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Clinical trial recruitment (CTR) initiatives can be highly successful

by Hugh G. Davis, Senior Instructor , Kriger Biopharmaceutical Career Training Program ,

This article has been published by the International Biopharmaceutical

The project is sponsored by KRC CRO and training services ( ) and ClinQua CRO ( )

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Over the last ten years, getting patients and doctors into clinical trials has become the most delay-ridden aspect of the drug discovery and development process. When implemented effectively, clinical trial recruitment (CTR) initiatives can be highly successful. Time lines can be dramatically reduced and recruitment targets can be met ahead of schedule; every day saved in the progression to marketing authorization can equate to millions of pounds made in patent-protected sales revenue.

However, great care is needed in the development of a CTR program. Considerable ethical scrutiny is applied to all patient recruitment materials and initiatives. For example, in 2002 the European Commission issued guidelines for consultation which require patient advertising and details of recruitment initiatives to be submitted to appropriate ethics committees.
Unfortunately, there is no simple code of practice established and no unified regulatory body and no recourse to appeal. If an ethics committee doesn't like what a CRO has planned, the CRO can't use it. In Europe, this aspect has yet to be effectively addressed.

Enhancing CTR is obviously an area in which great caution is required. Some investigating doctors, for example, question the need for extra activities as, they claim, there are sufficient numbers of suitable patients among those already attending their clinics. However, practical experience has shown that this is an over-estimation of the number of patients physicians will be able to recruit and it is estimated that only about 10% of a physician’s patients will actually wish to enroll in a clinical trial.

Perhaps more importantly, there are also objections raised from within the industry. These usually centre on a highly cautious approach to the ethics and legitimacy of patient-facing initiatives. Some nervousness is understandable given the strict controls that govern DTC marketing but for clinical research there is a critical need for increased patient understanding and education. The signs are that the caution of the industry is slowly giving way to a new openness and confidence.

A review of recent press coverage also highlights a deep skepticism of industry involvement in clinical research. If not approached ethically, a firm’s CTR campaign can leave them wide open to aggressive media criticism and adverse advocacy relationships. The key point to remember is that the objective of all this work is ultimately to improve care for the patient. A strenuous effort to maintain this focus throughout clinical development will ultimately allow pharma companies to reap considerable rewards.

Over the past several years these problems have been addressed in the US, where clinical research receives more and more active support of government bodies, advocacy groups, charities and patient groups. This provides a collaborative environment and ensures that there is always an independent counterpoint when the integrity of industry-sponsored studies is attacked.

The American public sees a vast amount of government-sponsored education, designed to maximize understanding of clinical trials. A quick look at and, both run by the National Institutes for Health, illustrates just how much work is being done. This in turn is supported by private efforts such as, which is currently offers a 300-page book on informed consent for patients.
The nature of American healthcare provision no doubt motivates patients to seek free or subsidized medication, but the investment, approach and partnerships in the US are demystifying clinical trials and generating considerable goodwill toward industry-driven research.

A recently announced US public/private partnership designed to improve trial recruitment demonstrates how support for industry research can be broadened. The initiative created a $6m fund, which the contributing pharma companies and National Cancer Institute will use to accelerate patient recruitment for Phase I and II cancer studies. Naturally, the credibility of the public bodies involved enhances the effectiveness of the scheme.



The effectiveness of technology transfer is one of the key determinants in the success of a contract-manufacturing project.

by Hugh G. Davis, Senior Instructor , Kriger Biopharmaceutical Career Training Program ,

This article has been published by the International Biopharmaceutical

The project is sponsored by KRC CRO and training services ( ) and ClinQua CRO ( )

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Just as there are CROs to provide clinical trial services, Contract Manufacturing Organizations (CMOs) exist to fill a market niche within the biopharmaceutical industry. Where a sponsor finds it self in a situation where it is necessary to outsource the manufacturing of a drug or device, the most critical component in the relationship with a CMO will be technology transfer. The effectiveness of technology transfer is one of the key determinants in the success of a contract-manufacturing project. In most cases, it is the biggest unknown with respect to timelines, cost and expertise from both the client’s and the contractor’s viewpoints. In spite of the fact that it requires expertise and involvement of both parties, the burden is invariably on the Contractor to demonstrate to the client that it can successfully perform technology transfer. The proficiency of a CMO in performing Technology transfer is determined by its experience in dealing with several types of projects, coupled with the strategies and tools that it employs. The advances in software technology have provided the opportunity to develop customized tools to address specific needs of technology transfer in bio/pharmaceutical manufacturing. We shall examine some tools and strategies that can be used in representing, communicating and exchanging project and process information throughout the different phases of technology transfer.

Technology transfer begins with the first contact between the client and the CMO and e nds with the timely execution of the production campaign. The first exchange of information occurs through an RFP provided by the client or through the information provided in response to a CMO’s questionnaire. In preparing these documents, every effort should be made to provide as much detail as possible about the project scope, the project deliverables and the extent of prior experience with the product and process. In addition, discussing the client’s prior experience with contract manufacturing can provide very valuable information for the CMOs. However, some of these documents do not offer all the information to determine project fit. In order to obtain all the relevant information, we are developing a user-friendly electronic questionnaire with a click-choose-check interface, enabling clients to submit the information electronically in a secure fashion. The information provided in the questionnaire is useful as an initial screening tool, since it is impractical to respond with complete detail to every request. Detailed information, if available, will result in quality responses from the CMOs.Project initiation typically follows the agreement between the client and the contractor. Project teams are assembled at this point with the respective project managers providing the interface between the teams for communication.

Process and project information transfer from the client to the contractor occurs typically by transfer of all the relevant documents. Information not received and distributed in a structured manner is of little value. Project managers play an important role in organizing the information available and presenting it to the entire team, as needed. Transferring the documents to departmental or functional managers may not be very effective, since everyone in the project team should know what information is available and be able to access the information when necessary. One effective strategy is to place any available document in a central document server. The meta-data of the information available could be summarized by the Project Manager to enable easy access to the appropriate files.

Information transfer and exchange have become even more challenging as companies are utilizing different CMOs during different phases of product development. Due to issues of confidentiality, open sharing of information is not possible between CMOs, requiring “indirect information transfer.” In addition, product development involving multiple companies is becoming common in the biotech industry. Information transfer in such situations can be challenging.

Transferred processes are often implemented at different scales or with modifications compared to the original process. The challenge of technology transfer stems from determining how the process can be implemented with the equipment, systems and space availab le to the contractor, while maintaining the quality requirements of the process/product. The process design should also take into account the expertise and extent of other support services (QC, raw materials testing, utilities, equipment wash, autoclaving, buffer prep, etc.) available to the project. The other dimension to this challenge is to achieve the throughput requirements dictated by economic reasons, especially in transferring in-house projects/ processes that may not have been constrained previously by time, resource and/or space availability. The only working strategy in overcoming these challenges is for the client and contractor teams to work very closely together to develop practical solutions. Early team building becomes valuable in these situations.

Scale-up/Engineering design calculations should be made to determine the size and scale of equipment needed, especially for long lead-time items. Quantity estimates of long lead time/large volume/quantity raw material should be made to ensure timely procurement. Developing and maintaining an updated equipment and materials database, comprising selected high-quality vendors, lead times, scale, size, storage, quotations, package sizes, sampling and testing arrangements, can be very valuable in readily evaluating options.

Engineering runs are performed at scale to identify and resolve process/equipment issues. It has become an accepted practice to include engineering runs as part of contract manufacturing projects, in spite of the resources they consume. It has become clear to the clients and the CMOs that a successful engineering run guarantees quality for the subsequent cGMP runs. During engineering runs, reviewed draft current Good Manufacturing Practice (cGMP) documentation is used. Modifications are made as necessary, with the goal of making them permanent in the Master Production Record. Engineering runs should also serve as invaluable tools for hands-on training. Adequate time should be allowed between the engineering runs and cGMP Production Runs for modification of the Master Production Record and for re-training as necessary.

Troubleshooting of process should be done during engineering runs, and a minimum of one problem-free engineering run should have been done before initiating the cGMP production campaign.

Completion of a few consistent cGMP production runs is the only indicator of the success of a tech transfer exercise and hence only then can tech transfer be considered complete. One cannot overemphasize the fact that a successful campaign requires concerted effort from all team members.

Ideally, a product will be produced by the same CMO from Phase I through to Phase III and commercial supply, taking advantage of the knowledge base and expertise gained by the CMO. However, it is not uncommon for clients to decide to manufacture in-house for later phase/commercial supply. In such cases, CMOs will have to perform tech transfer back to the client, following the same strategies outlined above. Therefore, a project may begin and end with Technology Transfer, requiring the team to be constantly aware of the progress of the project all the way through.

Contract manufacturing of biopharmaceuticals has become accepted as one of the primary routes of product development as companies are focusing more on discovering products. Technology transfer will, therefore, be one of the deciding factors in determining the fit between the client and the CMO, requiring both parties to learn to do it better. While we have introduced some of the tools that could be used to enhance the efficiency and overcome the challenges, there is clearly a need for “a better mousetrap.” Software-based tools will constitute one of the major areas for such improvement, as the biotech industry has tremendous opportunities to utilize new software technologies. The most important requirement, however, is a partnership between the client and the CMO that is built on trust.


The project is sponsored by Kriger Research - CRO and Training Services (  ) and ClinQua CRO (  )


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