Welcome to CMC Strategy Forum Latin America 2016c.ymcdn.com/sites/€¦ · · 2016-08-29CASSS and the United States Food and Drug Administration. ... CMC Strategy Forum Latin America

Welcome to CMC Strategy Forum Latin America 2016 On behalf of the CASSS Board of Directors and the CMC Strategy Forum Global Steering Committee, we would like to extend to you a warm welcome to the third meeting of the CMC Strategy Forum Latin America 2016. We are very pleased to have the strong support from COFEPRIS-Federal Commission for the Protection against Sanitary Risk Regulatory Agency in Mexico, as well as AMIIF, CANIFARMA and several other Latin America regulatory agencies (Brasil, Ecuador and Peru), as well as the continued support by CASSS and the United States Food and Drug Administration. The Forum will follow the established model of the CMC Forum series with focus on topics and regulatory updates relevant for Latin America and will feature an opening regulatory session that will include presetations from COFEPRIS, ANVISA, DIGEMID, as well as the FDA and EMA. In addition, FIFARMA is planning a half-day session to discuss transparency, as well as retesting, quality surveillance and pharmacopeia. The technical sessions will include discussion on lifecycle management control strategies and setting specifications, as well as risk management and established conditions. The success of the CMC Strategy Forum Latin America will depend on your active participation in discussing and raising issues pertaining to the development of biologics. We encourage you to participate whole-heartedly in the panel discussions that have been designed to stimulate exchange of ideas and information. We would like to thank the speakers and the panel members who are giving generously of their time and resources and to you for your attendance. We would also like to acknowledge the generosity of our strategic program partners for the continued support of the Forum series: AbbbVie, Inc., Biogen, F. Hoffmann-La Roche Ltd. and MedImmune, A member of the AstraZeneca Group. We are grateful for the expert management from CASSS and the audio-visual expertise of Michael Johnstone from MJ Audio-Visual Productions. Their experience and guidance in the preparation of this Forum has been invaluable.

ACKNOWLEDGEMENTS LATIN AMERICA SCIENTIFIC ORGANIZING COMMITTEE Daniela Cerqueira, ANVISA, Brasilian Health Surveillance Agency, Brasil Rocío Delgado Montero, DIGEMID, General Directorate of Medicines, Supplies and Drugs, Peru John Dougherty, Eli Lilly and Company, USA Rivelino Flores, CANIFARMA, National Chamber of the Pharmaceutical Industry, Mexico Fernando Fon, AMIIF, Mexican Association of Pharmaceutical Research Industries, Mexico Adriana Hernández Trejo, COFEPRIS, Federal Commission for the Protection from Sanitary Risks, Mexico Carmilia Jiménez Ramirez, Gilead Sciences, USA Bernardo Moreira, ANVISA, Brasilian Health Surveillance Agency, Brasil Fabiola Muñoz, ISPCH, Institute of Public Health, Chile Ana Padua, F. Hoffmann-La Roche Ltd., Uruguay Thomas Schreitmüller, F. Hoffmann-La Roche Ltd., Switzerland Carlos Solís, Psicofarma, Mexico Esenbeckia Yureri Torres Guzmán, COFEPRIS, Federal Commission for the Protection from Sanitary Risks, Mexico Jaime Uribe Wiechers, Probiomed S.A. de C.V., Mexico CMC STRATEGY FORUM GLOBAL STEERING COMMITTEE Siddharth Advant, Kemwell Biopharma, USA Daniela Cerqueira, ANVISA-Brasilian National Health Surveillance Agency, Brasil John Dougherty, Eli Lilly and Company, USA Yasuhiro Kishioka, PMDA-Pharmaceutical and Medical Devices Agency, Japan Junichi Koga, Daiichi Sankyo Co., Ltd., Japan Steven Kozlowski, CDER, FDA, USA Ingrid Markovic, CBER, FDA, USA Rohin Mhatre, Biogen, USA Anthony Mire-Sluis, AstraZeneca., USA Wassim Nashabeh, F. Hoffmann-La Roche Ltd., Switzerland (Chair) Ilona Reischl, AGES-Austrian Medicines and Medical Devices Agency, Austria Anthony Ridgway, Health Canada, Canada Nadine Ritter, Global Biotech Experts, LLC, USA Thomas Schreitmüller, F. Hoffmann-La Roche Ltd., Switzerland Mark Schenerman, MedImmune, A member of the AstraZeneca Group, USA Karin Sewerin, BioTech Development AB, Sweden

The Scientific Organizing Committee gratefully acknowledges the pharmaceutical and biotechnology industry for their generous support of the CMC Strategy Forum

Latin America 2016.

STRATEGIC PROGRAM PARTNERS

AbbVie, Inc. Biogen

F. Hoffmann – La Roche Ltd. MedImmune, A member of the AstraZeneca

Group

The Scientific Organizing Committee gratefully acknowledges the following media for their promotional consideration of the CMC Strategy Forum Latin America 2016:

LEADING MEDIA PARTNERS

BioProcess International

International Pharmaceutical Quality MEDIA PARTNERS

American Laboratory / LabCompare American Pharmaceutical Review

BioProcessing Journal The Analytical Scientist

The Medicine Maker The Pathologist

Technology Networks

CMC Strategy Forum Latin America 2016 Scientific Program Summary

Monday, 5 September 2016

07:30 – 17:00 Registration in the Regency Ballroom Foyer, 2nd Floor 07:30 – 09:00 Continental Breakfast Service in the Regency Room F, 1st Floor 08:45 – 09:00 CASSS Welcome and Introductory Comments in the Regency Ballroom A Wassim Nashabeh, F. Hoffmann-La Roche Ltd., Switzerland 09:00 – 09:30 CMC Strategy Forum Latin America 2016 Welcome and Introductory

Comments in the Regency Ballroom A Fifteen Actions for the Protection Against Health Risks

Julio Sánchez, Comisionado Federal, COFEPRIS, Federal Commission for the Protection from Sanitary Risks, Mexico

Regulatory Convergence: Recent Trends in the Regulations of Biotherapeutic Products in Latin

America Plenary Session in the Regency Ballroom A

Session Chairs: Wassim Nashabeh, F. Hoffmann-La Roche Ltd. and Jaime Uribe Wiechers, Probiomed S.A. de C.V.

09:30 – 09:55 Regulatory Framework for Biotherapeutic Products in Mexico: An Overview

Adriana Hernández Trejo, COFEPRIS, Federal Commission for the Protection from Sanitary Risks, Mexico

09:55 – 10:20 Brasilian Regulation of Biopharmaceuticals Bernardo Luiz Moraes Moreira, ANVISA, Brasilian Health Surveillance Agency,

Brasil 10:20 – 10:50 AM Break in the Regency Ballroom Foyer, 2nd Floor 10:50 – 11:15 Recent Trends in the Regulation of Biotechnological Products in Peru

Edith Roxana Vásquez Alaya, DIGEMID, General Directorate of Medicines, Supplies and Drugs, Peru

11:15 – 11:40 Regulatory Update from Europe Margarida Menezes Ferreira, INFARMED, National Authority of Medicines and

Health Products, Portugal

Monday, 5 September continued… 11:40 – 12:05 Regulation of Biotherapeutic Products: US FDA Perspective Leslie Rivera Rosado, CDER, FDA, USA 12:15 – 13:30 Buffet Lunch in the Regency Room F, 1st Floor 13:30 – 14:45 Panel Discussion – Questions and Answers

Adriana Hernández Trejo, COFEPRIS, Federal Commission for the Protection from Sanitary Risks, Mexico Margarida Menezes Ferreira, INFARMED, National Authority of Medicines and Health Products, Portugal César Moncayo, ARCSA, National Agency for Regulation and Control Health Surveillance, Ecuador Bernardo Luiz Moraes Moreira, ANVISA, Brasilian Health Surveillance Agency, Brasil Leslie Rivera Rosado, CDER, FDA, USA Edith Roxana Vásquez Alayo, DIGEMID, General Directorate of Medicines, Supplies and Drugs, Peru

14:45 – 15:15 PM Break in the Regency Ballroom Foyer, 2nd Floor 15:15 – 15:20 Introduction of FIFARMA

Thomas Schreitmüller, F. Hoffmann-La Roche Ltd., Switzerland (on behalf of FIFARMA)

Latin American Federation of Pharmaceutical Industry (FIFARMA)

Public Quality Control Testing of Pharmaceutical Products Workshop Session in the Regency Ballroom A

Session Chairs: Gustavo Grampp, Amgen Inc. and Janett Mugaburu-Richards, Pfizer, Inc. 15:20 – 15:30 Introduction - Private vs. Public Quality Control

Gustavo Grampp, Amgen Inc., USA (on behalf of FIFARMA) 15:30 – 15:45 Opportunities for Improved Access to Safe and Efficient Medicines María Guazzaroni Jacobs, Pfizer, Inc., USA (on behalf of IFPMA)

15:45 – 16:00 Local Re-testing – The Regulator’s Perspective

Iván Valentin Cruz Barrera, COFEPRIS, Federal Commission for the Protection from Sanitary Risks, Mexico

16:00 – 16:15 The Mexican Pharmacopeia (FEUM) as Standard of Pharmaceutical

Products Rafael Hernández Medina, Pharmacopeia of the United Mexican States, Mexico

Monday, 5 September continued… 16:15 – 16:45 Panel Discussion – Questions and Answers

Iván Valentin Cruz Barrera, COFEPRIS, Federal Commission for the Protection from Sanitary Risks, Mexico

María Guazzaroni Jacobs, Pfizer, Inc., USA (on behalf of IFPMA) Rafael Hernández Medina, Pharmacopeia of the United Mexican States, Mexico

Teresa de Jesus Olivo Rosales, Eli Lilly y Compañia de Mexico S.A. de C.V., Mexico

Sonia Mayra Pérez Tapia, UDIMEB, Mexico 16:45 – 16:55 Mini-break

Latin American Federation of Pharmaceutical Industry (FIFARMA) Transparency of Regulatory Decision Making Workshop Session in the Regency Ballroom A

Session Chairs: Silvia Moscoso Salcedo, AbbVie, Inc. and María Cristina Mota Pina, AbbVie, Inc. 16:55 – 17:05 Introduction

María Cristina Mota Pina, AbbVie, Inc., USA (on behalf of FIFARMA) 17:05 – 17:20 Transparency in Regulatory Decision Making – The Brasilian Way

Bernardo Luiz Moraes Moreira, ANVISA, Brasilian Health Surveillance Agency, Brasil

17:20 – 17:35 Transparency Policies in the EU from Clinical Trials to Pharmacovigilance Margarida Menezes Ferreira, INFARMED, National Authority of Medicines and

Health Products, Portugal 17:35 – 17:50 Transparency in Regulatory Decision Making on the Approval for Biosimilar

Products – The FIFARMA Position Thomas Schreitmüller, F. Hoffmann-La Roche Ltd., Switzerland (on behalf of FIFARMA)

17:50 – 18:20 Panel Discussion – Questions and Answers Margarida Menezes Ferreira, INFARMED, National Authority of Medicines and

Health Products, Portugal Iván González Del Valle, COFEPRIS, Federal Commission for the Protection from Sanitary Risks, Mexico Alberto Miguel Guzmán, COFEPRIS, Federal Commission for the Protection from Sanitary Risks, Mexico Carlos Lizardi, COFEPRIS, Federal Commission for the Protection from Sanitary Risks, Mexico Bernardo Luiz Moraes Moreira, ANVISA, Brasilian Health Surveillance Agency, Brasil Thomas Schreitmüller, F. Hoffmann-La Roche Ltd., Switzerland (on behalf of FIFARMA)

Alexis Serlin, CANIFARMA, Mexico

Monday, 5 September continued… 18:20 – 18:30 FIFARMA Session Summary and Conclusion

Thomas Schreitmüller, F. Hoffmann-La Roche Ltd., Switzerland (on behalf of FIFARMA)

18:30 – 20:00 Networking Reception in the Regency Room D1, 2nd Floor 20:00 Adjourn Day One

Tuesday, 6 September 2016 07:30 – 17:00 Registration in the Regency Ballroom Foyer, 2nd Floor 07:30 – 09:00 Continental Breakfast Service in the Regency Room F, 1st Floor

Lifecycle Management Part One: Control Strategy and Setting Specifications Workshop Session in the Regency Ballroom A

Session Chairs: Carmilia Jimenez Ramirez, Gilead Sciences and Jaime Uribe Wiechers, Probiomed S.A. de C.V.

08:45 – 08:50 Introduction 08:50 – 09:15 Statistical Control of Manufacturing a Biotechnological Drug

Lázaro Morales Reyes, COFEPRIS, Federal Commission for the Protection from Sanitary Risks, Mexico

09:15 – 09:40 The Role of Analytics in the Development of Advanced Process Controls Patrick Swann, Biogen, USA 09:40 – 10:05 Setting Specifications: From QbD to Continuous Process Verification Néstor Octavio Pérez Ramirez, Probiomed S.A. de C.V., Mexico 10:05 – 10:35 AM Break in the Regency Ballroom Foyer, 2nd Floor 10:35 – 11:50 Panel Discussion - Questions and Answers

Francisco Kuri Breña, Landsteiner Scientific, Mexico Lázaro Morales Reyes, COFEPRIS, Federal Commission for the Protection from Sanitary Risks, Mexico Néstor Octavio Pérez Ramirez, Probiomed S.A. de C.V., Mexico

Patrick Swann, Biogen, USA Cecilia Tami, CDER, FDA, USA Mauricio Trujillo Roldán, Universidad Nacional Autónoma de Mexico, Mexico 12:00 – 13:15 Buffet Lunch in the Regency Room F, 1st Floor

Tuesday, 6 September continued…

Lifecycle Management Part Two: Risk Management and Established Conditions Workshop Session in the Regency Ballroom A

Session Chairs: Joseph Kutza, MedImmune, A member of the AstraZeneca Group and Nadine Ritter, Global Biotech Experts, LLC

13:15 – 13:25 Introduction 13:25 – 13:50 Reducing the Complexity and Impact of Regulatory Changes in Latin

America Janett Mugaburu-Richards, Pfizer, Inc., USA (on behalf of the BioPhorum

Operations Group (BPOG), United Kingdom) Kavita Ramalingam Iyer, Merck & Co., Inc., USA (on behalf of the BioPhorum

Operations Group (BPOG), United Kingdom) 13:50 – 14:15 Reduction of Post Approval Change Reporting Categories or Data Provided

through Use of Risk Assessment Mic McGoldrick, Merck Sharp & Dohme, USA

14:15 – 14:40 Q12 and Perspectives on Post-approval

Renan Araujo Gois, ANVISA, Brasilian Health Surveillance Agency, Brasil 14:40 – 15:05 Will ICH Q12 Truly Go Beyond Q8/Q11?? Opportunities and Challenges Wassim Nashabeh, F. Hoffmann-La Roche Ltd., Switzerland 15:15 – 15:45 PM Break in the Regency Ballroom Foyer, 2nd Floor 15:45 – 17:00 Panel Discussion – Questions and Answers Ricardo Castro Acosta, Universidad Nacional Autónoma de Mexico, Mexico Mic McGoldrick, Merck Sharp & Dohme, USA Janett Mugaburu-Richards, Pfizer, Inc., USA (on behalf of the BioPhorum

Operations Group (BPOG), United Kingdom) Wassim Nashabeh, F. Hoffmann-La Roche Ltd., Switzerland

Kavita Ramalingam Iyer, Merck & Co., Inc., USA (on behalf of the BioPhorum Operations Group (BPOG), United Kingdom) Leslie Rivera Rosado, CDER, FDA, USA

17:00 – 17:30 Recap of Program Summary Slide Presentation

Carmilia Jiménez Ramirez, Gilead Sciences, USA Nadine Ritter, Global Biotech Experts, LLC, USA 17:30 – 17:45 Closing Remarks Thomas Schreitmüller, F. Hoffmann-La Roche Ltd., Switzerland 17:45 Adjournment

Regulatory Convergence: Recent Trends in the Regulations of

Biotherapeutic Products in Latin America Session Chairs: Wassim Nashabeh, F. Hoffmann-La Roche Ltd. and Jaime Uribe Wiechers, Probiomed S.A. de C.V. In this session, regulators that represent ANMAT (Argentina), ANVISA (Brazil), ARCSA (Ecuador), COFEPRIS (Mexico), DIGEMID (Peru), EMA (Europe) and FDA (USA), present an update about the regulatory framework for bio therapeutics, including the main challenges for its implementation and trends. For the panel discussion, the current trends in accelerated development strategies to speed up the access of unmet medical needs to the patients, as well as regulatory convergence, capacity building, principles of good review practices and traceability in pharmacovigilance will be discussed. We want to explore the initiatives the agencies have undertaken towards these topics, what are potential hurdles and how they have overcome. NOTES:

Short Biographies

Adriana Hernández Trejo COFEPRIS, Federal Commission for the Protection from Sanitary Risks Margarida Menezes Ferreira INFARMED, National Authority of Medicines and Health Products César Moncayo ARCSA, National Agency for Regulation and Control Health Surveillance Bernardo Luiz Moraes Moreira ANVISA, Brasilian Health Surveillance Agency Wassim Nashabeh F. Hoffmann-La Roche Ltd. Dr. Wassim Nashabeh received his PhD in analytical chemistry from Oklahoma State University in 1993, and his post-doctoral fellowship in bioanaytical chemistry from The Barnett Institute at Northeastern University. Following a two-year research appointment at PerSeptive Biosystems, Wassim joined Genentech (A member of the Roche Group) in 1996 as a scientist and has since held several positions of increasing responsibilities including associate director of the methods validation group, director quality control, director in the CMC regulatory affairs group, senior director of CMC policy & strategy, global head of technical regulatory policy for the Roche Pharma Medicines Group and most recently as the global head of policy and international operations in PTR. His current responsibilities include development and advocacy of Roche key external positions and policies with global health authorities, industry associations and scientific organizations, as well as management of Roche technical regulatory international operations. Leslie Rivera Rosado CDER, FDA Dr. Leslie A. Rivera Rosado is a senior regulatory scientist officer in the office of biotechnology products (OBP) at FDA’s Center for Drug Evaluation and Research (CDER) and a lieutenant in the U.S. Public Health Service Commissioned Corps. Her primary responsibilities as a product quality reviewer include the review of the chemistry, manufacture, and control (CMC) information submitted with investigational new drug and biologics licensing applications and related amendments and supplements and participating in pre-license and pre-approval inspections. Dr. Rivera Rosado earned a PhD degree in biochemistry, cellular, and molecular biology from the Johns Hopkins University School of Medicine in Baltimore, MD. She completed a three-year post-doctoral training program and was an Interagency Oncology Task Force (IOTF) fellow at the FDA prior to joining the review staff.

Julio Sánchez COFEPRIS, Federal Commission for the Protection from Sanitary Risks Julio Sánchez graduated from the Escuela Libre de Derecho in Puebla and completed his masters degree in economic development and international aid at the Universidad Complutense of Madrid, Spain. He served as deputy director of bilateral cooperation for Europe and Latin America and deputy director for multilateral cooperation of the United Nations and specialized organizations at the general attorney’s office. Mr. Sánchez also worked for the Federal Competition Commission, a career that began as deputy director for international cooperation and subsequently lead to being director of normativity of regulated sectors and general director for research of monopolistic practices. He served as head of the general directorate of procedures of the Federal Consumer Protection Agency. Later he worked at the Ministry of Public Security, at the Federal Police as an inspector of the Department of Intelligence for International Affairs. In the Federal Commission for Protection from Sanitary Risks, Mr. Sánchez has served as the federal commissioner’s chief of staff, commissioner of sanitary enforcement and is currently assigned as federal commissioner by the President of the Mexican United States. Jaime Uribe Wiechers Probiomed S.A. de C.V. With professional experience of over 22 years in the pharmaceutical industry, Jaime Uribe Wiechers has worked throughout his career in multiple roles in areas such as finance, information technology, quality, manufacturing and R&D of biopharmaceutical products. Since July 2016 he holds the position of CEO at Probiomed, the leading biopharmaceutical company in Mexico. Jaime has a degree in industrial engineering (UIA) and postgraduate studies in business management (IPADE) and industrial biotechnology (UAEM). He has published several scientific papers, presented at numerous conferences and collaborated with diverse conference presentations regarding biotechnology, quality and innovation in Mexico and internationally. Edith Roxana Vásquez Alayo DIGEMID, General Directorate of Medicines, Supplies and Drugs Edith Vásquez has more than six years of experience in regulatory affairs (interpretation of technical specifications, validations and stability studies) with knowledge in conducting extensive literature search and critical analysis of the scientific literature. She joined the biological products group from the directorate of pharmaceutical products as a technical evaluator in 2012. In her current position, Edith has the responsibility to evaluate the technical documentation that supports quality, safety and efficacy requirements of applications for the sanitary register of biological products. Edith graduated from the National University of Trujillo (UNT) in Lima, Peru in 2007 with a bachelors degree in pharmacy and graduated from the Peruvian University Cayetano Heredia (UPCH) in Lima, Peru in 2013 with her masters degree in clinical epidemiology. She participates in international training, workshops and conferences representing DIGEMID.

Presenter’s Abstracts

Fifteen Actions for the Protection Against Health Risks Julio Sánchez, Comisionado Federal COFEPRIS, Federal Commission for the Protection from Sanitary Risks, Mexico NOTES:

Regulatory Framework for Biotherapeutic Products in Mexico: An Overview Adriana Hernández Trejo COFEPRIS, Federal Commission for the Protection from Sanitary Risks, Mexico NOTES:

NOTES:

Brasilian Regulation of Biopharmaceuticals Bernardo Luiz Moraes Moreira ANVISA, Brasilian Health Surveillance Agency, Brasil NOTES:

NOTES:

Recent Trends in the Regulation of Biotechnological Products in Peru Edith Roxana Vásquez Alaya DIGEMID, General Directorate of Medicines, Supplies and Drugs, Peru Currently, Peru has 31 million of people, and three main public health system: 1) For formal employee (ESSALUD), 2) Public (MINSA) and 3) for militaries (FOSPEME and FOSPOLI) covering over 62% of the Peruvian population and has the challenge to elaborate regulations that ensure access to quality, safety and efficacy products.

Since the approval of the “Law on Pharmaceutical Products, Medical Devices and Sanitary Products” (Law 29459, 2009), and its regulations (Supreme Decree 016-2011-SA), which came into force in January 2012, DIGEMID has begun a process of elaborating complementary rules to fulfill its regulatory function. Between 2011 and 2016 several and different regulations have been approved related with the registration, re-registration, modification and cancellation of sanitary registration for pharmaceuticals. It is important to highlight the approval of the regulation for biotechnological and biological products which choose the similarity pathway.

According to Art. 103° of S.D. N° 016-2011-SA, modified by Art. 1° of S.D. N° 011-2016-SA, biological products are classified as: a) Immunological (vaccines, allergens and serums), b) Blood and plasma derived products, c) Products obtained by biotechnological procedures – Biotechnological products (DNA recombinant techniques, monoclonal antibody and hybridoma techniques, and d) Other biological products. So it represents a challenge in implementing new specific regulations.

In recent years, worldwide, there has been a great development of biological drugs, especially biotechnological drugs, which contribute to the treatment of many diseases. The high cost and limited access of those products, have generated worldwide set up strategies that facilitate access to them, been one of the most important the development of so-called biosimilars.

Between February and March 2016 two regulations have been issued by DIGEMID to regulate the sanitary registration of biological products in the country, which promote the access to quality, safety and efficacy biological products.

These are: • Supreme Decree N° 011-2016-SA (February 27th, 2016) regulation about the submission

and content of the documents required for the sanitary registration and re-registration of Biological products: Biotechnological products.

• Supreme Decree N° 013-2016-SA (March 1st, 2016) regulation about the submission and content of the documents required for the sanitary registration and renewal of Biological products that choose the Similarity pathway.

This has a positive effect on increasing access to medicines for the treatment of oncological diseases, autoimmune disorders, diabetes, among others; to improve the quality of life of patients afflicted with these diseases.

Finally, DIGEMID is leading a big effort to get new regulations with different approaches developing high quality standards on a worldwide regulatory framework. Currently, DIGEMID is developing new specific regulations for vaccines, blood and plasma derived products, other biological products, batch release, modifications in the sanitary registration for biological products and stability studies for biological products. NOTES:

Regulatory Update from Europe Margarida Menezes Ferreira INFARMED, National Authority of Medicines and Health Products, Portugal NOTES:

NOTES:

Regulation of Biotherapeutic Products: US FDA Perspective Leslie Rivera Rosado CDER, FDA, USA In the U.S., biologic drugs are regulated under provisions of the Food, Drug and Cosmetic (FD&C) Act and the Public Health Service Act (PHS) and are licensed under section 351(a) or 351 (k) of the PHS Act. The Office of Biotechnology Products, as part of FDA’s Center for Drug Evaluation and Research (CDER), Office of Pharmaceutical Quality (OPQ), regulates the product quality aspects of most biologic drugs. OPQ integrates review, inspection, surveillance, policy and research to ensure pharmaceutical quality throughout the product lifecycle. In 2015, in order to better manage the increasing number of biologic drug applications, OBP grew from two divisions, specialized in product quality review of either monoclonal antibodies or other therapeutic proteins, to four divisions. Each of the four new divisions of biotechnology review and research (DBRR) within OBP now manages a diverse portfolio of biotherapeutic products. This presentation will focus on the regulation of biotherapeutic product at the U.S. FDA including an overview of standard and expedited approval pathways and the draft guidance for Industry on Established Conditions. NOTES:

Regulatory Convergence: Recent Trends in the Regulations of

Biotherapeutic Products in Latin America Panel Discussion – Questions and Answers Adriana Hernández Trejo, COFEPRIS, Federal Commission for the Protection from Sanitary Risks, Mexico Margarida Menezes Ferreira, INFARMED, National Authority of Medicines and Health Products, Portugal César Moncayo, ARCSA, National Agency for Regulation and Control Health Surveillance, Ecuador Bernardo Luiz Moraes Moreira, ANVISA, Brasilian Health Surveillance Agency, Brasil Leslie Rivera Rosado, CDER, FDA, USA Edith Roxana Vásquez Alayo, DIGEMID, General Directorate of Medicines, Supplies and Drugs, Peru The following questions will guide the panel discussion:

• In recent years, the EMA and FDA have been focused on ways to maximize the benefit of existing regulatory pathways to facilitate early access to medicines, as per PRIME (PRIority MEdicines) and breakthrough therapies respectively. Could you kindly comment about your (the agencies) experiences as well as the challenges you were faced when evaluating these abbreviately developed products?

• Regarding regulatory convergence, the representative from DIGEMID and COFEPRIS could comment on the Asia Pacific Economic Cooperation (APEC). Regulatory Harmonization Steering Committee (RHSC) has a mandate to work towards achieving regulatory convergence by 2020 among the 21 APEC economies. How this has been progressing (opportunities and challenges) in your countries? Kindly comment also regarding the Centers of Excellence (CoE) related to capacity building.

• PANDRH has been changing their governance including new ways of workings and projects. COFEPRIS could comment about the expectations towards regulatory convergence?

• Thinking of speeding up the regulatory approvals based on reliance of other regulators, ARCSA could comment about the registration of medicines by homologation procedure available in Ecuador?

• Thinking of speeding up the post approval changes review, ANVISA has adopted a 1-week in loco regulatory audit. Could you share with others this initiative and how this has reduced the queue of the petitions under submission?

• One of the expectations in Argentina is the post approval changes guidelines for biotech products. How is the work in ANMAT on this regard and is there any interactions with the discussions going on at WHO and ICH level on this regard considering both organizations are working on post approval changes guidelines for biotech products?

• To all regulators: as biosimilars are coming, how to ensure the traceability in pharmacovigilance among all biologicals once the product is generally prescribed and reported in the Patient File Adverse Event by active substance name only in Public Institution? What is the position of your agency related to the WHO INN Biological Qualifier proposal?

• To all regulators: Which are the 3 highest priorities for your agency in 2016/17?

NOTES:

NOTES:


The Latin American Federation of Pharmaceutical Industry (FIFARMA) is a regional organization which was created on August 4, 1962, and represents eleven Research and Development Pharmaceutical Companies and nine local Trade Associations across the Latin American region. FIFARMA members are involved in the research and development of innovative healthcare products, and provide state of the art healthcare solutions through a variety of products and services aimed to improve and save patients’ lives across the globe, placing patient safety as one of our main objectives. In this effort to improve global health, FIFARMA works closely with intergovernmental bodies, nongovernmental organizations, Latin American health authorities and civil society organizations among others. Currently FIFARMA’s priority topics include issues around biotherapeutic products and their regulations, the sustainability of Latin America’s healthcare systems, policy issues around vaccines as well as transparency and ethics. FIFARMA is happy to contribute to this year’s CASSS LatAm Forum with two sessions. Session one will focus on issues around testing of approved pharmaceutical products on import and during market surveillance while session two will focus on transparency in regulatory decision making on biotherapeutic products. NOTES:


Public Quality Control Testing of Pharmaceutical Products Session Chairs: Gustavo Grampp, Amgen Inc. and Janett Mugaburu-Richards, Pfizer, Inc. To date, many health authorities throughout the world have implemented procedures to enhance product quality and safety that include testing of approved pharmaceutical products performed locally (inclusive of biotherapeutic products). This testing is also referred to as “quality control testing” and depending on the country, it can cover registration testing, import testing or surveillance testing. While public quality control testing may have been needed in the past, it can pose unique burdens to manufacturers and public test laboratories. Sponsors need to address different requirements from each country depending on the level of testing required and additional support is often required from the sponsor to enable public laboratory testing, especially for biotherapeutics (e.g., specialized equipment, training, and reagents). Also, test procedures and acceptance criteria for public testing are often linked to pharmacopeia standards, but in many cases monographs do not exist for a given product or may not be sufficient to ensure quality of complex products such as biotherapeutics. NOTES:

Short Biographies

Iván Valentin Cruz Barrera COFEPRIS, Federal Commission for the Protection from Sanitary Risks, Mexico Iván Valentin Cruz Barrera has more than twelve years of pharmaceutical industry experience in quality control, warehouse and production areas. In his current position as a manager of drugs and medicines at COFEPRIS he is responsible for assessing procedures for the following: license to manufacture granted on the basis of demonstrated compliance with good manufacturing practices, license to warehouse granted on the basis of demonstrated compliance with good distribution practices and lot release for biological products. Gustavo Grampp Amgen Inc., USA Dr. Grampp is an executive director of global operations at Amgen Inc. where he leads technical operations strategy for a therapeutic area franchise. Previous to this role, he was director of regulatory policy and lead external affairs related to biosimilars in Latin America and other regions. In this capacity, he has given invited presentations and authored peer reviewed publications concerning regulatory standards, pharmacovigilance, and manufacturing challenges for biotherapeutics. Before his engagement on biosimilars, Dr. Grampp led functional and cross functional teams in process development and product quality responsible for development and quality oversight of Amgen’s biologics manufacturing processes. Dr. Grampp earned his bachelor’s degree in chemical engineering at the University of Wisconsin and a PhD in chemical engineering from the Massachusetts Institute of Technology. Maria Guazzaroni Jacobs Pfizer, Inc., USA (on behalf of IFPMA) Maria Guazzaroni Jacobs has more than 30 years of pharmaceutical industry experience mainly in quality, both in Argentina and the U.S. She has been with Pfizer, Inc. since 1991 where she managed analytical laboratories, including the quality control laboratories, and was the Brooklyn site quality operations director, prior to assuming a center position. In her current capacity, she is responsible for developing strategies to address emerging regulations and guidance documents in the areas of GMPs and pre- and post-approval filings (Chemistry Manufacturing and Control, CMC), and assisting in development of company positions and responses to proposed regulations and guidances. Her focus is mainly US and Latin America. She holds a degree in pharmacy from the University of Buenos Aires, Argentina, and a PhD in organic chemistry from New York University.

Short Biographies continued

Rafael Hernández Medina Pharmacopeia of the United Mexican States, Mexico Rafael Hernández Medina is a pharmaceutical chemist who is part of the technical organization that normalizes the health products in Mexico. He has worked for the Mexican Pharmacopoeia as the internal coordinator of the biotechnological committee and others committees inside the institution since 1999. Additionally, he has served as the publications manager since 2005, contributing to the editing and revision of the entire publication. He is also in charge of training for the users of the Mexican Pharmacopeia. Rafael has been a professor at the National Institute of Public Health and at the National Autonomous University of Mexico with the item technical standards and sanitary regulations. He is also a member of the National College of Pharmacists Biologists and Chemists of Mexico. Janett Mugaburu-Richards Pfizer, Inc., USA Janett Mugaburu-Richards is a senior manager of global CMC and the biotherapeutic LATAM region liaison at Pfizer Inc. Janett has more than 15 years of pharmaceutical industry experience and has managed CMC (Chemistry, Manufacturing and Controls) regulatory strategy and preparation of regulatory CMC submissions for a diverse number of products, including innovative biologics and biosimilars. In her current capacity, she is also responsible for developing CMC strategies to address LATAM emerging regulations and guidance documents covering product development, registration and post-approval changes. Janett earned her bachelor’s degree in biology at Central Connecticut State University and an MS in health sciences from Quinnipiac University. Teresa de Jesus Olivo Rosales Eli Lilly y Compañia de Mexico S.A. de C.V., Mexico Teresa Olivo received a bachelor’s degree in pharmaceutics from the Universidad Nacional Autónoma de San Luis Potosi and a master´s degree in toxicology from the CINVESTAV of the Instituto Politécnico Nacional in Mexico City. Teresa has a solid background in regulatory affairs, pharmacovigilance, quality control and quality assurance with key performance skills such as leadership, self-management, motivation, planning, organization, coaching, results oriented and multicultural environment managements. Teresa has more than 20 years of experience working for the pharmaceutical industry and 18 years working for Eli Lilly in different areas. She started as microlab analyst and later as quality control supervisor. In 2000 she was moved to Indianapolis, Indiana as project leader in Eli Lilly and Company where she was responsible for developing a regulatory strategy to harmonize the insulin process in the Latin American countries. In 2010, she joined the medical division in Eli Lilly as regulatory associated director, developing regulatory and medical strategies for diverse new chemical entities. In 2012, the pharmacovigilance (PV) area became part of her supervision.


In this capacity, Teresa was responsible for reinforcing the PV culture, alignment to the company policies and PV regulations. Teresa has an active participation in the development of new regulations through the working groups from the trade associations and from the Mexican Health Authority. She participated in the discussions to implement the Mexican normativity for biocomparables / biosimilars products as part of the industry. Sonia Mayra Pérez Tapia UDIMEB, Mexico


Introduction – Private vs. Public Quality Control Gustavo Grampp Amgen Inc., USA (on behalf of FIFARMA)

Opportunities for Improved Access to Safe and Efficient Medicines Maria Guazzaroni Jacobs Pfizer, Inc., USA (on behalf of IFPMA) To help ensure drug product quality and safety, health authorities in many countries have implemented, or are considering implementing, quality control (QC) testing requirements for pharmaceuticals, biological/biotechnology, and/or vaccine products entering their countries—also referred to as import testing. A survey was conducted within the International Federation of Pharmaceutical Manufacturers & Associations (IFPMA) to analyze data on import testing, other categories of re-testing (e.g., post-marketing surveillance), and applied waiver types. The findings suggest that import testing does not add significant quality or safety benefits to patients, provided that the products are uninterruptedly controlled according to the globally harmonized manufacturing, distribution, and storage standards (GMP, GDP, GSP). In fact, it was observed that import testing could potentially increase risks to the patient by causing delay in the supply chain and other complexities. Historically, such testing requirements may have been necessary to prevent the distribution of unsafe or nonconforming drug product. However, laws, regulations, and regulatory oversight have changed significantly. Today, the pharmaceutical, vaccine, and biotechnology industries have developed and implemented robust quality management systems to ensure the identity, safety, purity and potency of its drug products throughout its manufacture and international distribution channels, thereby eliminating the need for this redundant testing. NOTES:

Local Re-testing – The Regulator’s Perspective Iván Valentin Cruz Barrera COFEPRIS, Federal Commission for the Protection from Sanitary Risks, Mexico To import and distribute drug products in Mexico, is required to have a Marketing Authorization approved by COFEPRIS, also holders of this Marketing Authorization must have adequate facilities for the safe operation, a department of pharmacovigilance and a department quality control to ensure the identity, safety, purity and potency of drugs product. There are legal basis for quality control of medicines, biologics / biotechnology as well as for vaccines described in the General Health Law, Regulation of Health Products and in the Official Mexican Standard NOM-059-SSA1-2015 Good Manufacturing Practices of medicines. NOTES:

The Mexican Pharmacopeia (FEUM) as Standard of Pharmaceutical Products Rafael Hernández Medina Pharmacopeia of the United Mexican States, Mexico As a regulatory tool, The Mexican Pharmacopeia (FEUM) in Mexico order the specifications for identity, purity and quality which must have a drug to be safe, compliance consequently it is a mandatory requirement for obtaining health registration from the COFEPRIS. To FEUM, the upgrade process is permanent and it affect all the major players in the pharmaceutical sciences: academy, authorities, associations and professional associations, also it has an inclusive process in which all stakeholders can provide content and issue comments to the monographs in process. In contrast with the past, nowadays it has increased the communication between the agency who is responsible for updating the FEUM and the drug manufacturer, as well as quality control laboratories, allowing functional monographs in accordance with the needs of the national pharmaceutical market. This interaction is essential in order to achieve a comprehensive regulatory framework for safe and effective medicines for the benefit of the population. NOTES:


Public Quality Control Testing of Pharmaceutical Products Workshop Session One

Panel Discussion – Questions and Answers Iván Valentin Cruz Barrera, COFEPRIS, Federal Commission for the Protection from Sanitary Risks, Mexico Maria Guazzaroni Jacobs, Pfizer, Inc., USA (on behalf of IFPMA) Rafael Hernández Medina, Pharmacopeia of the United Mexican States, Mexico Teresa de Jesus Olivo Rosales, Eli Lilly y Compañia de Mexico S.A. de C.V., Mexico Sonia Mayra Pérez Tapia, UDIMEB, Mexico The following questions will guide the panel discussion: This session will explore the rationale and role of public quality control testing.

• Is import testing redundant in the context of modern pharmaceutical quality systems? • Are pharmacopeia monographs well suited to quality control and surveillance of complex

products such as biotherapeutics? • Are there more efficient mechanisms than quality surveillance testing to ensure the quality and

safety of distributed pharmaceuticals? NOTES:

NOTES:


Transparency of Regulatory Decision Making Session Chairs: Silvia Moscoso, AbbVie S.A. and Maria Cristina Mota, AbbVie, Inc. It is in the general interest of patients, physicians, healthcare workers, producers and providers that there is a high level of public trust and confidence in the approved medical products. Developing and maintaining trust in approved medical products depends amongst other factors, on transparently developed regulations, and on their product specific application. Transparency is an important principle of good regulatory practice and as such any regulatory agency should be as open and transparent as possible about its working processes and how it comes to decisions. Regulatory agencies in Latin America are aware of this demand and are more actively involved in efforts how to increase transparency in the regulatory decision-making processes. Some of them like ANVISA or INVIMA publish already “Summary of Decision Documents” when approving and/or rejecting biosimilar/pharmaceutical products. Also the recently launched initiative from the International Pharmaceutical Regulators Forum (IPRF) on the publication of Public Assessment Summary Information for Biosimilar (PASIB) is highly valuable and properly implemented by regulatory agencies will significantly contribute to achieving transparency and ultimately trust with all stakeholders. The session will focus on transparency in the regulatory decision-making process with the view of regulators and industry on the initiatives that are being implemented worldwide. NOTES:

Short Biographies

Margarida Menezes Ferreira INFARMED, National Authority of Medicines and Health Products, Portugal Iván González Del Valle COFEPRIS, Federal Commission for the Protection from Sanitary Risks, Mexico Alberto Miguel Guzmán COFEPRIS, Federal Commission for the Protection from Sanitary Risks, Mexico Carlos Lizardi COFEPRIS, Federal Commission for the Protection from Sanitary Risks, Mexico Bernardo Luiz Moraes Moreira ANVISA, Brasilian Health Surveillance Agency, Brasil Silvia Moscoso AbbVie S.A. Maria Cristina Mota Pina AbbVie, Inc. Cristina is currently a director at AbbVie Inc. where she coordinates regulatory policy and intelligence activities for Latin America. Cristina worked for Boehringer Ingelheim for 13 years in different roles including quality, validation and regulatory affairs. Cristina attended Universidad Nacional Autonóma de Mexico where she got her pharmacy degree and a masters degree in industrial administration. Thomas Schreitmüller F. Hoffmann-La Roche Ltd., Switzerland (on behalf of FIFARMA) Dr. Thomas Schreitmüller holds a diploma and PhD in biochemistry from the University of Munich (Max Planck Institute for Biochemistry, Munich, Martinsried and Institute for Clinical Chemistry and Clinical Biochemistry University of Munich). In 1989, he joined Roche, holding various positions in the biotech area (e.g. analytical R&D, technical project management). Since 2003, Thomas was head of the department "Analytical R&D and Quality Control Biotech Products" at Roche Pharma Technical Operations in Basel, Switzerland. As of 2010, Thomas was the global lead for international regulatory policy for biologics within Roche’s regulatory policy group at Roche Pharma Technical Operations leading and coordinating the development of Roche positions on regulatory policy topics related to biotheapeutic and similar biotherapeutic products. Since 2015, Thomas is the head of regulatory policy group at Roche Pharma Technical Operations leading and coordinating Roche’s regulatory policy activities.


Alexis Serlin CANIFARMA, Mexico Alexis Serlin is CPO & country head at Novartis Mexico since August 2012. He leads the business strategy of Novartis’ operations, including direction of four business units and the management of over 1,200 associates all around the country. Serlin has had an outstanding career for more than a decade within Novartis Mexico. At this point, he has won numerous global awards due to the business performance he has been able to deliver. He has also held key positions at Novartis development in Latin America, working for pharmaceuticals’ subsidiaries in Brazil, Colombia, Mexico and his native Argentina. Before being CPO head at Mexico, he served as general manager at Novartis in the west of China from 2010 to 2012. Before joining the Novartis team, Alexis Serlin worked for five years at Procter & Gamble and at Banco Frances del Rio de la Plata. Alexis Serlin is fluent in Spanish and English. He holds an economics degree from the University of Buenos Aires and has completed different courses in leadership, management, marketing, sales and business.


Transparency in Regulatory Decision Making – The Brasilian Way Bernardo Luiz Moraes Moreira ANVISA, Brasilian Health Surveillance Agency, Brasil NOTES:

NOTES:

Transparency Policies in the EU from Clinical Trials to Pharmacovigilance Margarida Menezes Ferreira INFARMED, National Authority of Medicines and Health Products, Portugal NOTES:

NOTES:

Transparency in Regulatory Decision Making on the Approval for Biosimilar Products – The FIFARMA Position Thomas Schreitmüller F. Hoffmann-La Roche Ltd., Switzerland (on behalf of FIFARMA) NOTES:


Transparency of Regulatory Decision Making Workshop Session Two

Panel Discussion – Questions and Answers Margarida Menezes Ferreira, INFARMED, National Authority of Medicines and Health Products, Portugal Iván González Del Valle, COFEPRIS, Federal Commission for the Protection from Sanitary Risks, Mexico Alberto Miguel Guzmán, COFEPRIS, Federal Commission for the Protection from Sanitary Risks, Mexico Carlos Lizardi, COFEPRIS, Federal Commission for the Protection from Sanitary Risks, Mexico Bernardo Luiz Moraes Moreira, ANVISA, Brasilian Health Surveillance Agency, Brasil Thomas Schreitmüller, F. Hoffmann-La Roche Ltd., Switzerland (on behalf of FIFARMA) Alexis Serlin, CANIFARMA, Mexico The following questions will guide the panel discussion: This session will explore how is the topic transparency evolving worldwide and particularly in the Latin America region.

• Why are biosimilars raising the bar of transparency on the decision-making process? • How are the regulators addressing this topic? • What are the benefits of an increased transparency worldwide?

NOTES:

NOTES:

Lifecycle Management Part One: Control Strategy and

Setting Specifications Session Chairs: Carmilia Jiménez Ramirez, Gilead Sciences and Jaime Uribe Wiechers, Probiomed S.A. de C.V. The main goal of establishing a control strategy for manufacturing biologics is to ensure consistent process performance and consistent product quality. A solid control strategy is developed by combining multiple elements such as, but not limited to:

• A thorough understanding of the biophysical/biochemical properties of the molecule • Establishing defined manufacturing conditions • Controlling raw material inputs, physicochemical environment and critical process parameters • Executing adequate in process testing controls, as needed, throughout the progression of

manufacturing • Ensuring the output of the process results in desired product quality attributes within

specification limits There are multiple approaches to establishing a robust control strategy. The most common approach is a conservative one, whereby every aspect of the manufacturing process and final product quality attributes are evaluated against specified limits. Less conservative approaches have been successfully implemented by incorporating risk assessment and Quality-by-Design principles, leading to a design space defined by proven acceptable ranges for critical process parameters. New expectations of regulatory agencies, for example COFEPRIS, are pointing towards the requirement of continuous process verification. Therefore, new process development strategies should take into account that traditional control strategy approaches, based on limited process data, may not be sufficient. Quality-by-Design (ICH Q8 and ICH Q11) backed by design of experiment data should be given consideration early in process development. For follow-on products such as biosimilars, where a pre-defined target of quality attributes, in addition to CQAs, must be attained are in greater need of a solid scientific approach in constructing a robust control strategy. Establishing and maintaining appropriate specifications is both a regulatory expectation and critical to any control strategy. Per ICH Q6B, Specifications: Test Procedures and Acceptance Criteria for Biotechnological/Biological Products, a specification is defined as a “list of tests, references to analytical procedures, and appropriate acceptance criteria which are numerical limits, ranges, or other criteria for the tests described”. Specifications ensure a bulk drug substance or drug product meet quality standards for the drug’s intended purpose. A specification includes a list of general and product/process specific quality attributes, appropriate testing methodologies with acceptance criteria that address the physiochemical, biological, immunochemical, purity and strength of the product. Acceptance ranges, limits or other criteria are established from early bioanalytical development data and manufacturing knowledge. As knowledge is gained from process capability, understanding of product stability and clinical experience, early specification ranges may be re-assessed and adjusted, if warranted. NOTES:

Short Biographies

Carmilia Jiménez Ramirez Gilead Sciences Dr. Carmilia Jiménez Ramírez is a senior research scientist at Gilead Sciences, analytical operations biologics division. Her team is tasked with life cycle management of analytical control systems from early clinical stages through commercialization. Additionally, her team is in charge of authorship and developing strategies for analytical sections in regulatory submissions. She has previously held various scientific positions at Merck and Amgen within quality control and analytical development departments managing biologics programs for oncology, hematology, rheumatology and renal disease indications. She received a bachelor's degree in biology and premedical sciences from the University of Puerto Rico, Mayagüez Campus, a doctorate degree in microbiology and immunology from Temple University School of Medicine, Philadelphia, Pennsylvania, and has conducted research as a postdoctoral fellow at St. Jude Children's Research Hospital, Memphis, Tennessee. Francisco Kuri Breña Landsteiner Scientific Dr. Francisco Kuri Breña is currently the director of new developments at Landsteiner Scientific. He has worked in the development of new synthetic and biotechnological products, as well as projects of genomic medicine at Landsteiner Scientific since 2013. He is the coordinator of the Committee of Biotechnological Products of the Standing Committee of the Pharmacopoeia of the United Mexican States. Francisco is a member of the expert committee on biotechnology for national health regulations at the Federal Commission for the Protection Against Sanitary Risk (COFEPRIS), a founding member of the Chemical Society of Mexico and section morelos and industry committee of the Mexican Socity of Bioengineering and Biotechnology. Francisco Kuri Breña has a bachelor’s degree in chemistry and a master’s degree in organic chemistry from the National Autonóma University of Mexico. He holds a doctor of philosophy degree from the University of British Columbia in Vancouver, Canada, doing research in organic syntheses and biotechnology. Lázaro Morales Reyes COFEPRIS, Federal Commission for the Protection from Sanitary Risks Lázaro Morales Reyes has a degree in statistics from the Universidad Autónoma Chapingo as well as a masters of science in applied statistics from the Colegio de Postgraduados. As part of his work experience he has been a professor of statistics and mathematics in upper secondary education and a professor of statistics in graduate level clinical monitoring at the chemistry department of UNAM. He currently serves as the in the statistical director for the Federal Commission for the Protection against Sanitary Risk (COFEPRIS), in the areas of protocols bioequivalence, new molecules, biotech drugs and records.


Néstor Octavio Pérez Ramirez Probiomed S.A. de C.V. Dr. Nestor O. Pérez was born in the state of Oaxaca, Mexico. In 1995 he obtained a degree in chemist-bacteriologist-parasitologist from the National Polytechnic Institute where he also obtained a master of science degree with specialty in microbiology in 1998 and a PhD in 2001, both with honorific mention. He also obtained and MBA from the IPADE in 2016. He made research stays at several centers, including The National Institute of Epidemiological Diagnosis and Reference (INDRE), the Center for Research in Biological Nitrogen Fixation, el CINVESTAV-Irapuato and UCLA in the United States. From 2003 to 2005, he made a postdoctoral stay at the center for Disease Control and Prevention of USA (CDC) in Atlanta, Georgia, working in a project to develop vaccines against the hepatitis virus. Dr. Perez joined the first Mexican biopharmaceutical, Probiomed. This company has been a key player in the development of the first biopharmaceuticals in the country whose end users are patients with diabetes, cancer, multiple sclerosis and other chronic disease, which has direct impact on the economy of millions of Mexican families and the public health sector. Dr. Pérez has coordinated the development of biotech drugs. The technology used for manufacturing has been developed by national experts led by Dr. Pérez, from gene to drug product. Their efforts to provide the nation with solid knowledge have resulted in access of the population to biotech drugs improving the quality of life of Mexicans. Dr. Pérez has also maintained close collaboration with the Academy and has been director of six bachelors, two masters and two PhD theses. He has coauthored more than 40 papers and book chapters. His works have more than 300 citations. He has been awarded a patent by the IMPI. He belongs to the National System of Researchers Level I, is Member of the Mexican Academy of Sciences and was awarded with the Prize for Science and Technology of the State of Mexico 2013. Patrick Swann Biogen Dr. Patrick Swann joined Biogen in 2013 and is currently responsible for CMC regulatory strategy for Biogen’s development program portfolio. Dr. Swann joined Biogen after 15 years at US FDA where he was the deputy director of the division of monoclonal antibodies and also served as the biotechnology product representative for FDA on ICH Q11. Work is presented that was developed when Dr. Swann lead the analytical development group at Biogen. Pertinent to his presentation at the CMC Strategy Forum, he has authored or co-authored several publications on analytical methods and biotechnology product development and manufacture.


Cecilia Tami CDER, FDA Dr. Maria Cecilia Tami received an MS in biology and a PhD in the field of molecular virology from University of Buenos Aires, Argentina. Dr. Tami joined the FDA as a post-doctoral fellow at the division of emerging and transfusion transmitted diseases, CBER/FDA and then became a product quality reviewer in the office of biotechnology products in CDER/FDA. She is currently a product quality team leader in the division of biotechnology review and research 3, in the office of biotechnology products at the FDA. Mauricio Trujillo Roldán Universidad Nacional Autónoma de Mexico, Mexico Dr. Mauricio Trujillo Roldán has a doctorate in biochemical sciences and is a researcher and director of the bioprocess unit in the Institute of Biomedical Research, at the National Autonomous University of Mexico. His main research interests are focused on bioprocess engineering, particularly in aspects related to the phenomena of mass and momentum transfer in culture processes and scaling to industrial level. In his research group the production of recombinant proteins, polymers and metabolites of high added value in animal cell, bacteria and fungi cultures have been studied. Now, his studies have been based on the development of processes of bacterial cultures and scaling for commercial production of biofertilizers, and the production of biopharmaceuticals with high added value in cell cultures of high cell density, and their improvement, and as in the production of recombinant antigens for the production of new vaccines and new ways of diagnosing diseases such as tuberculosis. Dr. Trujillo Roldán is the author of 22 international articles in high impact journals and thirteen articles in national magazines. Moreover, Dr. Trujillo Roldán is the author of five technological developments, which have been transferred and are used by companies sponsoring these developments. He has directed one PhD thesis, six MS theses and sixteen bachelor’s theses. He currently leads two bachelor’s theses, five MS theses and four PhD theses. Jaime Uribe Wiechers Probiomed S.A. de C.V. With professional experience of over 22 years in the pharmaceutical industry, Jaime M. Uribe Wiechers has worked throughout his career in multiple roles in areas such as finance, information technology, quality, manufacturing and R&D of biopharmaceutical products. Since July 2016 he holds the position of CEO at Probiomed, the leading biopharmaceutical company in Mexico. Jaime has a degree in industrial engineering (UIA) and postgraduate studies in business management (IPADE) and industrial biotechnology (UAEM). He has published several scientific papers, presented at numerous conferences and collaborated with diverse conference presentations regarding biotechnology, quality and innovation in Mexico and internationally.


Statistical Control of Manufacturing a Biotechnological Drug Lázaro Morales Reyes COFEPRIS, Federal Commission for the Protection from Sanitary Risks, Mexico As we know, there is an intrinsic variability of the processes involved in the production of a biotechnological drug, so there is the need to establish a strategy to control the manufacturing process of these drugs through the monitoring and analysis of critical parameters process and critical quality attributes. A set of statistical tools to evaluate the statistical process control and product is presented as a proposal. This proposal includes an analysis through control charts, trend analysis and analysis of process capability (Cpk). This presentation is intended to provide guidance on what information must be reported annually from the date of issuance of the registration of an innovative biotechnological drug and for biosimilar biotechnological drug, during the lifecycle of the drug, according to the established in the numerals 6.1, 6.1.1, 6.1.2, 6.1.3, 6.1.4, 6.1.5 and 6.1.6 of Mexican Official Standard NOM-257-SSA1-2014, in terms of biotechnological drugs. NOTES:

The Role of Analytics in the Development of Advanced Process Controls Patrick Swann Biogen, USA Development and implementation of process analytical technology (PAT) and real-time release testing (RTRT) requires an approach to product development that emphasizes product and process understanding and process control, based on sound science and quality risk management (i.e., Quality-by-Design). Newer analytical approaches can be leveraged to improve product understanding and this improved product understanding can enable effective and more efficient control strategies. NOTES:

Setting Specifications: From QbD to Continuous Process Verification Néstor Octavio Pérez Ramirez Probiomed S.A. de C.V., Mexico The scientific rationale for setting specifications, both process and product has evolved in recent times. The proposal of QbD by the ICH has unified the basis for the industry in the use of the scientific approach to enhance the robustness of the process, support the validation process and simplify the process of setting process related specifications. The aim of this talk is to share a case study in the implementation of the design space for process conditions that support three important CQA’s, related to process and product related contaminants. The purification process of recombinant proteins in general, and monoclonal antibodies in particular, require the removal of unwanted impurities and contaminants. On this work we determine the design space for a multimodal chromatography with the target of removal of process and product related contaminants. Removal of host cell proteins (from upstream), protein A ligand (from capture chromatography), as well as the removal of dimers and aggregates (product related contaminants). Our study is based on design of experiments methodology. Here we propose the use of this powerful methodology in two steps. The first one is called optimization; on this step the best process conditions for the removal of contaminants were determined by response surface methodology using a face-centered cubic model with three variables. This optimization improves the recovery of the product. In the second step, the process robustness was evaluated and a design space was determined for the control of the process using a full factorial design 32 (two variables, three levels). This design space describes permitted process conditions (pH and conductivity) where the desired level of contaminant removal is met, thus scientifically justifying the Critical Process Parameters required for the reproducibility of the process. The process capacity (CpK) was determined using proper statistical algorithms. Continuous process verification, according to EMA/CHMP/CVMP/QWP/BWP/70278/2012-Rev1, is a scientific and risk based real time approach to verify and demonstrate that a process that operates within the predefined specified parameters consistently produces material which meets all its critical quality attributes (CQAs) and control strategy requirements. We propose that QbD and design of experiments are a valid scientific approach to enable continuous process verification. NOTES:

Lifecycle Management Part One: Control Strategy and

Setting Specifications Workshop Session Three

Panel Discussion - Questions and Answers Francisco Kuri Breña, Landsteiner Scientific, Mexico Lázaro Morales Reyes, COFEPRIS, Federal Commission for the Protection from Sanitary Risks, Mexico Néstor Octavio Pérez Ramirez, Probiomed S.A. de C.V., Mexico Patrick Swann, Biogen, USA Cecilia Tami, CDER, FDA, USA Mauricio Trujillo Roldán, Universidad Nacional Autónoma de Mexico, Mexico The following questions will guide the panel discussion:

• Describe best practices to establish control strategies and set appropriate specifications for early clinical stages versus late clinical stages.

• What are the differences in establishing control strategies between an innovator drug, for early clinical stages and a follow-on product, for example, a biosimilar?

• When is the right time, and what is the best way, if necessary, to revise an established control strategy?

• What is the best approach to justify exclusion of routine monitoring of a CQA for product release, if the manufacturing process has demonstrated control of the quality attribute?

NOTES:

NOTES:

Lifecycle Management Part Two: Risk Management and

Established Conditions Session Chairs: Joseph Kutza, MedImmune, A member of the AstraZeneca Group and Nadine Ritter, Global Biotech Experts, LLC Although the ICH Q8, Q9, Q10 and Q11 guidelines introduce opportunities for more science and risk-based approach for assessing changes through the lifecycle of products, post-approval ‘operational flexibility’ has yet to be achieved. To tackle this issue, work on the ICH quality topic Q12, Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management, was initiated in November 2014. The draft guideline introduces the concept of Established Conditions (ECs) within the dossier that would delineate the compliance information intended for lifecycle maintenance from other informational content required for initial approval. This session will consist of presentations focused on the current status of Q12 discussions and industry case studies highlighting the integration of quality risk management into lifecycle management. NOTES:

Short Biographies

Ricardo Castro Acosta Universidad Nacional Autónoma de Mexico Dr. Ricardo M. Castro Acosta is the current chief operating officer of LAMMB (National Laboratory for the Production and Analysis of Biotechnological Drugs and Molecules). He obtained the degree of MSc and PhD in biochemical sciences at the Instituto de Biotecnología of UNAM in 2009 and 2014, respectively. He is a current member of two committees at COFEPRIS: the Subcomité de Evaluación de Productos Biotecnológicos (SEPB) and Comité de Moléculas Nuevas (CMN). He belongs to the National Research System, Level 1 from 2015, has five research publications in international indexed journals and more than fifteen national and international presentations in meetings and conferences. He has been an invited speaker of the academic topic of biochemical engineering at Instituto de Investigaciones Biomédicas (IIB) of UNAM from 2009. Dr. Ricardo has strong bioprocessing skills, including upstream and downstream processes as well as experience in development of analytical methods, including capillary electrophoresis, high performance and ultra-performance liquid chromatography, mass spectrometry, spectroscopic and fluorimetric analysis. Also, he has experience in recombinant proteins production using the insect cells-baculovirus expressing vector system, including baculovirus expansion, virus titration, insect cell culture and infection, as well as extended experience in biochemical analyses of proteins and virus like particles focusing in protein quality and process development. He is an expert in production of virus like particles, purification and assembly. Renan Araujo Gois ANVISA, Brasilian Health Survillance Agency Renan Gois is a pharmacist who graduated in 2007 from UFRN. He has worked at ANVISA, the Brazilian Health Regulatory Agency, as a health regulation expert in the Office of Evaluation of Post Approval Changes of Small Molecules (GEPRE) since 2014. As part of his responsibilities, he integrates ANVISA’s group that discusses the development of ICH Q12 guidelines. Joseph Kutza MedImmune, A member of the AstraZeneca Group Dr. Joseph Kutza joined MedImmune in February 2007 and is currently a director and group manager in the regulatory affairs - CMC group. His focus in on post-approval lifecycle management of CMC changes for monoclonal antibody and vaccine products. His group is also responsible for providing regulatory support to biologics manufacturing and testing sites throughout the AstraZeneca network. Dr. Kutza is active in several professional societies and has served on multiple USP expert panels. Before joining MedImmune, Dr. Kutza worked at the US FDA for more than eleven years. As a product reviewer and team leader in the regulatory science and policy branch of the division of monoclonal antibodies he was responsible for product review of INDs, BLAs, and related amendments and supplements for monoclonal antibody products, development of agency-wide regulatory policy, and regularly participating in both pre-approval and biennial GMP inspections as a product specialist.


Mic McGoldrick Merck Sharp & Dohme Mic McGoldrick has worked for the last 28 years in the health care industry, with the last 15 years in vaccine regulatory and regulatory policy. During his work in regulatory, he has filed clinical trial applications, post-approval variations with a wide variety of complexity and has filed several new product applications worldwide. His current role is in evaluating guidances worldwide to provide comments back to agencies, impact to our company and for advocating regulatory policy. Mic has degrees in chemistry, microbiology and medical technology. Janett Mugaburu-Richards Pfizer, Inc. Janett Mugaburu-Richards is a senior manager of global CMC and the biotherapeutic LATAM region liaison at Pfizer Inc. Janett has more than 15 years of pharmaceutical industry experience and has managed CMC (Chemistry, Manufacturing and Controls) regulatory strategy and preparation of regulatory CMC submissions for a diverse number of products, including innovative biologics and biosimilars. In her current capacity, she is also responsible for developing CMC strategies to address LATAM emerging regulations and guidance documents covering product development, registration and post-approval changes. Janett earned her bachelor’s degree in biology at Central Connecticut State University and an MS in health sciences from Quinnipiac University. Wassim Nashabeh F. Hoffmann-La Roche Ltd. Dr. Wassim Nashabeh received his PhD in analytical chemistry from Oklahoma State University in 1993, and his post-doctoral fellowship in bioanaytical chemistry from The Barnett Institute at Northeastern University. Following a two-year research appointment at PerSeptive Biosystems, Wassim joined Genentech (A member of the Roche Group) in 1996 as a scientist and has since held several positions of increasing responsibilities including associate director of the methods validation group, director quality control, director in the CMC regulatory affairs group, senior director of CMC policy & strategy, global head of technical regulatory policy for the Roche Pharma Medicines Group and most recently as the global head of policy and international operations in PTR. His current responsibilities include development and advocacy of Roche key external positions and policies with global health authorities, industry associations and scientific organizations, as well as management of Roche technical regulatory international operations. Kavita Ramalingam Iyer Merck & Co., Inc. Dr. Kavita Ramalingam Iyer is a product lead within Global Regulatory Affairs Commercialization and Safety (GRACS) Organization leading multiple programs and product portfolios including novel mRNA therapy and combination products that cover investigational and commercial space across vaccines and biologics. Kavita has more than eight years of pharmaceutical industry experience leading vaccines


manufacturing, process development, establishment of GMP facilities, technology transfer, talent development and strategic initiatives and performed site audits. She is a certified lean six sigma black belt and has championed significant process improvements through employment of Kaizen, six sigma and lean principles. In her current role as a regulatory professional, Kavita is responsible for managing diverse and multiple product dossier life cycles; developing, shaping and implementing CMC regulatory strategies in compliance with global regulations, developing regulatory documentation to support worldwide registration, lead regulatory CMC representative on matrix teams and mentors early development and cross-functional teams. She also serves as a Merck Regulatory CMC representative in the industry form called BioPhorum Operations Group (BPOG); has given several conference talks and published multiple position papers in collaboration with industry experts addressing emerging regulations and guidance documents covering product development, registration and post-approval changes. She was one of the BPOG delegates who recently interacted with ANVISA and presented on complexity and impact of post approval changes. Kavita graduated with a PhD in biotechnology from Anna University, India and pursued here post-doctoral research at University of Minnesota focusing on antibody engineering and synthetic biology prior to joining Merck. Nadine Ritter Global Biotech Experts, LLC Dr. Nadine Ritter has been a protein scientist for over 30 years. She received her BS in biology/chemistry from the University of Houston, Clear Lake in 1984, and her MA and PhD in cell and molecular biology from Rice University in 1988, followed by a NIH postdoctoral project at the University of Texas, Houston in protein biochemistry. In 1992 she joined the biotech industry as a senior scientist at Abbott Laboratories. There, she engaged in the development, validation, tech transfer and troubleshooting of protein analytical methods for a wide variety of proteins and peptides. In 1998 she became director of analytical services at one of the first biotech CROs, BioReliance, where she managed contract R&D, GLP and cGMP laboratory operations and CMC analytical and stability studies for biotech products. In 2004, she became a senior CMC analytical consultant at Biologics Consulting Group, continuing to provide expert input to numerous product submissions and laboratory compliance operations around the world. In 2014, she launched Global Biotech Experts, a technical, regulatory and quality consultancy for product characterization, comparability, release and stability testing with expertise in standard and state-of-the-art physio-chemical and functional methods of analysis. Since 1999, Nadine has been a highly popular public and internal trainer in CMC analytical science and laboratory compliance for biotech products. She currently serves as chair of the scientific advisory board and guest instructor for the University of Maryland Baltimore County Biotechnology Graduate Program. She is on the board of directors of several professional organizations and industry journals, and has numerous publications on biotechnology analytical methods and laboratory quality practices. Nadine is frequently invited around the world to speak and write on biotechnology product development and commercialization issues, and compliance requirements for testing laboratories.


Leslie Rivera Rosado CDER, FDA Dr. Leslie Rivera Rosado is a senior regulatory scientist officer in the office of biotechnology products (OBP) at FDA’s Center for Drug Evaluation and Research (CDER) and a lieutenant in the U.S. Public Health Service Commissioned Corps. Her primary responsibilities as a product quality reviewer include the review of the chemistry, manufacture, and control (CMC) information submitted with investigational new drug and biologics licensing applications and related amendments and supplements and participating in pre-license and pre-approval inspections. Dr. Rivera Rosado earned a PhD degree in biochemistry, cellular, and molecular biology from the Johns Hopkins University School of Medicine in Baltimore, MD. She completed a three-year post-doctoral training program and was an Interagency Oncology Task Force (IOTF) fellow at the FDA prior to joining the review staff.


Reducing the Complexity and Impact of Regulatory Changes in Latin America Janett Mugaburu-Richards1; Kavita Ramalingam Iyer2 1Pfizer, Inc., USA (on behalf of the BioPhorum Operations Group (BPOG), United Kingdom); 2Merck Co., Inc., USA (on behalf of the BioPhorum Operations Group (BPOG), United Kingdom) The management of post approval changes for biologics and vaccines has become significantly challenging from a global perspective considering the complexity of supply chain and the diversity of regulatory expectations. While thorough regulatory review of Chemistry, Manufacturing and Controls (CMC) information is critical to ensure the safety, quality and efficacy, patients’ quick access to the products is hindered by sub-optimal collaboration among regulators, lack of harmonization in the regulatory requirements and extensive review times. Companies race to launch products to patients as soon as possible after clinical efficacy is demonstrated and often in post approval phase, changes such as increased batch sizes and new manufacturing facilities are needed to expand patient access. During the product life cycle, additional changes to improve product quality or process robustness are inevitable as companies gain experience in commercial manufacture. Benchmarking industry experience, currently the dossier approval timelines in Latin America region can range from 6 – 30 months. Thus, the primary challenges faced for filing of post approval changes in the Latin America region are tremendous variability in review and approval times coupled with diverse regulatory requirements in the individual markets across the region. The same core data and information supporting the post approval change may be reviewed repetitively by multiple individual regulatory bodies following unpredictable timelines. This results in a dramatic increase for potential for errors in regulatory compliance, complexity in managing inventory, manufacturing costs and risk of interruptions of the product supply to patients. This talk will discuss acceptance of global harmonization and science and risk-based approaches, where the safety, efficacy and quality of product can be assured without having to fulfill in entirety all regulatory requirements. It will also provide valuable insights into the benefits of aligning with global expectations and ICH guidelines, thus paving the path towards the desired goal of one global submission. Alternate regulatory strategies are proposed to enable quicker review, approval, and implementation times so that patients can have fast access to high quality products manufactured. NOTES:

Reduction of Post Approval Change Reporting Categories or Data Provided through Use of Risk Assessment Mic McGoldrick Merck Sharp & Dohme, USA Currently, there are a high number of post-approval changes needed to provide medicines to patients and they are impacted by long approval timelines and changing agency requirements. This causes inventory complexity, increase product cost and delays in access for patients. One way to decrease this impact is to use a risk assessment. The risk of the change is assessed to determine if it would negatively impact the product. Changes with low risk to the product can allow reduction in the data requirements or elimination of the filing completely. This can aid in the ability to continually manufacture quality products, increased availability for patients, and reduction in review times or review burden for agencies. NOTES:

Q12 and Perspectives on Post-approval Renan Araujo Gois ANVISA, Brasilian Health Surveillance Agency, Brasil The globalization of the pharmaceutical market requires the convergence of regulations around the world. Global harmonization is crucial to guarantee patients access to products with continuous improvement on their safety, quality and efficacy. The Internacional Council in Harmonization - ICH has been working on ways to promote this convergence. It is in development a new guide, ICH Q12, focusing on the lifecycle management, based on ICH Q8-Q11 concepts. NOTES:

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Will ICH Q12 Truly Go Beyond Q8/Q11?? Opportunities and Challenges Wassim Nashabeh F. Hoffmann-La Roche Ltd., Switzerland This presentation will focus on the current challenges and opportunities facing the development of ICH Q12, the first ICH Q document solely focused on post-approval changes for pharmaceuticals. Q12 is seen as a continuation of the ICH Quality vision that started with Q8 continuing through Q11. Q12 can potentially holds the promise of bringing meaningful and pragmatic benefits following implementation, something that have not yet been truly realized yet through implementation of Q8/11, so that the original promise of the ICH Quality vision can be realized. The newly introduced concept of established conditions will be discussed from a pragmatic perspective including examples of how such conditions could be selected for a biologic, and be linked to knowledge and risk calibration. NOTES:

Lifecycle Management Part Two: Risk Management and

Established Conditions Workshop Session Four

Panel Discussion – Questions and Answers Ricardo Castro Acosta, Universidad Nacional Autónoma de Mexico, Mexico Mic McGoldrick, Merck Sharp & Dohme, USA Janett Mugaburu-Richards, Pfizer, Inc., USA (on behalf of the BioPhorum Operations Group (BPOG), United Kingdom) Wassim Nashabeh, F. Hoffmann-La Roche Ltd., Switzerland Kavita Ramalingam Iyer, Merck & Co., Inc., USA (on behalf of the BioPhorum Operations Group (BPOG), United Kingdom) Leslie Rivera Rosado, CDER, FDA, USA The following questions will help guide the panel discussion:

• What is feasibility or potential acceptability of “outcome-based” approaches to ECs? • Does the type of EC (analytical or process) impact the acceptability of an “outcome-based”

approach? • What type(s) of Established Conditions can be negotiated with regulatory authorities? • What are some possible mechanisms in the Common Technical Document (CTD) structure for

identifying ECs? • What are some considerations for identifying ECs for late lifecycle products?

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