17^th European Biosimilars Congress April 04-05, 2024 Madrid, Spain

Biography:

Elena Salvaterra began to collaborate as independent researcher in non-profit organizations. Her research focuses on the ethics of human stem cells, bio-banking regulations, end of life decisions, capacity and informed consent, human biofabrication. Author of papers and books, she delivered conferences in several countries by giving a contribution mostly on ethics and regulations of science. She is also passionate of Arts and collaborates as photographer with the Lonon arts based research centre.

Abstract:

3D bioprinting of tissues and organs is considered the 4th industrial revolution in the field of medicine and biotechnology. The successful transplantation of an ear printed via 3D, performed in 2022 in the USA, confirmed the potential of this technology to transform regenerative medicine and surgery. However, bioprinting raises important ethical and legal issues that deserve a special attention. Considering that 3D bioprinting makes possible to fabricate body parts on demand, it is necessary to analyze at least the following issues: first, the ethical legitimacy of the human fabrication. What are the ethical conditions legitimizing the printing of vital tissues and organs for transplantation or regeneration? Then, to what extent is ethical using this technology for medical purposes? Biofabrication has the capacity to generate new human species as well as to overcome the natural boundaries of the human life. Where should it be drawn a threshold, if any? Further issues relate to the legal aspects of bioprinting and raises specific questions about a) the ownership of 3D bio-constructs, b) the consent to the medical uses of 3d bioprinting, c) the privacy protection, d) the intellectual property rights. This presentation aims to analyze these issues looking at the potentiality of 3D bioprinting to develop commercial profitable fabrics of vital human body parts.

Biography:

Mohamed Abdel Raof Elsis is working as a medical oncology consultant, HNH MADINAH branch, Kingdom of Saudi Arabia. He is having 14 years’ experience in the field of diagnosis and treatment of solid tumors including breast cancer, GI malignancies, gynecological malignancies, soft tissue sarcomas, bone tumors and lung cancer.

Abstract:

A biosimilar medicine is a biologic medication that is extremely similar to a reference medicine that the FDA has already approved. Kanjinti as an immunotherapy is biosimilar to Herceptin (reference medicine) with active ingredient trastuzumab. Clinics have had difficulties since switching from reference medicine Herceptin to a biosimilar for anti-HER2 therapy. There are extremely few or no real-world data on trastuzumab biosimilars available. To verify safety and efficacy. Therefore we conduct case report on Kanjinti. Female patient 45 years, Peri-Menopausal, married and has five children, negative family history of malignancy, At March 2023 patient diagnosed as left breast cancer. Patient did left MRM, revealed intra-ductal carcinoma grade III, With DCIS+ LVI, Pt2N2A, Er Week +Ve, Er -Ve, Her2 +Ve score 3, the initial decision taken is to give taxol with Trastuzumab with Pertuzumab X six cycles then to receive Trastuzumab with Pertuzumab for total doses (17 Doses). Patient received only one dose Taxol and medical report given to them, that patient is not eligible for treatment with Trastuzumab and Pertuzumab. So the decision was to give Adriamycin and cyclophosphamide (AC) Protocol X four cycles, then Taxol with Herceptin X three Cycles, then PORTH, after that continue Herceptin till total doses 17 doses with supportive treatment and hormonal therapy X five years, patient received four cycles AC protocol, then taxol 175 mg/m2 with Kanjinti x three cycles. The first loading dose of Kanjinti was 600mg, then maintenance dose 450mg then patient received PORTH and then continued KANJINTI with hormonal therapy NOLVADEX 20mg daily, received total seven cycles of KANJINTI with no adverse events, with good tolerance and excellent clinical response without any disease progression. That reflects the high efficacy and safety of trastuzumab biosimilar (Kanjinti).

Biography:

Francois Xavier Frapaise, MD, has over 40 years of international drug development, strategic planning and marketing experience at major pharmaceutical companies, including: Sanofi, Bayer and Abbott, and has held multiple C-level positions (CSO, CMO, CEO) in different Pharmacos in the US and Europe. He is currently heading a Clinical/Regulatory Consulting Company. Xavier has extensive experience in biosimilars development (Merck KGaA, Boehringer-Ingelheim, Pfenex) and more recently at Bio-Sourcing (Liege, Belgium). He held an academic position at the Thrombosis Research Center at the Loyola Medical Center in Maywood (IL). He holds an MD degree from Faculté de Médecine René Descartes, Paris France, and is an INSEAD alumni.

Abstract:

Background: Many patients, particularly in low-income countries, still have limited or no access to life-changing, therapeutic proteins in the treatment of diabetes, cancer or autoimmune disorders. The current, CHO-based manufacturing processes and clinical development model of biosimilars are expensive; furthermore, in most cases, large phase three trials do not provide meaningful information on the clinical equivalence (efficacy/safety/immunogenicity) between biosimilars and reference compounds. At the same time, the development of state-of-the-art orthogonal analytical methods has enabled a better understanding of the structure and structure–function relationship of biotherapeutics. An important evolution of the regulatory landscape has been observed, but the recent development of “affordable copies of biologics” could provide wider access to biologics; yet, this poses significant scientific and regulatory challenges. Observations: In recent years, many agencies, such as EMA and the FDA, have accepted applications for compounds, like peg-filgrastim, insulin, LMWH when validated surrogate markers of efficacy are available, as long as a state-of-the-art chemistry, manufacturing, and controls (CMC) package, along with phase one studies, are applied. However other regulators, hospitals drug committees, and clinicians continue to request evidence of efficacy/safety in patients before approving/prescribing monoclonal abs biosimilars. Large phase three trials do not provide the requested safety information, as safety is virtually impossible to compare with reference compounds in a population in which approximately 90% have adverse events, such as cancer patients. Immunogenicity is also difficult to compare in subjects who are immunocompromised and/or receive immunosuppressant therapy. Running large and costly clinical trials that are not likely to provide the expected evidence also raises ethical concerns. Recently, low- and middle-income countries have licensed more affordable copies of biotherapeutic products that do not or may not fulfill the requirements of WHO guidelines. This new generation of biologics provides obvious access opportunities for patients in emerging countries as the capital investment needed for manufacturing proteins from this transgenic goat model is without comparison with that of current CHO-based process; however, this manufacturing process differs from the current CHO processes, which offers new opportunities of access to treatment in low-income countries but raises significant scientific, legal and regulatory challenges. Simplification, increased flexibility and harmonization of the regulatory requirements should be on the agenda of those defining health policies, particularly in emerging countries.
Conclusion: We believe that newer technologies, including new manufacturing processes, increased regulatory harmonization, better understanding of biosimilar development objectives and methods, education of all stakeholders on biosimilars/emerging biologics would help ensure that patients have early access to life-saving compounds, the vast majority of which cannot currently afford.

Biography:

Mohadeseh Haji Abdolvahab received her PhD at Pharmaceutical science from Utrecht University in 2016. After PhD, she continues her research as a Postdoctoral researcher at Radboud UMC. She worked at International pharmaceutical companies i.e. MSD and Amgen as a Biological Critical Reagent specialist and OC scientist, respectively. Then, she came back to Iran and started her new challenge as an assistant professor at Motamed Cancer Institute in Tehran, Iran. She is currently the head of Recombinant Protein Department. She is expert in the field of biotechnology, pharmaceutical sciences and immunogenicity. Her knowledge and experiences have led to the establishment of FartakTeb start-up company to facilitate commercialization of her and co-workers research. She is also the executive manager of ACCEZON, a biotech-accelerator, and the coach of several start-ups.

Abstract:

Statement of the problem: Age-related Macular Degeneration (AMD) is the most common cause of severe visual impairment, or blindness worldwide. It is estimated that as many as 77 million people in Europe will be affected by the disease by 2050. Neovascular AMD (nAMD), the third leading cause of blindness, is a condition caused by the overgrowth of blood vessels in the retina as a consequence of agin. As a strategy for maintaining or improving visual acuity, treatment for nAMD focuses on inhibiting angiogenesis and vascular leakage. Therapies based on anti-vascular endothelial growth factor (VEGF) essentially work by blocking the activity of VEGF, the factor accountable for the excessive growth of blood vessels in the retina. Brolucizumab has been developed as a humanised, single-chain fragment of a monoclonal antibody (scFv) designed to block VEGF-A and reduce neovascularisation and vascular permeability.
Methodology and Theoretical Orientation: Due to the reductive nature of the bacterial cytoplasm, a well-folded, functional recombinant protein may be difficult to obtain. Using the CyDisCo system resolves this situation by pre-expressing a sulfhydryl oxidase and a disulfide isomerase, thus allowing for correct protein folding and function. In this study, the gene sequence coding for the Brolucizumab's biosimilar of interest was cloned into pET-24d(+) and codon‐optimized by Genscript. The plasmid harboring the biosimilar protein was co‐transformed with the CyDisCo expression vector pMJS205 into E. coli BL-21(DE3) cells and subjected to dual antibiotic screening.
Findings: The maximal yeild of soluble protein expression was achieved under 0.5mM IPTG induction in M9 culture medium, after 16 h at 30°C and 220 rpm. The highest amount of soluble protein fraction was extracted in lysis buffer containing 50 mM Tris–HCl pH=8, 1 mM EDTA and PMSF, per gram of cell pellet. Adding different NaCl concentrations to the lysis buffer showed that eliminating NaCl resulted in more soluble protein isolation.
Conclusion and Significance: The CyDisCo system could be promising in producing active, accurately disulfide‐bonded soluble proteins in E. coli cytoplasm.

Biography:

Luis Gerardo Alcala Carmona is a regulatory affairs expert based in Mexico City. During his career, he has shown a strong devotion to bringing into the market medical supplies of the best quality that are safe and effective for the patients. He has built differently proven regulatory strategies for national and international companies, having been able to collaborate with companies from around the World, such as the USA, Brazil, Argentina, Chile, Colombia, France, Germany, The UK, Italy, China, Japan, South Korea, among others. His expertise line includes medical devices, medical drugs, and biotechnology drugs, which include generic and innovative drugs. Having worked with new registers, variations, and renewals. Having been able to collaborate directly with Big Pharma Company, Luis also specializes in newly formed companies, always focusing on the best possible regulatory path and having in mind the safety of the patients, as he always says “We are all potential patients”.

Abstract:

Biological products, as well as other medical supplies, are regulated in each country by the competent health authority (HA). According to the FDA, they are used to diagnose, prevent, treat, and cure diseases and medical conditions. The difference with a more traditional drug is that the Active Pharmaceutical Ingredient (API), or APIs, are produced by processing chemical compounds, whereas in a biological drug, the active ingredient is known as Bulk Process Intermediate (BPI), and it is made by biotechnology in a living system, such as a microorganism, plant cell, or animal cell.

The first biopharmaceutical drug was approved in 1982 by FDA, recombinant human insulin. By 2022, FDA reports that there are over 621 FDA-licensed biologics products, and the global biotechnology market size was estimated at USD 1, 023.92 billion in 2021, with an expected growth during the next years. With this in mind, and considering that old patents are coming off, other companies can offer new biological products or biosimilar products. A biosimilar is defined by FDA as “A biological product that is highly similar to and has no clinically meaningful differences from an existing FDA-approved reference product” (a biological product previously approved).

Biosimilars have showed to revolutionized therapeutics alternatives, turn-over adverse prognostics and improve the quality of life for the users, we cannot forget that they must also prove to be a safe, purity, and with the necessary potency product. This is achieved with the help of, for example, new biomarkers, new comparative studies, new guidelines to serve as references for the manufactures, etc. In this occasion, we will review the last updates, with a special emphasis in the recent communications from FDA.

Biography:

Francois Xavier Frapaise, MD, has over 40 years of international drug development, strategic planning and marketing experience at major pharmaceutical companies, including: Sanofi, Bayer and Abbott, and has held multiple C-level positions (CSO, CMO, CEO) in different Pharmacos in the US and Europe. He is currently heading a Clinical/Regulatory Consulting Company. Xavier has extensive experience in biosimilars development (Merck KGaA, Boehringer-Ingelheim, Pfenex) and more recently at Bio-Sourcing (Liege, Belgium). He held an academic position at the Thrombosis Research Center at the Loyola Medical Center in Maywood (IL). He holds an MD degree from Faculté de Médecine René Descartes, Paris France, and is an INSEAD alumni.

Abstract:

Whether phase three clinical trials are necessary in biosimilar assessment is a complex issue with ongoing debate and evolving regulatory landscapes.

Even if current regulatory requirements still mandate require phase three clinical trials for most biosimilars, typically comparing the biosimilar to the reference product in terms of efficacy, safety, and immunogenicity. However, Regulatory agencies are actively exploring ways to streamline biosimilar development while maintaining patient safety exceptions are emerging; indeed, under specific conditions, regulatory agencies may waive or modify phase three requirements. This often depends on the complexity of the molecule, the availability of robust analytical data.

Many patients’ organizations and prescribers still express concerns on the true similarity of biosimilars with reference compounds. This is mainly because they ignore that the so-called “reference compounds” also change overtime.

Many arguments exist against running phase three trials: these include the High cost and time burden (Large-scale phase three trials can be expensive and time-consuming, potentially hindering access to affordable biosimilars); and for well-characterized biosimilars with high analytical similarity, extensive clinical data may not provide significant additional value. Ethical concerns have also been voiced as Exposing patients to additional clinical trials when adequate evidence already exists might be considered unethical.

Conclusion: We believe that the day will come sooner than later when virtually all biosimilars will be approved without phase three trials.