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Record W2908941652 · doi:10.1007/s43441-019-00036-y

Review of Drugs Approved via the 505(b)(2) Pathway: Uncovering Drug Development Trends and Regulatory Requirements

2020· article· en· W2908941652 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueTherapeutic Innovation & Regulatory Science · 2020
Typearticle
Languageen
FieldMedicine
TopicPharmaceutical studies and practices
Canadian institutionsUniversité de Montréal
Fundersnot available
KeywordsMedicineNew drug applicationPharmacyDrugApproved drugPharmacologyRisk analysis (engineering)Family medicine

Abstract

fetched live from OpenAlex

A 505(b)(2) application is a type of US new drug application (NDA) that contains full reports of investigations of safety and effectiveness, but where at least some of the information required for approval comes from studies not conducted by or for the applicant and for which the applicant has not obtained a right of reference. Most 505(b)(2) applications consist of changes to a previously approved drug product (ie, a new dosage form, new routes of administration, etc). Sponsors often face challenges determining the studies to be conducted to support approval via 505(b)(2) pathway. This 5-year (2012-2016) retrospective analysis reviewed approved 505(b)(2) NDAs available on the FDA website, to determine the nature of studies (preclinical, clinical pharmacology, and efficacy/safety) conducted for various types of submissions and to better understand the trends in terms of regulatory requirements. The database consisted of 226 NDAs. One hundred twelve of those 226 had complete FDA review information, with the following FDA submission classes being more prevalent: type 3, new dosage form; type 4, new combination; and type 5, new formulation or new manufacturer. Therefore, only these 112 NDAs were further examined as they could show trends in terms of the studies conducted for various types of applications. Based on the investigation of NDA review documents, coupled with guidance documents, decision trees for studies to be conducted have been developed, which may serve as a guide of recommendations for a successful 505(b)(2) development program and NDA submission.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.002
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Other design · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.827
Threshold uncertainty score0.458

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0020.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.003
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.084
GPT teacher head0.349
Teacher spread0.264 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it