Draft monograph: SS-31 (elamipretide) — disposition

§3Disposition and amendments

§3.1Disposition table

Table 1. Every submission with its disposition. Each row links to the submission in full.

§3.2Summary by disposition

Table 2. Counts by disposition, with the meaning of each.

§3.3Resulting amendments

1. The monograph should reproduce the approved labelling rather than paraphrase it — arising from DRAFT-SS-31-MONOGR/002. The approved indication and contraindications are now reproduced verbatim from the named authorisation with its version and date, and the posology section reports the labelled schedule and the schedules studied side by side, with the source of each stated.
2. The mechanism section is written with more confidence than the clinical section it precedes — arising from DRAFT-SS-31-MONOGR/003. Every pharmacology section now closes with a statement identifying which described actions are supported by clinical evidence assessed in §3 and which are not. The pharmacology itself is stated as the sources state it.
3. A purity figure from a certificate is quoted as though it were a content figure — arising from DRAFT-SS-31-MONOGR/004. Purity and content are now reported in separate rows with separate definitions, and the monograph states that a purity figure sets no bound on content and that a content figure requires a determination against a standard of assigned content.
4. A near-isobaric analogue is not distinguished by the identity determination described — arising from DRAFT-SS-31-MONOGR/005. The analytical section now states the resolving power required to discriminate the pair, names the pair explicitly, and records that an identity claim made below that resolution is not conformant with the identity standard.
5. Every contributing trial shares one sponsor and the monograph does not say so — arising from DRAFT-SS-31-MONOGR/006. Sponsor concentration is now stated with the certainty rating, and the monograph records how many independent sponsors contributed evidence to each assessed outcome.
6. The compound is supplied under names the monograph does not list — arising from DRAFT-SS-31-MONOGR/007. The synonym list is extended to include every name the Institute can evidence from a document it holds, each recorded with its source. Names asserted without a supporting document are not added, and the distinction is stated at the head of the list.
7. The pharmacokinetic section does not connect half-life to the dosing schedule — arising from DRAFT-SS-31-MONOGR/008. The pharmacokinetic section now states approximate time to steady state alongside the half-life and dosing interval, with the assumption of first-order elimination stated, and records where the assumption is not supported for this compound.
8. The monograph does not tell a reader that two vials of the same compound may not contain the same… — arising from DRAFT-SS-31-MONOGR/010. A standing paragraph now appears at the head of §8 in every monograph, stating that a determination applies to the lot measured and that a label mass is not a determination.
9. Two factual descriptions of the sponsor's programme are inaccurate — arising from DRAFT-SS-31-MONOGR/011. The trial status now reads as completed at a pre-specified interim analysis, with the analysis identified, and the dose is stated in the unit used in the approved labelling. The submission is identified as an industry submission on its face in accordance with…
10. The same concept is given three different names in one document — arising from DRAFT-SS-31-MONOGR/012. A single term is now used throughout for each defined concept, and the glossary entry is linked at first use within each section rather than once per document.
11. Nothing is said about impaired renal or hepatic clearance — arising from DRAFT-SS-31-MONOGR/013. The pharmacokinetic table now carries renal and hepatic rows in every monograph, populated with the study where one exists and with an explicit statement of absence where none does.
12. Anti-drug antibody data are omitted — arising from DRAFT-SS-31-MONOGR/015. Anti-drug antibody incidence and any reported association with loss of effect are now reported where measured, and recorded as not measured where the contributing trials did not assess them.
13. The preclinical section is extensive and the clinical section is not — arising from DRAFT-SS-31-MONOGR/016. The preclinical section is reduced in length, placed after the clinical assessment rather than before it, and opens with a standing statement that an effect observed in an animal model is not a clinical outcome and does not support a certainty rating.

References cited on this page

References are numbered in order of first citation in this document. Each superscript in the text links to its entry below.

1. International Organization for Standardization. ISO/IEC 17025:2017 General Requirements for the Competence of Testing and Calibration Laboratories. ISO/IEC Standard 2017;3rd edition. identifier not held by the Institute

Identifiers are reproduced only where the Institute holds them. Where a digital object identifier or PubMed identifier is not shown, the Institute has recorded the journal and year and has not constructed an identifier.