Application of single-use technology

Sterilization is an important and critical requirement for various pharma processes, where each item must be sterilized before being used.

Sterilization techniques sometimes become ineffective due to many reasons such as human involvement during transportation, or maintenance of equipment. However, recent technological advancement has enabled pharma industry to use disposable items, which are used only once and not requiring sterilization.

Single-use technology is gaining momentum because of its many advantages, which we will discuss later in this article. One of these advantages is that it eliminates the human involvement during routine processes, eliminating problems. 

What is a single-use technology?

Single-use technology refers to pharmaceutical equipment designed for one-time use, and after that they discarded. Their design and physical structure do not allow them to be used again.

Additionally, treating single-use items such as sterilizing them is impossible. Doing so will alter the physical and chemical characteristics and composition. 

Single use technology is an alternative to the existing traditional equipment such as stainless steel vessels, because they are used many times, and requires sterilization every time that are being used for removing contamination and microorganisms.

Single use technology components are available for the entire process life cycle, involved in pharmaceutical production such as storage, manufacturing, transferring and fluid related components. The material of construction for single is technology is plastic that is suitably composed to prevent harm and reaction with different fluids and chemical. They can also sustain different physical attributes such as pressure and heating.

Advantages

Let's discuss some advantages of single use technology

Flexibility

Flexibility means to quickly adapt to changing requirements and processes. 

For Pharma operation it refers to quickly adopting to different product and operation requirements. Single Use Technology has the advantage of flexibility to adopt to different products and process requirement. Single use equipment and components can be quickly re purpose or adjusted to every individual products requirement. 

The equipment or components can be installed or uninstall without any sterilization or any other requirement to become part of the process and equipment.

 Single Use Technology components do not require any cleaning and related quality screening and testing.

The above characteristics of Single Use Technology provides flexibility in the routine production process, and saves a great deal of time between different stages of production processes.

More safety

Single Use Technology offers maximum inherited safety as compared to other stainless steel components. They are discarded after every processes, so traditional contamination source i.e. remaining from previous batch is automatically eliminated. 

Secondly, since they are not sterilized, it automatically removes problems due to errors in the sterilization process.

Less maintenance

Single use technology components requires less or no maintenance and save resources due to maintenance.

For repairing a traditional system, dedicated resources and time is required, such as shifting the equipment to its designated maintenance place, workshop or vendor place. It also requires spare parts during maintenance. These factors, and like these increases the overall maintenance cost.

The time is also a factor in the maintenance of traditional equipment. Even, if less time is spent during maintenance, additional time is spent on testing and verifying the equipment's performance, and shifting the equipment back to production place is also a time consuming process

For large maintenance activities, time consumed is increased due to the volume of maintenance. The maintenance can also suffer, if the required spare parts are not available.

Modular design

With the Single Use Technology, it is possible to design a purpose built system that can be customized for varying manufacturing requirements. 

Design change can be done in less time because it does not require sterilization and clearing. It also prevents cross-contamination between the processes

Less processing time

Single Use Technology requires less processing time, and as a result production is increased. This is essential for critical products which requires less time to market for reason such as pandemic or market requirements

Examples of single use technology

Some example of single use technology is a described below

Single use tubing

Single use tubing are disposable components that are used to create a fluid path such as compressed, Nitrogen, Steam or Oxygen between different parts of an equipment. They are made up of disposable  material such as plastic. When require they are directly connected at their point of use, without any processing. After production process tubing discarded, and cannot be used further.

Single-use tubing are used in pharma processing in highly critical areas, such as clean rooms to prevent contamination. 

Some factors to consider when using single-use tubing, are mentioned below

● Type of fluid. The fluid being used for single use tubing, is critical because it can impact the material characteristics during production. For example, fluids can be of acidic nature, having specific pH,  biological or  protein based

● Physical parameters of the process being carried out is critical for material selection. For example, temperatures and pressure. 

Single use mixer

Another form of equipment that use Single Use Technology are mixer. They are used to mix solids with solds, solids with liquids and liquids with liquids, depending up on the process requirement

It consists of single use disposable bag that is being held and fixed in a metallic structure to hold the bag. Single use disposable agitator is fixed at the bottom to mix the material in it. After, the process is completed, the disposable bag is removed and replaced with another new bag to continue with the next process

It's advantage over traditional stainless steel base mixer is that it eliminate the need of cleaning through CIP or SIP. The mixer is simply replaced after each process. 

Single Use reactors

Bioreactors are used by API company to manufacture active for Pharma industry.  Single use technology can also be used to manufacture bio reactor. It includes a disposable bag to produce different chemicals

The disposable bag is fixed between metallic structure for holding, and the chemical are filled into the bag. Chemical reaction and associated processes occurs inside the bag, as a part of process requirement . It's advantage over traditional reactor is that it can provide high degree of contamination prevention without  associated quality checks for ensuring cleaning and sterility. 

Regulatory consultation for single use technology

Regulatory requirements for single is technology at describe below

United States FDA

The United States FDA is the regulatory body for the United States. It's GMP guidelines provide general characteristics of the manufacturing items.

The United States FDA, 21 CFR 211 "Current good manufacturing practices for finished pharma products" describes in its sub part, section 65 "equipment" construction defines the following

The equipment surface should not react with any drug products, or absorb it and alter the safety, identity strength, quality or purity of the product.

In an another guidelines, "Changes to disposable manufacturing materials: Question and Answers guidance for industry", describes the manufacturing chemistry and controls for post approval changes to disposable manufacturing materials, that a manufacturer can used in pharmaceutical or biological product manufacturing

The above guidance applies to biologics and license application products to

● Under section 351(a) or 351 (k)  of Public Health Science act

● Human drug products

United States pharmacopoeia

Some relevant guidelines related to United States pharmacopoeia are mention below

USP < 661.1 > "Plastic Material of Construction"

This is the updated version of the USP<661>, and provides test mechanism for the material from which packaging components are made. 

The purpose of USP 661.1 is to characterize the material of construction so that it can be evaluated for safety and compatibility. According to this guideline a material of construction of plastic item is considered satisfactory if it passes the following attributes

● Identity of the material

● Biological reactivity of the materials under test

● Physiochemical properties

● Composition

● Extractable elements

USP 665

The USP 665 provides guidance for qualifying plastic elements used in the manufacturing of Pharmaceutical drugs. Some points according to USP 665, are mentioned below

● It's purpose is to characterize the material used in the manufacturing of plastic, that are being used in the manufacturing of Pharma drug products.

● All the possible extractable must be define for a given material

● After identification, possibility of leachable from the material should be identified to determine the suitability of using material with the pharma product.

EU GMP

● Risks: The EU-GMP defines some risks related to single use technology which include but not limited to

o The interaction between product and contact surface

o Fragile nature of system

o Increased in complexity of material operation

o Risk of holes and leaks. 

o Compromising of the system when other packages opened

o Risk of particulate contamination

● Sterilization process for single use system should be validated, free from any adverse impact

● Suppliers must be assessed for selection

● Absorption and reactivity of pharma product with contact surfaces must be evaluated

● Single use system should be designed to maintain integrity throughout the process including structural integrity, especially, when exposed to extreme conditions

● Acceptance criteria corresponding to risk of the products should be established. On receipt, the user must verify that each unit has been designed and manufactured according to the approved specifications, including visual inspection of outer packaging, label printing and review of attached documents

● Manual handling of single use technology should be performed according to strict controls and verified accordingly

About the Author:

Muhammad Asim Niazi

Muhammad Asim Niazi has a vast experience of about 11 years in a Pharmaceutical company. During his tenure he worked in their different departments and had been part of many initiatives within the company. He now uses his experience and skill to write interested content for audiences at PharmaSources.com.