Ready to use containers in pharmaceutical industry

The pharmaceutical industry is bracing for setting new standards, in response to varying patient requirements. These new standards have been mainly fueled by advancement and innovation in pharmaceutical industry, and interestingly it is impacting all components of pharmaceutical industry. The latest is the trend of manufacturing patient-specific drugs. 

The varying patient needs are shifting focus on manufacturing patient-specific drugs rather than general population-based products. As with the manufacturing, packaging is also shifting its focus in response to latest trends

Packaging for pharma drug products has previously been manufactured to fulfil general-purpose dose requirements. However, since pharma products focus on new challenges, issues, and problems, the packaging sector also join their hands in facilitating them. 

Ready to use containers are one of the latest trends; they eliminate the need for on-premises sterilization, increases the capability of a container against contamination and shortens the time to pack.

What is ready-to-use container?

Ready-to-use containers are pre-sterilized (un-filled) containers packed in appropriate packaging material. In contrast to traditional packaging containers, they do not require sterility methods to prevent hazards. They do not require specialized (classified) areas during storage (before filling), since their packaging is suitable to prevent damage. 

During manufacturing, packaging and other relevant processes of ready to use containers, strict control of contamination & sterility is maintained, making it safe from all hazards. Additionally, traditional sterilization and sterility methods are not required at during manufacturing process at the pharma facility. For this reason, they can be directly used on filling machines without the need for intermediate steps and operations, including the washing and depyrogenation process. 

Ready-to-use containers are physically packed in a packaging called Nests. It contains a specific number of containers in it. For this purpose, the filling machines are designed with specialized input feed to accept the nests. The filling machine automatically collects individual container without human intervention. 

During the filling operation, the nest is collectively fed into the machine, which automatically picks up the individual container and fills the required pharma product in it. This is equivalent to same process with the traditional filling machines where containers are added in a tray.  

Ready-to-use containers allow pharma drug manufacturers to quickly respond to changing supply demands due to less inherit time.

Eliminating intermediate steps during product manufacturing, means that the area and equipment for these processes are also not required at the pharma drug manufacturer's location. Time is also reduced since containers are directly fed to the filling machine, which is the major driver towards less time to market, which we will discuss later in this article

The conventional and old method has been delivering un-filled containers to the filling departments of a pharma manufacturer, where they undergo a series of steps, as mentioned above, for the product's safety, integrity and quality. These intermediate steps require a lot of resources, such as testing, equipment, personnel, area and time to execute, ultimately adding to the cost of the product. 

Types of ready-to-use containers in the pharmaceutical industry

Ready-to-use container technology is currently being implemented for sterile products such as injectable. Containers used in injectable are presently being produced through this technology.

Let's discuss some products available under this category.

Ready to Use Vials

Ready-to-use vials include vials, rubber stoppers and pre-sterilized seals and are directly fed to the filling machines. Commonly, they can be custom-manufactured depending on the customer's demands. This means they can suit the customer's product requirement, even if the dosage is in non-standardized volume and type. 

The material of manufacture for vials is commonly of parenteral grade, such as borosilicate glass. Stoppers are made up of suitable materials with high chemical purity and low gas permeability. Similarly, stoppers comprise of  suitable material with high container closure integrity and product protection. 

Ready to Use Syringes

Ready-to-use syringes are injection syringes that can be directly fed to filling machines. Some variants also allow filling the product, called prefilled syringes.

It consists of a syringe body made of polypropylene material with a pre-assembled lounger. At the top is a lock mechanism and protective cover to cap and protect the syringe. The protective cover is tamper-evident and efficiently detects if it is tampered with. 

The ready-to-use syringes are directly fed to a filling machine, known as a prefilled Syringe – PFS machine. This machine fills the product in it, and the patient can directly administer it without needing to fill the pharma product in it. 

The volume and capacity of the ready-to-use syringe are pre-determined according to the customer's requirements. 

Ready to Use Cartridges

Ready to use cartridges can be directly processed on the filling machine without contamination, hazard or contact with any object. They are packed and fed to the filling machine in nested form.

Ready-to-use cartridges are made up of pharma-grade glass, such as borosilicate glass. 

Advantages 

Some advantages we can benefit from include the following

Flexible infrastructure

For necessary reasons, traditional glass containers require cleaning and sterilization to prevent contamination and eliminate foreign particles. Since each pharma manufacturer has different strengths of each product, they require separate resources such as sterilization and filling lines, or at a minimum, separate change parts. Additionally, some products require separate area tools. 

Ready-to-use containers have undergone these processes by their manufacturer. They are directly fed to filling machines without investing in or developing intermediate equipment. It also eliminates the need for relevant areas for these intermediate equipment (area, personnel, and instruments). This feature can save pharma manufacturers time and money in developing its area and equipment. It also saves time and investment on area approval, accreditation and maintenance. 

Flexible Operations

Conventional systems have different container sizes for each dose that require dedicated equipment, instruments, accessories and areas. At a given time, is possible that a specific dose-size equipment remains idle (due to no product requirement from the supply chain department), while continuing to consume resources to keep equipment and area in a production-ready state.

For traditional containers, it is also necessary for the pharma manufacturer to procure individual container size for individual product size. If the required container size is not available, the pharma manufacturer is forced to adjust its product strength according to available container sizes. 

Ready-to-use containers can be custom-made according to the manufacturer's requirements, and more than one dosage size can be used to be filled on a single filling machine. As a result, resources for only single machine (instead of multiple machines) are consumed, decreasing the operational cost. Especially when a specific dosage size remains idle due to the unavailability of a production plan.

Less Time to Market

Conventional containers for sterile products require series of steps and tests that could take longer  - the minimum can be around one week. The manufacturer must wait for these steps and until results are announced cannot market its product. The intermediate steps also require safety measures and relevant testing that contributes to the release time. For these reasons and alike, conventional procedure takes more time before it gets into the market and ultimately into the hands of patients. 

Read-to-use containers significantly reduce the time to market, and the product lands in the patients' hands in less time. This is due to the elimination of time-consuming processes in ready-to-use technology. Ready-to-use containers are pre-sterilized, and their relevant quality checks are performed at their manufacturing stage. The processes and quality testing at the washing and sterilization phases are also reduced, effectively increasing the market time. 

The filling operation is compatible with quality protocols and can be qualified in less time than conventional.

FDA Guidance on Dose Banding of Ready to Use container

The FDA issued a guidance on dose banding for ready-to-use containers, titled Human Prescription Drug and Biological Products--Labeling for Dosing Based on Weight or Body Surface Area for Ready-to-Use Containers--"Dose Banding". This guidance aims to target the labelling of ready-to-use containers based on weight or Body Surface Area.

The primary purpose of this guideline is to ensure that all drug content is administered to the patient and that it is well-spent in case the patient's required strength is insufficient with a single container. It solves this problem by assisting pharma product manufacturers to label their products based on weight or Body Surface Area

According to this guideline, the FDA suggests

• Display dose banding information on the container and its approved dose strength. It should also include guidelines for its end-user to select ready-to-use containers based on the patient's weight. 

• Where applicable, provide scientific information supporting the labelled dose banding values. A detailed overview of the approved and proposed dose 

• Provide detailed information about the available ready-to-use container and dosage values. 

• If the available dosage falls outside capacity of available ready-to-use containers, provide details about the recommended dosages ( w.r.to available dosage types)

Some specific steps advised according to these guidelines,  for product manufacturers, includes 

• Performing validation studies on the manufacturer's proposed dosage and verify its safety and efficacy.

• Provide data of validation studies to the regulatory bodies during their inspection

• Updating relevant labelling to incorporate new guidelines (stating clear guidelines for selecting and administering these containers according to weight or BSA)

• This guideline seems to add extra burden or process for the ready-to-use container manufacturer. However, it saves the drug wastage and simplifies the medication errors. 

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.