8^th International Conference and Exhibition on Pharmaceutical Regulatory Affairs and IPR June 08-09, 2018 Philadelphia, Pennsylvania, USA

Aysu Yurdasiper Erdem has obtained her BSc and MSc Degrees in Faculty of Pharmacy from Ege University respectively, followed by a PhD Degree from the same department. She has studied as a PhD student with TUBITAK Scholarship in Cardiff University, Welsh School of Pharmacy, Cardiff, UK. Her work is focused on dry powder inhalers, dermal delivery (topical, transdermal drug systems), controlled release formulations (nanoparticles, microparticles) for drug delivery. She is Editor in Chief for American Journal of Drug Delivery and Therapeutics and also Editorial Board Member of several international journals. She has filed a national patent on dry powder inhaler formulation. She has been working as a Researcher in the Department of Pharmaceutical Technology, Ege University. Her current research interests focus on development of novel nano-micro medicine including polymers and in vitro-in vivo evaluation for treatment of respiratory diseases.

Statement of the Problem: Asthma is a heterogenic disease occurring in both adults and children worldwide. Over the past decade, orally inhaled fixed-dose agents have emerged as an important therapeutic class for treatment of asthma. Current guidelines recommend inhaled corticosteroids as the basis of initial controller treatment. Several factors such as correct use of inhalers and adherence to the treatment affect the outcome of the disease and have been described to be major barriers for successful treatment.

Objective: The objective of this study was to develop Fluticasone Propionate (FP) Dry Powder Inhalers (DPI) containing different carriers using spray drying technique and characterize the powder in terms of aerosolization, flow properties in order to determine which formulations could be the most suitable for pulmonary delivery.

Materials & Methods: Trehalose, Mannitol and Leucine were used as carriers. The mixtures were spray-dried with constant stirring using a Buchi Nanospray Dryer B-90. A simple, rapid, accurate and sensitive method was developed for quantitative analysis of FP using High Performance Liquid Chromatography (HPLC) with UV detection. The chromatography parameters were Thermo Scientific Hypersil ODS C18, (5 μm, 4,6x250 mm). The isocratic mobile phase was acetonitrile:water (65:35; v/v) at a flow rate of at 1.0 mL.min-1. The determinations were performed using UV-V is detector set at 238 nm. The in vitro aerosolization performance was investigated using Next Generation Impactor (Copley).

Results & Discussion: SEM images of DPI formulations showed almost spherical structures with particle size 1-5 μm. Also the sizes of the particles were determined by laser diffraction with a dry sampling system (Mastersizer 3000 Malvern instruments). Process yield values were higher than 86.±2.8% and encapsulation efficiency values were above 81.±3.2%. The optimized formulation developed in this study exhibited good in vitro aerosolization properties. The Carr’s Index is higher for the formulation with trehalose.

OumKaltoum Lahlou is a Pharmacist and has a Master’s in Compliance in Pharmaceutical Industry from the University of Barcelona, Spain. She is Head of the Regulatory Affairs of North and West Africa region at Merck since 2013. She worked eight years at Bayer in Barcelona then in Casablanca in different positions: Quality Assurance, Industrial Development Department Manager before joining the Regulatory Department. She is a Member of Africa Regulatory Network in IFPMA. She participated as a Writer in the Edition 2016 of the International Pharmaceutical Journal: “Pharmaceuticals Policy and Laws”; Article 7: African Regulatory Harmonization: AMRH Program; “Towards African Regulatory Harmonization Processes–Accelerating patient access to medicines.

The role played by properly functioning regulatory systems towards enhancing access to essential medicines for patients is crucial. This is especially the case in Africa which has seen progressive growth in the regulatory environment. At the center of this growth has been the African Medicines Regulatory Harmonization (AMRH) initiative. This initiative seeks to strengthen regulatory capacity and encourage harmonization of regulatory requirements–with the ultimate aim of expanding access to quality, safe, and effective medicines for patients in need in Africa. A lot of progress has been made during the last years, with initial focus on the East African Community, where harmonization related regulations have already been implemented. The same is now being rolled out in other regions such as West Africa and the Southern African Development Community. Removing bottlenecks and reducing redundancies in regulatory processes that slow access to medicines for patients in need today is critical. In this sense, collaboration between the World Health Organization and relevant stakeholders, including the research-based pharmaceutical industry, on collaborative registration procedures that support fast and efficient review and approval of essential medicines in Africa is essential. African regulatory harmonization offers many benefits to regulatory authorities, patients in Africa and industry alike–and most critically for the protection of public health. In this regard, it should be noted that the AU, through its technical arm, the New Partnership for Africa’s Development (NEPAD) Agency has established a medicines regulatory harmonization initiative with the ultimate aim of establishing one central regulatory body in Africa, the African Medicines Agency (AMA).

Joel Finkle is the Director of Regulatory Innovation and IDMP Strategy for ACUTA. In this role, he brings new technologies and regulatory data standards to ACUTA’s bio/pharmaceutical customers to ensure compliance and process improvements, as well as providing the focal point within the company for other industry standards and regulatory guidance. He came from a background of pharmaceutical industry with software and consulting vendors, with over 30 years’ of experience in software development and support of electronic submissions, publishing, and document. He is currently a Member of the HL7 Regulatory/Clinical Information Management group, and the IRISS Forum

The ISO standards for the Identification of Medicinal Products (IDMP) were established in 2012 and updated in 2017. The first region to implement them will be the European Medicines Agency (EMA), which plans to use it to replace their current drug registration system called XEVMPD. Compliance with IDMP will require gathering data that is mostly locked up in narrative documents and systems outside of regulatory control, but has great potential to serve as a master data management system for EMA for improving public safety through better adverse event signal detection, reduction in prescribing errors, and prevention of counterfeit or contaminated product reaching the market. This session will discuss the progress being made toward implementing the standard in Europe as well as in other regions, and will demonstrate the approach needed to gather the information required for compliance.

Eleonora Babayants is the Founder and President of Galaxy Consulting and she is a Documentation Management Professional and hands-on consulting with over 25 years of experience in documentation and records management, document control, regulatory compliance, internal and external auditing, electronic document management systems, information governance and change  management. Her past work includes development and implementation regulatory compliance processes and procedures, leading implementation and administration of document control systems in full compliance with regulatory requirements, enabling enterprise search, improving systems information architecture, creating and implementing users training programs. She led electronic document management systems selection and deployment, administered and supported these systems, web information portals, knowledgebase applications, recommended and implemented re-structuring of the content and the information architecture of these systems. She worked very closely with IT to do feasibility assessment and to capture users’ requirements. She wrote technical documents and created document templates. Her experience spans multiple industries including biomedical, pharmaceutical and medical devices companies.

Documentation is a critical tool for ensuring GxP/GMP compliance. This is what GMP states about document control. Each manufacturer shall establish and maintain procedures to control all documents those are required. In the regulated environment which must be GxP/GMP compliant, document control is the cornerstone of the quality system. It is so important that if an external audit identifies deficiencies in the document control system, the entire organization can be shut down. There are also GMP requirements for information technology. For a drug to be produced in a GxP/GMP compliant manner, some specific information technology practices must be followed. Computer systems involved in the development, manufacture and sale of regulated product must meet certain requirements. Change control within Quality Management Systems (QMS) and Information Technology (IT) systems is a formal process used to ensure that changes to a product or system are introduced in a controlled and coordinated manner. In the regulated industries, manufactures are required to use a change control procedure. In this presentation, I will discuss the connection between GxP/GMP and document control. I will describe details of document control procedures and the role of quality assurance in the documentation systems. I will review GMP requirements for information technology and how computer systems including documentation management systems must meet GxP/GMP requirements. I will also review change control procedure and how it should be used in GxP/GMP environment.

Yavuz is the chairman of Istanbul Consulting Group. ICG(Istanbul Consulting Group) was founded in 2013 and provided guidance to the Turkish ministry of health as part of a World Bank project.Yavuz is currently the Director of Avcılar Hospital R&D Center, Chief Medical Officer of Lifematrix GmbH and Corporate Communication Director of Sumitomo Group/ Expel Ä°laç. He previously managed the largest distributor of Siemens Healthcare in Turkey managing 250 employees. Previously he worked as the Market Access & Health Policy Director for AIFD in Turkey. Yavuz previously worked as the Vice President of Ipsen pharmaceutical and Director of Teva pharmaceutical in USA managing large clinical trials as well as Investigator Initiated Trials and developing relationships with Key Opinion Leaders. Previously, Yavuz was the Associate Director at KV Pharmaceuticals and Director in Clinical Development department at Forest Laboratories.

Pharmaceutical, Biotech and Medical Device companies are constantly evaluating how decisions at the US ,Europe, Turkey and emerging markets are taken at the federal and state level and how it will impact provider and patient access and coverage to their therapies. To gain these critical insights, government affairs & medical affairs teams require speaking with those on the

frontlines of healthcare delivery - physicians, allied healthcare professionals, payers, and patients. New generation government engagement and commercial diplomacy approach developed by ICG ( Istanbul Consulting Group) will be provided with unique cases. Dr. Yavuz Selim SILAY a global leader and seasoned expert in government engagement, commercial diplomacy, corporate communications, government affairs & medical affairs will discuss how companies utilizing government affairs and medical affairs teams should engage decision makers, payers, physicians and acquire these insights in a convenient, costeffective, and compliant manner in this current changing global regulatory landscape.

Prof. Raymond C. Jagessar obtained his BSc (Distinction) in Chemistry/Biology from the University of Guyana (1992) and his PhD from the UK (1995). He held three Post Doctoral Research Fellowships at the University of South Carolina (USA), Wichita State University (USA) and the University of the West Indies (1996-1999). He has also won several international awards, amongst them are Chartered Chemist, CChem and Fellow of the Royal Society of Chemistry, FRSC, UK. His research interests are broad, covering the spectrum of Pure and Applied Chemistry, Chemical Biology, Pharmaceutical and Medicinal Chemistry. He has published over seventy (70) research articles, five book chapters and presented at several international conferences. He is currently Professor in Chemistry at the University of Guyana (South America)

Diabetes mellitus also is a group of metabolic diseases in which a person blood sugar level is higher above the threshold limit. This may result from the inability of the pancreas to secrete insulin or the body cells are resistant to insulin. Diabetes results in a wide range of ailments in humans that can ultimately lead to death. These include: heart diseases and stroke, nerve damage, diabetic neuropathy, erectile dysfunction, retinopathy, slow healing of cuts, burns and wounds, high blood pressure and cholesterol, diabetic nephropathy, nerve damage, leading to nausea, constipation or diarrhea. Thus, diabetes is a serious disease worldwide. The status of diabetes (diabetic mortality and diabetic morbidity) in Guyana was investigated over a period of time 2003 to 2008.There was a general increase in the diabetic mortality number from 2003 to 2008. This may have been due to the eating habits and lifestyle of the populace in that region. Over the period 2003 to 2008, the average mortality of 403.5±29.30 was observed. A variance value of 162, 812.25 was computed. The confidence at the 95% level was calculated to be 403.5±9.57. Morbidity is the state of being diseased. This was recorded over the period 2003 to 2009. For the years 2003 to 2008, a mean morbidity of 9,506.71±496.86 was recorded. The confidence interval was found to 9,506.71±139.12. In general, there was an increase in morbidity from 8,920 in 2003 to 15,727 in 2009. The highest entry of 15, 727 were obtained in 2009. Diabetes can be controlled by both synthetic and herbal treatments. Synthetic treatments include the use of Insulin Secretagogues (Sulfonylureas), biguanides, Thiazolidinediones, α- Glucosidase, Glucagon etc. Herbal treatments include plant parts from Momordica charantia, Phyllanthus niruri, Cajanus cajan, Desmodium barbatum, Tinospora cordifolia, Azadirachta indica, Abrus precatorius, Catharanthus roseus, Centella asiatica, Curcuma longa, Phyllanthus emblica, Piper betle and Sphaeranthus indicus. 

Muhammad Naeem has 19 plus years diversified experience in Quality Operations, Regulatory Affairs, Research and development and Operational Excellence. He is RAC-Global certified. He is an active member of ISPE, PDA and RAPS, USA. He has an extensive knowledge of ICH, USP, BP, and HACCP. He has lead several Investigational/Developmental and Technical/Analytical Projects at CMOs in USA, Europe and Pakistan. Some of the major pharmaceuticals he served are Pfizer & Takeda (USA), CCL Pharmaceuticals and Indus Pharma (Pakistan). He has strong scientific, analytical, planning, managerial and training skills. He has attended many national and international conferences as a speaker on Quality Risk Management, Data integrity, Pharmacovigilance, QMS elements, Validation,

cGMP Guidelines, etc.

Introduction: The use of multiproduct facilities for the production of pharmaceutical products is need of time to allow products to be brought to patients in a timely and cost-effective manner. Doing this safely requires an understanding of the products, the facilities, the processes, and the equipment and the risks posed by this combination. The major risk of concern  ithin shared facilities is the risk of cross-contamination. New GMP guidance for the EU came into effect in 2015 that requires a risk management process to determine if products can be safely manufactured in shared facilities. This new GMP requirement left industry unsure how to perform and document these risk assessments. User must understand the relationship of hazard, exposure, and risk. If done properly, the stakeholders should be able to demonstrate a full understanding of the processes being evaluated. A consistent approach across the hazard continuum is integral in this approach so that the regulators can be confident that a well thought out plan to reduce risk to an acceptable level has been established. Professionals in the pharmaceutical industry should move forward with a consistent approach on setting acceptable limits to assess the

potential of cross-contamination causing an undue risk to patient safety. This approach is intended to enable manufacturers to implement appropriate controls to facilitate safe and affordable drug product manufacturing without complicating the engineering solutions

Recommendations: it has become clear that in the pharmaceutical sector, an adequate risk management system is not only required by regulatory stakeholders but may also result in a competitive advantage when appropriately implemented. Hence, to be prepared for future challenges, more predictive and proactive strategies towards product and process development, quality assurance and quality control, product life-cycle management and business operations in general are required. Risk management can be seen of one major aspect of these approaches with the goal to facilitate innovation and continuous

improvement. The chosen system in quality management represent major aspects of the pharmaceutical quality assurance system and their enhancement with regard to risk management can be well used as primer for further integration activities.

Conclusion & Significance: It is important to have an escalation process that allows management to be informed of areas that have risk that is unacceptable or near unacceptable. The holistic approach that is described in this course is predicated on the fact that all of those involved have received appropriate education or training and have ready access to supporting risk assessment and management documentation.

Jacob Adegboyega Kolawole has completed his PhD from the Ahmadu Bello University, Zaria and The Robert Gordon University, Aberdeen, UK (1996). He is the Dean, Faculty of Pharmaceutical Sciences, University of Jos and Consultant at West African Health Organization on development of guidelines and training manuals for pharmaceutical finished products, pharmaceutical raw materials, standard operating procedures for laboratories and bioavailability/bioequivalent. He has more than 40 publications in international journals.

The manufacturing, distribution and use of drug (medicinal) products involve some level of risk. Quality risk management is a valuable component of an effective quality control system in the pharmaceutical industry. Built in product quality should be maintained throughout the product lifecycle such that the attributes those are important to the quality of the drug (medicinal) product remain consistent with those used in the clinical studies and production and assured by quality control mechanisms and tools. An effective quality risk management approach can further ensure the high quality of the drug (medicinal) product to the patient by providing a proactive means to identify and control potential quality issues during development, manufacturing and distribution. Additionally, the use of quality risk management tools can improve decision making in quality management systems as a whole for best quality products and not only when quality problem arises. Effective application of quality risk management principles can facilitate better and more informed decisions and provide regulators with greater assurance of a company’s ability to deal with potential risks and regulatory compliance.

Raymond C. Jagessar obtained his BSc (Distinction) in Chemistry/Biology from the University of Guyana (1992) and his PhD from the UK (1995). He held three Post Doctoral Research Fellowships at the University of South Carolina (USA), Wichita State University (USA) and the University of the West Indies (1996-1999). He has also won several international awards, amongst them are Chartered Chemist, CChem and Fellow of the Royal Society of Chemistry, FRSC, UK. His research interests are broad, covering the spectrum of Pure and Applied Chemistry, Chemical Biology, Pharmaceutical and Medicinal Chemistry. He has published over seventy (70) research articles, five book chapters and presented at several international conferences. He is currently Professor in Chemistry at the University of Guyana (South America)

The search for alternative complementary natural medicines to replace synthetic antibiotics is on the increase, considering the side effects produced by synthetic drugs, some of which are irreversible. The aqueous extract of leaves of Phyllanthus acidus, Sphagneticola trilobata and Doliocarpus dentatus’s bark, uncombined and combined in the absence and presence of Zn2+ were tested against selective pathogenic microorganism such as S. aureus, E.coli., K. pneumoniae, P. aeruginosa and C. albicans using the Disc Diffusion Assay. The area of zone of inhibition, Azoi was taken as an indicator of the plant extract’s

antimicrobial potency. The highest Azoi of 165.05 mm2 was induced by P. acidus extract against E. coli. In the absence of Zn2+, zero Azoi was observed for the combined extract of P. acidus + S. Trilobata, S. trilobata + D. dentatus and P. acidus + D. dentatus against S. aureus and K. pneumoniae. The combined plant extract, without Zn2+, seems to induce a higher Azoi against E. coli, K, pneumoniae, C. albicans and P. aeruginosa in comparison with the individual plant extract. As an example, the combined plant extract of S. trilobata and D. dentatus induces Azoi of 122.66 mm2, whereas S. trilobata induces AzoI of 117.79 mm2. For the combined plant extract with Zn2+, a lower Azoi was induced, compared with the individual plant extract. Selective

antimicrobial activity was observed for the uncombined and combined extracts, with and without Zn2+ against some of the pathogens. For example, P. acidus aqueous extract showed Azoi of 165.1 mm2 against E. coli, whereas S. trilobata showed Azoi of 67.17 mm2 against E. coli i.e., a selectivity ratio of 2.5 vs. E.coli with respect to the above two extracts.

James R Bruno has over 40 years of industrial experience working in the manufacturing and development of API’s. After many years of working in lab through senior positions in the pharmaceutical manufacturing sector, he has began consulting in 2002 working with emerging pharmaceutical company to help to develop their API’s and dosage. In addition, he has continued to consult in the area of new technology including continuous chemistry, chromatography and various other chemical transformations’. His objective has been to bring new technologies into the commercial work to safely and economically produce API’s. He has obtained his Master’s in Chemistry from St. Joseph’s University in Philadelphia and MBA Degree from Rider University located in Lawrenceville, NJ. He is also served on the Scientific Advisory Board. He has published numerous papers in many of the pharmaceutical journals.

The chemical industry has looked at the use of continuous reactions for many years. In fact, the only industry sector not involved in continuous chemistry has been the manufacturing of pharmaceutical ingredients. More recently, the manufacturing of API’s has seen a push into continuous chemistry and the FDA is helping to lead the charge. However, from a regulatory point of view, we may see a major switch in how we produce our products. The concept of a batch will change dramatically and the requirements for validation will need to be adaptive to a new manufacturing paradigm. In addition, the switch to continuous reactions could benefit the overall economic and safety of drug production. This presentation will look at the issues around manufacturing API’s and the regulatory changes required moving from batch to continuous. The presentation will focus on the definition of the batch and the critical parameters working in continuous reactions.

Rashid Mahmood has Master Degree in Analytical Chemistry and MS in Total Quality Management. He has 15 years of experience of Pharmaceutical Quality

Operations and has participated in many international conferences as a keynote speaker. He has presented various talks in USA & China on Cleaning Validation, cGMP Guidelines, Quality Risk Management, Role of Mass Spectrometry in Pharmaceuticals and on new Drug Delivery Systems. Currently he is working as a Senior Executive Manager Quality Operations for Surge Lab.(Manufacturer of Microencapsulated APIs, Liquid & Dry Powder Parentrals) which is the best export oriented company of Pakistan

Every product or process has associated risks. Zero risk reduction is not a realistic goal nevertheless protection of patient by managing this risk in the quality system and manufacturing process is being given prime importance in the pharmaceutical industry. Quality Risk Management (QRM), a systematic process that assesses risk to the quality of a drug product across the lifecycle. QRM gives a company the ability to maintain compliance while also identifying product issues that could be harmful to the consumers, some being susceptible patients. One of the primary principles of QRM states, “the degree of rigor and formality of quality risk management should reflect available knowledge and be commensurate with the complexity and/or criticality of the issue to be addressed.” Therefore, a QRM framework can be applied to all levels of potential risk to the safety of a product, and it does not have to be done in a long, arduous process. With this in mind, quality risk management can and should be integrated into the daily operations of any company that wants to maintain a focus on product integrity and patient safety. Assessing, reviewing, and rating risks can then become a natural reaction to product and operation issues. ICH Q9 and FDA guidance document on quality risk management provides a detailed information for the use of risk management tools in pharmaceutical product development and manufacturing quality decision making. Effective quality risk management can facilitate better and more informed decisions, can provide regulators with greater assurance of a company’s ability to deal with potential risks, and might affect the extent and level of direct regulatory oversight.

Bernice Brempong holds a Bachelor degree in Pharmacy from University of Ghana, Legon. She has extensive experience in hospital practice, community practice and pharmaceutical production. She has worked in several pharmaceutical industries including Ernest Chemist in 2013 and Entrance Pharmaceuticals in 2016/2017 where she gathered practical experience and later assumed the Chief Executive Officer position in Makhealth Pharmaceuticals Limited. Makhealth Pharmaceuticals is currently putting up a WHO-GMP compliant facility in collaboration with international partners for the production of solid and liquid oral dosage forms and sterile products including dropper products, parenteral and vaccines. Makhealth intends to collaborate internationally in contract manufacturing and also to act as the state-of-the-art manufacturing industry in Sub-Saharan Africa.

Good Manufacturing Practice (GMP) is part of the quality management system which ensures that products are consistently produced and controlled to meet quality standards appropriate for their intended use as required by the  arketing authorization, clinical trials authorization or product specification. Current Good Manufacturing practice (cGMP) is aimed at managing and minimizing the risks inherent in pharmaceutical manufacturing to ensure that the quality, safety and efficacy of products are reproducible. Such risks are essentially human errors which occur during the handling and processing of materials and machines. While most pharmaceutical industries from the industrialized world work tirelessly to comply with cGMP requirements to produce in compliant facilities, industries in the developing countries have not been able to meet

most of these requirements. Factors such as lack of skilled personnel with technical know-how, weak regulatory systems, lack of appropriate equipment, machinery and technology and high cost of manufacturing drugs thus modern equipment and technology among others have been identified as some of the major factors within the sector bringing about the differences we see today in developing countries. In conclusion, GMP guidelines provide the requirements that a manufacturer must meet to ensure that their products are consistently high in quality, from batch to batch, for their intended use in order to always prevent harm from occurring to the end user.