Quality and Regulatory Issues Related to Continuous Manufacturing of Biologics

Abstract

Introduction:
Continuous Manufacturing involves the continuous feeding of input materials into the transformation of in-process materials within, and the concomitant removal of output materials from a manufacturing process based on ICH guideline. In these systems, all the processes from raw material to final finished product would be continuously produced. The project aims to: Investigate the challenges and issues of producing a drug from API (Active Pharmaceutical Ingredient) to the final product using “Continuous Manufacturing (CM)”.

Methods: In several interviews, with experts from pharmaceutical companies, information is gathered about the challenges which exist for them to transfer a production line from a batch-based system to a continuous manufacturing line. Moreover, a designed process would be chosen and a comparison study will compare the challenges of transferring the process to a continuous manufacturing while focusing on the regulation and GMP issues.

Results: It was concluded that from a regulatory point of view, authorities are welcome to any changes as long as the manufacturer could provide data that they have complete control on the process. However, it is harder for manufacturers to convince the authority for the conversion for their production line to CM compared to starting a new production line with CM systems.

Conclusion: It was conducted that converting batch systems to CM is not economically beneficial for manufacturers. Due to this reason CM system would be only beneficial when there is a high demand for a product or a new production line is going to be built.

Popular Abstract (Swedish)

Läkemedelsindustrin är en av de viktigaste aspekterna i det moderna samhället. Denna industri har tillåtit forskare att förbättra människans levnad och ger patienter världen över hopp att deras sjukdomar kan bli behandlade. Läkemedelsindustrin har inte sett så många förändringar när det kommer till produktioner av små molekyler och API under de senaste årtiondena. Men världen förändras. Nya sjukdomar, pandemier, och mer behov av läkemedel och behandlingar världen över har utmanat industrin. Dessutom, i samband med biotekniska och biofarmaceutiska framsteg, behövs ny teknologi. Forskare har, för att industrin ska kunna anpassa sig efter nya behov och utmaning, utforskat denna nya teknologin.

Ett av områdena som forskare har utforskat under de senare åren är utökning av produktionsnivån hos företags produktionslinje. Det finns flera sätt att nå ett sådant mål att öka produktionsnivån för att nå upp till allmänhetens behov, som att bygga nya fabriker, ha fler arbetsskift i fabriken, och att effektivisera produktionslinjen. En av idéerna för att förbättra produktionslinjen hos befintliga produktionslinjer är genom att konvertera befintliga system till kontinuerlig produktion. Kontinuerlig produktion är ett produktionssätt som förbättrar produktionsnivån genom att sammanställa alla driftsenheter till en enda. Detta skulle låta producenten öka produktionshastigheten genom att sänka tiden det krävs för transport, minska förvaring och minska arbetskraften som krävs.

Dessa system skulle tillåta företag att producera fler läkemedel och behandlingar på kortare tid, och därmed möta allmänhetens behov vid händelser av läkemedelsbrist eller pandemier. Hälsomyndigheter vill dock vara säkra på att dessa system är trygga utan risk för att skada patienter. I denna uppsatsen kommer författaren undersöka möjligheten att implementera dessa system för att producera biologiska läkemedel. Denna uppsats fokuserar på att intervjua professionella som jobbar inom farmaceutiska företag, för att undersöka utmaningar och problem med användningen av Kontinuerlig Produktion. Efter utformningen av en kontinuerligt process för produktion av trastuzumab, som används för att behandla bröstcancer, presenterades denna process för professionella för att få deras åsikt. I intervjuer framgick det att det Kontinuerliga produktionssystemet har vissa fördelar i vissa delar av produktionen, vilket tillåter industrin att göra deras process säkrare för patienten. På grund av brist på reservdelar blir dock dessa system inte ekonomiskt fördelaktiga i många fall. På grund av denna anledningen har Kontinuerlig Produktion inte implementeras i speciellt stor utsträckning världen över.

Popular Abstract

The pharmaceutical industry is one of the most important aspects of modern human society. This industry has allowed scientists to improve mankind's life and gives all patients around the world a hope to treat their disease. The pharmaceutical industry has not seen that much changes when it comes to production of small molecules and API for the past decades. However, the world is changing. New diseases, pandemics, and more demand around the world for drugs and treatment have been challenging the industry. Moreover, with the advancement within biotech and biopharmaceutical new technology are needed. In order for the industry to adapt itself with new demands and challenges, scientists have been researching and investigating new technology.

One of the areas which scientists have been investigating for the past years is increasing the production rate of companies' production lines. There are several ways to reach such a goal in order to increase the production rate to meet the demand of the public. This includes building new factories, having more working shifts in the factory and improving the production line to be more efficient. One of the ideas to improve the production rate of existing production lines is to convert existing systems to Continuous Manufacturing. Continuous Manufacturing is a mode of production which increases the production rate by compiling all units of operation in one. This action would allow the manufacturer to increase their production speed by lowering the time needed for transport, storage, and man power.

These systems would allow companies to produce more drugs and treatments in a shorter time, thus meeting the public demand in the case of drug shortage or pandemic. However, health authorities want to be sure that these systems are safe and would not harm patients by any chance. In this thesis the author is going to investigate the possibility of implementing these systems to produce biological drugs. This thesis focuses on interviewing professionals who work in pharmaceutical companies, to investigate challenges and problems to use Continuous Manufacturing. After designing a continuous process for production of trastuzumab which is used in the treatment of breast cancer, this designed process was presented to professionals for their opinion. It was understood from interviews that the CM system has some advantages in some parts of manufacturing which allow the industry to make their process safer for the patient. However, due to shortages in spare parts and implementing, these systems are not economically beneficial in a lot of cases. Due to this reason Continuous Manufacturing has not been implemented in a meaningful number around the world.

• author: Ziarati, Sorosh
• supervisor: Lars Nilsson
• organization: Food Technology and Nutrition (M.Sc.)
• course: KLGM05 20221
• year: 2022
• type: H2 - Master's Degree (Two Years)
• subject: Technology and Engineering
• keywords: Continuous Manufacturing, Regulation, Continuous freeze drying, Biopharmaceutical, Trastuzumab, Pharmaceutical Technology
• language: English
• id: 9086574
• date added to LUP: 2022-06-14 08:37:08
• date last changed: 2022-06-14 08:37:08