During the last decade there has been a significant change in the pharmaceutical and biotechnology industries. Pharmaceutical giants have been merging, while emerging biotechnology companies have accelerated R&D activities. Within the pharmaceutical sector, it was important to merge pipelines to develop and maintain market share when key products were going off patent, while in the biotechnology sector, it was equally important to simply establish a presence. Ultimately, the first company to develop and market a new treatment for a particular therapeutic area will be significantly ahead of its competitors. The need to accelerate product introductions has forced the pharmaceutical and biotechnology industries to focus efforts on drug discovery and marketing. Consequently, outsourcing has become a viable strategic option to accelerate product launches.

Restructuring within these newly merged pharmaceutical companies has led to the elimination of non-strategic functions. Often the departments that were most affected were the clinical supplies departments. In the biotechnology sector, companies are often structured virtually and therefore lack the facilities and expertise to generate clinical supplies in-house. As a result of these trends, the area of contract clinical supplies development has increased dramatically. Contractors are quickly becoming strategic partners in product development. Not only do contractors offer a facility for clinical supplies development, they also offer benefits in numerous other areas.

Why Use a Contractor?
Retaining an entire clinical supplies department and specialized packaging staff may not always be justifiable to an organization. By contracting this work out, study sponsors avoid the added overhead of a clinical supplies department. As a result of constantly changing personnel dynamics, contractors are very effective at managing personnel requirements. They can adjust resources to other areas, such as commercial packaging, or reduce temporary staff when the need may arise. Contracting out clinical supplies development work may be of benefit to both organizations.

Contractors often see a variety of clinical supply designs. They are not limited to following a standard methodology when developing clinical supplies, because clinical supply needs vary from client to client. Contractors can use this vast experience to offer creative solutions to their customers. Offering these solutions is as important as steering a customer away from areas that may have not been successful for the contractor or its clients in the past. For example, to ensure higher patient compliance it may be more effective to package solid dosage form products in blister cards. However, the additional cost of blister packaging may be cost prohibitive to the customer, or the product may be unsuitable to blistering. An alternative may be to use multiple color-coded bottle labels (yellow = morning dose, blue = afternoon dose and orange = evening dose) to increase patient compliance. Contractors with vast experience can offer simple yet effective solutions such as this to increase the study’s success. Steering customers clear of potential pitfalls will help to ensure that clinical supplies stay on schedule and on budget.

As with all R&D programs, staying within budget is essential. A significant cost of the clinical supplies may be the packaging components themselves. Often Phase I and Phase II clinical trials have few patients (20–300) and therefore, buying “one time” packaging components such as blister cards and patient kits in low volumes may not be possible or may be cost prohibitive. Contractors frequently purchase high volume items from their preferred vendors for their clinical and commercial supplies needs. Often, low volume items such as blister cards or patient cartons can be made on a “sample line” at no cost to the contractor. These savings can then be passed on to the client.

In both sectors, R&D programs are equally important to the success of these companies. An important part of any R&D program is the development of clinical supplies. A well-planned and executed clinical trial is critical to the success of any new product. However, a study sponsor may not always realize that the planning necessary to develop clinical supplies is equally as important as the preceding R&D program. If a study sponsor outsources the development of clinical supplies to a contractor, the sponsor at some point realizes that it is not only seeking clinical supplies development, but is also in need of a reliable partner to assist in delivering clinical supplies on or ahead of schedule. The contractor can play a crucial role in generating clinical trial supplies by lending its expertise and experience in creating solutions that will maximize the effectiveness of a clinical trial. Specifically, effective project management offered by the contractor can be crucial to the success of the study sponsor’s clinical program. In order to manage a clinical supplies development program, several key elements need to be considered by both the contractor and study sponsor to ensure a successful development program.

Confidentiality Disclosure Agreement
It is worth noting that, prior to any project-specific discussions commencing, it is incumbent on the study sponsor and contractor to execute a Confidentiality Dis-closure Agreement (CDA). Often it is reviewed by both parties’ legal counsel and may take some time to complete. In order to expedite the CDA, approval by both parties and to commence project-specific discussions, it may be appropriate to initiate negotiations via fax or e-mail while the original copies are in circulation. Once the CDA has been executed there should be no hindrance to communications between both parties in order to determine project-specific compatibility.

Project Questionnaire
A good method for contractor project managers to obtain pertinent information from a study sponsor is through completion of a project questionnaire. A project questionnaire can clearly define the project scope and minimize misunderstandings about project details, timelines and responsibilities of both parties. In addition, the project questionnaire is also a useful tool to communicate project requirements to all involved on the contractor’s development team. If completed thoroughly, a project questionnaire should answer all pertinent clinical supplies needs.

Examples of Clinical Study Supplies Needs include:

The completion of a very detailed questionnaire by the customer will ultimately highlight whether the contract organization has the capabilities to handle the development of the study sponsor’s supplies, or if capital investment of any kind is required in order to complete the project.

A good project questionnaire should also capture all relevant project information that a project manager will need to develop a cost proposal and project timelines. Should the proposal be approved, the project questionnaire can be used as a solid foundation for the development of the clinical supplies. A well thought-out project questionnaire is an invaluable tool. It is a solid first step in good communication between the study sponsor and the contractor.

Developing a Study Plan
Once the contract is awarded, the process of generating clinical supplies begins. Specific discussions regarding clinical supplies manufacturing, packaging and labeling can occur at any time during the study sponsor’s planning for the clinical study. The contractor is frequently not included in these discussions until after it has been awarded the contract, when most other study objectives are near completion and only the clinical supplies are needed. In order for the contractor to begin effective planning for the project, it is always helpful for the contractor to have a fully approved study sponsor’s protocol. Sometimes, only a working copy of the study protocol may be available from the study sponsor. Either way, this document is invaluable to the contractor and should be made available so that the contractor project manager can become familiar with clinical study requirement. Once the clinical supplies program has been confirmed, the program should be plotted onto a timeline and documented on a study plan.

A study plan is a document that breaks down the supplies into its simplest elements.
These elements are essential for a detailed analysis of the clinical supplies requirements. It should include, and not be limited to:

One particular area of clinical supplies that may re-quire extra attention is stability testing of the clinical supplies. On occasion, study sponsors know exactly what is needed and other times they require assistance to generate a suitable stability protocol for their clinical supplies. Either way, stability-testing requirements need to be addressed early on in project planning. It is always a good idea to have a stability manager’s assistance with direction in this area.

Several items need to be analyzed and addressed, which in the end can significantly affect study timing and the ability to generate an effective protocol that meets the clinical study requirements. These include, and are not limited to, availability of validated methods, method transfer timing, stability protocol generation, duration of stability testing, concurrent stability and any third party testing. Ultimately, specific stability-related discussions early in the project planning cycle could significantly reduce the amount of time to release the supplies to the clinical sites.

Facilitating a Quality Audit
When compatibility between the customer and contractor is identified, there is always the small hurdle of a quality audit to overcome. Preparing for any audit is no easy task. However, an effective means of ensuring a successful audit is for the contractor to frequently audit its own systems either with internal resources or with outside consultants. Self-auditing twice a year is a good practice to implement, as it will identify weaknesses or areas for improvement. Once a study sponsor commits to auditing a contractor, an effective practice for the contractor in preparing for an audit is to ask the study sponsor’s audit team for an agenda. An agenda will assist the contractor’s organization by preparing in advance all relevant documentation to make the audit proceed seamlessly. In addition, the agenda should be forwarded to all contractor departmental managers for review. A final reminder a day or two before the audit to all employees confirming the customer’s audit visit is also good practice. Quality audits will eventually be the deciding factor for the awarding of the contract by the study sponsor to the contractor; therefore, extra care and effective communication within the contractor organization are critical for a successful audit.

A contractor project manager should ensure that an experienced Quality Assurance person assists with the audit. The assistance of Quality Assurance is invaluable. Furthermore, at the audit introduction meeting, all relevant facility managers and directors should be available to meet the auditors. During this time, the auditor will lay out his or her expectations and address any other items not included on the agenda. This is also a good time to clarify any points, ask relevant questions and develop a good rapport with the auditors prior to beginning any serious review. Relevant personnel can be called into the audit as necessary and should remain on stand-by for the duration of the audit. Finally, as with any quality audit, the contractor’s entire standard operating procedures (SOPs) manuals should be made available in the audit meeting room for easy access to the auditors.

Packaging Clinical Supplies
The packaging information section of the study plan must be very detailed. It will specifically illustrate in detail how the contractor intends to package the study sponsor’s clinical supplies. Once a study plan is generated, reviewed and approved by the study sponsor, the information can then be used to generate packaging batch records. Detailed packaging batch records are essential. Not only can they give specific direction to packaging personnel when packaging the clinical supplies, they are also important in terms of finished product review and contain critical information for a full assessment should a non-conformance investigation be required.

A key component of a packaging batch record is the packaging procedure section. It may be too time consuming and costly for a project manager to be present throughout the entire packaging operation to assist in clarifying information for packaging staff. Therefore, a little extra time spent on creating clear and comprehensive procedures in this section, describing exactly what is required, can avoid confusion and save a lot of time when it comes to the actual packaging of the clinical supplies.

Packaging Personnel Requirements
Packaging personnel needs must be addressed well in advance of the packaging start date. A review of the study plan and timeline with packaging and quality assurance managers is necessary to determine personnel needs and project scheduling. One method a project manager can use in determining personnel requirements is by developing a standard template for packaging operations. For example, packaging staff would note the amount of time it takes between line startup, the packaging operation and line clearance.

Example:
Labeling 100 bottles = 2 hours x 2 persons
Blistering 100 strips of 9 capsules = 1 hour x 3 persons
Filling 100 bottles with 50 capsules = 3 hours x 3 persons

This data can then be entered into a spreadsheet and, after several projects, a reliable database can be developed and maintained to assist in determining future personnel needs. A project plan, effective communication and a packaging operation database are excellent tools in determining personnel needs and reducing down time. This in turn can become an effective management tool to assist both the customer and contractor.

Project-specific Training
In conjunction with a detailed batch record, it is also a good practice to include project-specific training for packaging, quality assurance and any other project-related personnel. Project specific training sessions can take little time and be of significant benefit in the end. It is easier to clarify any issues or questions at this time than risk mislabeling clinical supplies in the packaging hall. To save time and be more effective, training can occur at the same time as the assembly of the study sponsor’s sample supplies (be sure to mark all components as “sample”).

At this time a thorough review of the packaging steps in the batch record should be completed with the packaging personnel assigned to that project. All project specific training should be documented on a Clinical Supplies Training Record and attached to the batch record. Finally, making oneself accessible throughout the packaging operation, with an occasional visit to the packaging hall, is recommended to project managers, should any questions arise during this operation.

Since packaging of clinical supplies is a specialized process within the pharmaceutical industry, it will be in the best interests of the contractor’s packaging department to keep personnel specifically trained in packaging clinical supplies on staff for such occasions. If resource issues arise, a pool of temporary staff may be brought in for non-specialized packaging needs. Developing a good relationship with a personnel agency that can supply the contractor’s organization with quality people to assist with non-specialized packaging operations can assist with this whenever the need may arise.

The successful development and generation of clinical supplies is a vital part of any pharmaceutical R&D program. Contract organizations that have effective clinical supplies project managers are an invaluable resource to study sponsors whenever they need to outsource clinical supply manufacturing, packaging and labeling. Not only must project managers be knowledgeable in manufacturing, packaging, stability and quality-related issues, they also need to be well versed in effective communication and problem solving. Through a complete project review with the study sponsor at the initial stages of the clinical supplies program development, an effective project manager can assist the client by lending experience and expertise in developing creative solutions to make their clinical study a success.