CONTRACT MANUFACTURING OF DRUG-ELUTING MEDICAL DEVICES
SSF contract manufacturing services provides complete support for innovators in both the pharmaceutical and medical device industries for the development of drug-eluting medical devices.
We are the only medical device contract manufacturer in the world who has the depth of engineering experience and pharmaceutical licensing to offer complete start to finish drug eluting product development and manufacturing.
PARTNERING WITH SSF
SSF’s Tustin, California facility is licensed by the State of California as a Drug Manufacturing Facility. Our business model, quality system, and facility layout are all designed for maximum flexibility in meeting the myriad requirements of our various clients. SSF’s Engineering and Quality Departments assist our drug-device clients in areas including design, feasibility, prototyping, clinical builds, and commercial release.
SSF can deliver deep expertise in material science, biochemistry, mechanical engineering, process design, and quality systems to match each client’s specific needs. We work with many bioresorbable materials as well as silicone and can manufacture drug eluting components as well as complete drug eluting combination products.
We can work with a provided API or compound an API specified by our client. Typical work flow involves procuring an API, compounding the drug into silicone, fabricating a drug component, and assembling this component into a complete combination product.
CONFIRM API IDENTITY
All APIs, whether procured by us or supplied by our clients, are analyzed using in-house FTIR capabilities. This not only ensures compliance with the CFR regulation but also provides redundant security for our clients and our staff.
DETERMINE API TEMPERATURE STABILITY
Most drug molecules have an upper temperature limit above which they undergo chemical change and loss of efficacy. If this temperature limit is not known by our client, or not available in the literature, SSF will coordinate DSC (Differential Scanning Calorimetry) testing to determine temperature process limits.
SELECT OPTIMAL MATRIX MATERIAL
Most active pharmaceutical eluting components sequester the API within a curable matrix material. Silicone elastomers and gels as well as bioabsorbable polymers are frequently used. Chemical compatibility of the API with the matrix material must be considered, as the drug must not interfere with the vulcanization of the matrix and the cure chemistry of the matrix must not alter the drug. Fabrication methods (molding, extrusion, casting, etc) as well as the target elution rate of the drug will also impact the choice of the matrix material.
OPTIMIZE API MIXING PROCESS
API content homogeneity within a component, within a manufacturing lot, and between different lots of components, is mission critical. Quite simply, optimizing the mixing of the drug and the matrix material is as important as any service we provide. SSF has invested in state-of-the-art compounding technology. Viscosity, API particle size, drug loading, and scalability are all considerations in determining the most appropriate mixing equipment and process. In-house HPLC testing allows us to rapidly assess in-process API content uniformity.
OPTIMIZE MANUFACTURING PROCESS
Rheometry is an extremely useful test for determining optimal time-temperature parameters for the vulcanization of silicone-drug components. Rheometry testing is performed at a temperature, determined by DSC, that will not affect drug stability. Analysis of the rheometry tests allows a relatively straightforward determination of the time required at temperature to complete vulcanization of the silicone-drug mixture.
DEVELOP LOT ACCEPTANCE CRITERIA
We work closely with our clients and Regulatory bodies to develop lot acceptance criteria for drug device combination products manufactured by SSF. Lot acceptance tests such as total drug content and elution rate profiling can be performed by SSF in our analytical laboratory via HPLC analysis.
COMBINATION PRODUCT DESIGN AND ENGINEERIING CONSIDERATIONS
Silicone rubber has been used in medical implants for more than 50 years. It has a proven track record as an inert and stable biomaterial.
Because of their helical conformation and weak intermolecular attraction, silicone polymers and elastomers exhibit high free volume. This in turn contributes to the exceptional permeability of polydimethylsiloxane (PDMS) elastomers and gels. It’s been shown that silicone elastomers are 25 times more permeable to oxygen than natural rubber and over 4000 times more permeable than polyvinylchloride. Compared with polyethylene, silicone is 1000 times more permeable to progesterone.
Considered as a group, silicones may be unique insofar as the polymer and elastomer can be modified to meet the various requirements of specific drug-device combination products. Polymers can be modified by the choice of pendant groups which in turn will affect the steric characteristics of the system. Crosslink density between polymer chains can also be controlled via chain length as well as by adjusting the number and position of reactive sites. Alternatively fillers can be added, removed or changed to further adjust drug release rates. Drugs found in combination products vary widely in terms of molecular weight and chemical structure. Silicones can be tailored in many ways to provide a range of properties such that drug elution rates can be modified and controlled. Silicones also offer a number of cure systems such that a drug incompatible with one system may be compatible in another.
In their purest form most Active Pharmaceutical Ingredients (API) exist as fine powders. Designers of drug-device components must therefore choose an appropriate matrix material such that the drug powder can be sequestered, formed into shapes, and subsequently placed in the body or in contact with skin.
Appropriate matrix materials must be physically and chemically compatible with the drug as well as provide the required drug release profile.
Other important factors in determining the suitability of matrix materials include the intended fabrication method (molding, extrusion, casting, etc), processing temperatures, and the effect of drug loading on compounding and manufacturability.
Biodurability must also be considered. Some implantable drug eluting combination products are designed to be absorbed by the body as the API is depleted. Many others however are intended to remain in vivo for extended periods of time.
SSF offers deep engineering and design expertise for manufacturing both biodurable and bioerodible drug-device components.