Comments Urge Changes to Emergency-Use Injectors Guide
Hyman, Phelps & McNamara has asked FDA to provide examples to clarify specific items in the agency’s draft guidance on “Technical Considerations for Demonstrating Reliability of Emergency-Use Injectors Submitted under a BLA, NDA or ANDA.” The draft guidance focuses on emergency-use injectors marketed with a drug/biological product as a prefilled single entity combination product or as a co-packaged combination product assigned to CDER/CBER. The guidance defines reliability as the probability that the injector will perform as intended, without failure, for a given time interval under specified conditions. It also describes information and data that FDA recommends be included in marketing applications to demonstrate that an emergency-use injector is reliable, including the details of an example of an acceptable approach for the mathematical model, statistics, fault tree analysis, and use of certain current good manufacturing practice requirements for combination products to establish reliability of the emergency-use injector.
In comments to FDA, the law firm said examples would be helpful for “the analysis of design verification and validation of the reliability requirements (line 237); adequate manufacturing and in-process controls and release activities (line 246); and adequately defined acceptance activities for the supplied components to ensure that the manufactured combination product has the required design attributes to ensure the reliability specifications are achieved (line 248).”
Hyman Phelps also suggested that if the reliability requirements will be transferred to manufacturing processes, it then would be helpful to provide guidance on the expectations for acceptable production. Commenting on the draft guidance’s section on “Activities when Implementing Emergency-Use Injector Design or Manufacturing Modifications,” where FDA describes processes for evaluating modifications to design or manufacturing, the law firm requested that a flow chart be added to guide the decision-making process FDA expects to be utilized by industry.
Comments submitted by the Journal of Validation Technology and Journal of GXP Compliance’s editorial advisory board focused on problems with epinephrine products (emergency-use injectors and non-injector products). “Epinephrine injector performance problems still remain despite device re-design some years ago,” the group wrote. “Products from different suppliers require new and repeated training of users to learn device operation techniques due to design differences. The impact of interchangeability between products and the possibility of receiving multiple different products cannot be ignored.” The board urged FDA to include human factor elements or initiate other activities to address the operational differences between emergency-use products. “Alternate products must demonstrate equivalence in drug effects as well as reasonable similarity in device operation,” it said.
Additionally, it asked FDA to address in the guidance look-alike and sound-alike errors with epinephrine and ephedrine. “These words are similar in appearance and may be easily misread, especially when reading written handwriting with incorrect spelling,” the board wrote. “Epinephrine is 100-1,000 times more potent than ephedrine; erroneous administration of epinephrine may have significant adverse effects.” It proposed that FDA accept “adrenaline” as an acceptable alternative to epinephrine, as it would eliminate the epinephrine-ephedrine naming confusion as well as the epinephrine mg/mL - ephedrine mg/mL visual similarity. “Labeling with both names could help facilitate ultimate transition to a single preferred name,” the board recommended.