Pharmaceutical companies are turning to drug delivery technologies to boost pipelines and compensate for patent losses. Currently marketed drugs are being repositioned through reformulation using novel drug delivery technologies and drug delivery approaches are being considered early in the development program of new chemical entities. Transdermal drug delivery is an attractive area of research due to the development of patch technologies that can be used to deliver drugs that are typically administered by injection in an effort to increase compliance and improve outcomes.
The 4P team is experienced in developing a broad range of transdermal drug delivery technologies. These range from conventional transdermal systems to novel transdermal technologies for use in the delivery of water soluble small molecules as well as peptides, proteins, vaccines and macromolecules that are typically delivered by needle injection. The company’s team also has experience with developing oral drug delivery technologies, medical devices, and diagnostics, skills which it leverages for the development of combination products.
4P specializes in accelerating products from concept to proof-of-concept, by moving quickly from the establishment of preclinical feasibility to the demonstration of proof-of-concept in humans. Once the product concept is demonstrated in humans, 4P leads the execution of the clinical/regulatory program as well as the tech transfer process, supports design for manufacturing, and manages its key contract manufacturing relationships during scale-up and commercialization.
4P Therapeutics has developed an efficient preclinical model to assess the feasibility of delivering a compound using drug delivery technologies. The model is designed to establish pre-clinical feasibility followed by proof of concept in human clinical trials. Potential partners interested in developing products with 4P Therapeutics are not required to invest significant capital and resources upfront. Once the feasibility has been established and considerable risk has been mitigated, 4P Therapeutics and its partner can then choose to enter into a broader product development agreement.
A preclinical feasibility project consists of the following steps:
- Evaluate the physicochemical characteristics and delivery requirements of the compound
- Select the delivery technology that has the best chance of success
- Develop and qualify analytical and bioanalytical methods
- Develop formulation/device configuration for in vitro and pre-clinical testing
- Conduct in vitro and in vivo testing using pre-clinical models
- Optimize formulation to meet target delivery profile if necessary
- Finalize the drug delivery configuration to be used in initial clinical testing
Once preclinical feasibility is established and the drug delivery configuration is determined, the next step is to further develop the Chemistry, Manufacturing, and Controls (CMC) aspects required to support filing an IND (FDA) to proceed into a Phase 1 clinical trial. These include the development of the small scale manufacturing process suitable for clinical trial lots and the qualification of the associated test methods, establishment of the specifications, and performing stability studies and lot release tests.
4P capabilities include small scale manufacturing processes for transdermal patches, drug solutions and devices. These include film casting, die cutting, lamination, assembly, and pouching. Transdermal patch manufacturing processes are initially developed to support in vitro and in vivo research studies and then transitioned to clinical manufacturing under FDA current Good Manufacturing Processes (cGMP).
Once proof-of-concept is established in humans and the target performance is achieved, the drug delivery system design is locked and the manufacturing process is transferred to a contract manufacturer for scale-up. 4P has the experience to lead technology transfer to establish a manufacturing process that can be scaled up for pivotal clinical trials at a representative commercial scale. Once the process and methods are transferred, 4P will manage the project to ensure the key milestones related to initiation of pivotal trials are met.
4P has the broad engineering expertise necessary to develop drug-device combination products. These products typically involve integration of enabling electromechanical technologies with the drug formulation to achieve the desired performance in terms of pharmacokinetic profile, bioavailability and other key attributes. Capabilities include electromechanical device design, materials science, software engineering, product design for human factors and usability, and failure mode and effects analysis (FMEA).
4P Therapeutics performs clinical research in compliance with FDA Good Clinical Practices (GCP) and ICH guidelines. Clinical Research supports development of drug delivery products from early stage exploratory studies through pivotal trials. 4P has extensive experience in designing early stage clinical studies to evaluate drug-device combination products. In addition, 4P can leverage its dedicated Phase 1 clinical site to accelerate the path to proof-of-concept in humans.
4P can take a lead role performing all sponsor obligations or work with partners in a support role. Services include clinical protocol design, informed consent preparation, development of the investigator’s brochure, IRB submissions, Trial Master File maintenance, clinical monitoring, data management, medical writing, biostatistics, pharmacokinetic analysis and auditing.
Regulatory Affairs develops and maintains the US FDA Investigational New Drug application (IND) required for drug delivery products in which the drug is responsible for the primary mode of action. Capabilities include IND creation, amendments and maintenance, leading FDA meetings and correspondence (e.g., Pre-IND Meetings), filing IND annual reports, and developing regulatory strategies for drug delivery products. 4P can hold the IND as the sponsor or perform transferred obligations in a support role.
4P Therapeutics is committed to developing products that can safely and effectively deliver medicines to meet the needs of patients and physicians. The 4P quality system governs the design, development, testing, manufacturing, and clinical testing of device, drug, biologic, and combination products intended for human use. We achieve this by implementing design, development, and manufacturing processes in compliance with 21 CFR §210&211 (drugs), 21 CFR §820 (devices), and 21 CFR §3&4 (combination products). 4P typically utilizes a system-wide design control process to develop drug delivery products in compliance with 21 CFR §820.30.
4P can either take the lead to perform all quality functions for a product development program or can perform in a support role for our partners. Supporting functions include assessment and auditing, drug or device supplier qualification, and quality oversight.
Project management systems are used to define, track and manage development projects. This is particularly critical for drug-device products that typically have multiple partners, suppliers and contract research organizations involved. 4P utilizes various tools and processes to meet timelines, stay under budget and achieve development program milestones. These include project management plans, task tracking, critical path analysis, and multidisciplinary project reviews.