Industry calls for changes to FDA guidelines for enteral tube drugs
Posted on August 10, 2021 | By
Drugmakers and Industry Groups Call for Changes to Recently Released U.S. Food and Drug Administration (FDA) Draft Guidance on Assessing the Suitability of Oral Drugs for Feeding Tube Administration enteral.
The guidance, released for comment in June, provides recommendations for in vitro testing of oral drug products to demonstrate their suitability for enteral tube delivery. The guide specifically excludes oral solutions from its recommendations. (RELATED: FDA provides draft guidelines for enteral-tube drugs, Regulatory guidance June 2, 2021)
The FDA said advice is needed in this area because in vitro oral drug testing that could be given through an enteral feeding tube is “not sufficiently widespread or consistent”, and labeling statements often vary in content and format.
The agency received nine comments from several drug manufacturers, the generic drug industry group, the Association for Accessible Medicines (AAM), and two medical professionals.
In its comments, the AAM asked the FDA for additional details on the comparative analyzes that must be performed by generic drug sponsors to establish therapeutic equivalence. “It is not clear what standards the generic sponsor should apply to identify the most risky formulations, especially in cases where, based on the differences in the design of the [reference listed drug] RLD and generic, the risk level of a dosage can vary between the two. The guidelines did not provide clarity as to the conditions under which one or more comparative study (s) may need to be performed for multiple strengths of the proposed generic, ”wrote the AAM.
Mark Klang, president of the drug-nutrient interaction section of the American Society for Parenteral and Enteral Nutrition, called for several changes to the guidelines, but praised the FDA for making progress in this area.
“Feeding drugs through a feeding tube is a complicated process because it has to compete with nutritional support given by the same route. Most drugs have not been evaluated for the tube feeding route. Crushing of drugs and / or extemporaneous preparation may result in changes in drug absorption and result in both toxicity and sub-therapeutic administration depending on the formulation. It is indeed admirable that the FDA has developed guidelines for oral drug manufacturers to perform appropriate testing to ensure safe delivery through the feeding tube, ”he wrote.
However, Klang suggested that the FDA expand the guidelines to treat oral solutions, which can present their own challenges when given through an enteral tube, and noted that “oral and catheter-type syringes are no longer the norm for the patient. administration by feeding tube. All supply tubes are converted to En-Fit type connections, and testing to assess potential clogging should be performed on the most used devices.
Several drug manufacturers made specific comments on the guidelines.
Boehringer Ingelheim asked why the guide does not cover oral solutions and whether the agency is considering a draft guide to deal with such products. The company also requested clarification on the dissolution profiles referenced in the guidelines. “What should be the baseline dissolution profile for this test?” Is it the dissolution profile of the dispersion of the freshly prepared drug product or the dissolution profile of the undispersed drug product? Asked Boehringer Ingelheim.
Apotex, in its comments, asked the FDA to clarify the number of test and reference product units that should be evaluated for each tube tested. “If the entire representative selection of the tube is subjected to comparisons in vitro study with n = 12 of tests and reference products, the applicant will need to acquire a very large volume of reference product and tubes, which can be extremely difficult to obtain and will cause a delay in the submission / approval of a generic. The company suggests that the FDA recommends “at least 3 units of test product and 3 units of reference product [for] each selected tube.
Viatris raised two concerns with the guidelines as written. First, the company said the guidelines are silent on generics that are Q1 / Q2 (qualitatively and quantitatively equivalent) to RLD. “When ANDA pharmaceuticals are Q1 / Q2, it may not be scientifically justified to require the same in vitro enteral tube test as an RLD, ”Viatris wrote. The company has also sought guidance from the FDA for situations where an ANDA applicant discovers that an RLD is extremely difficult to deliver through an enteral tube.
In addition to the recommendations in the draft guidance, Merck asked the FDA to also authorize the use of a risk-based assessment on a case-by-case basis, “taking into account the properties and interactions of the drug product. , enteral tube (s), medium, and other factors, as the basis on which to make specific recommendations on in vitro test.”
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