The rapid development of antibody therapies has significantly changed the therapeutic landscape over the past35 years There are many promising options that haev emerged as our understanding of the immune system has become more nuanced.
For this assignment, you have been given the task of assessing the production process of one of these antibody therapies that is under development and how it may be scaled-up and optimized. With the rush to get effective therapies into clinical studies, there are many things to consider downstream: it will take time to establish a large-scale production pipeline but there are limited facilities for that production. What may have worked for small-scale preclinical studies may not be optimal at large scale, and there is a large unmet need once therapies are approved but also a high likelihood that needs will evolve and there will be a need for testing. Do you think the biologic you are assessing should be given priority?
Week 7 Details
1) Identify an antibody-based therapy currently undergoing clinical trials in the US here, by looking under the column “Interventions” and choosing a Biological:” which is being compared against Placebo or standard of care (please do not pick a small molecule drug, Device, Other, Diagnostic Test etc. nor a combination therapy involving multiple drugs). You can pick an antibody biological at any stage of active development: https://classic.clinicaltrials.gov/ct2/results?term=antibody&Search=Apply&recrs=b&recrs=a&recrs=f&recrs=d&age_v=&gndr=&type=Intr&rslt=&phase=0&phase=1&phase=2
2) Carry out independent research into this therapy and how it is currently produced. Normally there are papers listed on the clinicaltrials.gov page, or you can search PubMed, Google Patents, the UMGC library or similar services for information. Identify at least one peer-reviewed publication that describes the bioproduction of the therapy. If you are unable to find a description of how the therapy is produced in a fermenter / bioreactor, please go back to step 1 and choose a different drug / biological. Please do not pick a small molecule drug which is synthesized by chemical reactions because you will not be able to answer the assignment questions. Not all drugs / biologics are equally well described in the literature. In grading I will take this into account – if your antibody is first-in-class or generally less common, you will be rewarded more for information you do find or best guesses based on similar products.
3) Write a concise and articulate report written in prose, addressing the following five points:
Biologic: What is the name of the biologic? Is this a antibody that is already approved for other indications? Who is sponsoring the trial? What stage of development is the biological (what clinical trial phase) and what indication is being examined?
Expression system: What is the expression system used? Why is this the optimal choice? Describe at least 3 strengths and 1 potential weakness of the expression system for bioproduction of this therapy. (if you can’t find information on an expression system, please go back and choose another therapy)
Genetic manipulation: Describe how the organism is genetically engineered for production of the biologic, citing at least one peer-reviewed article or patent. What are the key steps that have been taken to validate and optimize yield? (if you can’t find information about the genetic manipulation steps please go back and choose another therapy)
Bioprocessing pipeline: Identify at least one peer-reviewed article or patent that describes production of the therapy. Describe the production process, noting the current scale of production, and specific upstream steps, fermentation conditions, type of bioreactor used, how biomolecules are harvested, and downstream processing. Are there any steps that may be optimized? If the paper describes small scale production (< 100L), describe how you would scale up production, noting any changes you would make for large-scale production.
Alternative strategies: How else can the same drug be produced? Describe other potential expression systems or bioproduction methods that might: 1) improve yield and reduce costs, 2) decrease production time or process complexity, or 3) improve clinical efficacy or reduce side effects. What are the biological and commercial advantages of your chosen drug and production method compared to alternate therapies for the same indication under development? Do you think your therapy will make it to market and be successful? If so, why; if not, why not?
Grading Details
What: The assignment should be no more than 750 words, excluding references, and written in prose using APA format and the guidance given in the syllabus. There should be at least 5 references outside the readings for this course.
