Regulatory Affairs and Clinical Trials: MediSan Case Study Analysis

This case study examines the role of a Regulatory Affairs (RA) manager at MediSan, a pharmaceutical company facing the challenge of transitioning to electronic submissions (eCTD) and expanding into new markets. The study outlines the steps involved in new pharmaceutical product development, from research and development to market launch, emphasizing the importance of the RA department in maintaining regulatory compliance, managing clinical trials, and securing marketing authorization. The analysis covers the dossier process for new chemical entities (NCEs), relevant legislation and guidance for eCTD submissions, and the documentation required. The case study explores the challenges MediSan faces in adopting eCTD, including training RA managers and outsourcing software solutions. It also highlights the need for RA professionals to develop expertise in software efficiency, documentation management, and strategic implementation of electronic processes. The study underscores the importance of skills such as project and documentation management, as well as the need for the company to select appropriate software providers. Finally, the case study emphasizes the necessity for the RA department to ensure the safety, legal compliance, and proper execution of clinical trials for successful product launches.

Running head: REGULATORY AFFAIRS
REGULATORY AFFAIRS
Name of the Student
Name of the University
Author Note

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PART 1
1.1 RA Department
New pharmaceutical product development is comprised of several steps in process of
commercialising of the product. The steps include the research and development phase in which
the discovery and the exploration of the product would be done. Other than these phases the
target selection, lead generation would also be done along with the phase 0 to II clinical trial
would be done. After these phases the proof of concept of the active molecule would be assessed
and on the basis of that assessment the clinical development would be preceded which again
include the phase III clinical trial and filling as well. The product would be launched in the
market in period of the last confirmation phase [1].
The regulatory affairs (RA) specialists are the persons and on them the business
personnel are dependent for the law and regulation maintenance that is the licensing process of
the products. The regulatory affairs department is the working body which observes and analyses
the whole product development process and the analysis result would be assessed by this
department for the licensing and the product launch in the market. The RA department need to
ensure the protocols of the clinical trial and all the phases of the product development maintained
in the process and record all the changes in the process as well. However, the clinical
development process dependent on the research and the effectiveness data of the product on the
basis of the active molecule effectiveness detection and the target selection. The RA department
is responsible for the development of the license for the product marketing on the basis of the
government regulations for the pharmaceutical products. The product development and the

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marketing of the product should follow the international laws of the product manufacturing and
the safety control of the products and this aspect would be observed and recorded by the RA
department personnel. On the basis of the consent of this department the product or the drugs
would have the license for launching in the market. The RA department has a working body
which works on the marketing strategies such as the advertising policies and the endpoint
availability of the product acceptance also devised by this working body. On the other hand the
strategic body of the RA department needs to develop the proper planning for the web
development, posters, attractive packaging and other process for the proper marketing and the
success of the product in the market along with the legislation maintenance for the product
development. The regulation maintenance for the product development depends on the
transparency of the product development process along with the proper clinical trials. The
clinical trial includes the animal especially the mammalian testing and this process should be
done with the government consent of animal health acts and devoid of any harm to the animals.
All these factors should be recorded and maintained by the RA department for the successful
product development and launch in the market. On the other hand the chemistry and the control
of the product should also be maintained by the RA department along with the manufacturing of
the product [2].
1.2 (a) Dossier for a new NCE
There are several personnel involved in the dossier process of the NCE including the
scientists, although they are not the stakeholders in the process of the regulation maintenance and
the eCTD reports. There are several legislative acts in order help these working bodies to
develop a product without any threat of duplication of the product along with the fluency and the

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conciseness maintenance of the product development process. The scientists however, develop
reports on the product development process and based on that report the RA department would
be able to develop the plan of the marketing and also develop the legislative factors for the
product marketing. The report of the scientists also helps in the planning of the marketing
authorisation of the product.
The pharmacological, pharmacokinetic and the toxicological assessments of the active
molecule of the drug should be assessed on a priority basis for the proper evaluation of the
product efficacy. The scientific report should be assessed and on the basis of this report the RA
department would be able to develop the marketing plan and the scientific report would be
comprised of the dossiers of the NCE as well. The marketing and the legislative consideration is
the most important factor for a product development and the process would be dependent on the
clinical trials as well as the chemical testings and all these records are used to develop the
marketing authorisation of a drug. The standard of vital importance to the pharmaceutical
industry and its suppliers and the primary packaging material should be considered as the one of
the primary factors for the marketing authorisation and it is known as ISO framework.
Other than the animals, final clinical trials would be done on the humans and the
internationals safety, standards and the ranges of the side effects would needed to be maintained
in the clinical trial process [3]. The guidance for the non clinical safety is factor for the clinical
trials and the factors of the side effects of the drug as well and this guidance is provided by EMA
department. Thus the RA department needs to interact with EMA department as well. The human
trials needs scope and time duration as well and need to focus on without harming the subject of
the test as of the international health laws [4]. All these factors should be maintained for the

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product development process and the RA department is solely responsible for the marketing
authorisation and all the product development steps. There is a possibility of post market analysis
of the product which can be termed as the phase IV clinical trial.
1.2 (b) Legislation and guidance for eCTD
In terms of the non clinical trials the pharmacological and the toxicological understanding
and effects should be assessed for the knowledge of the clinical trial and marketing of the drug
[5]. In the EMA website all the toxicological and the pharmacological qualities are mentioned in
the Annex 1 to Directive 2201/83/EC Module 4. This module is needed to be considered in the
licensing of the product and the marketing policies as well. The factor of licensing would be
observed and controlled by the RA department in order to file the marketing authorisation of the
product on the basis of the ISO framework in the national and the international market. Annex 1
to Directive 2201/83/EC Module volume 10 also mentioned some factors for the EMA or MA
application which provides the information about the investigational medicinal trial and this is
included in the Part D clinical trial [6]. The five categories of this clinical trial process includes
the pharmacology, pharmacokinetics, study report, toxicology and the literature references used
in the Module 4 in the process of the product development and the marketing authorisation.
1.2 (c) Documentation provided
At the time of applying for the MA the EMA provides a checklist for the easier and more
consistent applications which can be stated as the eligible documents in the eCTD submission
process. eCTD documentation is the most important factor for the process and also the
information about the non-clinical studies should be uploaded as well [7]. Module 2 and 4 are the

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documents that contain the CTD non-clinical documentations and the Module 2 summarises the
whole process thus it is important to be uploaded properly. Module 4 on the other hand provides
the non-clinical study report including pharmacological, toxicological, pharmacokinetics and
literature references along with the study reports.
PART 2
2.1 Transition to eCTD
The pharmaceutical companies find it harder in the present condition as the online tools
are taking over the markets and the competitors of MediSan also incorporates the online tooling
processes for the advancement in their marketing and the product development. MediSan on the
other hand a traditional pharmaceutical company depends on the ownership factor than the
management team however; in order to survive in the market they also adapted some of the
advanced tools and system. As of that the corporation taken the step to appoint RA managers to
observe and control the factors of the laws and regulations of the product development process
which was done by the QA department before and their responsibility was actually the
manufacturing process [8]. MediSan also realised that they need to focus on the European market
and international market as well thus they need more quality products. The company was
working on the regulation process by means of the paperwork process and the new condition as
of 1st January 2018, the EMA requires all that regulatory submissions in the online process that is
the web submission. Thus the RA manager would be needed to plan the medicinal product
authorisation on the basis of the Decentralisation and the Mutual Recognition Procedure in order
to transit the eCTD process. This process should include the compliances of the timeline

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indicated, baseline preparation, document management system update and all these factors would
be controlled and observed by the RA manager. Another challenge for the company is to train
the RA manager about the software knowledge of the eCTD documentation as they did not use
the RA department and the online process before. The possible solution for this factor is to use
the outsourcing from the software and the regulation maintenance companies for the software
work however, these companies should be able to meet the deadline in order to do the process
properly [9]. This outsourcing process would be expensive and with the less knowledge about
the process along with fewer resources would be a huge hurdle for the small pharmaceutical
company like MediSan.
2.2 Electronic submission support
The RA manager needs to develop the knowledge about the efficiency in the software
and the electronic process of the submission of the CTD. The pharmaceutical companies should
be able to devise the most efficient ways of the software learning of the RA managers in order to
sustain and stand above other companies in the market. The RA manager should have the
knowledge about the hyper link and the cross referencing process for the CTD submission. RA
professional of a pharmaceutical company should develop him or her for the knowledge of the
electronic pathway usage and also have the efficiency about the documentation management as
the CTD submission process requires high documentation and management of these documents
as well. The RA department needs to focus on the product development process and ensure all
the safety and the legal procedures are maintained for the product development and the clinical
trials also needed to be done in the proper way for the product launch as well [10]. However, the
RA professional of a small company can be facing difficulties in these processes as the company

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never used the software process before and the knowledge of the software can be difficult as
well. The hyper linking and the cross referencing process could be difficult as well. On the basis
of this condition it can be said that the RA professional should develop his own knowledge and
develop strategies for the process. The eCTD process needs strategic implementations and the
resource for the training of the RA personnel as well. The project management skills and the
documentation management skills on the other hand should be the key aspects of RA personnel
and these skills should be achieved by RA personnel on their own capabilities and knowledge.
The company should also find the suitable software provider and for the CTD submission and
the professionals should have the knowledge and experience for the usage of the software and
management as well. In the process of adaptation of the electronic process for the CTD
submission gives rise to several questions such as; Is the company have the proper resource? Do
all the preparations done for the process? Does the company have the properly trained and
knowledgeable staffs for the process? Does the company need to make organisational changes in
order to create the eCTD submission process? All these questions should be assessed before the
adaptation of the process of the eCTD process. The RA manager should be able to assess all
these factors along with the marketing and the product development process for the licensing and
the marketing authorisation of the product [11].
2.2 (a) Significance of issues
The EMA guidance helps the companies in the submission of the eCTD documents to the
National Competent Authorisation for the licensing and the regulatory works for the product
launch in the market. The company should change the work environments and the policies for
the betterment of the work force and the flow. The RA personnel are responsible for all the

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changes and the observation of the regulatory factors of the company and on the basis of their
legal actions the company work on the regulatory changes as well. The information of the
strategic changes is the factors that would be obtained by means market research and the
knowledge of legal changes of the national and international laws of pharmaceutical. The
pharmacological, toxicological and the pharmacokinetic aspects of the active molecule of the
drug need assessment of the RA personnel [12]. In this case the RA personnel got the idea of the
mutagenic activities of the active molecule of the drug which would be launched by the MediSan
Company for the advancement in the market. However, there is no carcinogenic activity test
done by the company scientists thus the legal factors of the marketing launch was not complete.
The RA personnel need to observe all the side effects of the drug and if the side effect or the
negative effects of the drug found to be under the regulatory limits of the MA then the eCTD
documentation would be done and the product would be marketed on the basis of that clinical
trial process. In this context it can be said that the clinical trials are the most important factor for
the market launch of a pharmaceutical product and the clinical trial would be documented as the
eCTD submission to the National Competent Authority and the EMA [13]. The RA personnel of
the company should strategically analyse all the factors and help the company to devise a better
marketing plan for the product. However, the new rules of the online tooling for the licensing
and documentation of the products pose a real threat for the small pharmaceutical company. In
case of MediSan the RA personnel would be the new staff as the company is a traditional one
and recently adapted to the new regulation for the sustainability in the market. The strategy of
the company includes the internationalisation with a new product and the RA manager is
appointed for the regulatory work as well. Hence, the RA personnel should have the knowledge
of the pharmacological concepts along with the legal aspects of the marketing and product

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development and the software knowledge would also be important for the task. Strategic issue
can arrive after the implementation of the eCTD. The resources are needed to be supervised by
the trained person that is the RA staff [14].
2.2 (b) Plan
The issues should be addressed with utmost priority and the planning for the working on
the issues should need the training and proper checking of the factor. The RA personnel should
be trained with the software usage and also need to know the factor of the legislative factors of
the eCTD uploading. The RA staff should assess the entire requirement on the basis of the CTD
submission in the EMA website. The need of following all the NCA and the EMA
documentation guidelines for the MA application is the most important factor for the RA
personnel. The legal requirements should be assessed with the help of the Annex 1 Modules
found in the instruction of the EMA website for the eCTD submission. However, the RA staff
should be able to access the website and the software and for that reason the training on the
process needed in a more accurate way. As a traditional company MediSan needs to implement
the training process for the RA staff in order to provide the proper resource for them to address
the factors of the EMA submission and acquire the marketing authorisation for the product. On
the other hand the clinical trials of the product should be addressed in all the aspects. Here, the
mutagenic test was done by the scientists however, the testing of the carcinogenic effects of the
drug never have been processed thus the clinical trial report would be incomplete [15]. It is
needed to be done in order to provide the proper data on the effect of the drug. In other words the
data or the information about the clinical and non-clinical trial should focus on every aspect in
order to describe all the factors of the drug. In order to address all these factors the RA staff

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should consider all the aspects of the testing and clinical trials and observe all the factors that
provide the data about the product [16]. The post market feedback should also provide in the
EMA submission to develop the proper marketing authorisation. The Article 59(3) and 61(1) of
Directive of 2001/83 should be followed in the process of the eCTD submission and all these
factors should be done on the basis of the time management and also proper knowledge about the
legal factors of the submission process and the ISO licensing of the drug for the marketing
authorisation [17]. The plan should incorporate the factors of the financial management,
scientific data of the clinical and non-clinical trials and the marketing process of the drug in
order to attract the target population towards the product. Marketing authorisation is the factor
that should be utmost importance for the RA staff and for that reason the knowledge and training
is needed for the factor. The third party software companies also can be considered for the
development and betterment in the licensing process of the drug however, that is not a secure and
reliable process in this aspect.
PART 3: Update of SmPC / PLs
3.1 Directives and Guidance Document
Summary of Product Characteristic supply (SmPC) is comprised of a range of
information about the product for the patient and the doctor. In US this information is termed as
the Prescribing Information. This document is the basis of the approval of the drug in the Europe
or US continent. Thus it is an important factor for the licensing and the marketing of the product
among the national and the international market as well. The SmPC should be uploaded with the

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help of the life-cycle of the product and that helps in the emergence of new data. It serves as the
detail information of EMA website [18].
3.2 Templates
SmPC documentation should be uploaded for every drug in the EMA website along with
the CTD documentation for the validation and the licensing of the product. The proposed SmPC
with the dossier of the specific medicine should be submitted to the competent medical authority.
It will be evaluated later and approved on the basis of the proper documentation and information
about the clinical, non-clinical trials along with the proper dossier process as well. After the post
marketing experience obtained that is the clinical trials, epidemiological data, adverse side effect
reports and others, those will be uploaded to the dossier for the assessment of the competent
authority and the SmPC report would be updated in accordance with the data uploaded. SmPC
can also be updated after the safety communication update for the better assessment of the data
updated. However, all the factors of the updating should be done on the basis of the EMA
website provided template. The product information would be uploaded in the specific structures
of the template. The templates are divided into two factors on the basis of the user satisfaction or
user convenience that are for the applicants and the marketing authorisation for the human
medicines. The European medicine Agency’s Working Group works on the review process of the
updated template of documents and develop the Quality Review of Documents. The company of
the product should be able to assess all the factors of the document updating and the RA
personnel of the company should be responsible for the factor of the development of the
document and the uploading process as well. The company should be able to provide a document
that should be filled with proper data and the document should not be exhaustive for the review