Understanding Submission Packages – Variation Across Regulators and Study … · 2015-12-03 · report the results of these trials, it is important to determine the appropriate

India SDE 2015 | 1

Understanding Submission Packages – Variation Across Regulators and Study Types

Hyderabad, IndiaJuly 25th 2015

2 | India SDE 2015 India SDE 2015 | 3

WelcomeDear Single Day Event Attendee,

We, on behalf of the organizing committee, welcome you to this PhUSE Single Day Event in Hyderabad.

Since its inception, PhUSE has expanded from its roots as a conference for European Statistical Programmers to a global platform for the discussion of topics encompassing the work of Data Scientists, Data Managers, Biostatisticians, Statistical Programmers and eClinical IT professionals. Since 2013, the PhUSE India Working Group has focused on organizing events in India.

As with previous PhUSE SDEs, the day will provide you with the opportunity to hear from experts from across the sector and offer a unique opportunity to meet your peers to discuss the future of various regulatory submissions. Throughout the day, as a group, we will explore the evolution of regulatory guidelines and the implications, “lessons learned” from submission packages and the components required for the submission packages. You are encouraged to ask questions during sessions and to speak directly with presenters throughout the planned networking breaks. Our goal is that you take away from today’s event, thoughts, ideas, new concepts and inspiration gleaned from the discussions and deliberations.

Thank you to all our presenters and panelists for sparing their time to join the group today. We value and appreciate the planning, commitment and attention that has been put into each of the sessions which will undoubtedly make this event a resounding success.

We thank our sponsors: Cytel, Navitas, PPD, SAS, Sciformix and Theorem for their support of this PhUSE Single Day Event in India. Looking at today’s remarkable attendance, we hope for many more events in India and Asia in future.

Best Regards,

Dr. Vishwanath (Mahesh) Iyer and Dr. Nand Kishore Rawat

We hope you enjoy the event and learn about the pharma industry in general and about various regulatory submission packages in particular. Today will also provide you with great networking opportunities

AgendaTime Title and Speaker08:30 - 09:00 Registration and Light Refreshments09:00 - 09:15 Welcome and Overview of PhUSE

Vishwanath Iyer, Novartis & Ajay Sathe, Cytel09:15 - 09:30 Keynote Speech

Vishwanath Iyer, Novartis09:30 - 10:15 Clinical Study Reports: Variation Across the Study Types and

Reporting Formats Across Different Health AuthoritiesRajendra Wable, Sciformix

10:15 - 11:00 Overview of Periodic Safety Reports for Regulatory SubmissionSoujanya Konda & Vijaychand Alapati, inVentiv Health Clinical

11:00 - 11:15 Morning Break11:15 - 12:00 Variation Across Different Therapeutic Areas (TAs) in

Submission-Ready Clinical Data StandardsVinay Somashekar, PPD

12:00 - 12:45 Submission Packages and Changes to Regulatory Guidelines in the EU RegionRajesh Murarishetti, Navitas

12:45 - 13:15 Quiz13:15 - 14:00 Lunch14:00 - 14:45 What is Validation in SAS Context?

K.V. Palanichamy, PRA Health Sciences14:45 - 15:30 OSI Requests in Submission

Sarmistha Acharya & Swetha Poondra, Novartis15:30 - 15:45 Afternoon Break15:45 - 17:00 Panel Discussion and Q&A

Vishwanath Iyer, Novartis, Anil Golla, Cytel, Praveen Madhusoodanan, Parexel & Neeta Korlepara, Novartis

17:00 - 17:15 Wrap-Up & Closing RemarksAjay Sathe, Cytel

Vishwanath IyerNovartis

Nand Kishore RawatCytel


Speakers and Abstracts09:30 - 10:15 Clinical Study Reports: Variation Across the Study Types and Reporting Formats Across Different Health AuthoritiesRajendra Wable, Sciformix

AbstractBiopharmaceutical companies engaged in the development of a new drug or generic drug conduct clinical studies to establish the safety and efficacy of their product across various therapeutic areas and geographic regions. The clinical study reports (CSRs) for submission to the health authorities are required to be in compliance with the International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) and other applicable international and regional regulatory requirements and must meet high-quality standards to provide the most concise yet comprehensive summary of the study. The ICH GCP guideline and associated ICH document guidelines (ICH E3 and ICH M4E) provide the unified ethical and scientific framework, structure, and methodologies for the reporting of clinical research in the EU, Japan and the US and are also adopted by most of the non-regulated countries. Clinical drug development programs vary widely in the number of studies performed and the number of patients studied. In order to report the results of these trials, it is important to determine the appropriate format for CSRs (e.g. full, abbreviated, synopsis, supplemental) with advice from the health authority. Generally, a full CSR is submitted for all clinical and human pharmacology investigations that contribute to the evaluation of effectiveness for the proposed indication or that otherwise support information included in labeling. For studies that ultimately do not contribute to the evaluation of the effectiveness of a product for a specific indication or for seriously flawed or aborted studies, abbreviated or synopsis formats of CSR can be used. An addendum to the original

CSR can be used to present additional or follow-up data from a study. The specific requirements for data presentation and/or analyses depend on specific situations and the type of applications (e.g. IND/CTA/MAA/NDA, etc.), which could differ among regions and cannot be described in general terms; it is therefore important to refer to region-specific clinical guidelines and to discuss data presentation and analyses with the reviewing authority whenever possible. Detailed written guidance on statistical approaches is available from some authorities. Most of the regulatory agencies (e.g. the US FDA, Japan, and the EU) accept the reports or application packages submitted only electronically in e-CTD format while other non-regulated countries (e.g. ROW countries) still accept paper or non e-CTD submissions. Generally, to fulfill the global regulatory requirements for reporting results from clinical studies, primary outcomes for clinical studies (Phase I to IV non-pediatric studies) are reported to the applicable regulatory authorities within one year of completion of the study. In the EU, the results from pediatric studies are generally required to be reported within six months of completion of the study. The requirement can be satisfied by submission of a CSR, CSR synopsis, or a similar summary of study results and conclusions.

BiographyDr. Rajendra Wable, a regulatory writing coach at SWRA, is a postgraduate veterinary pathologist [BVSc & A. H (DVM) and MVSc (Veterinary Pathology)]. His industrial experience includes regulatory scientific writing (pre-clinical and clinical) and

safety assessment of pharmaceuticals in GLP-compliant environments. He is currently managing several regulatory writing projects (pre-clinical and clinical) and providing support to the global pharmaceuticals for product registration in international markets.

Rajendra has hands-on experience of authoring a variety of regulatory submission documents including protocols, clinical study reports, investigator’s brochures and common technical document modules (non-clinical and clinical overviews and summaries, integrated safety and efficacy summaries) required for CTA/IND/NDA/IMPD/MAA applications. He is also experienced in developing strategies to respond to health authority queries, biowaiver applications and biological characterization of pharmaceutical impurities. He has worked as a study director/study pathologist for various regulatory toxicity studies and managed several PK, PD and toxicology projects. He has a clear understanding of the drug development process and CTD submission and is very much familiar with global data management systems that are used by global pharmaceutical companies. Rajendra has participated and presented research papers at various conferences, mainly in the area of disease pathology and regulatory writing. He has also been actively involved in training and mentoring writers for various scientific writing projects.


Speakers and Abstracts11:15 - 12:00 Variation Across Different Therapeutic Areas (TAs) in Submission-Ready Clinical Data StandardsVinay Somashekar, PPD

AbstractThe objective of standardizing study data submissions is to accomplish an acceptable degree of ability to communicate and exchange data which is accurate, reliable and consistent, by secured means using different database management tools, software applications, and networking systems. This process of exchanging data-transformed information (clinical or operational) is stored unaltered. There are a set of pre-defined steps by the Food and Drug Administration (FDA) to standardize the data submission process. Some of the pre-defined steps will differ for each of the TAs. Sponsors will need to create “custom domains” when the standard domains do not meet their needs and will have to submit certain efficacy data. This can be defined as TA standards. TA standards are supplemental considerations, and recommendations, which are specific when sponsors submit study data using the FDA therapeutic area standards. This presentation will provide an overview of the therapeutic area standards development, which prioritizes the data standards for distinct TAs. In addition, this would include the TA standards development process and inclusion of some new domains related to TAs in the latest version of SDTMIG. An outline of the specification for some TA domains will be discussed.

BiographyVinay Somashekar holds a master’s degree in statistics from Bangalore University, Karnataka. He has significant experience of working with major CROs globally and across different therapeutic areas including but not limited to dermatology,

oncology, gastroenterology, neurology, musculoskeletal and infectious diseases. His expertise includes CDISC (SDTM, ADaM) guide implementation, generating safety and efficacy analysis reports for clinical trial data (Phase I through to III). He is currently working as a programmer analyst at PPD, Bengaluru, India.

10:15 - 11:00 Overview of Periodic Safety Reports for Regulatory SubmissionSoujanya Konda & Vijaychand Alapati, inVentiv Health Clinical

AbstractIn a clinical trial, it is crucial to assess the risk–benefit of a medical product and whether it can be overcome by regular analysis of safety data by periodic reporting. Sponsors or market authorization holders need to submit the safety information to regulatory authorities during drug development and also when the drug is on the market. There are various periodic reports with different requirements and various teams working on the same reports to provide the information. This presentation will discuss various periodic safety reports including DSUR, PSUR, IB and orphan designation annual reports and their respective purposes for submission of the trial.

BiographiesVijaychand Alapati is a registered pharmacist and has completed his MPharm. Vijaychand is currently working as a senior safety associate at inVentiv Health Clinical. He has over four years’ experience in the pharmacovigilance

industry including the processing and quality checking of spontaneous literature, post-marketing surveillance cases, writing product guidance documents and study guidance documents. He also has experience in configuring PMS studies in Argus console.

Soujanya Konda is currently working as a senior CDMP at inVentiv Health, Hyderabad and has been working in SAS programming and clinical data management for over seven years. She is a Base SAS-certified programmer; her projects involve the

reporting and managing of clinical trial data and end-to-end process in clinical data management.

Soujanya holds a Master of Science in Biotechnology and a Postgraduate Diploma in Bioinformatics. She was a gold medalist in an inter-university seminar conducted by VSL College, Kakinada.

Soujanya presented two papers at the PharmaSUG International Conference 2015 in Orlando: “Grooming of Coarse Data by Smart Listing Using SAS System” and “Use of SAS Reports for External Vendor Data Reconciliation”. She also presented the paper “Implementation of SAS Programming for Data Cleaning” at ConSPIC 2014, organized by the Indian Association for Statistics in Clinical Trials (IASCT).


Speakers and Abstracts14:00 - 14:45 What is Validation in SAS Context?K.V. Palanichamy, PRA Health Sciences

AbstractThis topic arose from the speaker’s experience of interacting with SAS programmers either on the job or while interviewing candidates. It was observed that the term validation is being understood in different ways and that when asked what is validation of SAS programs, a satisfactory response was not provided. An attempt is being made to look at the concept of SAS program validation in the context in which the FDA defines it. The audience will be taken through validation, as it is required by the FDA and other regulators, and will examine what is being done as part of validation activities, including the different ways of looking at the concept of validation in other disciplines and how we extrapolate it to our context.

BiographyPalanichamy (Palani) completed his PhD in Agricultural Statistics at the Indian Agricultural Statistics Research Institute, New Delhi, India and has a rich industrial experience spanning over 23 years. He started his career with Torrent Pharmaceuticals

Limited as a biostatistician when bio activities were at an evolving stage globally. Over the years he has worked with Ranbaxy, GSK, Novo Nordisk, Novartis, GVK Bio, Tata Consultancy Services (TCS) and INC Research. He has been instrumental in setting up biostatistics teams at Novartis, TCS and INC Research (Kendle). Palanichamy currently works at PRA Health Sciences based in Chennai as Director of Clinical Programming and set up the team from scratch.

12:00 - 12:45 Submission Packages and Changes to Regulatory Guidelines in the EU RegionRajesh Murarishetti, Navitas

AbstractA regulatory submission for a healthcare product includes any documentation or information submitted to a regulatory agency for review, notification or in response to a request for additional related information.The format can be paper or electronic, or both. The amount of information involved and its required complexity can vary significantly. A licensing application for a drug or biological product may contain hundreds of paper volumes whereas a response to an agency’s question for a clarification may involve a single page.

Due to the enormous amount of information presented in a marketing application, agencies are encouraging applicants to submit applications electronically in required formats that can facilitate their regulatory review (for example, eCTD, NeeS).

Variations are defined as changes to marketing authorization, i.e. administrative, quality, safety and efficacy. Variations to medicinal products can be classified in different categories depending on the level of risk to the public or animal health and the impact on the quality, safety and efficacy of the medicinal product concerned, which needs to be notified and approved depending on the type of variation. MRP, DCP and CP are the different types of submission procedures in the EU. This presentation will discuss submission types/timelines, components of submission packages and types of variations.

BiographyRajesh Murarishetti currently works at Navitas as a regulatory operations manager. He is a submissions specialist with over nine years’ experience in the pharmaceutical industry (regulatory affairs), primarily in submission management and

e-Submissions (e-CTD, NeeS), submission planning, content authoring, component co-ordination, assembly, internal review, despatch and archiving of regulatory submissions to different markets, i.e. Europe, Asia, Africa, and the Middle East. Prior to this, Rajesh worked at Aurobindo Pharma Limited, Aventis Pharma Limited, Novartis and Mac-Chem Products, India. Rajesh has an MPharm (Pharmaceutics) from Periyar College of Pharmaceutical Sciences, Trichy. Dr. M.G.R Medical University.


15:45 - 17:00 Panel Discussion and Q&AVishwanath Iyer, Novartis, Anil Golla, Cytel, Praveen Madhusoodanan, Parexel & Neeta Korlepara, Novartis

BiographiesVishwanath (Mahesh) Iyer is Head of Oncology Biometrics at Novartis, Hyderabad, heading up a team of biostatisticians, SAS programmers and data analysts. He holds a doctorate in Statistics from Temple University,

Philadelphia. Mahesh has been involved in analyzing and reporting clinical trial data since 1998 with companies including Boehringer Ingelheim and Bristol-Myers Squibb, and specifically for oncology studies since 2000. In addition, Mahesh has been active in the statistical research community, with a primary focus on multiple comparison procedures. Mahesh is actively involved in teaching at multiple institutions in India and adjunct faculties at The Institute of Ayurveda and Integrative Medicine at Bangalore, serves on the Advisory Council of India for the DIA, serves as the Secretary for the Indian Association for Statistics in Clinical Trials (IASCT), is on the Board of Studies for Statistics at Manipal University and is also a co-editor for a pharmaceutical journal.

As VP for Services at Cytel, Anil Golla is responsible for existing client engagements and building new verticals. Prior to Cytel, Anil held leadership positions at Novartis, serving as Function Head for Clinical Trial Services and Head of Oncology Data

Management where he worked on establishing business units serving CPOs, GMA, oncology and regional entities.

Prior to this, Anil worked at Accenture as the general manager for a pharma client engagement in their BPO services division and at Merck & Co where he was responsible for delivery, business development and application support.

With over 19 years’ experience, Anil brings expertise in providing strategy, design, development and management to the pharma industry, supporting the clinical services domain.

As Director for Services at PAREXEL, Praveen Madhusoodanan is responsible for the India operation, providing all database and statistical programming services across multiple clients. Prior to PAREXEL, Praveen held

leadership positions at Accenture, serving as Vice President at New Jersey, USA with overall responsibility at account level, providing end-to-end clinical data services for large pharmaceutical companies.

Prior to that, Praveen was with SEDOC Pharmaceutical Medicine AB, as an associate director for a CRO based in Stockholm, Sweden, leading the Clinical Data Management Department.

Panelists

Neeta Korlepara is the Group Head in Oncology Submission Management at Novartis, responsible for authoring clinical and regulatory documents for global submissions.

Neeta is a physician of alternate medicine with over 15 years’ experience, having spent the last seven years working in a major pharmaceutical company. She has extensive experience in authoring safety documents, and has established processes in her department for new documents released by health authorities (for example, the EU risk management plan).

Speakers and Abstracts14:45 - 15:30 OSI Requests in SubmissionSarmistha Acharya & Swetha Poondra, Novartis

AbstractThe goal of the OSI, the Office of Scientific Investigations, is to verify the integrity of efficacy and safety data submitted to the US FDA in support of new drug applications and to ensure that the rights and welfare of human research subjects are protected.

On-site inspection is one of many tools the US FDA has for ensuring the integrity of data, the health and welfare of research participants, and the protection of public health. Hence, the US FDA requests summary-level clinical site data set in electronic form for new drug applications (NDAs), biologics licensing applications (BLAs), and NDA or BLA supplemental applications submitted to the Center for Drug Evaluation and Research (CDER)/Center for Biologics Evaluation and Research (CBER). This presentation will discuss examples of data and listings created for the OSI request and how these can be interpreted.

BiographiesSarmistha Acharya is a principal programmer at Novartis. She has worked at Novartis since 2006, having joined as a graduate. Sarmistha has a master’s in statistics from the University of Burdwan, West Bengal.

Swetha Poondra is a senior programmer at Novartis. Prior to this, she worked at Accenture, Mumbai (2010-2012), Novartis (2008-2010) and Sristek (2006-2008). Swetha has over eight years’ industry experience and has a

master’s in statistics from Osmania University, Hyderabad.


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Understanding Submission Packages – Variation Across Regulators and Study … · 2015-12-03 · report the results of these trials, it is important to determine the appropriate