=Paper=
{{Paper
|id=Vol-2973/paper_180
|storemode=property
|title=BPM Support for Regulatory Compliance in ATMP Development Processes
|pdfUrl=https://ceur-ws.org/Vol-2973/paper_180.pdf
|volume=Vol-2973
|authors=Zeynep Ozturk Yurt
|dblpUrl=https://dblp.org/rec/conf/bpm/Yurt21
}}
==BPM Support for Regulatory Compliance in ATMP Development Processes==
https://ceur-ws.org/Vol-2973/paper_180.pdf
BPM Support for Regulatory Compliance in ATMP
Development Processes
Zeynep Ozturk Yurt
Department of Industrial Engineering & Innovation Sciences, Eindhoven University of Technology, Eindhoven, The
Netherlands
Abstract
Advanced Therapy Medicinal Product(ATMP) development processes are associated with inefficiencies
due to lack of an efficient and effective management methods that can support scientists in working
towards regulatory compliance. This research addresses this problem by proposing refined solutions
based on knowledge-intensive Business Process Management(BPM). Here, methods will be developed
to support scientists in planning a development process that is compliant with regulations. These
methods will be based on the knowledge on process modelling, goal modelling and context-aware
business processes. Thereby, this project will provide an exemplary approach for supporting compliance
management in knowledge intensive processes. The methods will be implemented in a software and
evaluated through a real-life ATMP development case.
1. Introduction
Advanced Therapy Medicinal Products (ATMPs) are medicines for human use that offer new
opportunities for treatment of many diseases, based on biomedical technology [1]. Development
of ATMPs involves several stages and the overall aim in these stages is to develop a safe and
effective medicinal product. This is accomplished by collaboration of many stakeholders, where
scientists and regulatory consultants are the main ones. Figure 2 in the Appendix describes the
main phases and stakeholders in ATMP development.
ATMPs are especially known for their complex regulatory framework. ATMP regulations
do not induce strict rules on how things should be done throughout the development. Instead,
they involve high-level goals that should be considered in order to demonstrate that the ATMP
being developed is safe and effective. There are alternative ways of achieving these goals. Also,
regulatory requirements vary depending on the development context. Here, context is defined
by the properties of the ATMP. For instance, for different ATMP types (Tissue Engineered
Product(TEP), Combined ATMP etc.) or different regulatory classifications of the components of
an ATMP (e.g., biomaterial in an ATMP classified as starting material or excipient etc.), different
regulatory requirements apply. Also, it is not possible to define the context fully before the
development process starts. Instead, different options (e.g., classifying the ATMP as Combined
ATMP or TEP) are investigated throughout the development. The flexibility in defining the
Proceedings of the Best Dissertation Award, Doctoral Consortium, and Demonstration & Resources Track at BPM 2021
co-located with the 19th International Conference on Business Process Management (BPM 2021)
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context and variability of regulatory requirements based on context makes it challenging for
scientists to manage the regulatory aspects of ATMP development.
Despite its complexity, management of regulatory aspects of ATMP development processes
is currently done by scientists in an ad-hoc fashion, which is not efficient. Research shows
that, ATMP development processes are associated with many hurdles such as reworks and even
withdrawal of the ATMP due to shortcomings in providing adequate evidence of regulatory
compliance [2]. This contributes to increased development costs and time-to market. Lack of
regulatory knowledge among scientists is an important factor for these hurdles [2]. Being an
expert, scientist requires minimal guidance about the scientific aspects of ATMP development
processes. However, establishing and maintaining the link between the scientific development
process and the regulatory framework of the ATMP development is challenging for the scientists.
Therefore, this project will focus on bridging the gap between scientific and regulatory
aspects of the ATMP development to help scientists manage the process more efficiently and
effectively.
2. Research Questions, Related Work and Intended Solution
In this project, I propose to support ATMP development processes with Business Process Man-
agement (BPM). Traditional BPM focuses on managing predictable and routine work. However,
managing unpredictable, flexible KiPs, is an emerging topic within BPM [3]. Considering its
characteristics (See Table 1 in the Appendix), ATMP development processes are KiPs. Yet, exist-
ing solutions from knowledge intensive BPM do not address our problem, as discussed in the
following paragraphs. For applications of BPM to be successful, adapted process management
approaches that fits to the characteristics of specific process under consideration is vital [4].
This leads us to the Main Research Question.
Main Research Question: How to support preclinical ATMP development processes
with BPM in order to help scientists manage regulatory aspects of development pro-
cess more efficiently and effectively?
The focus of this project is to support scientists in working towards regulatory compliance.
For traditional business processes, business process compliance is a well-studied area of research
within BPM [5]. There are also significant efforts on compliance management for flexible and
KiPs [6, 7, 8]. However, the regulatory requirements for ATMPs have a different nature compared
to regulatory requirements for other domains. They are stated as high-level goals, rather than
specifying “how” the development process should be performed. Therefore, it is not possible to
formalize the ATMP regulations with traditional formalisms, such as the ones in[5]. Moreover,
expert interpretation is required for compliance assessment, which makes the assessment
flexible. Therefore, a traditional business process compliance management approach is not
feasible for this case and a different approach is required. Hence, RQ-1 is formulated.
RQ-1: How to align scientific development processes with regulatory requirements
to help scientists plan the development process?
RQ-1 aims to support scientists in creating a process plan that is in line with the regulatory
compliance requirements. To formalize the ATMP regulatory requirements, I will use goal
models and to represent development process plan, I will use flexible process models. Here, the
challenge arises from the variability of ATMP regulations. ATMP regulatory requirements vary
with respect to the context of development (See Section 1 for the definition of context) and this
variability should be represented in the goal models. My intention is to introduce contextual goal
models [9] for this purpose. I will also investigate context modelling approaches in BPM [10, 11].
Additionally, applicable regulatory requirements are determined as the context becomes certain
throughout the process. So, the requirements are flexible. Therefore, I propose to develop a
method that will check the alignment between the scientific development process plan and
the goal model of the predefined context and provide recommendations (e.g., prioritization
of activities that support multiple goals and/or that should be performed for a wide range
of potential future contexts) to make sure the process plan addresses regulatory goals in an
efficient and effective way.
In BPM, there exists previous studies to align goal models and process models [12, 13, 14, 15,
16]. Also, the concept of context is not new in BPM [11, 10, 4]. However, our intention here is
not only to align the goal and process models or design context-aware processes but also to
provide recommendations for better alignment between the process and its goals and creation
of an efficient process plan. Additionally, the focus of our method is to support regulatory
compliance, which is a different setting compared to model alignment and context-awareness
studies in BPM.
Building upon RQ-1, RQ-2 focuses on providing regulatory compliance support during
execution of the scientific development process, formulated as below.
RQ-2: How to provide insights about the achievement of regulatory goals during
the scientific development process to support scientists in making decisions about
the adjustment of the planned development process?
The method will provide insights about how the results obtained throughout development
process contribute to the achievement of regulatory goals. Based on this insight, the expert
will be able to make informed decisions about the adjustment of the development plan, e.g.
changing the context or redoing process steps. This insight will be provided by reasoning with
goal models[17]. Since regulatory goals in ATMP development do not indicate crisp boundaries
and values for assessment, the reasoning approach will be enhanced by fuzzy decision making
approaches.
In BPM, there are some approaches developed for guiding KiPs in adjustment decisions, that
are relevant for RQ-2 [18, 19, 20, 21]. However, these approaches support decisions based on
historical knowledge about previous cases. ATMP development is a new field with also a huge
variability between different projects. Also, no historical data from previous projects is available
for use. Therefore, existing approaches are not suitable for our project. Consequently, input
from experts will be used to make the adjustment decisions.
Lastly, RQ-3 will be answered to evaluate the methods developed.
RQ-3: How can the proposed methods be evaluated?
This PhD project is a part of Horizon2020 iPSpine project1 , in which an ATMP for lower back
pain is being developed. The methods will be demonstrated on the iPSpine process management
platform, to be developed for iPSpine project, and evaluated by questionnaires with scientists
using the platform. Please see Figure 3 in the Appendix for the positioning of research questions.
1
https://ipspine.eu/
3. Research Methodology
The proposed research methodology, explained on Figure 1, is based on the design science
research framework created by Hevner et al.[22].
Figure 1: Research Framework
4. Scientific Importance and Relevance to BPM
The PhD project helps to improve the efficiency and effectiveness of ATMP development
processes, by developing a BPM-based approach that supports scientists in managing regulatory
aspects of ATMP development processes in a structured way. Thereby, from the BPM point of
view,this PhD project provide an exemplary approach for supporting compliance management
in flexible KiPs with vague and flexible regulatory requirements.
References
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A. Appendix
Figure 2: ATMP Development Process & Stakeholders (Stakeholders and Scope of PhD Project in bold)
Figure 3: Research Questions
Table 1
Characteristics of KiPs and Relevance for ATMP Development Processes
Characteristics of Characteristics Description ATMP Development Processes
KiPs
Knowledge-driven The status and availability of data In many cases, emerging knowl-
and knowledge objects drive hu- edge/data together with scientists’
man decision making and directly interpretation determine flow of
influence the flow of process ac- process actions.
tions and events.
Unpredictable The exact activity, event and knowl- ATMP development is an ex-
edge flow depends on situation- ploratory process. Neither the
and context-specific elements that process nor the knowledge related
may not be known a priori, may to the product being developed can
change during process execution, be fully prescribed a priori.
and may vary over different process
cases.
Emergent The actual course of actions gradu- It is a search process where realiza-
ally emerges during process execu- tions throughout the process and
tion and is determined step by step, availability of certain data/knowl-
when more information is available edge shape the process step by step.
Constraint- and rule- Process participants may be influ- Compliance regulations and related
driven enced by or may have to com- guidelines should be taken into con-
ply with constraints and rules that sideration throughout the process.
drive actions performance and de-
cision making.
Non-repeatable The process instance undertaken to Development processes are hardly
deal with a specific case or situation repeatable since in every case, sci-
is hardly repeatable, i.e., different entific approach, materials used
executions of the process vary from and/or aim of the study and hence
one another. related process requirements are
different.
Collaboration- Process creation, management and ATMP development process in-
oriented execution occurs in a collaborative volves many partners with differ-
multi-user environment, where hu- ent roles: scientists from different
man centred and process-related fields, project managers, regulators,
knowledge is co-created, shared companies etc. Each stakeholder
and transferred by and among contributes to the process.
process participants with different
roles.
Goal-oriented The process evolves through a series Every step (or combination of steps)
of intermediate goals or milestones in the ATMP development aim to
to be achieved. achieve a certain goal related to
the product being developed e.g.
achieving certain levels in safety, ef-
ficacy, biomechanical properties of
the product etc..
Event Driven Process progression is affected by Development process is affected by
the occurrence of different kinds the occurrence of different kinds of
of events that influence knowledge events which may be resulting from
workers’ decision making. other scientific or project related ac-
tions.