Industry and Regulator Panel Discussion on Digital Transformation
A panel discussion held on 27 April 2022 during the 2022 ISPE Europe Annual Conference focused on Digital Transformation.
Panelists in the room and remote included:
The discussion was moderated by
In his introductory remarks, Christian Wölbeling raised the following points related to the ongoing digital transformation in the pharma industry.
- Transformation of pharmaceutical business processes and procedures from paper base to a digital platform requires that these process and procedures are mature and part of an effective pharmaceutical quality system (PQS). The maturity of your PQS can be assessed using the ISPE Advancing Pharmaceutical Quality (APQ) program. To make successful transformations you must be at least at Level 3.
- ISPE’s Pharma 4.0™ initiative is providing practical guidance, embedding regulatory best practices, to accelerate Pharma 4.0™ transformations. An ISPE Good Practice Guide containing examples is under development. As part of the background work for this initiative, the Pharma 4.0™ team identified that an end-to-end “holistic” control strategy is required.Read "A Holistic Approach to Production Control."
- A survey conducted by the Pharma 4.0™ team in 2017 identified the following top benefits of successful digital transformation:
- Quality and compliance
- Cost saving
- Time saving
Do you agree with the identified benefits?
Carmelo Rosa started by saying that regulators did not have very different expectations since they were looking for an effective control strategy, data integrity, and quality oversight.
There are still issues with digital transformation, which need attention such as: hacking interfering with production, “lost” data, and system not designed correctly, which compromises product availability.
Ib Alstrup confirmed that companies appear to “lose” data.
Carmelo Rosa went on to say that good digital systems really helped during the pandemic.
David Churchward said that regulators were in favor of digitalization, which generated more data. Generally, more data should lead to more information and subsequently to more knowledge. The data, however, must be generated for a purpose.
Brendan Cuddy asked if an ISPE survey could dig further into reasons for improved quality, for example reduced deviations and improved supply security?
What are the challenges of digital transformation?
David Churchward commented that organizational change management was a much-underestimated challenge. A well thought out data structure is required to allow data to be analyzed and transformed into information and knowledge. Has the organization sufficient money and resources to implement the transformation?
Carmelo Rosa considered that there were challenges convincing management to invest. FDA has itself invested in digitalization, for example tracking commitments made by companies at inspections.
Brendan Cuddy reflected that there were challenges for regulators developing suitable guidances since companies are using different approaches to digitalization. He did confirm that changes to legislation were not required in the EU. There are many issues with terminology and definitions, which may require revision of EU GMP Annex 11. There are also continuing discussions regarding what information should be included in a dossier.
Brendan did comment that he would value ISPE’s input of terminology.
From an inspector’s viewpoint, there is a challenge regarding how to assess the effectiveness of a company’s PQS to support the transformation.
Ib Alstrup supports use of digital technology. The European Union has a GCP Q&A web site (see https://www.ema.europa.eu/en/human-regulatory/research-development/compliance/good-clinical-practice/qa-good-clinical-practice-gcp#gcp-matters-section) relating to use of computerized systems in clinical trials. This could be helpful when considering outsourced activities to a cloud provider. For example, updates to questions 8 and 9, which have been agreed by EU 27 inspectors’ agencies have been published. When services are outsourced to a cloud provider the sponsor/company remains responsible for the data.
Carmelo Rosa observed that in his experience companies generate data which nobody looks at, asking what are these data for and what is their purpose? He went on to note that there are questions regarding how electronic data are presented to regulators. With paper it is straightforward, however, with digital it is not so clear. However, the data are presented, the data should tell the story clearly regarding how a batch was manufactured. Terminology is important including its consistent use. As an example, in one inspection the term “calculation” was used variably and was misunderstood by the inspector.
Teresa Minero as ISPE moderator commented that the ISPE Pharma 4.0™ team recognized the importance of terminology and that a comprehensive glossary will be included in the forthcoming Pharma 4.0™ guide.
What are the red lines for use of artificial intelligence (AI) – can it be used for batch release?
Brendan Cuddy commented that perhaps an application Dossier is a red line since this has to be reviewed manually and any use of AI explained in it.
Carmelo Rosa wanted to ask the question back to the industry: How do you assure quality? How could records be reviewed? How is assurance given? How is quality oversight performed? How is assurance given that records have not been altered? The level of proof rests on industry.
Ib Alstrup agreed with these comments. People need to remain responsible, for example it is not acceptable to say, “machine made a mistake.” The Qualified Person (QP) role is important and needs to be thought through. Somebody has to be responsible.
Does QP knowledge of digitization have to be tested?
David Churchward stressed that a QP does need to understand, however, they do not have to be an expert. The QP must have confidence in the team that designed and built the digital system.
What are the expectations for industry on digital transformation?
Brendan Cuddy repeated that the EU was looking at the legislation, however, it was considered that current legislation supports the transformation and change is not required. Terminology was again recognized as a challenge. The EU inspectors working group is considering whether EU GMP Annex 11, Computerized systems and maybe Annex 15, Qualification and Validation require modification.
Carmelo Rosa mentioned that there was a need for further collaboration between regulators, and between regulators and industry. FDA supports introduction of new technologies. He stressed that lack of guidance does not mean that new, proposed technology will be rejected. Agencies can help. Industry should not have a fear of rejection by regulatory agencies.
This is brief and informal synopsis of a discussion among regulators from various countries and regulatory organizations during the ISPE European Conference on 27 April 2022. It has not been vetted by any of the agencies or regulators cited in this article.