Draft monograph: BPC-157 — submissions
The 8 submissions received, published in full with declared interests and secretariat responses.
§2Submissions and responses
8 submissions were received. Each is published in full below with its declared interest, the secretariat response and the disposition. The Institute publishes submissions it did not accept in the same form as those it did.
A purity figure from a certificate is quoted as though it were a content figure
The respondent submits on the draft monograph for BPC-157. Repair peptides are where the distance between the preclinical literature and the clinical literature is widest, and a monograph earns its place by measuring that distance.
The draft quotes a purity percentage from supply documentation in a sentence about how much compound a vial contains. Chromatographic purity is a relative area within what was detected; it is not a mass fraction and it does not bound vial content.
The respondent, an analytical chemist, proposes that purity and content never appear in the same sentence without an explicit statement that they answer different questions.
The secretariat accepts this submission. The conflation is the error the Institute most often corrects in supply documentation, and it appeared in an Institute draft.
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.
The indication table mixes approved indications with uses for which the compound is merely supplied
The respondent notes that the draft on BPC-157 carries no controlled human trial, and submits with that in view.
The indication table lists indications in a single sequence. Some are approved by a competent authority, some are the subject of trials that have not reported, and some are uses observed in supply with no trial evidence at all.
The respondent states that the three categories should not share a table without being distinguished in it.
The respondent read submission 001 after drafting this one and has not altered it, the two points being distinct.
The secretariat accepts this submission. A shared table is an implicit claim of comparable standing.
The indication table now carries a status column with three values, approved, under investigation and supplied without trial evidence, and the value is stated for every row. Rows in the third category also state that no certainty rating is assigned because there is no evidence base to rate.
The interaction section lists mechanisms rather than interactions
The respondent has read the draft covering BPC-157 and makes one submission.
The section describes pathways by which an interaction could occur. It does not say which interactions have been observed, in what setting, or with what consequence. A reader dispensing alongside other therapy cannot act on a mechanism.
The respondent proposes that observed interactions be separated from theoretical ones, and that the theoretical ones be labelled as such.
The secretariat accepts the separation and declines to expand the section beyond the evidence.
The interaction section is now divided into interactions reported in clinical use and interactions predicted from mechanism, with the second labelled as prediction. Where neither exists the section says so in one line rather than being padded.
A near-isobaric analogue is not distinguished by the identity determination described
Having read the draft monograph on BPC-157, the respondent puts one point to the committee.
The identity determination described in the draft resolves the compound from unrelated substances but would not distinguish it from a closely related analogue whose mass differs by approximately one dalton.
The respondent proposes that the monograph state the resolution required for that discrimination, and state that a nominal-mass instrument reporting an integer mass has not made it.
The secretariat accepts this submission. The point is decisive where one member of a near-isobaric pair is an approved medicine and the other is not.
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.
The monograph does not tell a reader that a stated mass may be substantially counter-ion and water
This submission addresses the draft on BPC-157 from the standpoint of a reader who meets the compound in supply material before meeting it in a journal.
The draft quotes vial contents in milligrams without stating whether the figure refers to peptide content or to total solids. For an acetate or trifluoroacetate salt of a peptide, the difference between the two can exceed a fifth of the stated mass.
The respondent, an analytical chemist, states that this is the single most consequential misreading in the field and that a monograph that does not address it directly is leaving the reader to discover it.
The secretariat accepts this submission. Moderate certainty evidence from published analytical surveys suggests that content and total solids are routinely conflated in supply documentation, and the draft did not warn the reader.
The monograph now states, at the point where vial contents are first mentioned, that a mass figure is uninterpretable unless it states whether it is peptide content or total solids, and cross-references the content standard in the analytical series.
Absence of evidence is presented in a form a reader will take as negative evidence
The draft on BPC-157 was read against the sources cited in it, and this submission arises from that comparison.
Where the Institute has identified no study, the draft states that no evidence was found. In several places that sentence sits immediately after a paragraph describing an adverse outcome, and the juxtaposition invites the reading that the compound was studied and found wanting.
The respondent proposes a standing formulation, used identically wherever the situation arises, distinguishing an outcome that was studied and not demonstrated from an outcome that has not been studied at all.
This point is adjacent to the one made in submission 003 and the respondent puts it in a form the secretariat can act on.
The secretariat accepts this submission. The two states are different, they support different decisions, and the draft rendered them in language a reader could not reliably separate.
A standing formulation has been adopted and is applied wherever an evidence gap is recorded, distinguishing an outcome assessed and not demonstrated from an outcome not assessed. The formulation is identical at every occurrence so that it can be recognised at a glance.
Preclinical findings are reported without the model that produced them
The respondent read the draft on BPC-157 and has confined this submission to one matter.
The section reports effects on healing, on mitochondrial function or on cognition without stating whether the observation was made in a cell line, in a rodent, or in an isolated tissue, and without stating the dose relative to anything a person would receive.
The respondent proposes that every preclinical statement carry its model and its dose, on the ground that a reader cannot otherwise judge how far the finding travels.
Submission 001 concerns the same document. The respondent’s point is a different one.
The secretariat accepts this submission. A preclinical claim without its model is not a citation, it is an assertion with a reference attached.
Every preclinical statement in the series now carries the model and, where the source reports it, the dose and the route.
The absence of a rare harm in the trial set is presented as reassurance
The respondent read BPC-157 in draft. The point applies to it and to the series generally.
The draft states that a specific serious event was not observed in the contributing trials. The respondent states that trials of the size conducted here could not have detected an event at the frequency in question, and that reporting the absence without that arithmetic converts an uninformative result into a reassuring one.
The respondent proposes that the detectable frequency be stated wherever the absence of an event is reported.
The secretariat accepts this submission. The Institute's own framework treats an absent event in an underpowered set as uninformative, and the draft departed from it.
Wherever the monograph reports that an event was not observed, it now states the total exposure and the frequency the contributing trials could have detected, so that the absence is read as the limit of the evidence rather than as a finding.
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.
- 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.