service by METTLER TOLEDO provides specific recommendations on testing frequencies and procedures for each weighing instrument. Maintain accurate measurement results with minimal testing efforts and rely on audit-proof documentation to ensure regulatory compliance. How can the results from a weighing risk-assessment be incorporated into standard operating procedures (SOPs) to ensure consistent process quality? METTLER TOLEDO offers a consulting service to help you establish globally harmonized and auditproof SOPs. 6 METTLER TOLEDO Pharma & Biotech News 22

7 Download our new checklist Ensure Diligent Implementation Standardize Calibration Deviations from defined SOPs often occur during routine testing. This is why select METTLER TOLEDO weighing terminals feature an integrated functionality that puts your testing procedures into practice. Test Manager GWP alerts you to and guides you through scheduled routine tests. Variance in calibration standards and procedures can negatively impact measurement consistency. We calibrate your weighing devices regardless of the brand according to the same standards and operating procedures. This ensures total consistency over the lifetime of your instruments. METTLER TOLEDO Pharma & Biotech News 22 7

8 Laboratory Automation Eliminating the Rotten Apple with LabX Software LabX software integrates METTLER TOLEDO lab instruments and maintains data integrity by automatically storing complete data sets and transferring data between instruments. According to the US Food and Drug Administration, data should meet the criteria of being attributable, legible, contemporaneous, original, and accurate (ALCOA). This focus has highlighted the importance of laboratory administrative work. Using the example of a titration workflow, we demonstrate the usefulness of LabX software for ensuring data integrity. tag, which is attached directly to the beaker to help prohibit potential permutations. When titration begins, all accumulated results, raw data and metadata are automatically transferred to the LabX database. LabX connects various laboratory instruments from METTLER TOLEDO to one system. The entire sample information only needs to be recorded once and is then transferred automatically and unambiguously. By removing the need for manual data recording and data entry, valuable time is saved on each sample and transfer errors are easily avoided. Holding it all together with LabX Workflows involving more than one instrument may result in transcription errors when values are manually transferred between instruments. LabX in combination with a SmartSample kit helps improve this workflow by automatically transferring sample data from a balance to the titrator as well as to LabX. First, sample data is stored in the RFID (radio-frequency identification) 8 METTLER TOLEDO Pharma & Biotech News 22

9 NEW Hygienic Tank Scales Prevent Cross-Contamination The risk of batch rejection or even product recall because of cross-contamination is imminent in pharmaceutical production. As a consequence, companies implement rigorous cleaning procedures. Hygienically designed equipment can be cleaned quickly and easily and reduces cross-contamination risk. When tank inventory must be monitored accurately, weigh modules are the measurement equipment of choice. They provide a higher accuracy than other measurement technologies such as flowmeters and do not come into direct contact with processed materials. Accurate and hygienic Because material contact is avoided, tanks outfitted with weigh modules are an ideal solution when both accuracy and hygiene are required. However, tanks are often placed directly in hygienically sensitive environments and thus are subject to the cleaning procedures prevalent in pharmaceutical production. Good Manufacturing Practice (GMP) puts great emphasis on the prevention of crosscontamination and requires that equipment be suitable for easy cleaning. The new SWB805 MultiMount weigh module is specifically designed for hygienically sensitive environments. It is certified by NSF International according to hygienic equipment-design standards and fulfills EHEDG design requirements. Designed for cleaning Key features such as mirror-polished stainless steel, self-draining surfaces and a fully sealed load cell make sure that the weigh modules can be cleaned quickly and thoroughly. The SWB805 MultiMount weigh module is the right choice when designing low-risk tank weighing solutions for clean-room applications. New Weigh Module SWB805 MultiMount NSF International certified Fulfills EHEDG design requirements Self-draining for fast drying Mirror-polished for low bacteria accumulation Stainless-steel load cell IP68 / IP69K protected OIML, NTEP, ATEX, FM approved Capacities: 110, 220, 550, 1100, 2200, 4400 kg METTLER TOLEDO Pharma & Biotech News 22 9

10 Improved Fermentation Productivity More Batches and Higher Yield in Italian Fermentation Plant The advantages offered by digital sensor technology are convincing more and more pharmaceutical companies to switch from analog systems to Intelligent Sensor Management (ISM ) technology. One such company is Patheon Capua. Now they are benefiting from greater productivity and reduced batch failure. Global science company Patheon is a North American multinational pharmaceutical company. It has annual net sales of around USD 2 billion and employs approximately 6,000 people worldwide. Patheonʼs Capua facility outside Naples, Italy is a Contract Manufacturing Organization dedicated to the production of pharmaceutical API and pharma and food enzymes. With over 20 reactors, the facility is one of Italyʼs largest fermentation plants. Over the last few years, ph and oxygen measurement points installed on the reactors were changed from standard analog sensor systems to METTLER TOLEDOʼs digital Intelligent Sensor Management (ISM) technology. This task was overseen by Sergio Andreutti, Reliability Engineer at Patheon in Capua. Pharmaceutical & Biotechnology News spoke to him about the move to ISM. Mr Andreutti, what issues were you having with the analog sensors you were using? Firstly, we had to keep a dedicated log book for each sensor to record calibration data, etc. That was very inconvenient and carried too much risk of information being entered or read incorrectly. We also had to calibrate ph sensors twice: in the workshop after maintenance and again after connection in the field. Obviously this meant we were spending a lot of time on calibration. And thirdly, we had no real idea as to when a ph sensor would no longer measure reliably or when an oxygen sensorʼs membrane would need exchanged. What first attracted Patheon to Intelligent Sensor Management? When we discovered that we could record and trace the history of sensors, such as the number of CIP or SIP cycles theyʼd been exposed to and calibration history, we became interested in ISM. In 2011 we were planning to change our control system for fermentation operations. We took the opportunity to move from analog sensors to state-of-the-art technology, and so we decided to implement ISM. According to your experiences, what are the most important benefits that ISM technology has brought to your plant s processes? Mainly two. Firstly, traceability. With ISMʼs isense software we can trace all the information about sensor use, maintenance weʼve performed on sensors, and also can follow-up all the aspects of a sensorʼs performance over its life. This is Mr. Sergio Andreutti, Reliability Engineer at Patheon s Capua facility. 10 METTLER TOLEDO Pharma & Biotech News 22

11 very important when we have to analyze some process failure, or the performance of a sensor, and to study how to assess the maintenance activities on a sensor. And with ISMʼs diagnostics we can plan well in advance when to maintain or replace a sensor. The other important benefit is that this technology allows us to reduce maintenance activities due to the fact that we do not need to calibrate sensors two times. Now we just calibrate in the workshop and connect the sensor to the transmitter in the field. This has allowed us to reduce the turnaround around time between fermentation runs. Thanks to that we have increased fermenter availability in order to raise batch numbers and to add new campaigns over the year. What cost savings has ISM delivered? Of course spending less time calibrating sensors has reduced costs but the main savings have been achieved through increasing plant reliability and reducing the number of failed or low yield batches due to sensor failure. Are you planning to expand the use of ISM in your processes? Our fermentation processes are now fully-covered with ISM technology. There are downstream processes where we can implement ISM and weʼre now looking at how to do that. Find out how much you can save with ISM: METTLER TOLEDO Pharma & Biotech News 22 11

12 Investment for Future Growth Improving Packaging Line Productivity New Industrial Weighing Catalog Industry research suggests that demand for pharmaceutical products is set to continue with the growth patterns seen in recent years. The need to review and refine packaging line processes to harness capacity and maximize output has never been greater. Free Download Our performance optimization guide for the pharmaceutical industry focuses on checkweighing technology and explains the valuable functions and add-on features that can improve packaging processes. The guide provides an overview of mechanical and software options that can help to optimize packaging line performance, check for package completeness and increase overall equipment effectiveness (OEE). Download Checkweighing Guide: METTLER TOLEDO Group Industrial Division Local contact: For more information Subject to technical changes 09/2017 METTLER TOLEDO. All rights reserved Document No MarCom Industrial