Getting on Top of the Quality Pyramid

On March 20-21 2018 I was fortunate enough to attend the Paperless Lab Academy 2018 held at the Grand Hotel Dino in Baveno on the shore of Lake Maggiore in Italy, a beautiful setting for a very well run conference by NL42 Consulting. One of the highlights of the conference for me was a workshop I attended by the CEO of Caliber Technologies, Sekhar Sathya, on solutions to achieve QA/QC goals every day in a paperless environment and the following is a summary of this workshop.

Current status of paperless automation?

Sekhar set the scene by reviewing current status. Paperless automation has been a subject for some time and, while significant progress has been made in QC and QA via LIMS and Quality Management Systems (QMS), manufacturing and other departments are yet to catch up. Furthermore, the FDA, with the help from the ISPE, has introduced Guidelines for Quality Metrics and, to meet these guidelines which will be enacted as regulations sooner rather than later, requires a solid base of data from which Quality Metrics can be built. In this way, Sekhar introduced the concept of a Quality Pyramid whose base needs to be rich in accurate, appropriate and adequate data from sources such as QC, QA, warehouse, manufacturing, environmental monitoring and training while the Quality Metrics include OOS detected inside the company and outside (market and customer complaints) and the quality culture of the company.

Analysis of FDA 483 Warning Letters

Quality Control

An analysis of 483 notifications shows that 59% of them relate to QC and these were fully categorized, for instance 33% of them relate to procedures not being documented. Relevant to QC laboratories, common challenges include re-writing and calculation errors, lack of information, insufficient training, improper review and lack of controls. In fact, the non-conformances can be understood in terms of the 4M rule which breaks them down into factors related to Man, Machine, Method and Materials. Caliber products address all aspects of controlling these factors and hence stopping 483's.

Embodying all these principles, Caliber implemented the first fully integrated paperless Laboratory in India, at Adcock Ingram in Bangalore. This implementation featured:

  • Seamless integration with SAP
  • Integration with various types of Instruments including Empower 3 CDS
  • On-line entry of observations in Tablets and Terminals
  • Integration with DMS  for generation of Sample Dossiers
  • Integration with QMS in case of OOS and OOT

Quality Assurance

Traditional QA processes include dealing with market complaints, change management, deviation management, audit Management and CAPA but it is no longer this simple. The FDA and other agencies are increasingly looking at self regulation and that shifts a lot of responsibility onto QA. Current QA challenges now include PAT, process improvement and manufacturing excellence with increasingly smart working expected from QA to spearhead the quality of the goods. Deriving meaningful conclusions needs data that is relevant and current and QA has become the focal point for self governance for 24X7 audit readiness.

Caliber QAMS provides all the tools for QA personnel to keep on top of the new wave of challenges.

Manufacturing

22% of 483's relate to Batch Records and Manufacturing, the great majority of which are to do with written procedures and record keeping with challenges around control of document templates; review, approval and issuance; and corrections. Again, moving to an electronic batch record management system brings many benefits towards fighting the paper monster!

  • Access controlled & version controlled structured templates
  • Elimination or drastic reduction in human errors in record keeping, calculations and transcriptions
  • Configurable document workflows with review and approval processes
  • High level of automation and integration of process clearance, equipment clearance, dispensing and integration with ERP
  • Control of equipment and material usage with eLogbooks
  • Facilitates
    • Improved efficiency in utilization of  resources
    • Continuous  Process Improvement
    • Compliance with  guidelines/regulatory norms on Batch Automation and Electronic Documentation like ISA 88, 95, US FDA 21 CFR part 11
  • User Configurable Workflows, Templates, Reports, Dashboards, Labels etc.
  • Extendable to support R&D development & pilot batch studies

The Near Future

The ISPE Quality Metrics Initiative has recommended the following set of starting metrics:

  • Lot acceptance rate at site level
  • Lot acceptance rate at product level within a site
  • Critical complaints at product level
  • Critical complaints at site level
  • Deviations rate at site level

In addition, a 15-question survey of the prevailing quality culture at a site was developed to assess how this may impact quality performance outcomes. It measure five cultural elements: leadership, governance, integrity, mindset and capabilities. The availability of effective systems for Quality Metrics tracking and review is fundamental to a successful Quality culture.

Putting it all together

Sekhar rounded off the workshop by drawing all the strands of thought together into the Caliber Quality Pyramid concept. Caliber, with multiple products for Pharma, has built a comprehensive solution for Quality Metrics with individual warehouses for each product and a Master Warehouse for all the products featuring one place analytics and data harmonization. Automated systems store, archive and maintain source data and ensure accurate, appropriate and adequate data as its foundation.

The end result is that, in just a few clicks, a full Product Quality Review can be accessed. In other words APQR becomes Anytime PQR.

Further Information

If any of the issues discussed in this article are of interest to you, please feel free to contact me on mark@discoveryanalyticalconsulting.com for further information or to arrange a demo of any Caliber products.

Mark PortsmouthComment