This piece of writing is a detailed reflection of a college based visit to the Pfizer biotechnology manufacturing plant situated in grange castle, Dublin. this trip was directly related to both immunology and drug delivery modules and was intended to broaden our knowledge on the topics and to view the real life applications of various academic concepts. we were given in sight as to what the tour would entail, it would comprise of a short lecture, a problem based workshop followed by a short tour of the laboratories. this aided us as it provided an opportunity to re-familiarise with relevant course material and to think of some relevant questions to ask the Pfizer employees.
although we received this brief description of our day i still did not know what to expect. the first thing that struck me about Pfizer was the sheer size of the building, it is understandable as it is a manufacturing plant with many different sectors and operations but is still a surprise. As we entered we were given visitor identification cards and taken to a conference room in which we would begin our activities. the first activity was a detailed talk by Orla Cunningham in which a presentation was given on drug discovery and bio-therapeutics as a whole. we were eased into this presentation and as it went on it became apparent that i have covered the material in the presentation to some extent in college modules. Orla began by giving a brief background to Pfizer, i was surprised to hear that Pfizer is currently the only company to be doing drug discovery as i thought every company underwent drug discovery to some extent. this trip continuously challenged my preconceptions about the modern day pharmaceutical industry and painted a picture as to what a multinational pharmaceutical company is truly like. i have a avid interest in drug discovery, research and development, which made this presentation exciting to view. related modules such as drug discovery, drug delivery, immunology and biotechnology aided me hugely when it came to understanding some of the more advanced sections of the presentation.
after the presentation by Orla we received a short break, when we returned we underwent a two hour workshop that was ran by two researchers named Fred and Matthew. we were split into our predetermined groups and were presented with a pharmaceutical research based problem. the problem put forward involved a newly found cytokine that has the ability to induce asthma in humans. we were tasked with finding a way to neutralise the cytokine using the information provided. the neutralising agent had to be safe, efficacious and have an acceptable manufacturing profile. we were given relevant information to aid us in solving this problem. we were shown that a secreted decoy receptor protein existed that neutralises cytokine binding to the receptor one chain. also Receptor one had a moderate binding affinity; receptor two had no detectable binding affinity but Together the two chains bind cytokine with high affinity. from this information there were several routes we could take to neutralise the cytokine and it was seen that each group’s approaches varied to some extent. there were five main questions to be answered with regards to this problem, these covered the method of neutralising, pre clinical models, anticipated challenges, half life and other aspects of the drug discovery process. we were given an hour to organize a solution to the problems proposed, this required us think logically and apply knowledge learnt in college to a real pharmaceutical problem. we chose to use the decoy receptor as a method of neutralising the cytokine. the decoy receptor will block the cytokine from binding to receptor one. with regards to assays we proposed an in-vitro assays along with ex-vivo cell based assays to find a lead neutralising agent and to optimise it. In preclinical testing we had a choice to use mice, sheep or monkeys for toxicity and efficacy testing. The percentage sequence homology with human cytokine was given; the mouse was 55%, the sheep was 76% and the monkey was 94% we chose to use mice for toxicity testing as they are cheap and can be easily used in multiple generation studies. if the therapeutic is non toxic then preclinical studies can proceed on cynomologous monkeys in which efficacy studies can be done. the next question was to assess the challenges that may be encountered in developing a therapeutic. possible challenges proposed would be thermal stability as biotherapeutics can be temperature sensitive, therapeutic dose and toxicity. we also took into account the solubility and viscosity of the product as it will be delivered as a subcutaneous injection. the next question was to propose how to increase the half life of the therapeutic therefore increasing the length of time needed between doses which will enhance patient compliance. as a group we proposed ways to achieve a longer half life, one way was to increase the concentration within acceptable limits to stay in the system longer. another way is to bind the drug to a polymer such as polyethylene glycol (PEG). this will increase the size of the compound lengthening half life. the last question we were asked was to assess how the body would react to the therapeutic. we deduced that every protein that enters the body can be considered foreign therefor there is a capacity for immunogenicity. ways of correcting or improving this would be to humanize the protein and use anti histamines to reduce the localized reaction.
The final task was to present this material to the class, lectures and speakers. we went as a group to present our solution and listened to the other presentations. this was beneficial as we could see what route other groups went to reach a solution. the workshop as a whole was an interesting and beneficial experience, we used and improved skills that are very applicable to pharmaceutical research such as logical thinking, teamwork, time management and presentation skills. the content matter of the workshop was somewhat new to me, most of my college modules focus primarily on small-molecule therapeutics but this workshop focused on bio-therapeutics this was refreshing and highly interesting as bio-therapeutics is an established and ever growing market.
After the workshop we were split into two groups and were taken on a tour of the research labs. the labs were somewhat more basic than what i expected but this was one of many laboratories present in the plant. from observing some of the instrumentation in the lab I could apply and understand some of the techniques and assays that Orla had previously talked about in the presentation better. my only disappointment was that we did not get to see the manufacturing sector of the plant as this is strong interest of mine. I feel that the day as a whole was helpful in various areas of my academics, it gave me an insight to the workings of a corporate research job and aided me in choosing my career choice post academia.
Drug Delivery E-portfolio 