Table 1.

Risk assessment and evaluation toward designing a master file for a medical device product.

Characteristics	Hazard (potential cause of failure)	Harm (potential event of failure)	Reduction measures
PREMARKET LIST
Raw materials do not meet desired specification	Unreproducible synthesis, purification, or isolation.	Unable to release/accept raw materials for processing into final device. Raised costs to manufacturer.	Implant an effective quality system. Control and monitoring of personnel and equipment.
Raw materials do not meet desired specification	Presence of impurities in the starting materials	Toxicity in the final product.	To characterize the raw materials.
The viscosity of the solution is low	Wrong choice of polymer	Incorrect function of the product.	To characterize the material following Pharmacopeia
The processing of the material is not reproducible	The polymer is not following specification.	Delays to production	To characterize the materials using highly sensitive methods.
Product is not possible to be sterilized.	Massive contamination during production or product handling. Degradation during sterilization.	Aseptic processing might not be feasible- product cannot be marketed	To study the effect of agents used for sterilization To change the way of sterilization.
PRODUCT DESIGN
Mechanical properties of the product are not adequate for the application.	The material degraded during storage.	Incorrect function of the product.	Definition of mechanical properties according to state of art.
The material is not adequately stored.	Material decomposed	Incorrect function of the product	Characterization of the product before its use
The device is not stable.	Fast degradation.	Avoid of regeneration or efficacy.	To perform degradation studies in vitro.
IN VITRO USE
The material is cytotoxic.	Presence of impurities in the product.	Unable to be used in vivo.	To purify the product extensively. To develop validated and standardized in vitro assays of toxicity
The personnel do not correctly evaluate the material.	The cell model is not representative for the application	False biocompatibility.	Extensive in vitro characterization.
ANIMAL MODEL
Macrophages are observed at the site of implantation.	Foreign body response is observed.	Limited biocompatibility.	Wrong choice of materials.
The material produces inflammatory responses in animals	Adverse reactions in vivo	Product cannot be translated	To develop an integrated strategy for toxicity testing in vitro.