The MHRA (Medicines and Healthcare Products Regulatory) has published a guidance on medical device stand-alone software (including apps) in March 2014.
The following guidance is for healthcare and medical software developers who are unsure of the regulatory requirements for CE marking stand-alone software as a medical device.
Read it online here: OPEN EXTERNAL LINK
Read more about App Validation and the US FDA Guidance for Industry
Question #3 of the Q&A section:
How do the Part 11 regulations and “predicate rule requirements” (in 21 CFR Part 211) apply to the electronic records created by computerized laboratory systems and the associated printed chromatograms that are used in drug manufacturing and testing?
Some in industry misinterpret the following text from “The Guidance for Industry – Part 11, Electronic Records; Electronic Signatures – Scope and Application” (Part 11 Guidance; lines 164 to 171) to mean that in all cases paper printouts of electronic records satisfy predicate rule requirements in 21 CFR Part 211.
“Under the narrow interpretation of the scope of part 11, with respect to records required to be maintained under predicate rules or submitted to FDA, when persons choose to use records in electronic format in place of paper format, part 11 would apply. On the other hand, when persons use computers to generate paper printouts of electronic records, and those paper records meet all the requirements of the applicable predicate rules and persons rely on the paper records to perform their regulated activities, FDA would generally not consider persons to be ‘using electronic records in lieu of paper records’ under §§ 11.2(a) and 11.2(b). In these instances, the use of computer systems in the generation of paper records would not trigger part 11.”
The Part 11 Guidance also states (in lines 150-152), that:
“…persons must comply with applicable predicate rules, and records that are required to be maintained or submitted must remain secure and reliable in accordance with the predicate rules.”
For High Performance Liquid Chromatography (HPLC) and Gas Chromatography (GC) systems (and other computerized systems involving user inputs, outputs, audit trials, etc.), the predicate rules, such as 21 CFR 211.68 and 21 CFR 211.180(d), require the electronic records themselves to be retained and maintained in accordance with those regulations. 21 CFR 211.180(d) requires records to be retained “either as original records or true copies such as photocopies, microfilm, microfiche, or other accurate reproductions of the original records.” 21 CFR 211.68 further states that: “[H]ard copy or alternative systems, such as duplicates, tapes, or microfilm, designed to assure that backup data are exact and complete and that it is secure from alteration, inadvertent erasures, or loss shall be maintained” (emphasis added). The printed paper copy of the chromatogram would not be considered a “true copy” of the entire electronic raw data used to create that chromatogram, as required by 21 CFR 211.180(d). The printed chromatogram would also not be considered an “exact and complete” copy of the electronic raw data used to create the chromatogram, as required by 21 CFR 211.68. The chromatogram does not generally include, for example, the injection sequence, instrument method, integration method, or the audit trail, of which all were used to create the chromatogram or are associated with its validity. Therefore, the printed chromatograms used in drug manufacturing and testing do not satisfy the predicate rule requirements in 21 CFR Part 211. The electronic records created by the computerized laboratory systems must be maintained under these requirements.
We recognize that there are cases where it could be appropriate for the printed chromatogram to be used within laboratories for the review of test results. Similarly, it also may be acceptable to provide the printed chromatogram during a regulatory inspection or for application review purposes. However, the electronic record must be maintained and readily available for review by, for example, QC/QA personnel or the FDA investigator.
In summary, decisions on how to maintain records for computerized systems should be based on predicate rule requirements. We recommend that these decisions be supported by a sound risk assessment.
References:
• Guidance for Industry – Part 11, Electronic Records; Electronic Signatures – Scope and Application ( http://www.fda.gov/cder/guidance/5667fnl.pdf )
• 21 CFR 211.180(d): General Requirements
• 21 CFR 211.68: Automatic, Mechanical, and Electronic Equipment
Source: http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm124787.htm
Want to know more about raw data, master data and meta data management for GMP compliance?
Contact us at: talk@comes-services.com
EU GMP Kapitel 4 – Dokumentation – Rohdaten und elektronische Dokumentation richtig bewerten und verwalten:
Wie sind GMP Dokumentationsanforderungen und Gute Dokumentationspraxis in elektronischen Systemen darstellbar? Was sind Vorgabe- und Nachweisdokumente und was davon Rohdaten oder Metadaten? Wie verhält es sich mit Signaturen, wenn das Masterdokument elektronisch definiert ist? Wie sind konforme Ausdrucke (true / exact copy) zu erzeugen? Was bedeutet Datenmanagement (datability) bezogen auf ein PQS und Knowledge Management?
Das sind typische Fragen, die oft gestellt werden – und in der PTS Schulung beantwortet werden:
Komplexe Anforderungen an GMP-Dokumentation
Die GMP-Dokumentation ist das Kernelement zum Nachweis der Erfüllung gesetzlicher Anforderungen. Nicht nur bei behördlichen Inspektionen, sondern vielfach auch bei Lieferantenqualifizierungen steht eine Überprüfung der Dokumentation im Mittelpunkt zur Beurteilung der Qualität. Im Intensivtraining lernen Sie u.a. als Verantwortlicher diese Dokumentation zu erstellen, als Auditor diese zu prüfen und/oder als Qualitätsleiter/QP diese zu genehmigen und freizugeben.
Kenntnisse eines Experten für Dokumentation
Aktuelle gesetzliche Vorgaben stellen detaillierte Anforderungen an Vorgabedokumentation, spezielle Dokumente und aufzeichnende Dokumente. Sie lernen im Intensivtraining die Besonderheiten, die Inhalte und die Anwendungen der GMP-Dokumente kennen.
Als Experte für Dokumentation sind Ihre Kenntnisse über gesetzliche Anforderungen, Umsetzungen in die Praxis, Schulungen von Mitarbeitern, Mitwirkung bei der Planung und Implementierung elektronischer Systeme etc. nötig. Sie erhalten diese Informationen beim Intensivtraining. Zudem erhalten Sie einen vertiefenden Einblick in die Erstellung auswertender Dokumente wie z.B. in Reviews und Berichten.
Besuchen Sie die PTS Schulung am 11. bis 13. November 2014 – lesen Sie mehr: http://www.pts.eu/k2278.html
Partnership Announcement Novatek and CCS
Montreal, Canada / Ravensburg, Germany, April 11th, 2014
Novatek is delighted to announce a strategic partnership with comes compliance services (CCS). comes compliance services is a European based, highly experienced consulting company specializing in simplifying and streamlining EMA, FDA, ICH, GHTF quality systems, and fulfilling validation and regulatory compliance requirements.
This partnership will allow comes compliance services to continue to expand its excellent compliance services by utilizing Novatek as partner to provide Quality & Compliance services throughout Europe especially to the German-speaking region. The two firms compliment one another’s solutions and service offerings and will work together to provide clients with excellent services in cGMP Compliance, Project Management, Quality Systems Improvement and Validation.
About Novatek International
Established in 1996, Novatek International (www.ntint.com) is leading provider of regulatory compliant software solutions for the Pharmaceutical Industry.
Novatek’s products are business ready, off the shelf and modular providing individual expert solutions with the flexibility of full integration to Nova-LIMS productivity package.
The flagship products Nova-EM for Environmental Monitoring and Nova-Stability for pharmaceutical stability testing have been industry standard for over 10years. Novatek Software has consistently met the requirements of Pharmaceutical Companies and Regulatory Agencies globally. Novatek products deliver value through reducing product time to market, improving process efficiencies, reducing the risks of product contamination and exposure from Regulatory Agencies.
Contact us for more information at: talk@comes-services.com
The EMA has published the “Guideline on process validation for finished products – information and data to be provided in regulatory submissions”. This Guideline will come into effect on 15. July 2014.
This guideline replaces the previous note for guidance on process validation (CPMP/QWP/848/96, EMEA/CVMP/598/99). The guideline is brought into line with ICH Q8, Q9 and Q10 documents and the possibility to use continuous process verification in addition to, or instead of, traditional process validation described in the previous guideline has been added and is encouraged.
Download Guideline: EMA process validation final Feb 2014
Contact us at talk@comes-services.com for more information.
Ermatingen, Switzerland / Ravensburg, Germany, March 17th, 2014
Mediantis Consult GmbH and CCS are delighted to announce the strategic alliance between both consultancy service providers to the regulated industries.
Both companies are providing professional services covering Best Practice approaches of modern quality management and value-driven consulting.
The core capabilities of both companies complement perfectly one another, focusing on GCP & Medical Device quality concepts and GMP and application service platforms.
Mediantis Consult GmbH, managed by Dr. Sabine Schäfer-Preuss and Dr. Iris Teutsch and the CCS network resources, managed by Mr. Markus Roemer, are thereby enabled by a comprehensive skills and expertise set to provide excellent services to their clients.
This extraordinary partnership will allow both providers to continue to expand their excellent services ranges and areas by utilizing each other as partner to provide compliance services throughout Europe.
The two firms complement one another’s service offerings and will work together to provide clients with excellent services in GMP & GCP compliance, Quality Management Systems, Inspection Readiness Programs, Audit Management, Training, and Validation.
About Mediantis Consult GmbH
Mediantis Consult GmbH provides high value professional consulting services for Pharma, Biotech and Medical Device Industries:
Read more: http://www.mediantisconsult.com
About comes compliance services (CCS)
comes compliance services is a premier consulting company specializing in simplifying and streamlining quality systems, and fulfilling validation and regulatory compliance requirements. The services and products are available to GMP, GDP, GLP, GCP and medical device regulated companies and suppliers. CCS is based on a global and comprehensive network setup and can deliver dedicated subject matter experts to different fields and subjects:
Read more: www.comes-services.com and www.auditservicecenter.com.
The classical V-model is very often used as the a conceptual model for validation. Most of the V-models are purely designed on a system-based approach, showing in the left wing all sorts of specifications, from URS to design specifications and the right wing all related test phases. Moving away from such a system-based approach in order to follow a risk based approach towards the quality decision making process might impact the existing V-model and a new approach should be used (click picture to enlarge).
As EU GMP Annex 11 states that applications, and not computerized systems, should be validated, and in real terms we do not validate a computer or system itself, the objective of validation is focused to the quality decision, which is based on the information (recorded in reports and records) derived or given by the entire process, whereas several systems or equipment might be relevant process elements.
EU GMP Chapter 4 – documentation – defines the so called instructions and records/report type. Also the term raw data is used. A GMP record contains such raw data, meta data, master data, on which a decision maker (e.g. Qualified Person, Quality Assurance) is making a quality decision (e.g. Batch Release).
Based on the IT basis such records might support electronic records or is still based on paper records. Ideally all steps (from 10 to 100) are interconnected by the qualified IT architecture.
The fundamental risk is that a wrong quality decision would be made on the basis of insufficient, faulty, tampered or missing data, directly impacting product quality, data integrity, and patient safety. So each system providing data to a GMP relevant record (e.g. Certificate of Analysis, Batch Records, etc.) should be seen as a data sources, forcing, collecting, monitoring, analyzing or calculating data along the entire data flow.
Potentially the highest risk is in each manual step, where data is entered by an operator – whereas a qualified interface of e.g. scanners are reducing the risk of faulty data entries (steps 20, 40, 60, 80).
Step 10 defines critical process parameters, which are derived from product critical attributes, linking product (license) to the process. If a Quality by Design approach is followed, the Design Space will be the basis for the Control Strategy.
A modern approach to computer system validation requires the mapping of the data objects and flows to the final documentation in GMP records. This approach should include the verification of data integrity, as required by EU GMP Annex 11 and US-FDA 21 CFR Part 11.
On the other hand there must be a comprehensive IT strategy including systems, platforms, and interface technology in order to reach the goal of a full electronic recording of all relevant processes. By the way, companies implementing such a holistic data management approach increase efficiency and productivity extensively: Implementing GMP datability & compliance as guarantor of success.
For more information contact us at: talk@comes-services.com or use our online contact form.
Die erste Draft Version des neuen Anhang 15 – Qualifzierung und Validierung – wurde von der EMA veröffentlicht.
Nachdem im Jahr 2012 die EMA QWP Guideline zur Prozessvalidierung (siehe: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2012/04/WC500125399.pdf) veröffentlicht wurde und auch die US-FDA eine Guidance for Industry im Jahre 2011 (siehe: http://www.fda.gov/downloads/Drugs/Guidances/UCM070336.pdf ) publizierte, werden nun auch die Aspekte aus dem ICH Q11 – QbD (siehe http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2011/06/WC500107636.pdf) in der Draft Version des Annex 15 verarbeitet.
Nutzen Sie unbedingt die Chance die Draft Version des Anhang 15 zu kommentierten.
Draft Version EU GMP Annex 15: http://ec.europa.eu/health/files/gmp/2014-02_pc_draft_gmp_annex.pdf
Leider wurde die Vorlage für die Kommentierung von der EMA “gut” versteckt. Das MS Word Dokument (Formblatt Kommentierung) erhalten Sie hier: http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2009/10/WC500004016.doc
Ihre Kommentare müssen Sie dann via Email schicken an: ADM-GMDP@ema.europa.eu UND sanco-pharmaceuticals-D6@ec.europa.eu. Schicken Sie bitte die Kommentare im offenen MS Word Format und nicht als PDF Dokument!
Aus unserer Sicht ist die aktuelle Draft Version, die zur Kommentierung veröffentlich wurde, sehr undurchsichtig und unzureichend formuliert. Auch die Referenzen zur QWP Guideline und ICH Q11 und weitere zeigen erhebliche Inkonsitenzen und unklare Definitionen und Festlegungen.
So unterscheiden sich alleinig schon die Festlegungen, was zu einem Prozess und Lebenszyklus gehört, die unterschiedlichen Definitionen, sogar im Anhang 15 selbst. Zur Qualifzierung und Validierung wurde dann noch der Schritt der Verifizierung aufgenommen, ohne dies näher zu beschreiben. Es ist sicherlich empfehlenswert, dass zu allererst eine Festlegung der Definition eines Prozesses selbst erfolgen sollte. Die QWP Guideline beinhaltet beispielsweise im Anhang 1 ein sogenanntes Process Validation Scheme, das sehr sinnvoll ist, aber im Anhang 15 nicht direkt genannt wird. Der ICH Q11 gbit eine Control Strategy vor, die in einem Dokument “manufacturing process development” definiert sein soll.
In Kapitel 3.2 wird beispielsweise definiert, dass eine URS (für new facilities, systems or equipment) erzeugt werden muss, und dass die URS “should be a point of reference throughout the validation life cycle”. Dass aber die Anforderungen aus einer Prozessspezifikation erzeugt werden müssen, und demzufolge alle Prozesselemente (ob als System, Equipment, Gebäude, etc. definiert wären) entsprechend qualifiziert sein müssen, ist nur unzureichend formuliert. Als Lebenszyklus findet man diesen auf Produkte, Prozesse, Validierung und natürlich Daten. Ob dieses Dokument dann VMP genannt wird, und ob dies “pro Site” erzeugt wird, sollte nicht als eine Anforderung in den Annex 15 münden. Interessant könnten aber entsprechende Prozesse sein, die von externen Firmen (outsourced activities – Kapitel 7 EU GMP) durchgeführt werden. Die aktuelle Draft Version des Anhang 16 fordert hierfür ein “comprehensive diagram”, das ebenso als Grundlage zur Prozessvalidierung gelten sollte.
Ob nun einzelne Prozessschritte wie Reinigung und Transport, die natürlich wichtig sind, einzeln genannt werden müssen, auch noch in der Verbindung des Worts “Verification”, sollte diskutiert werden. Prozesse bestehen aus Prozesselementen und Prozesschritten, eigentlich über den gesamten Warenfluss (Ausgangsstoffe bis zum Fertigarzeimittel). Daher sollten Prozessbeschreibungen den gesamten Material-, Personal- und Datenfluss beinhalten, in den entsprechenden Umgebungen und Vorbedingungen.
Die aktuelle Draft Version beihaltet viele Punkte zur Diskussion und Bewertung. Daher nochmals unsere Empfehlung, damit die EMA Arbeitsgruppe die aktuelle Version verbessern kann:
Nutzen Sie unbedingt die Chance die Draft Version des Anhang 15 zu kommentierten.
Falls Sie Fragen zum Thema haben, kontaktieren Sie uns bitte: talk@comes-services.com
Erfolgreicher erster QPmeetsIT Dialog initiiert durch comes compliance services und Systec & Services.
Am 4. Februar 2014 trafen sich zahlreiche Experten zum ersten QPmeetsIT Dialog im Karlsruher Schlosshotel. Als Medienpartner konnte der Editio Cantor Verlag (ecv) für die Veranstaltung gewonnen werden.
Moderne Qualitätsphilosophien propagieren einen Paradigmenwechsel hin zu kontinuierlichen Verbesserungen durch schlanke Qualitätssysteme und fundiertem Qualitätsrisikomanagement. Aber wie setzt man diese Vision wirklich in die Tat um?
Dieser Frage gingen die vier Referenten Dr. Bernd Renger, Markus Roemer, Lukas Eberle und Titus Krauss zusammen mit den Teilnehmern nach.
Dr. Renger konnte aufzeigen, dass zwingend Handlungsbedarf besteht, da die neu gefassten Regularien (Annex 16 aber auch der bestehende Annex 11) zwingend die Einbeziehung von Software-Lösungen fordert. Hier sieht er die Sachkundige Person (Qualified Person) mit in der Verantwortung. Markus Roemer stellt dar, wie sich diese sich verändernden Regularien auf die Validierungsansätze und die Validierungsmethoden auswirkt. Beides untermauerte er mit praxisnahen Beispielen.
Am Nachmittag zeigte Titus Krauss, wie die Anforderungen mit methodenbasieren Datenmodellierungen sowie Software-Lösungen bereits heute erfüllt werden können. Anhand einer Live-Demo konnten sich die Teilnehmer ein Bild der von der Lösung machen. Im Anschluss konnte Lukas Eberle live vorführen, dass F. Hoffmann-La Roche diese Methoden und Software-Lösungen bereits praktisch im Einsatz hat.
Die Resonanz der Teilnehmer war durchweg positiv. Alle Teilnehmer regten an, diese Dialogreihe fortzusetzen. comes compliance services und Systec & Services werden diesem Wunsch gerne entsprechen.
Mehr Informationen: QPmeetsIT – Agenda, Feb 2014
Impressionen QP meets IT – Schlosshotel Karlsruhe:
Mobile applications (apps) can help people manage their own health and wellness, promote healthy living, and gain access to useful information when and where they need it. These tools are being adopted almost as quickly as they can be developed. According to industry estimates, 500 million smartphone users worldwide will be using a health care application by 2015, and by 2018, 50 percent of the more than 3.4 billion smartphone and tablet users will have downloaded mobile health applications.
Mobile apps are software programs that run on smartphones and other mobile communication devices. Mobile medical apps are medical devices that are mobile apps, meet the definition of a medical device and are an accessory to a regulated medical device or transform a mobile platform into a regulated medical device.
Apps can be used in several areas and for different objectives. Consumers can use both mobile medical apps and mobile apps to manage their own health and wellness, such as to monitor their caloric intake for healthy weight maintenance. Other apps aim to help health care professionals improve and facilitate patient care, are used in combination with Blood Establishment Computer Software (BECS), may support GCP case report forms (CRF), or are a verification tool for falsified products (GMP & GDP).
In any case such apps must be validated according best practice (e.g. ISPE GAMP 5) and related quality standards. CCS is one of the few and leading compliance consulting firms supporting the design, development, operation, and validation of mobile apps, which are used as medical devices or in any GXP related area / function.
Contact us today at: talk@comes-services.com
We will let you know more about modern and innovative apps and how to register, qualify, document, use, and operate them.
