Filling of drug substance: 5 threats you should know

micheal-eder

Michael Eder

March 20, 2023

Table of contents

Show

The filtration and filling of drug substances, if not done correctly, can cause severe problems. If the production steps in drug substance management from compounding to filling, labeling and dispensing of a drug substance leaves space for contamination risks, this can lead to product loss or unwanted alterations of the product. Delays in drug product manufacturing, higher costs of clinical trials and severe health risks for patients can be consequences.

Moreover, the filtration of drug substances or active pharmaceutical ingredients as they are also known is necessary in order to achieve a contaminant free pharmaceutical product. Other than certain small molecule drugs or proteins like monoclonal antibodies for instance are often especially prone to contamination risks because they cannot withstand heat treatments for sterilization1. Consequently, product fill and transport are among the different steps of the drug product supply chain.

Therefore, GMP and regulatory instructions issued by the FDA good manufacturing practices have to be exercised before biological products leave the manufacturing facilities in filled vials, pre-filled syringes or bioprocess containers. However, even though good manufacturing practices (GMP) are followed, the different steps in fluid management are still prone to errors. Learn the five threats in order to save time and money.

1. Leakage and breaking of bioprocess containers

If a container is damaged, contaminated or breaks during manufacturing or transport, it can have serious consequences. Product loss can lead to production delays to patients. In addtion, contamination of a drug substance that goes unnoticed during monitoring can cause health risk to patients. Therefore, integrity testing and visual inspection of bioprocess containers during filling is an important process with enormous impact.

2. Contamination of the drug product

Sterility of modern parenteral pharmaceuticals like vaccines and other injectable drugs is to be protected. Cleanrooms with an ISO classification and equipment in accordance with biopharma standards are only one of the basic requirements during drug development (for example by a third party CDMO). 

Although drug substance handling has to follow certain guidelines to protect drug products from the risk of contamination, errors are always possible. Accidental contamination of the product through human intervention of operators remains to be a risk. In contrast to the risk of human errors from manual handling, aseptic filling with automated processes have been shown to minimize this risk by eliminating the factor of exposure to human-transmitted materials.

Read more: Drug substance vs. drug product – the differences

Contamination of the drug product

3. Incorrect filtration processes

Since the filtration of biopharmaceuticals is used to purify the bulk drug substance and rid it of unwanted microbes, incorrect filtration processes pose a serious threat to a successful manufacturing process. It can leave contamination of a drug substance unnoticed, resulting in defective products, which is why constant quality control is essential.

4. Inaccurate filling process

Usually, small volumes of ATMPs (advanced therapy medicinal products) were distributed manually into small single-use bags. Nevertheless, this procedure brings several riks, including cross contamination, inconsistent cell counts and overfilling, which can result in product loss.

RoSS.FILL Lab Scale is a fully automated cGMP-compliant aseptic filling technology for up to 12 small single-use bags of 10mL to 500mL.

5. Bottleneck due to insufficient scalability

Through insufficient scalability in the filling process, a bottleneck is likely to occur. Especially in high demand situations like during the Covid-19 pandemic, it is necessary to operate large scale production of excipient substances and quick distribution as fast as possible. Nevertheless, many systems are limited to capacities between 1 and 100 liters, whereas the modular system by Single Use Support can be used for capacities between 10 and 1000 liters.

The advantage of state-of-the-art scalable single-use solutions where a filling line can be used flexibly, does not only apply in demanding situations like a pandemic but allows for a more efficient production in general and reduces on-site footprint.

eBook_Filling Gaps in Managing Large Volume of Biologics_Single Use Support

eBook: Filling Gaps in Managing Large Volumes of Biologics

Aseptic aliquotation and cryopreservation of drug substances are crucial process steps in bioprocessing. Even though they’re not in the spotlight of biomanufacturing. In drug development and drug delivery, biologics must be transferred at numerous occasions. Along the journey of monoclonal antibodies, vaccines and more, the drug substance passes lots of process steps where liquid transfer is required. This is relevant for the transitions between upstream processing, downstream processing and fill & finish, but also within these manufacturing milestones. The market of fluid & cold chain management has great growth potential and is on its way to professionalization and industrialization. To meet the challenges of manufacturing drug substances, Single Use Support helps manufacturers and CDMOs to advance their fluid & cold chain management process to achieve a secure and efficient process for liquids on the basis of single-use bags.

Further risks in the aseptic filling process and how to resolve them

The sensitive process of aseptic filling is prone to risks caused by human errors or faulty equipment. However, not only the risk of contamination is a big challenge, also temperature control plays a big role when working with fragile structured protein solubles.

To help reduce bottlenecks and allow for a contamination-free product, Single Use Support have developed automated end-to-end solutions to fill the gap between downstream and the fill-finish process. Through the automated sterilization of tools and containers, the aseptic and automated aliquoting systems can take over tasks that are too sensible or toxic to be carried out manually.

Further risks in the aseptic filling process and how to resolve them
Whitepaper RoSS.FILL_Automated Aseptic Filling

Whitepaper: Automated Aseptic Filling

Automated Aseptic Filling Unprecedented flexibility to filling well

Automated single-use bioprocesses taking over

Automated bioprocessing solutions are the future and especially systems based on single-use technology components have a number of benefits that surpass the advantages of employing tried-and-tested, established platforms:

  • Flexible use of add-ons (such as filters, connectors …) as needed
  • Limitless scalability (both ways) with single-use bioprocess containers of any volume
  • User-friendly integrability, adaptability and operation

Most importantly, the move towards automated systems will optimize output and at the same time prevent loss of drug substance by eliminating manual handling steps to rule out the risk of contamination and ensuring sterility.

FAQs about drug substance filling

What is the filling process in the pharmaceutical industry?

The filling process in the pharmaceutical industry is the process of aseptic filling different drug substances into single-use systems, such as bottles and bioprocess containers.

What does fill finish mean in pharma?

Fill-finish in pharma marks the end of the manufacturing process where a drug product is filled into a bioprocess container and packaged for transport and distribution to health care centers.

What are aseptic formulation and filling processes?

Aseptic formulation and filling processes are the different steps from making a formulation, filling it into a container, inspecting, labeling and packaging, while keeping the product free from contamination.

Further articles about drug substance filling

Automated aliquoting system: From small volume aliquoting to bulk filling with RoSS.FILL

Automated aliquoting system: From small volume aliquoting to bulk filling with RoSS.FILL

Be it small volume or bulk filling – aliquoting is a necessary step in biopharma manufacturing at every scale. In this article, we will cover the topic of automated aliquoting systems like RoSS.FILL.

RoSS.FILL CGT_Product photo

Liquid handling in biopharma: Efficiency gains with automated systems

Liquid handling is one of the cornerstones in countless biopharmaceutical manufacturing processes. In this article, we will illustrate how automated systems can improve efficiency – along with several other aspects.

tubing-solution

Bioprocess tubing – choosing the right option

Tubing solutions in the field of biopharmaceuticals encompass a wide range of applications, each with its own set of unique challenges and requirements. In this article, we will illustrate them in more detail.

RoSS.FILL Bag_Product Photo_Single Use Support-6

Fluid management in biopharma: Advantages of single-use systems

Major changes in biopharma industry require new approaches along the supply chain of most innovative biologics – including fluid management. Here's to discover how single-use products help to achieve considerable improvements.

fluid-manager

Fluid management systems: 7 considerations to be made

What are the necessary considerations when implementing automated fluid management systems in biopharma? In this article, we will discuss seven of the most important ones.

micheal-eder

Michael Eder

Senior Marketing Manager

Michael Eder, MA, is Senior Marketing Manager at Single Use Support. He is expert in pharma and health communication with his 8+ years experience in pharma. After completing his master's degree in International Healthcare Management at MCI The Entrepreneurial school in Innsbruck, he has gained experience in the pharmaceutical field. Michael creates articles about Freeze Thaw applications and Platform solutions from Single Use Support and is the author of current news with Single Use Support worldwide. 

More from Michael Eder

Vaccines

The development process of biosimilars

The development process of biosimilars slightly differs from the one of their reference biologics. In this article, we will discuss each phase in detail.

micheal-eder

Michael Eder

May 13, 2024

Vaccines

Biomanufacturing: Process, steps and challenges in manufacturing biologics

As biologics have become a central pillar in today’s healthcare sector, their manufacturing process increasingly draws attention. In this article, we will discuss the process step by step, including challenges and possible ways to overcome them.

micheal-eder

Michael Eder

May 13, 2024

Read more about Fill & Filtration

Fill & Filtration

Aseptic filling machines for pharmaceutical liquids

Aseptic filling machines are widely adopted in the biopharma industry. From individual components and equipment to considerations like scalability – in this article, we will take a closer look at these systems.

micheal-eder

Michael Eder

January 16, 2024

Fill & Filtration

Aseptic filling & processing of biologics

Many drug products require aseptic conditions along their entire production process. In this article, we will discuss essential considerations on aseptic filling in the biopharma industry.

micheal-eder

Michael Eder

January 16, 2024

Fill & Filtration

Aseptic filling of large volumes of drug substances

Especially in large volume drug manufacturing, aseptic filling can be a challenging yet all the more important task to ensure product safety and effectiveness. In this article, we will discuss what manufacturers ought to be aware of.

micheal-eder

Michael Eder

January 16, 2024

Fill & Filtration

Automated aliquoting system - for small & large volumes

Be it small volume or bulk filling – aliquoting is a necessary step in biopharma manufacturing at every scale. In this article, we will cover the topic of automated aliquoting systems like RoSS.FILL.

micheal-eder

Michael Eder

November 14, 2023