When we speak of a pharmaceutical product and producing it in a controlled environment with extreme contamination control measures, and especially with parenteral products, pharmaceutical companies aim towards zero tolerance of pathogens, endotoxins, and other non-organic contaminants. While the uninformed may think that once the product rolls off the assembly line to be packaged,we need no longer worry, that’s far from the case.

I recently spoke with Fran DeGrazio, Vice President Marketing and Strategic Business Development at West Pharmaceutical Services about packaging.

Controlled Environments: What are the challenges in pharmaceutical packaging and how have they changed in the last decade?

Fran DeGrazio: With the advent of biopharmaceuticals, one of the larger issues is producing primary packaging components that are compatible with the special attributes that are associated with the biotech products. This involves concerns like sensitivity to certain ingredients which may come out of the packagingas leachables.

CE: So when you know what the sensitivities are, what do you do?
FD: There are, for example, films and coatings that can be used as barriers to help minimize that. These can minimize the transmission of leaching andalso help improve general chemical compatibility and other problems.

CE: What other problems?
FD: For example, when delivering certain types of proteins, there is likelihood that these drug molecules can adsorb to the glass packaging containers and thereby have less amount of drug available for treatment. In order to minimize or eliminate these issues, we have a material called CZ™ Resin. It is a plastic material, made up of a cyclic olefin polymer, available as a vial and syringe. The properties of the material lend itself to have lessof a propensity for protein adsorption, versus say, traditional glass.

CE: Then you need to know all the potential adverse effects of different chemicals on the drug?
FD: Yes, another example is certain drugs may be sensitive to sulfur, which is a common constituent in some rubber elastomer formulations. Another sensitivity may be to silicone oil. Silicone oil is commonly used as a lubricant, whether it is in a prefillable syringe system or as a lubricant on stoppers as they get assembled onto vials. Sometimes there are certain proteins that can bevery sensitive to silicone oil. A droplet of silicone oil, if it got into the solution, could act almost like a nucleus to cause agglomeration of the protein. Another benefit of the CZ™ Resin syringe system is that it does not utilize silicone oil. This is a very unique feature which is extremely beneficial forcertain biopharmaceuticals.

CE: So match the coating to the material?
FD: The trick is not only the coating itself, but the whole component which the coating is a part of, because there is no coating that is 100% impervious. So over time, depending on conditions, depending on what the drug product is, depending on sterilization cycles, all these things can have an impact. You can’t look at it as just a film, you have to look at it as a totalproduct.

CE: Is choosing the materials and the coating an art or a science?
FD: It is really a combination of both. It has gotten more scientific than it used to be. But it is really experience, knowing your materials, and working closely with your customers. One thing you can be confidant of, is it is not a “one size fits all” kind of thing.

CE: I suppose the other problem is how the product will be used in the field.
FD: Definitely. Absolutely. Even something as simple as a stopper and vial. You really need to know how it is going to be used in the field. This is why I think it is important to work with your packaging suppliers. For example, take a vial stopper assembly. What kind of needle is going to be used? Is it going to be a multi-dose application or will a spike go through it? Typically those kinds of issues really cause a problem once the product is out in the field because the chemical aspect is typically addressed throughout stability. It’s understanding delivery systems and devices, and their associatedfunctional attributes that are also critical.

CE: And I suspect training of field use is important?
FD: You are absolutely right on that. Let’s go back to what people think is a relatively simple package—a stopper and vial. We actually had an example of a nurse who could not get a needle into the stopper, so removed the stopper. What worse scenario could you ask for?

CE: How would you sum it up?
FD: There’s no perfect material. You are always balancing properties.It comes down to experience, judgment, and knowing your materials.