•SWIFT accelerates evaluation and optimisation of product performance using in vivo clinical data to direct formulation design in real time.
•SWIFT studies enable you to make decisions on formulation changes based on emerging clinical data.
• This integration of formulation development, GMP manufacturing and clinical testing activities can reduce time from initial prototype development to clinical evaluation in as little as 6 months.
Traditional pharmaceutical development pathways perform product development and clinical testing sequentially, despite the fact that the in vitro tools available to formulators provide no guarantee of success in complex in vivo conditions. The result is a process that is almost trial and error, with performance not fully understood until the last stages of lengthy and expensive development and scale up cycles. If the desired outcomes are not achieved, the process will either need to be repeated with an optimised product or the programme cancelled.
BDD SWIFT provides an alternative to this classical model by enabling product performance to be optimised using continuous feedback from real clinical results to direct formulation design in real time. This integration of formulation development, GMP manufacturing and clinical testing activities can reduce time from initial prototype development to clinical evaluation to just 6 months while dramatically improving chances of a successful outcome.
There are 3 key stages in a successful SWIFT clinical study:
1. Formulation Design –incorporate carefully considered variables within a pre-determined design space to allow optimisation of formulation performance in vivo
2. Clinical Trial Design – an adaptable clinical trial design enabling rapid optimisation of your product with the minimal number of study arms
3. Rapid evaluation of pharmacokinetics – quick and accurate results from each study arm allows time to evaluate data and initiate nimble formulation changes before the next dosing
1. Formulation Design
Following identification of a target product profile, an optimised prototype formulation is developed to match the target in vitro specification. During the development process, variables will be identified which could affect the in-vivo performance of the product. With BDD SWIFT, our formulation team will work closely with your development scientists to identify these variables and create a design space to allow clinical optimisation of your product.
Possible variables include:
• Ratios of excipients – Testing variable amounts of excipients such as pH modifiers, absorption enhancers or disintegrants to achieve optimal blood plasma levels.
• Drug dose – Changes to product formulations may enhance or reduce blood plasma levels of a drug. This can be observed early with BDD SWIFT and product dose amended accordingly.
• Regional absorption – modified or value added medicines may result in the release of products at different regions of the GI tract, where rates of absorption are unknown. SWIFT allows real formulations to be tested at distinct sites of the GI tract to define absorption characteristics and incorporate this knowledge into product design.
These can be combined with other variables such as fed/fasting states to further increase the amount of useful data generated from a single study.
Once the variables have been identified, the boundaries of the design space will be fixed using cornerstone prototype formulations.
Generally one or two variables will be included in the design space, however up to four variables may be incorporated depending on the complexity of the formulation. Clinical trials can be run with formulation variants within the design space and formulation changes made between study arms based on emerging interim safety, pharmacokinetic and scintigraphic clinical data.
2. Clinical Study Design
The trial design will vary depending on the study objectives but will typically be an exploratory, non randomised trial including multiple dosing periods in a fixed number of subjects.
The clinical program will include provisions for the pre-determined formulation design space allowing formulation composition changes within an adaptive trial design framework. The four cornerstone prototype formulations from the design stage will be manufactured to GMP and the data included in the Clinical Trial Application to the regulatory bodies. An algorithm will be designed and incorporated into the clinical protocol to guide the decisions made following analysis of pharmacokinetic, scintigraphic and safety datasets after each study arm.
Different go/no go stages can be incorporated into the algorithm to provide the greatest flexibility with the clinical study and responsiveness to the results as they are generated.
This adaptive trial design ensures that optimal results are achieved from the clinical study using the minimum number of arms and study subjects.
BDD Clinical Capabilities
BDD’s clinical trial unit is located within Glasgow Royal Infirmary in the UK.
The clinical trial unit is ISO 9001:2015 accredited and is routinely inspected and audited by clinical trial Sponsors and the UK Competent Authority, the Medicines and Healthcare products Regulatory Agency (MHRA).
BDD provide expertise in developing and running Phase I-IV clinical trials. Our dedicated team can provide a full level of service including:
Ethical and regulatory approval processes
Clinical trial document design
Volunteer/patient recruitment and screening
GMP manufacture of IMP
Data management and analysis
ICH clinical study report
An onsite ward accommodates overnight patient stays, if required, for monitoring or to ensure compliance with study lifestyle or dietary restrictions. Our GCP-trained locum medics provide medical cover for all trials and we work closely with hospital physicians, who we routinely appoint as Principal investigators.
The clinical trial facility has an MHRA approved GMP manufacturing suite where we manufacture Investigational Medicinal Products expertly to ensure regulatory compliance and the highest quality of clinical data. Formulations can be manufactured and QP released in a little as 4 hours to enable rapid transfer to from manufacture to clinic for dispensing and clinical administration.
3. Rapid Evaluation of Pharmacokinetics
BDD can provide the SWIFT service from formulation design or using formulations that have been developed in our clients lab. Typically, from receipt of API and identification of the target product profile, the BDD development team will develop the target product and prototype cornerstone formulations within 6-8 weeks. This process may take longer for complex formulations or for more difficult to handle API. Future success of the SWIFT protocol depends on a strong formulation base and its worth investing some time at this stage.
Clinical trial set up procedures and regulatory documentation can be started prior to completion of the development phase to expedite the clinical approvals process. The clinical team are co-located with and work closely with our formulations lab to share expertise and knowledge which is brought to every client project to ensure that what we deliver goes beyond your expectations. Each SWIFT project is managed by a SWIFT project manager who has experience working in both development and clinical and will ensure smooth and rapid transitioning from the laboratory to clinic.
Advantages Offered by BDD Swift Studies
In vivo testing of more than one formulation variant in a single clinical study significantly improving opportunities of achieving the desired pharmacokinetics.
Early indications of the development projects feasibility without the significant financial and time commitments traditionally associated with manufacturing clinical trial batches.
Early testing in small patient groups before expanded testing with an optimised formulation, minimising the number of patients or volunteers that may be unnecessarily involved in clinical trials.
Single contract for development and clinical testing, streamlining contracts and negotiations.
Enables products to get into the market faster bringing significant gains through early revenue generation.
Since our formation in 2001, BDD Pharma has completed clinical studies across a wide range of therapeutic areas and different dosage form types. At the heart of everything we do is a solid scientific base on which quality products can be built.
Traditionally, pharmaceutical product development encompasses an element of trial and error.
BDD SWIFT accelerates evaluation and optimisation of product performance using in vivo clinical data to direct formulation design in real time. SWIFT studies enable decisions to be made on formulation changes based on emerging clinical data. This integration of formulation development, GMP manufacturing and clinical testing activities can reduce time from initial prototype development to clinical evaluation in 6 months.
BDD has helped our clients find solutions at all stages of the development process, providing scientific evidence to underpin pivotal decisions from early product design to the generation of phase IV data supporting product claims and informing patients of product benefits.
One of the key things that we have learned is that great products are developed when clinical and development teams work together from the start.