Nancy St. Laurent, Senior Engineer
Sterile Facilities/Packaging Systems
“Innovation” is a term not normally applied to pharmaceutical packaging. There are many reasons for this, mostly due to the requirements to comply with product safety, efficacy and quality. The immediate container/closure system has to be tested and be compatible with the intended drug it will contain.
Changes in these systems have to undergo stability testing. In many cases, it is not economical to change a container/closure system. Where there are significant advantages, particularly for a different administration method, it takes years of thorough testing and filing of these changes with the FDA.
This article will discuss the many advances that have been made to all phases of packaging, including immediate container/closure systems as well as devices and other packaging innovations. It will also discuss the effects these changes have on packaging equipment.
Packaging is defined by the new ISPE Baseline® Guide for Packaging, Labeling and Warehousing Operations as filling the dosage form in the immediate container/closure system and other ancillary packaging.
Container/Closure InnovationsFor years there was little change in traditional container/closure systems.
There were bottles for tablets, and they evolved into various shapes and sizes. Then childproof closures were added to these bottles. Childproof closures have evolved as well, although a lot of improvement is still needed in this area. While traveling recently, I purchased a bottle of analgesics that I was unable to open. Fortunately I had a pocket knife in my suitcase. I literally took this knife and removed the entire skirt of the cap before I was able to open this childproof cap. Then you also have to contend with all types of induction seals and outer bands for tamper proofing.
Blister packaging has evolved into many new and innovative packages. Many of the new packages are designed for patient compliance. You read constantly that most patients do not take all of the recommended drugs prescribed for them. The new packages are designed for weekly and monthly supplies, some actually with prescription and non-prescription doses, such as Actonel® that is prescribed once a week but is supplied with calcium tablets for the other six days of the week. These blisters can be in cards, wallets, or folded boxed packages. Most blisters are produced for over-the-counter supply. Some blisters are very easy to open, but some are extremely difficult to open, requiring scissors or some sort of assistance in opening. The equipment, the equipment settings and the materials used can have an impact on the structure of the package and the ease of opening.
Some concern has been recently expressed over the repackaging done by mail order and traditional pharmacies. They repack most drugs into new bottles with new closures and do not always include patient information or desiccants that may be included with the initial packaging from the pharmaceutical company. The choice of closure is not always available from the mail order companies but it is an option from most traditional pharmacies. Traditional pharmacies do include detailed patient information. In some cases, the pharmacy will supply you with the original package from the pharmaceutical company, complete with desiccant and patient information. Where the product is produced as a monthly supply, you most always receive the original package.
Parenteral drugs were traditionally in syringes, vials, sometimes ampoules, IV bottles and bags. Although the containers are still very similar, there are many different types of administration devices. These include safety syringes, adapters for saline flush, multiple IV’s. There are multi-part syringes and vials with both lyophilized and liquid products. There are auto injectors, multiple auto injectors containing two drugs, needleless injectors and a new micro-delivery system for vaccines.
Alternatives to glass for parenterals are starting to enter the market. Worldwide, many plastics are used in blow/fill/seal operations for parenteral products, but there has been a reluctance to use this technology in the U.S. for human injectables. The U.S. does use this technology for animal health injectable products. There is, however, a new material that is being considered for use. Cyclic Olefin Copolymers (COCs) are a new family of materials suitable for high-performance optical, medical, electrical, packaging, and other applications. This material is a credible alternative to glass in the design of pharmaceutical primary packaging, including injection devices such as films, pre-filled syringes, vials, bottles and other containers.
Other innovations in production and on the horizon are many unique inhalation devices. These range from the traditional nasal sprays to powder inhalers. In some cases, the package is the device, and in others, a tablet can be placed into a device. Continuous innovation is anticipated in this area to ensure the best adsorption of the drug as possible.
Now we also have a multi-phase, multi-compartment clear capsule that can deliver incompatible compounds in a single dosage form with different release profiles. This technology could be used to deliver multiple drugs at different times to the patient.
Patches, needleless injections and many other innovative administration devices are on the market, and many more are on the horizon, such as drugs being embedded into dissolvable strips by using the same technology as oral care strips.
Ancillary Packaging InnovationsSome of the devices discussed above fall into this category as well. For example, inhalable powder may already be packaged into a blister prior to being packaged into the device used for inhalation.
One of the earliest additions to the primary package was tamper-proof packaging. This was applied initially to the bottle and then eventually progressed to the immediate carton with shrink wrap, glued ends and so forth.
Traditionally, plastic thermoforming has been used for multiple products in a package. In Europe the alternative to this is cardboard blanks that are used to form trays and cartons, eliminating the plastic use.
Some of the innovations in packaging are intended to provide more information for hospitals and consumers, and to counteract counterfeiting activities.
Bar coding is now required on all unit dose packages supplied to hospitals. This has been a challenge, particularly for those products in blister packages. RFID technology is being added to packages in an attempt to thwart counterfeit activities. Secure shift inks used on bank notes are being evaluated for incorporation into packages. In some instances, combinations of identifications are being used to protect the product more thoroughly. Multi-part labels that contain patient information or duplicate information for physicians are another new innovation.
A unique technology was discovered in England where it was found that each piece of paper, cardboard, or label has its own characteristics. The company is Ingenia Technology and has a new code. It has been described as being like a fingerprint or DNA sequence for the item, is unique for every document, card and carton, and can be used to uniquely and unambiguously identify the item.
Equipment ImpactAs each of the above changes is implemented, there is a subsequent impact on the equipment required to put the dosage form into its package. In some cases, this is an addition to existing equipment, such as bar code printing, bar code scanning, RFID coding and reading; devices can be added to existing labeling, cartoning and case packing equipment. In other cases, very sophisticated custom-designed equipment needs to be developed, particularly when new methods of administration are invented. Inhalation therapy, new administration devices, and strips that dissolve in your mouth all require new and unique equipment.
As packages become more innovative, equipment suppliers are improving the equipment manufactured for pharmaceutical companies. Equipment that is easier to operate, easier to clean and easier to validate is being mandated by the pharmaceutical industry. The days of painted packaging equipment on the packaging floor are long gone.
SummaryOne of the future trends is targeted medicine for specific individuals. This could involve all new product formulation, new product combinations and hence new packages for the consumers. It could also lead to an entire new industry, an intermediate industry that formulates product/product combinations for individuals. Some research hospitals are doing this now for targeted types of cancers.
Companies are forming partnerships with other operating companies and with packaging material and medical device suppliers for new and creative administrative devices and packages. As consumers become older and medical technology improves, we should anticipate increasing improvements in packaging. We hope package designers will continue to create packages that are easier to open and easier to use, which could encourage patient compliance.