FDA/GMP trends in production & technology - Part 2

Data integrity requirements

Data integrity has been in the focus of regulatory scrutiny for some years now. Pharma Congress 2019 has therefore dedicated a two-day conference to the topic. The diverse issues made it possible to take a look at data integrity requirements from different viewpoints - from system and manufacturing to inspectors and suppliers.

Management responsibility - the myth of human errors

With European GMP and ICH Q10 regulations regarding data integrity in mind, Klaus Eichmüller reminds us of the leading management's responsibility for the content and application of Pharmaceutical Quality Systems (PQS). He poses the question whether "human errors" are a sufficient justification for deviations. If human errors are indeed the reason for deviations, however, training programs and the increased use of data governance models should move into the centre of considerations.

Data integrity - everybody's responsibility?

As with other regulatory activities, data integrity must be part of GxP. Without the serious handling of data, GxP cannot be implemented. Everybody is responsible for data integrity, not just QA or production. The Qualified Person (QP) in particular is reliant upon the integrity of all GxP-relevant data when releasing batches. But not only QPs rely on data integrity. Based on a data integrity program, production and laboratory staff as well as QA must be trained regularly regarding the importance and relevance of data. Such an approach would be the only one to ensure an adequate assessment of the data integrity of systems, processes and organisations.

Recommendation

Thursday, 15 May 2025 13.30 - 17.00 h

Fundamentals of Manual Visual Inspection - Live Online Training

Supplier support for implementing data integrity

To ensure data integrity, not only procedural activities are required. Effective technical measures are also needed. In order to implement an efficiente-compliance approach, such things as sensible user management, sufficient access controls, precise time stamps and Audit Trails, electronic signatures, etc. are necessary. More than 25 years after the publication of EU GMP Annex 11 (Computerised Systems) and more than 20 years after the publication of 21 CFR Part 11, suppliers should be able to support compliance requirements. The pharmaceutical industry needs systems to technically support compliance requirements urgently. It is no longer acceptable to sell products to the regulated pharmaceutical industry which do not support the required GxP-compliance.

Paperless Laboratory - myth or reality?

A case study from a contract laboratory shows the benefits of a consistent data integrity and e-compliance strategy. Not only was the level of regulatory compliance increased significantly in this case, a fundamental approach to sustainability was established at the same time. To produce less or no paper and to rely on electronic documentation made the consolidation and improvement of workflows and of the controls required possible without increasing the workload. The combination of effctive technical controls and sensible use of the dual control principle in electronic process steps generated a significant rise in efficiency as well as reducing the required storage capacity for paper.

Inspector's expectations regarding data integrity

Based on the PIC/S draft document PI 041-1 Draft 3 and WHO TRS Annex 5, Arno Terhechte from a local German authority and Ib Alstrup from the Danish DMA showed various examples of inspector expectations towards data integrity with regards to inspection subjects and practice. Both put emphasis on the importance of data definitions and data flows, including data flow disruptions. They also pointed out the necessity of implementing a sensible and reliable Audit Trail, and stressed the importance of the Audit Trail Review process.

Modern Qualification: ECA Good Practice Guide "Modern Qualification"

Based on the ECA Good Practice Guide "Modern Qualification", a conference focussed on the involvement of suppliers was established for the first time. The guide itself addresses modern cooperation approaches of pharmaceutical companies and their suppliers and is based on the latest GMP requirements for Quality Risk Management. It is founded on a common project model and includes useful templates which may be used by pharmaceutical companies and suppliers as part of a cost-efficient project approach.

The guide was developed by a joint initiative of international pharmaceutical companies and suppliers of pharmaceutical equipment. After being reviewed by inspectors, the guide was first introduced in the presence of American and European inspectors in September 2018 in Berlin. Participants of the event focussing on suppliers had the opportunity to suggest topics for the new version which was published in October 2019.

The inspector's point of view

Klaus Eichmüller from a local German authority introduced the European requirements for qualification and validation. He emphasised that the current European regulations of Annex 15 of the EU GMP Guidelines were built on a long European history and developed together with non-European regulatory authorities, including the FDA. The inclusion of Quality Risk Management is the most significant new requirement. Annex 15 is compliant with the FDA Process Validation Guide. It does, however, contain more specific notes on qualification activities. The current Annex 15, Klaus Eichmüller stressed, intends to allow for more flexibility for the pharmaceutical manufacturer as well as the supplier involved, depending on the project. According to him, the key to avoiding unnecessary repetition of qualification activities lies in the cooperation with the supplier.

The pharmaceutical industry's point of view

An example for the use of the ECA Modern Qualification Guide from an industry standpoint was provided by Eve-Maria Baumgartner. The project she presented allowed detailed insights into how successful cooperation with a supplier was established and how project management, quality unit and various experts were connected cost-efficiently. The case study included several useful "lessons learned" for other companies.

The suppliers' point of view

Dr Berhold Düthorn from Valicare finally presented the suppliers' viewpoint on the issue of qualification. He states that a mutual understanding of user requirements, design documents, testing activities and ultimately qualification activities is the basis for a successful and cost-efficient project. In his lecture, he discussed risks and pitfalls because of which qualification projects may fail. He gave recommendation on how a successful customer-supplier-relationship may be ensured inside and outside of Europe.

 

Author
Dr Andreas Mangel
... is Operations Director and organises and conducts courses and conferences on behalf of the ECA Academy in the areas sterile production and computer validation.