Missing the human interaction too much

What will make this edition very special beside the fact of returning to see you all, is the strong desire to ease discussions.  At the PLA, like everyone, we are tired of static virtual events, static team online meetings and we are really missing real discussions with the audience. We want to hear from you and we want you to get the maximum out of it.

As such the agenda structure will be revised allowing much more space for Q&A sessions and panel discussions.

in order to stimulate the discussions we have put together a series of topics with our keynote speakers. The Paperless Lab Academy® is all about digital data management in manufacturing company. Whether the final products are to be quality controlled or proper laboratory services, whether the department is R&D, IT, Operational Excellence or Quality, whether the major concern is efficiency, integration, harmonisation or compliance, we aim at covering them all at its best for you to get a better understanding and bring back to your team meaningful information.

Science, Technology and Data

The word around us is evolving at incredible pace and companies need to embrace this evolution. Speakers from Roche, Novartis will share their experience in bringing different functions, process, and products into the digital world.  Igor Menghini , Head Software Product Management at Roche will also share their experiences in assessing technologies, their concerns and approaches to ease implementation. 

As such Vijay Raju, Global Head of Analytical R&D at Novartis AG, will share updates in their user centric approach pursued in engaging the scientists to understand their pain points, defining future solutions and designing the prototypes. Everyone is also looking for updates on their very smart approach for ensuring the buy-in of the laboratory users, through a digital pilot laboratory which everyone can visualise as the new processes to be implemented, they get user acceptance before full scale implementation. 

Cloud and Security

Cloud has immense potential, but most companies are only scratching the surface. The adoption of cloud principles, such as infrastructure as code (IaC) and security as code, help to automate good-practice (GxP) compliance processes so the organisation can move quickly while staying secure and compliant. See as example Automating GxP compliance in the cloud: Best practices and architecture guidelines.

Security measures available are multiple, like segregation of protected or sensitive data from non-sensitive data, encryption of  sensitive data while in transit or also at-rest, robust access control with use mechanisms that define privilege access, multi-factor authentication, etc. 

Considering SaaS solution providers vs on-premise ones is today a necessary move toward newest digital dimensions. 

Digital Transformation Journey 

Simon Brem, Head Laboratory Systems and Standards at Carbogen Amci will share pragmatical experience on their digital transformation journey. Their analytical labs in Switzerland are mostly paperless for more than 10 years now and currently working on a global rollout of a new LIMS system. Simon Brem will elaborate on ‘soft and hard’ key factors and learnings for project success. He will also explore the benefits of agile business process design and discuss on the benefits of external expertise and benchmarks

From last Paperless Lab Academy® edition in India, SGS already shared with the audience that like many life sciences organisations, their quality environment was heavily paper based and document centric. They needed a digital system that could incorporate efficient electronic workflows to manage quality events, audits, SOPs, quality documents and employee training records. In order to achieve an ambitious timeline for the rollout, they preferred to opt for the out-of-the-box option with minimum customisation. In this precise edition, Ulrich Martens, Global Head Quality, Business IT & Business Excellence at SGS will share their experiences on global implementations, the impact of the human factor and change management, the relevance of establishing valuable, strong, trustful long term relationship with their solutions providers.

Typically , digital winners rely on scalable software-based business models that can rapidly scale up the number of users and revenue with only minimal changes to the underlying cost structure.

Finding the true value of lab and plant data

Lloyd Colegrove, Data Services Director at Dow Chemicals ( now retired and consultant ) will share their journey.The journey towards a major chemical company’s vision for the artful use of large structured and unstructured data sets in real-time plant operation and problem solving is a story of technology, salesmanship, and the hard work of convincing a company in love with Excel spreadsheets, and problem solving after-the-fact, that significant value lies in already collected and often under-utilised plant data sets. Part of the story includes the application of artificial intelligence, but AI is not the solution, it is a solution.

Through the use of volunteer audience participation and a few artful stories, this talk will discuss real-time analytics success stories that are actually simpler than “AI” infused solutions, discuss where AI fits in the chemical industry, and highlight some experiences from 30 years of engagement in chemical manufacturing that can bring tremendous bottom-line value to your chemical operations.

Rethinking strategy for the post pandemic era

McKinsey survey confirms that the future will belong to companies that put technology at the center of their capabilities, and leadership mandate. The pandemic has impacted the pace of business, forced companies to revisit and even reconsider their business model.  Technology capabilities is critical to companies’ COVID-19 exit strategies as well as to what comes next. CIO have a stronger voice within the organisation and CFO are allocating budget for making digital and technology investments across the business model.

We’ll be looking to discuss further with you about the pandemic effect on your daily work?  was there a digital fix to alleviate the team ? What works better than before? What didn’t? Can we get better prepared for what might be coming next?

Compliance, Quality Standards and Integrity

It goes without saying that scientific data management requires of special attention regarding integrity and compliance. A lot can be discussed here, further more than just ALCOA, FAIR, Archiving, Backups, etc. Mark Newton  and Bob McDowall,  our keynote speakers subject matter experts will take us through the concepts and more over through real cases.

They will be running a specific panel discussion in which you need to be prepared to be challenged and best to summarise this space is the title of Bob McDowall presentation The Answer’s Digitisation, What’s the Question? 

Bob is an analytical chemist with 50 years of experience, including working in the pharmaceutical industry for 15 years and afterward working for the industry as a consultant for 29 years. Bob has been involved with the automation of laboratories since 1980 and has over 35 years experience of validation of computerized systems and is the author of a book on the validation of chromatography data systems.His latest book is Data Integrity and Data Governance: Practical Implementation for Regulated Laboratories published in 2019 by the Royal Society of Chemistry. He is a member of the GAMP Data Integrity Special Interest Group, contributing to the Records and Data Integrity Guide in 2017 and two Good Practice Guides. Bob McDowall is also the author of the “Questions of Quality” and “Focus on Quality” columns in LCGC Europe and Spectroscopy magazines, respectively.

Reading current journal, scientific magazines and listening to presentations about automating a laboratory, you could be forgiven the assumption that many organisations are at the cutting edge of technology. However, when you see many medium and small sized laboratories nothing can be further from the truth. Many laboratories and regulatory authorities have forgotten the need to keep current with technological advances. Therefore, regulated GMP laboratories must automate and remove paper if they are to survive in a stringent data integrity environment. How should we change this? just you do it! comments Bob McDowall

Mark Newton is an independent consultant in laboratory informatics and data, data integrity, validation of computer systems/spreadsheets, analytical instruments and LIMS/ELN. He has 30+ years of pharmaceutical experience in QC Labs, computer systems validation and lab informatics at Eli Lilly. Mark co-lead Eli Lilly’s data integrity remediation program for QC Labs worldwide in 2012, consulted and audited several Lilly sites preparing for data-integrity focused inspections. He is a co-leader for the GAMP Data Integrity Special Interest Group and Chair of ISPE Global Documents Committee. Co-author of “Harmonizing USP <1058> and GAMP for Analytical Instrument Qualification”  Schuessler, Newton, Smith, Burgess, McDowall. Pharm. Engineering, Jan/Feb 2014. Co-editor of the GAMP Good Practice Guide “A Risk-Based Approach to Compliant Computerized Laboratory Systems” Nov. 2012.

Commitment to healthy measures

We know that coming back to event like the Paperless Lab Academy® is the one of the first to coming back to normal life together. Above all, laboratories have been put under the microscope in these past months and an amazing international work has enabled the production of vaccines in record time. the knowledge sharing, data exchange, data process and automation has enabled this speed of answer to the world. The laboratory informatics industry is booming with amazing modern solutions that can really be the answers to the laboratory needs today. Because the lab of the future is today!

Come and join us!

Join the experts, your peers, the solution providers… Come and join the discussion! Register Now

They have confirmed their presence

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The Paperless Lab Academy^® works in providing the audience food for thoughts in their digital transformation journey and in coordinating access to the latest technology offering of the lab informatics industry.

Fact is that when looking at laboratory and quality processes to be digitalised, several layers need consideration and multiple questions need answers. It is not always easy to even understand where to start and how to formulate decisions. A strong recommendation is to start with mastering your own data life cycle, and as such verify that the required regulatory compliance are observed in each steps and phases: eConnect, eManage, EDecide & eArchive.

Master you  Data Life Cycle

That is why we’ve collected a series of presentations developing further more from Raw Data capture moment to efficient use of the data for analytics, business and artificial intelligence.

Whether they are raw data from chromatographs or any other analytical instruments, they have been at the heart of many data falsification and poor data management practices found in many FDA warning letters since the Able Laboratories fraud case in 2005.

Breaches to data integrity can be avoided by creating flawless data transfer from instruments to systems, including avoiding use of spreadsheets for calculations. If you’re open of being challenged We Mr. Bob McDowall, we warmly recommend you to attend his provocative yet funny and to the point presentation: Are Spreadsheets a Fast Track to Regulatory Non-Compliance?

Consider an electronic process with validated calculations and electronic signatures 

The message will be reinforced by Mr. Mark Newton´s presentation on Data Forensics with a  pragmatic example and exercise about the importance of metadata. The information about the data that brings a deeper understanding about the quality of the final results. 

Mark is a co-leader for the GAMP Data Integrity Special Interest Group and Chair of ISPE Global Documents Committee. Co-author of “Harmonizing USP <1058> and GAMP for Analytical Instrument Qualification” and Co-editor of the GAMP Good Practice Guide “A Risk-Based Approach to Compliant Computerized Laboratory Systems”.

Systems Integration approaches 

Yet more instruments are involved in a analytical processes and additional metadata and unstructured data are to be facilitated alongside the raw data. Andreas Steinle from Roche Diagnostic will take us through their very specific Instrument integration strategy and journey and explain how to unlock your analytical instrument data for data science 

Mr. Vipul Krishan Yamdagni, now independent GMP consultant and advisor, brings 34 years experience in the industry with major Indian Pharma organisations about digital strategy and systems integration. Vipul will share his view on  Digital Pharma Laboratory – challenge | opportunity | way forward 

Implementation experiences by time of COVID

Despite the pandemic situation and the lockdown, manufacturing companies had to react quickly to the situation, remain productive while implementing safety procedures for their employees.  Three presenters will explain us how they’ve overcome the situation, implemented solutions and taken benefit of them during this though and challenging moment.

Ms. Preeti Gaonkar, SEAP Quality Excellence Manager at SGS India Private Limited will explain how they have accelerated  their quality with digital transformation. By implementing of a Quality Management System digital system they could incorporate efficient electronic workflows to manage their quality events, audits, SOPs, quality documents and employee training records.

Mr. Albert Almajano, Chief Information Officer at Indukern Group will share their company strategy and experience in remaining focused to the implementations during the lockout situation with his presentation, Albert will show us a Roadmap to Digitalisation with Success

Mr. Sergio Nasi, Head of IT Operations Laboratory Execution at Boehringer-Ingelheim  will provide and overview of an ongoing implementation of a laboratory execution system and explain how additional challenges and opportunities the global COVID-19 pandemic have meant to the project implementation. Sergio will help us to Define your own pathway to the paperless QC laboratory: lessons learned from an ongoing project

Data Analytics and Artificial Intelligence

Toni Manzano, Chief Science Officer, R&D Director and Co-founder at Bigfinite brings a strong experience on data analytics, machine learning, artificial intelligence and sound knowledge on all related algorithms and statistics concepts behind. A unique opportunity to listen to an AI specialist with strong domain knowledge of the manufacturing industries.

Do not miss  the opportunity to benefit from his presentation and learn about Data Centricity: What is behind the AI implementation in Pharma

Dr. Lloyd F. Colegrove, Director at  Dow Chemicals, now retired and consultant, has spent 7 years in Polymer Research in Dow (R&D and TS&D) before moving into Manufacturing in an Analytical Improvement role and then a Quality Leader for five Dow businesses before moving to help establish a new capability called Fundamental Problem Solving, where top chemists and engineers work on complex, often multi-effect, plant problems. With this established, he refocused his efforts working to establish the data initiatives that support this work. Lloyd´s talk “Digital Transformation in the Chemical Industry. The Devil’s in the Details” will feature artificial intelligence as an example of a key future value delivery mechanism in digital transformation. The road to installing AI in the Chemical Industry is fraught with challenges and many dead ends.

Those are the topics and presenters  that you should expect to listen to and discuss about during the Paperless Lab Academy 2020 India online event.

Make sure to Register  for you to access the virtual event platform !

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The QC laboratories work in a highly regulated environment where effective electronic data management processes ensuring Integrity are a must. Therefore, these processes are still largely based on paper, preventing efficiency improvements that could be really useful.

The renewed attention of the authorities inspectors to the Data Integrity is pushing towards the management of instruments GMP data output in their original electronic format, preserving their contextualization (meta-data), any exceptions, quality control records and, in some cases, the Dynamic format that allows the data processing, including the re-evaluation of results or the execution of queries.

But the retention of data in electronic format has some pitfall. As an example, most of the software that manage analytical instruments do not provide any mechanism to record the data review by means of an electronic signature. While the GMPs require to document the data review.

The review in electronic format is available only on the most advanced platforms for Chromatographic Data Management System, for HPLC or GC. Simple instruments (ph-meters, scales, legacy instruments, etc) and also UV or IT spectrometers, titrators, densimeters, etc. do not support the electronic review, therefore the results are often printed in order to collect the signatures for the review.

With Ioi it’s possible to carry out the electronic review using electronic signatures and increasing the lab efficiency.

Electronic Review by Ioi – Integration of instruments

This feature, improved in the version 2.0 of the system, is designed to automate a business process This involves capturing what has been acquired by the field (measurement, notes, signature, contextualization, etc.) so that a reviewer can retrieve the electronic data to analyse and review for the final approval, through electronic signature, in a fully paperless process.

The new release of Ioi – Integration of instruments offers a fully paperless Electronic Review feature for almost all the data acquired, generated and processed. Based on the fact that this amount of collected data needs to follow a specific review flow, Ioi supports the Electronic Review feature to accomplish the whole life-cycle of every measurement and each meta-data related to it.

This functionality allows to carry out:

• Electronic Review configuration
• Measurements Review based on a configured contextualization
• Ioi Audit Trail Review
• Instrument Logbook Review

Measurements Review can be configured to meet the customer procedure. In this way, review permissions need to be associated to the reviewer role to let him/her access to such a process.

Ioi supports electronic signatures, which are required by the system for some specific actions, such as confirmation or rejection of a measurement or a performed review.

Ioi can be used in two different scenarios.

• A “less-paper” scenario, where at the end of the measurement and review process, Ioi is used to generate any required report (including the review), such as:
  • Measures Review notes and signature
  • Sample\Analysis sheet master container approval cycle
  • Instrument Logbook review details
  • Audit Trail review details
• A paperless scenario, where Ioi can transfer the results to an upper level system (LIMS, ELN, etc.). In this scenario it could be possible to interface the instruments directly to the LIMS or ELN, but each instrument would require a specific interface. Instead, Ioi can be quickly interfaced to the whole instrumentation and to the LIMS/ELN with a single interface.

In both cases, the original data are retained on Ioi.

Ioi – Integration of instruments goals… we haven’t forgotten the Data Integrity

Along with the electronic data management, the integrity of data is also crucial. Ioi – Integration of instruments, designed on the concepts of security, reliability and robustness of data. It represents the ideal starting point to achieve concrete Data Integrity-compliant results in the lab.

In conclusion, Ioi achieve these main goals:

• guarantee the Data Integrity compliance
• increase the process reliability reducing manual transcriptions
• improve lab efficiency optimizing the business processes (up to 50% of time saving)
• improve performances according to the regulations requirements
• enables a paperless, or at least a less-paper, lab

The Ioi application is fully validatable versus the requirements of FDA 21 CFR-11 and Annex 11 to European GMP (including Data integrity).

Quick installation of Ioi – Integration of instruments

Moreover, it’s quick installation (weeks) and simple management make it easy to realize typical lab processes without the complexity of projects such as ERP, LIMS or ELN. At the same time, Ioi does not replace these systems, but rather it gives its best when it’s placed between laboratory instruments and a LIMS (Laboratory Information Management System).

In case of a future ELN or LIMS implementation, the presence of a single interface thanks to Ioi, instead of an interface for each instrument, allows to preserve the investments.

Ioi is vendor-independent (all brands of instruments are interfaced) and is a web-based system.

If you want to know  all the capabilities of the Ioi Electronic Review feature , we invite you to contact us at info@inpharmatic.eu or visit our website www.inpharmatic.eu.

Emmanuele Dicerto, Chief Technology Officer at Inpharmatic

Inpharmatic is a team combining professionals with more than 25 years of experience in the pharmaceutical industry and a new generation of software designers, coordinated by project managers of international experience. The team aims to add the benefits of efficiency and integration to the systems compliance with the requirements of Data Integrity. In this way, investments in Data Integrity become a competitive advantage for the pharmaceutical industries. Inpharmatic is enlarging and structuring its organization in order to support the success of the proposed solution.

Gold sponsor at #PLA2021 , will be exhibiting and  Presenting a workshop ” Learn how to solve legacy instruments DI gaps with an instrument integration platform” 

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At present, in the labs, there are still “legacy” measuring instruments, i.e. instruments that are there since ever and very often they’re not fully compliant to Data Integrity requirements. Usually, the remediation of their Data Integrity gaps is an issue, because a compliant new instrument is either not available or, for any reason, the instrument cannot be substituted, or it is not worth a substitution.

In other cases, as a remediation activity, it is foreseen the installation of the vendor proprietary software that puts the instruments in compliance, but in this way several new software will be introduced in the lab. These ones require a specific validation exercise and the following administration activities, different passwords to remember for the analysts, etc.

Many alternatives try to solve the Data Integrity Gaps

Several powerful applications promise the benefits of instruments integration (LIMS, ELN…) and this seems to be for sure the best solution. But these applications require up-to-date instruments and complex projects to be implemented, in the meanwhile, DI gaps remain for months or even years.

As an alternative, the implementation of an integration platform, a middleware, can put the legacy instruments into compliance and can be the first step towards a full lab digitalization. Its quick installation and simple management make it the ideal starting point to achieve concrete DI-compliant results without the complexity of projects such as ERP, LIMS or ELN.

At the same time, this middleware does not replace these systems, but rather it gives its best when it is placed between laboratory instruments and a LIMS (Laboratory Information Management System).

Using this middleware integration platform, users have the opportunity to:

• Save time, digitalizing the entire process of measures acquisition;
• Review the measures;
• Become familiar with IT systems and better understand the potential and the critical issues of these
  ones, preparing themselves for more challenging projects and for the eventual achievement of a
  completely digitalized scenario.

Why Ioi, Integration of Instruments 

Ioi is a middleware platform that captures laboratory instrument measurements, overcoming the Data Integrity gaps of legacy (but also new) instruments by collecting all the necessary metadata: who did the measure, the date/time of the measure, the instrument ID, the sample ID, the measure engineering unit, etc.

In other words, Ioi digitalize the tickets, because it stores the measures and the related metadata in a secure database (SQL) in full compliance with Data Integrity and without any paperwork.

Preserve your investments by interfacing Ioi

From a practical viewpoint the operator, by the use of a tablet, can:

• Log into the system (also using the credentials of the company network);
• Identify the sample reading the sample ID;
• Identify the instrument automatically or reading the ID;
• Read automatically the measurement of the instrument;
• Sign electronically the measurement (where applicable);
• Time stamp the measure with date and time taken from the network.

Further, Ioi preserves your investments: since when you implement other systems, like LIMS or ELN, you integrate all instruments by interfacing Ioi (one single interface) instead of interfacing every single
instrument (several interfaces).

The platform is scalable, so it’s possible to add new instruments at any moment with a simple
configuration and validation (GAMP sw category 4 instead of scripts belonging to category 5).

Some additional advantages are:

• Centralized access management (the same access credentials applied to several instruments) with benefits for:
  Users: only one password to remember and to change in case of expiry;
  Administrator: only one account to setup for each user (also by network domain).
• Automatic time synchronization from the network;
• Automatic recording of the Sample/Batch ID;
• Automatic instrument logbook.

Gold sponsor at #PLA2020 , exhibiting and  Presenting a workshop ” Learn how to solve legacy instruments DI gaps with an instrument integration platform” at #PLA2020

Emmanuele Dicerto, Chief Technology Officer at Inpharmatic

 

 

 

 

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Transforming your laboratory and quality processes from paper-based to paperless ones require you to build on a very dedicated team for a lab informatics implementation and a very specific digitalization project. One key team member is your software vendor. 

At the Paperless Lab Academy^®, we discuss about  the key aspects of such projects like for example how to set a realistic project scope, which milestones and expected outcomes are to be expected at short, medium and long term…

We’ve got through the change management aspect too, by implementing activities that would ensure that the human factor of the project would be carefully considered.

Fact is that little is mentioned about the key partner collaboration agreement to be set up. The software vendor is about to be your key partner in your project and crucial for an effective, compliant and successful software implementation and workflows validation.

During a software selection process we normally tend to focus on the product. Yet the vendor ability to stand along with you during the implementation is directly related to their own quality processes. Your ability to easily implement and validate the software is directly related to their software design.  It is about evaluating your provider and elaborate an accurate Risk Management.

The Academy Training proposes you a dedicated workshop 

Practical examples of Risk Management will be used throughout the workshop to demonstrate areas of focus, high risk and areas of low risk.

During a 4 hour workshop,  Mark Newton will take you through his best practices in software implementation and as such in vendor selection management. Mark brings his 35 years of experience in the pharmaceutical industry in QC Labs, computer systems validation and lab informatics at Eli Lilly.

Mark is also a very active member at the ISPE (1).  Co-leader for the GAMP Data Integrity Special Interest Group and Chair of ISPE Global Documents Committee.
Co-author of “Harmonizing USP <1058> and GAMP for Analytical Instrument Qualification”  (2)
Co-editor of the GAMP Good Practice Guide “A Risk-Based Approach to Compliant Computerized Laboratory Systems” (3)

Last but not least, Mark is part of the advisory board of the Paperless Lab Academy^® and contributes also with articles and webinars about #dataintegrity 

BENEFIT OF THE ACADEMY TRAINING 

Monday, April 20, 2020 | pre-congress day | Baveno, Italy

BOOK HERE

(1) International Society for Pharmaceutical Engineering,  ispe.org 

(2) “Harmonizing USP <1058> and GAMP for Analytical Instrument Qualification”  Schuessler, Newton, Smith, Burgess, McDowall. Pharm. Engineering, Jan/Feb 2014

(3) GAMP Good Practice Guide “A Risk-Based Approach to Compliant Computerized Laboratory Systems”

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Process capability – what has changed over the years?

The importance of process capability was highlighted when reviewing QC analytical records for a firm where the ability to generate an analytical value “right first time” was better 2-3 years ago than today.  Same method, same equipment, and even a few personnel added to the QC Lab.  So what changed?  Manufacturing output more than doubled over 3 years with more line extensions.  Manufacturing now produces more batches and more stability samples. Manufacturing capability improved, while the QC Lab capability did not; in fact, the equipment is now older and more likely to fail than before.  Out of date methods were not consistently able to generate values that could be released the first time, so rework (and investigations) began to take away from bench time.  A downward spiral of issues and investigations resulted in slipped schedules and unhappy customers, putting everyone on edge.

Process Capability and personnel pressures

When any process (purchasing, manufacturing, lab, calibration) is not sufficiently designed to work right the first time, every time at the timeliness of output demanded by customers, the outcome will be pressure applied to the organization. Personnel are tempted to falsify data or take improper shortcuts to “get it out the door” and relieve this pressure.  Culture can mitigate the situation by reminding people that honest reporting of data and issues is expected and supported by the organization.  That does not make the pressure go away—it is a temporary “escape valve” for that pressure.  Pressure is minimal when repeatable processes meet the demands.

Process Capability: the QC lab blind spot

Once the root cause –lack of capability—is understood, its application yields some immediate insights. First, labs are trouble spots for data integrity because they are rarely designed to be capable.  Yes, admit it.  Manufacturing processes are designed to a known quantity of output.  QC Labs, as a routine, are not.  From a data perspective, a QC Lab is a miniature production process with people, procedure steps, equipment, vessels, inputs and output (data). It can be modeled just like a manufacturing operation. The capability could be known.  But why is it so seldom done?

• There are many lab methods—several times more than manufacturing processes;
• QC Labs rarely have support specialists as do their Manufacturing counterparts: planners, equipment specialists, validation specialists, process design/engineering, IT, etc. Many QC Labs do all functions internally;
• Site leaders often have no insight into their QC Labs because their career progression did not include a QC Lab rotation.

The results are QC Labs with capabilities not matched to the Manufacturing operations they are tasked to support.

Process Capability: manufacturing’s moment of truth

Lack of capability can also impact Manufacturing operations.  Processes created under inflexible time constraints (e.g. first to file, exclusivity period) are at risk for this same issue.  These processes can lack the rigorous design space develop that assures a high probability of right first time.  This observation is consistent with the increased data integrity issues in generic firms where the perfect combination of low profit and timing pressures to file can result in manufacturing processes that can be validated but are not capable of “right first-time” outputs that keep a plant on schedule.

Death of the quality culture

An unintended consequence of non-capable processes is the death of the quality culture.  How?  Human nature kills it.  In developing a quality culture, personnel are told to “stand up and speak up” when there are issues.  Great.  If the voice is heard and a solution is developed, the issue is closed, and that complaint is no longer heard.  But process capability issues are more involved: they require development, validation, regulatory submission and approval.  This takes time and money; therefore, these issues will continue to be reported, week upon week, until the line supervisor says, “Enough! I hear you! Stop reporting that!” And here is the death of “stand up and speak up”—the boss just effectively said, “shut up and sit down”.  When issues exist that will require months to resolve, it is important to provide some means of keeping the issue visible to personnel, such as a workroom board.  The issue—and its estimated date of resolution—must be visible, to stop re-reporting, thereby frustrating line supervisors.  To keep “stand up and speak up” alive, the organization must deliver solutions to issues that hinder capability or human nature kills the culture.

Development – what is the root of the problem?

Little has been written about the link between Development/MS&T teams and data integrity in GMP operations, yet poorly developed processes add considerable pressure to GMP operations when they fail the “right first time, every time” standard.  There is a direct causal link between development/support practices and GMP conformance.  Your Development team has considerable influence over your data integrity pressures by the robustness of their efforts.

It is acknowledged that many methods are registered and can require considerable resources to update them.  This is where efforts like ICH Q14 (2) can help reduce the unnecessary regulatory burden that now impedes industry progress in adopting better analytical technologies.  At the same time, an assessment of time spent in additional testing, investigations, and documentation may conclude that the investment will be repaid in a short time period.  My former employer once estimated the time to write a deviation report at 40 hours.  That is probably a low estimate in today’s environment.

Looking for capability issues

Is lack of capability an issue in your organization?  There are questions and metrics that can provide insights to you:

* What is your site’s conformance to schedule? When operations routinely fail to meet the schedule is a lack of process capability the root issue?

* What is the “right-first-time” percentage for your various processes?  Is it near 100% or more like 80%? Each failure involves extra work by someone. There soon is a point where the extra work is better spent on a better process;

* Do you routinely have backlogs in any part of your process?  Instead of people issues, perhaps the issue is your process;

* Does a bottleneck remain even after people have been added?  This is a flag that the issue is not people, but rather process;

* If there have been productivity gains in one area of the operation, were supporting operations also improved at the same pace?  Or were they considered at all?

Linking Process Capability to Data Integrity

Based on such experiences, it is worthwhile to add a question when investigating data integrity issues in your organization:  Was a process-related deficiency a potential contributing factor to the issue?  It is too simple to blame data integrity failures on behaviors and ignore the source of the pressures that pushed them toward the undesired actions.

Eighty-five percent of the reasons for failure are deficiencies in the systems and process rather than the employee. The role of management is to change the process rather than badgering individuals to do better. – W. Edwards Deming

Process capability has a direct relationship to data integrity pressures. We need to consider process capabilities in all areas of the site to assure that pressures on our people are minimized, and people can focus on making safe, effective medicines that patients expect.

Special thank you to Bob McDowall (McDowall Consulting Ltd) for reviewing this document prior to submission.

References

• ISPE Cultural Excellence Report, April 2017. Available from ISPE (ispe.org)
• International Conference for Harmonization. Q14 Analytical Procedure Development (www.ich.org/page/quality-guidelines)

Mark E Newton, Heartland QA
Mark Newton is an independent consultant who specializes in data integrity, laboratory informatics, computer systems validation, and Quality. He has 35 years of experience in the pharmaceutical industry.
He can be contacted through LinkedIn:  linkedin.com/in/mark-newton-3848236

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One of the most difficult types of systems to be put in compliance are simple tools, such as scales, pH meters, conductivity meters, etc.

For these tools, the guidelines consider acceptable that the data are printed on a receipt (static format), but recommend that the metadata, such as date and time and the identifier of the instrument, are also printed. Then the analyst must write down the reference to the sample, sign the print and fix it in his notebook or analytical sheet.

As a result, the date and time of the instrument must be synchronized and locked. Unfortunately, not all the tools have a password to limit the modification of date and time to an independent user. In this case, it is possible to replace the instrument with one protected by a password.  It is an expensive solution.  Even if renewing the tools is desirable, it is not always affordable or not for all instruments at the same time. However, even in the case of tools with a password, it is costly to manage these passwords procedurally and to synchronize the time (at least twice per year in order to switch to and from daylight saving time). Last but not least, it is time-consuming to attach the paper receipt (or any photocopies in case of thermal paper). This is an important inefficiency factor that could benefit from a paperless solution.

An alternative solution is a “middleware” like the Inpharmatic Integration of instruments (Ioi). This software is a sort of “wrapper” that adds-on to the measuring instrument taking care of the measurement metadata such as sample-id, date-time, operator identity, electronic signature (where applicable) …

From a practical viewpoint the operator, by means of a tablet, can: 
• Authenticate (also using the credentials of the company network)
• Read the sample number through a barcode or data matrix;
• Read automatically the measurement from the instrument;
• Sign electronically (where applicable)
• Take date and time automatically from the network

All these information are recorded in a secure DataBase (SQL), in full compliance with Data Integrity and without any paperwork to store the raw data.

At this point, we have two possible scenarios: the paper-based and the paperless ones

In a paper-based lab scenario, data can be printed in summary reports: by batch, by analysts, by instrument, …  The Instrument log book can be automatically generated too.

In a paperless lab scenario, as suggested by the name “middleware” the measurements can be transferred to a LIMS (Laboratory Information Management System), or an ELN (Electronic Laboratory Notebook) making the management of these measures completely paperless. In this scenario, Ioi can also act as a Smart Gateway by providing a single point of interface to several instruments by taking care of the communication to different instruments of different suppliers (the only requirements for the measuring instruments is the possibility to interface to a printer).

Over 5 instruments, it may be convenient to go for the implementation of an Ioi middleware

Other advantages of this software, whether it is connected to a LIMS or not, is that it reduces administrative tasks. In fact, they have centralized access management, which can be associated with company network security. And, as anticipated, it does not require date and time synchronization, since it is automatically synchronized with the company network.

In conclusion, as a rough estimation, if the number of simple instruments to be put in compliance is lower than 5, their compliance by procedural management is sustainable, over 5 it may be convenient the implementation of the Ioi middleware.

The post How to comply Data Integrity with simple instruments appeared first on .

[Free Webinar: Wednesday, November 21th 2018 – 15:30 CET ] 

So many topics under one single line!

Mark Newton is your expert to listen to when comes to understand compliance at the laboratory

Presenting: Mark Newton, principal at Heartland QA 

Mr. Newton is an independent consultant with 30+ years of experience in pharmaceuticals as a laboratory scientist, then as a QA professional, supporting LIMS systems, standalone lab instruments, lab informatics and metrics, validation, quality systems, and data standards.  Mark has been deeply involved in data integrity audits and data integrity training to people in QC Laboratories, Manufacturing, and IT.

Mark is also an important contributor at the International Society for Pharmaceutical Engineering.

• Current Chair of the ISPE Global Documents Committee
• Current co-leader of the ISPE/GAMP Data Integrity Special Interest Group
• Co-author for “GAMP Guide: Records and Data Integrity” April 2017
• Co-author of “Harmonizing USP <1058> and GAMP for Analytical Instrument Qualification”  Schuessler, Newton, Smith, Burgess, McDowall. Pharm. Engineering, Jan/Feb 2014
• Co-editor of the GAMP Good Practice Guide “A Risk-Based Approach to Compliant Computerized Laboratory Systems” Nov. 2012

Outline of the first one-hour webinar course in which Mark will introduce the topics to be developed further in future sessions.

An interesting approach, challenging questions, solid conclusions from a 30 years experienced and well-known expert.

Context of the Instrument Qualification Activity

• Is it Validation, Qualification or Verification?

  • ASTM E2500 definition
  • News flash: Regulators don’t care!

• Benefits of doing the exercise, even for non-regulated labs

  • Question: if I could give a value +/- 25%, is that good enough?
  • Question: if the result might have calculation errors, is that acceptable?
  • Question: is it acceptable to let everyone in the lab change method calculations or configuration without telling anyone?
  • Question: more efficient to design technical controls or do more procedural (human) controls for every test?

The Lab results have a real Direct Impact on product quality! It’s really about Data, not Equipment: Data Lifecycle vs Equipment Lifecycle. Data integrity is not just for GMP activities

• Three questions to answer:
  • What activities will we perform?
  • How extensive does the activity need to be (robust)?
  • How thoroughly do we need to document the activity?
    • Example: Research vs QC Lab

Crafting an Organizational Approach to Analytical Equipment

• Holistic Approach (vs Qualify Equipment/Validate Software)
• Spectrum: USP <1058> and GAMP Lab Guide
• Putting it together: A Continuum of Activities
  • Criteria for the continuum:
    • Data Complexity (overall)
    • Factor: Vendor Dependence
    • Factor: Configurability
    • Factor: Electronic Records; Electronic Signature

Verification Activities and Deliverables

• Using the Continuum to Create a Grid of Activities
• Verification Planning (keep it simple!)
• Requirements: Critical step to get it right
  • Security/network/firewall
  • Access controls by design: some considerations
  • Factors to consider in the requirements phase
    • Access roles/duties (segregation)
    • Data integrity (identify records that need audit trails)
    • Traditional considerations: data inputs, calculations, reports, interfaces, environment
    • Leveling Requirements: User and functional, or one set?
    • Critical requirements (regulatory expectation)
      • Approach to managing requirements for future upgrades
    • Traceability
      • A powerful demonstration of control
    • Design Qualification (joining DQ with Requirements in a Simple Way)
    • Configuration
      • What most do wrong/why the configuration is a challenge
      • Value-added configuration documentation
    • Testing
      • Changes to accommodate holistic approach (IQ/OQ/PQ vs Unit/Integration/System)
    • System Acceptance
      • Normal Process
      • Managing Exceptions (or, how to avoid regulatory entanglements)
    • Operational Phase vs Development Phase

Vendor Management/Selection

• Often neglected, but Important to Success
  • Irrelevant terms, based on experiences: ISO, Market Leader, Long Relationship….
• Involving the Right People (who is needed, and why)
• Multiple Goals: vendor capabilities, data integrity gaps in product
• A wasted exercise when:
  • Does not lead to changes in our validation approach
  • Done too late/after the product is purchased (no influence on price!)

Efficiency in Verification Activities

• Designing Verification for Re-Use/Replication
  • Design protocols for re-use!
  • 90% re-use is better than 0% (Perfect is the enemy of Good)
  • Discuss: a process for multiple configurations
  • Discuss: a process for R&D/Development/GxP use

Mark´s webinar is part of the Academy Webinars Program, an initiative launched by the Paperless Lab Academy to maintain the momentum of the Congress acknowledged as a learning platform.

The post Qualification of Analytical Systems for Regulated Laboratories appeared first on .

by Mark Newton, Principal at HeartlandQA, mark@heartlandQA.com

To a careful observer, the realm of Data Integrity currently has signals that indicate which direction the regulators—and hence, the industry—will be moving.  My crystal ball is currently aglow with these future visions, in no particular order

1. The Data Periodic Review is coming

The subject was introduced in the recent MHRA Final Guidance for GXP Systems (1).  I discussed this topic last October at the ISPE/GAMP Annual Meeting in San Diego in my presentation on Data Integrity metrics.  It is a logical development:  GAMP 5 has a system lifecycle, and includes a Periodic Review to assure that systems remain in a state of compliance; GAMP Records & Data Integrity defines a Data Lifecycle, working in parallel to the system lifecycle.

So, if you have two parallel lifecycles, and one has a periodic review, why would you not expect the other (parallel) lifecycle to have a periodic review? 

Only makes sense.

That was the logic for my presentation point at the ISPE/GAMP 2017 Annual meeting, and MHRA sealed the deal with their final guidance. 

Write it down. Data Periodic Reviews are on the horizon!

2. Data Integrity remediation and governance will find its way into research

Gupta (2) reported that 40% of clinical researchers were aware of at least one instance of misconduct that was not reported. Wow!

So, there is widespread misconduct in research—no real surprise there.  The FDA alone has written over 130 Warning Letters and 483s in the past 3 years due to integrity violations, and GxP labs are a small percentage of labs compared to research of all types.  Add the fact that research labs have little oversight and no regulatory inspections—all making fraud more difficult to expose. Taken together, these factors (more labs, less oversight, no inspections) indicate a huge issue to be uncovered.

Detection capabilities have improved–inspectors are learning forensic inspection techniques and applying them with great success.

What is missing?

An organization with a vested interest in vetting the research to protect themselves, and the willingness to borrow and use forensic techniques from regulators.  Perhaps NIH, a publisher, or a university/medical center.  Once they conduct forensic data evaluations, misconduct is exposed, and the research data integrity avalanche starts rolling.

Once rolling, it will be big. Very big.  And expensive.  You have been warned.

3. Data Provenance will gain importance

Think beyond our current focus that data be recorded accurately (along with metadata) at the time of collection.

The next logical step is to assure that we have the “chain of data” from the source (raw) data all the way to where that data is used to make a business decision.

This chain is probably documented now in validation/process documents, known only to the validation team and not to the users who are making the decisions.  The next step is to put that chain (provenance) in a format available to the business user at decision time or provide that user with a link back to the source data. At a minimum, business users should be aware that they are about to make decisions with a data field(s) that came from a different source.

Blockchain has been suggested as a possible solution for this issue, and it does have potential, since it embeds transfer history into the blockchain; however, applications would need to extract the history from the chain and make it available to the user at the decision point.

Don’t expect people to jump to another app to read the blockchain provenance—isn’t going to happen.

Time to plan for complete data provenance, available to the business users who make decisions, at the time the data supports a regulated decision.

In all of these, we are drawing conclusions from events already happening around us.  Be wise and start planning now.  Avoiding future change only makes it more expensive—and harder to take.

REFERENCES

• Medicines & Healthcare products Regulatory Agency (MHRA). ‘GXP’ Data Integrity Guidance and Definitions. March 2018.https://mhrainspectorate.blog.gov.uk/2018/03/09/mhras-gxp-data-integrity-guide-published/
• Gupta, Ashwaria. Perspectives in Clinical Research. 2013 Apr-Jun; 4(2): 144–147.URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3700330/ 

Mark Newton (retired – Associate Sr Consultant QA at Eli Lilly  ) has 30+ years of experience in pharmaceuticals as a laboratory
scientist, then as a QA professional, supporting LIMS systems, standalone lab instruments, lab informatics and metrics, validation, quality systems, and data standards.  Has been deeply involved in data integrity and data integrity training to people in QC Laboratories, Manufacturing, and IT.Current Chair of the ISPE Global Documents Committee
– Current co-leader of the ISPE/GAMP Data Integrity Special Interest Group
– Co-author for “GAMP Guide: Records and Data Integrity” April, 2017
– Co-author of “Harmonizing USP <1058> and GAMP for Analytical Instrument Qualification”  Schuessler, Newton, Smith, Burgess, McDowall. Pharm. Engineering, Jan/Feb 2014
– Co-editor of the GAMP Good Practice Guide “A Risk-Based Approach to Compliant Computerized Laboratory Systems” Nov. 2012.

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