The unsung hero

The unsung hero

Clinical trial product packaging is a miniscule but an important process for the success of a clinical trial. Arshiya Khan gives an in-depth profile on clinical trial product packaging.

“If manufacturers of healthcare products created a list of important factors required for a successful clinical trial (CT), often packaging would rank at or near the bottom,” starts off Steve Jacobs, President and Global COO, Bilcare, hitting the right note over the grim scenario of CT packaging in India. While most manufacturers believe that chemical makeup or technologically superior devices are most important indicators of clinical success, those that provide packaging services like Jacob contend. “Clinical supplies are often of little concern, but they are key to CT success. If clinical supplies are not handled well, it could cost a company millions of dollars in case the study is invalidated. Added to that, a package that appears third rate or difficult to use may also result in the loss of trial participants. Hence, designing patient compliant packages can greatly improve a company’s ability to show in a statistically significant way that a product works,” feels Vinc-ent Santa Maria, President, Bilcare. And if done properly, it can help to speed a drug to market. If done poorly it can invalidate an entire trial.

CT packaging can be simple or complex, depending on factors like how close the manufacturer feels the product is to market? Or how much time is allotted for package development? After this, packagers can start developing packaging materials and components any time from product conception until the stage at which the product is ready to enter clinical trials. “It is the responsibility of clinical packaging organisations, like Bilcare, to reduce the level of attention and importance paid to the clinical supplies materials by the pharma industry. This will thus, allow them to concentrate their efforts on core activities which are focused on developing new products and chemical entities for to improving the safety and wellness of the communities that they serve,” he adds.

Step by step

Clinical packaging first starts with primary packaging and labelling. Primary packaging is achieved by placing clinical material in a container such as a sachet, bottle or blister package. The next stage is secondary packaging or kitting includes steps that help manage or improve usage compliance of the primary packaged material. An example of secondary packaging is the walleting of blister packages in cards that can help identify that a specific product is to be taken at a specific period. Kitting of clinical supplies is also aimed at improving patient compliance and may include the assembly of bottles or blisters into specially designed kits that consolidate medications for a particular subject. “Patients play a critical role in clinical trials so suppliers must find a way to ensure patient compliance by providing easy to follow label directions,” opines Jacobs. “The packaging must be done in such a way that even if one has to go back and trace he should know with 100 percent accuracy what product the patient took,” he adds. Other components include kit assembly and labelling, final preparation for storage and distribution to clinical sites. The quality, security and barrier properties of packages can affect the outcome of a trial. This will help to manufacture, pack and label the material in a manner that it supports the design.

Unlike commercial packaging, an effective clinical supplies package draws no attention to the package other than the information or configuration required, to ensure the highest level of patient compliance. Avoiding any shortcut CT packaging must be examined just as carefully as commercial packaging. “Clinical package designs are primarily focused on performance. Most designs of clinical packages are intended to ensure that the clinical supplies do not negatively effect the outcome of the clinical study,” says Santa Maria. As a result, the selection of packaging materials are made keeping in mind maximum protection of the product. They may also use protection barriers that are far more superior (and costly) than would be required in a commercial package. “Companies are now exploring efficient means in screening packaging materials at the clinical level, so that late stage clinical trials are conducted in similar packaging materials as that of the commercial packages,” he adds.

  • Packaging must maintain product sterility and give proper directions for use, to the end user–healthcare providers or patients participating in the trial

  • Study drug material effectively for cost or availability. This may require the use of options such as booklet labels and Interactive Voice Response System (IVRS)/ Interactive Web Response System (IWRS)

  • Ensure the overall design of the package and the execution of the packaging process does not introduce any variation that may inadvertently un-blind the clinical trial materials

  • Ensure that the designs of the primary and secondary packages are designed and assembled in such a fashion that is easy for the clinical subjects to conform to the dosing regimen outlined in the clinical protocol. Additionally, approved clinical labels must provide sufficient guidance and clarity to ensure patient compliance while still adhering to appropriate regulatory requirements

  • Ensure that the design of the packaging is adequate in protecting the clinical material from environmental stresses that would alter the safety or efficacy of the study material

  • Comply with GMPs (Good Manufacturing Practices) and GLPs (Good Laboratory Practices)

Factors

There are many factors that determine the nature of clinical trial packaging. Firstly packagers seek only one answer from the manufacturers. What is the goal of the clinical trial? Contract packagers stress the importance of early consultation so that they can get a clear answer and understanding of the manufacturer’s goals. In addition there are other factors like the number of dosage forms, stability and potency of the drug product and the amount of time and money a sponsor wants to spend on developing the packaging before it is launched in the market? The earlier the supplier involves in the process the better it is for the product. “Early supplier involvement in the design process provides the best opportunity to increase compliance and produce the best product packaged on time,” agrees Jacob. “To help manufacturers reach clinical trials quickly while creating reliable packaging, Bilcare offers a complete range of services from package design and production to labeling and clinical trial product inventory control to global distribution,” he informs.

Advancements and trends

2007083169-3028946Technology has successfully found place in this industry as well. In order to keep pace with the growing industry, Clinical Trial Material (CTM) providers have gained advances in technology through booklet labels, infrared label reading equipment, electronic inventory and batch record modules, bar coding systems to track the materials, batch records for packaging, the receipt of the materials into the packaging rooms, finished goods leaving the packaging rooms, to the finished goods state than through distribution to the clinical site.

With the proliferation of public sector capital investment and advances in medical sciences in recent years, the growth in biotech industry has accelerated. This has meant increase in CTM demand as well. “As the biopharmaceutical industry matures, the number of product candidates from these companies entering clinical development is growing rapidly, thus driving demand for CTM services,” avers Santa Maria. The latest trend is outsourcing. More and more companies are looking for outsourcing as an answer to the saturation of their internal capacity. “Biotech companies tend to have limited resources, which they use for their research platforms, and thus outsource a larger portion of the required drug development services. Therefore outsourcing is viewed as a strategic action rather that a tactical reaction in this segment as well,” opines Santa Maria.

Companies today are gradually realising the value of a partner that specialises and has expertise in the area of CTM. “By partnering with a CTM supply specialist pharmaceutical and biotech companies are able to complete trials more efficiently and to focus internal resources on their core activities,” feels Santa Maria. In a scenario when large pharma companies tend to focus on acquisitions and partnerships, smaller companies tend to be solely focused on their proprietary technologies and core competencies in discovering new drugs. Outsourcing CTM is more popular and favoured by small companies. The reasons are simple. Firstly, establishing an internal CTM supply chain requires large investment and secondly a CTM division at a smaller company would be redundant at peak times, as they are less likely to have a steady stream of drugs in the clinical trial phase.

Hurdles

This expanding segment has a few hurdles to cross before it makes a significant impact. There is a huge requirement of expertise to scan multiple countries and follow the clinical trial protocol to maintain the quality as per international standards. Added to the woes are the increasingly complex nature of trials and regulations. “The number of CTs taking place has increased globally and are becoming more complex. In addition, government regulations are progressively becoming more stringent, demanding studies with a larger patient population base,” informs Santa Maria

Conclusion

The few layers of plastic or paper are as important as the pharmaceuticals or medical devices housed within. It protects its contents and successfully communicates instructions to users while meeting the requirements of the clinical trial protocol.

With the emphasis on quality and the expanding biotech and pharma industry, corporates are slowly but gradually realising the importance of CTM even though they don’t rank it in its most wanted list. Packaging the CTM is indeed a very critical component. Even a slight error can lead to fatal results to the extent of turning a positive one to an adverse one and vice versa. The time has come where these unsung heroes are given their due share of importance that they deserve.

arshiya.khan@expressindia.com