Packaging & Bottling - Signed and sealed

Fitting news: The choice of seal can help create operational efficiency and eliminate potential sources of bioburden and particulates

Sylvia Marzotko, discusses how to increase patient safety through clean sealing in a Q&A.

What role do caps and seals play in terms of high-quality in pharmaceutical manufacturing?

Many pharmaceutical and packaging manufacturers have placed emphasis on materials in direct contact with the drug product itself, such as the glass vial, plastic syringe, and elastomeric stopper or plunger. Additional packaging elements, such as caps and seals, were little thought of. However, in recent years, regulatory guidelines have influenced the requirements for crimping processes significantly.

What regulatory guidelines do pharmaceutical and packaging manufacturers have to take into consideration?

The European Medicines Agency (EMA) Annex 1 “Manufacture of Sterile Medicinal Products” specifies that the manufacturing of sterile products is subject to “special requirements in order to minimize risks of microbiological contamination.”

When it comes to processing, precautions must be taken to minimize contamination during all stages before sterilization, and the EMA refers in particular to two processes in the fill-finish area of those manufacturing plants that also perform aseptic filling: Aseptic Crimping and Clean Crimping.

What are the specifics for aseptic crimping?

Aseptic crimping requires the use of sterile seals. A drug product’s biological and particulate cleanliness is best assured using aseptic crimping processes and pre-sterilized components. For aseptic crimping processes, as well as for reflecting the trend toward controlling particulate cleanliness, knowledge about particle specification limits may be requested.

In order to meet aseptic crimping requirements there are high-quality sterile seals available that have a specified bioburden level prior to sterilization (as referred to in EMA Annex 1 Clause 80) as well as a specified particulate level.

How does clean crimping differ from this?

For the clean crimping process, capping and crimping is performed in a non-aseptic environment under Grade A (Class 100/ISO 5) air supply. EMA Annex 1, Clause 120 notes that when vial capping is undertaken outside of the aseptic core, “vials should be protected by Grade A conditions up to the point of leaving the aseptic processing area, and thereafter stoppered vials should be protected with a Grade A air supply until the cap has been crimped.”

Although for clean crimping processes the use of unsterile seals is not excluded by the EMA Annex 1, there is a growing uncertainty regarding the introduction of potentially biological contaminated components into the clean crimping area and the effects on operational efficiency that this might cause.

In order to meet regulatory requirements and ensure clean crimping procedures,  pharmaceutical and biopharmaceutical companies increasingly have turned towards ready-to-sterilize and ready-to-use sterile packaging components and product qualities.

Are  there any sealing components which meet especially the needs of pharmaceutical companies performing clean crimping?

Yes, there are high-quality seals available that meet the needs of companies performing clean crimping. These seals have a bioburden level controlled and specified before sterilization and are developed for clean crimping under grade A air supply.

Using high-quality packaging components ensures a stable crimping performance, which minimizes the risk for introduction of external contamination, line stoppages and equipment down-time.

What do drug manufacturers have to keep in mind when choosing the right seals?

Just as different drug products may require different primary containers (i.e., those with a high pH level may require a polymer container to ensure efficacy), secondary packaging also maintains a variety of levels to ensure that the right quality is provided for the drug product and the manufacturing process. For many, a high-quality sealing component that is vision controlled, consistent and reliable during the capping process is an excellent choice. In particular, this type of seal can be a cost-effective method for clean crimping processes.

Increasing quality levels for seals would include sterile, ready-to-use components that have specified and controlled bioburden levels before sterilisation. It is expected that this type of seal will become the future standard for clean crimping under Grade A air supply.

Whether a manufacturer decides to use aseptic crimping or clean crimping, the choice of seal can aid in the process by helping to create operational efficiency and eliminate potential sources of bioburden and particulates. High-quality seals are intended to meet operational and regulatory challenges and consistently achieve reproducible and safe container integrity for the drug product. Use of such a seal will increase filling line efficiency and drug product safety, helping to meet the regulations and expectations of an industry for which quality is an ever-growing concern.