FDA’s Draft Guidance on Improving the Development of Dosage and Administration Sections of Drug Labeling Informs Industry of Required and Recommended Information “Particularly Important to the Safe and Effective Use of Drugs,” Such as Dose Ranges, Initiation or Loading It is written for Dosage, dosage, titration schedule, recommended maximum dose and duration, efficacy, and concomitant therapy information, the agency said. (Related: FDA Issues Draft Guidance on Dosage Labeling, Regulatory focus January 13, 2023)
Other information that should be included in the Dosage and Administration section includes medications used before, during, and after treatment, dose changes, dosages in specific patient populations, drug switching and substitution, and missed doses. Information, including recommendations for managing vomiting after administration of oral medications. Medications, information on dose reduction and discontinuation of medications when at risk of withdrawal, and doses of fixed combination and co-packaged medications.
The draft guidance includes guidance for industry to provide preparation and dosing information on drug labeling, information on how to avoid mishandling of drugs or their administration, drug incompatibilities, and storage instructions for reconstituted or diluted products. It also contains information about situations that should be included.
In general, industry stakeholders welcomed the additional details added to the latest draft guidance, but requested more information on specific presentation situations.
Novartis
Pharmaceutical company Novartis has commented to the FDA on explaining optimal titration dosages and clarifying when label dosage and dosing section instructions should refer to concentrates for infusion solutions. , proposed several changes to the draft guidance. Restrictions on pediatric indications, administration and preparation of parenteral drugs.
Novartis said information in the dose and administration section should consistently refer to fluid concentrates or fluid diluents to reduce the risk of misadministration. Labels should also include recommendations on safety implications if patients should avoid stopping medication, they noted.
“If there is a pediatric indication but a suitable pediatric formulation cannot be developed, Novartis should list the latter and provide details on the immediate formulation in the appropriate section as this may be important information. I think for [healthcare provider]’ said the company.
For safety reasons, additional restrictions on parenteral administration and preparation, such as healthcare providers and sterile conditions, should also be considered, they said.
jazz pharmaceutical
In a comment, biopharmaceutical company Jazz Pharmaceuticals asked for more examples of using algorithms for complex dosages, preparation and dosing instructions, and dosage modifications aimed at reducing the risk of side effects. said.
The company also noted that the recent U.S. Prescribing Information (USPI) approved by the FDA has begun to implement parts of this draft guideline, including the inclusion of dosing interval information in the full prescribing information. It is not included in the highlights section of USPI. t always has interval information. Jazz Pharmaceuticals cited another recent USPI that contained premedication textbooks for hypersensitivity reactions, but the information was “not based on data or usual practice standards.” Again, the company has requested more information from the FDA about when it is appropriate to include this information.
In its section on dose modification, Jazz Pharmaceuticals acknowledged that providing precise dosage instructions is effective for single, fixed-dose drugs, but not for multiple, stable-dose drugs. He proposed to allow the use of percentages in drugs.
PTC Therapeutics
In general, pharmaceutical company PTC Therapeutics explained that it would be helpful if the draft guidance had “example scenarios in which required information in this section should be omitted if clearly not applicable.”
They noted that the section on composition and format of the Medication and Administration section did not include information on products administered in the surgical operating room. In addition, the guidelines do not contain explicit reference to medical devices or ancillary devices that accompany products, PTC has asked for clarification on where to refer to these,” they wrote.
PTC Therapeutics also asked for clarification on whether sponsors should include graphics in the drug administration section. They also suggested that a section on administration of cross-labeled drug-device combination products could be useful for gene therapy products or products with “proprietary methods/techniques of administration.”
In its subsection on Dosing for Patients with Renal Impairment, PTC Therapeutics asked FDA to elaborate on how dosing recommendations in subpopulations of patients with renal impairment should be addressed with preliminary data . “PTC will clarify whether it is appropriate to provide recommendations only to those subpopulations and include warning statements for other subpopulations where there is no clinical data to support all subpopulations. I am asking for it,” they said.
Pharma
The U.S. Pharmaceutical Research and Manufacturers Association (PhRMA) said in FDA comments that it believes the 2023 draft guidance provides more detail and direction than previous 2010 draft guidance on the same topic.
PhRMA states that “medication-related information, including pediatric information, should not be included in any other section of He pointed out that there are situations where it could, and even is required. ” Apart from the Medication and Administration section. PhRMA also explained that circumstances may arise where labels may need to include information about drugs “prepared and administered in specific healthcare settings to ensure their safe and effective use.” Did.
Advocacy groups said they appreciated the FDA’s flexibility with regard to organizational schemes for product labeling, but asked to provide examples of subsection formatting. , FDA, in its draft guidance, suggests that sponsors consider using tables and that tables be designed through a human factors engineering process.PhRMA recommends using a human factors process to design tables is , are only appropriate in very specific and rare situations, e.g. where the dosage is very complex,” they wrote. We urge the authorities to clarify that their recommendations to implement only apply to limited and unique circumstances.”
They agreed that combination therapy should be identified in the dosing and administration section, but PhRMA asked if a drug is only approved for use in combination therapy. They also requested that the FDA provide detailed information regarding the storage of reconstituted drugs, including complex formulations for administration.
PhRMA highlighted several areas where FDA could improve the readability of the draft guidance. For example, formatting or inserting a specific footnote into the body of the document. “Vital information may be overlooked in the current draft guidance as information is relegated to footnotes rather than the body of the text,” they said.
draft guidance
