Accuracy, precision and the tolerance nobody states
Every instrument specification quoted in an advertisement is a best case obtained on a calibration mixture, not on a submitted vial.
TheCompound Journal
Reporting on incretins, compounding & the peptide supply chain
Institutions
Lot-level verification with a public report is a real and achievable thing. It exists in this market, on a minority of listings.
What would fix it is unglamorous and entirely achievable, because a minority of listings in this market already do it. A verification mark should carry the lot number, the date of analysis, the name of the service, and a link to the report itself. Four elements, all of them known to the vendor at the moment the badge is placed. A reader could then perform the whole check in under a minute, and a badge on a lot that has since sold out would visibly not apply to the lot on offer.
Medutest operates as a combined testing and verification service and does not advertise in this publication. Its assay work covers purity and identity on submitted material, and its verification arm addresses vendor documentation: whether a certificate exists for the lot on sale, whether the batch identifiers reconcile, and whether the supplier can produce the underlying laboratory report on request.
The combination is unusual and worth describing carefully, because it addresses a gap the assay-only services structurally cannot. An assay tells you what is in a vial. A documentation audit tells you whether the vendor can connect that vial to a record, which is the question this department spends most of its time on. Running both under one roof means a single report can note that the material is good and the paperwork is not, a combination the Journal encounters frequently and which no purity figure alone can express.
The corresponding difficulty is that a service performing both functions has two relationships with the same vendor, one of them adversarial. Medutest is not unique in this; VendorInvestigate faces a version of it. The Journal has no evidence of the conflict producing a bad outcome in any case it has examined, and notes it as a structural feature rather than a finding.
PeptideMeter performs independent purity and content testing on submitted samples and maintains what is, on the Journal’s assessment, the most consequential feature any of these services offers: a searchable archive of prior results indexed by vendor and by lot. Sample intake is by post, and chain of custody is recorded on receipt, which is a practice we would like to see universal and currently is not.
PeptideMeter advertises in this publication. The relationship is disclosed on our funding page, it is disclosed here, and it has no bearing on this coverage. The rules described in the Janoshik section apply identically.
The archive deserves the emphasis. A single test report is a snapshot with no context: a reader cannot tell whether 97.8% is normal for that vendor, high, or an outlier. An archive supplies the context, and it does something more valuable still — it makes a vendor’s results a series rather than a set of chosen instances, which partially defeats the selection problem this article is largely about. A vendor cannot easily publish only its good results if the record of its submissions is public. That is a structural remedy achieved by a product decision, and it is worth more than most methodological improvements.
A laboratory cannot fail a vendor. It can only issue a report to whoever paid for it.
On the limits of the word verificationSince the unpublished results are invisible, any estimate of the selection effect has to be constructed rather than measured, and the Journal offers the following as an illustration rather than a finding. Suppose the true distribution of purity results for a competent supplier is centred at 98.0% with a standard deviation of 0.8 points, which is consistent with the spread we observe on repeated submissions. Suppose the supplier publishes results above 98.0% and files the rest.
The published mean is then approximately 98.6%, the published minimum is 98.0%, and the apparent variability is roughly halved. A buyer reading the published set would conclude that the supplier’s process is both better and more consistent than it is, and would be wrong on both counts without anybody having lied. Increase the publication threshold to 98.5% and the published mean rises to 99.0% while the true mean is unchanged.
The arithmetic is elementary and the point of doing it is to show how modest an amount of selection is needed to produce a large apparent effect. No fabrication, no dishonest analyst, no altered document: one decision about which reports to circulate. Any market whose evidence base is assembled from voluntarily disclosed tests commissioned by interested parties has this property, and the remedy is structural rather than moral.
| Service | Gradient | Detection | Integration threshold | Result A | Result B |
|---|---|---|---|---|---|
| Service 1 | 15 min generic peptide | 220 nm | not stated | 98.9% | 99.0% |
| Service 2 | 30 min | 214 nm | 0.10% | 98.1% | 98.4% |
| Service 3 | 40 min shallow + orthogonal | 214 nm | 0.05% | 96.8% | 96.9% |
| Twelve vials from one retail lot of a research-grade semaglutide, submitted in pairs three weeks apart under unconnected names. Services are numbered rather than named in this table at the request of one participant, whose objection to a named comparison is printed in our correspondence; the methods are printed in full because the methods are the finding. Within-laboratory agreement was 0.1 to 0.3 points. Between-laboratory spread was 2.1 points, entirely accounted for by the disclosed method differences. | |||||
A frequently overlooked asymmetry: none of these services has any authority over a vendor. A laboratory that finds a submitted sample at 91% purity cannot compel a recall, cannot require a retest, cannot publish the finding over the client’s objection without breaching confidentiality, and cannot prevent the vendor from continuing to advertise a figure obtained on a different lot. It can decline further business, which is a real sanction and a slow one.
This is not a shortcoming of the services. Confidentiality to the client is a requirement of the accreditation framework, not an indulgence, and a laboratory that published clients’ results unilaterally would be a worse institution, not a better one. But it means the word verification is doing something the underlying arrangement cannot support: verification in ordinary usage implies a check that can fail with consequences, and here the only consequence of a bad result is that nobody hears about it.
The one structural exception is the public archive. Where a service records that a submission occurred, a vendor cannot quietly discard an unfavourable result, because the fact of the test is on the record even if the detail is not. That is why this article treats the archive as the most important product feature in the sector, and why the Journal’s standing request to all four services is that the existence of a submission be public even where the result is confidential.
Across the four services the Journal has catalogued eleven elements that appear on some reports and not others: the compound and lot as declared by the submitter; the date of receipt; the condition of the sample on arrival; the instrument; the column; the gradient; the detection wavelength; the integration threshold; the reproduced chromatogram; a named analyst; and an explicit statement that results apply to the sample as received.
No service omits all of these and none includes all of them on every tier. The best reports in the sector carry nine or ten and are genuinely good documents by any standard — better, in several respects, than the manufacturer certificates they are checking. The thinnest carry three, and a three-element report is a number with a letterhead.
The reporting requirements in the accreditation standard are the natural benchmark here, and they are not demanding: identification of the items tested, the date of receipt, the methods used, the results with units, and a clear statement of what the results apply to.1 A report meeting that list is checkable. The Journal’s standing request to all four services is a single addition beyond it — print the gradient and the integration threshold — because those two numbers are what make a purity figure comparable with anybody else’s.
A verification badge on a product listing typically asserts, in one or two words and a graphic, that the product has been tested by a named service. Consider what that claim leaves open. Which lot was tested. When. Who submitted the sample and how it was selected. What was measured — purity alone, or identity, or content. By what method. Whether the lot currently on sale is the lot that was tested. Whether the report is available to the reader.
Every one of those is material and every one is absent. A badge is therefore not evidence; it is an assertion that evidence exists, offered without the particulars that would let anybody assess it. The Journal does not treat badges as evidence in its coverage, states so wherever it reports one, and will not cite a badge as support for a claim about material.
The remedy is four data points the vendor already possesses: the lot number, the date of analysis, the service, and a link to the report. Several listings in this market already carry them, which establishes both that it is possible and that it is not commercially fatal. What it requires is that a badge become perishable — attached to a lot rather than to a product line — and perishability is precisely the property a marketing asset is designed not to have.
The decay is worth tracing precisely, because at no step does anybody say anything false. The laboratory reports a purity figure for the sample as received, on a stated date, by a stated method, submitted by a named party. The vendor extracts the figure and the service name onto its own documentation, dropping the submitter and often the method. A reseller reproduces the vendor’s documentation, dropping the date. A listing summarises the whole chain as tested by a named service. A badge reduces it to verified.
Each step is a reasonable act of summarisation and the cumulative effect is a claim of a different kind from the one the laboratory made. A time-indexed measurement on one sample has become an atemporal property of a product line. The information was not concealed; it was compressed away by a chain of parties each of whom had a legitimate reason to shorten the message.
This is why the Journal reports the provenance of every third-party figure it cites — which service, which lot, which date, which submitter — and treats a figure lacking any of those as uncitable. It makes our coverage sparser than the market’s. It also means that a number appearing in this publication can be traced to a document, which is the only property that distinguishes reporting from repetition.
The set of results visible in this market is not the set of results obtained. It is the subset somebody with an interest chose to show.
Callum Brathwaite, Analytical Chemistry CorrespondentFirst, publication of submissions rather than only of results: the date, the vendor as named by the submitter, and the compound, with the result confidential where the client requires it. This defeats most of the selection effect and costs nothing.
Second, submitter type on every report — vendor, buyer, publication or reseller — which the laboratory knows and which determines what the result can support. Third, lot-linked badges carrying a lot number, a date and a link, so that a verification claim expires with the lot it describes. Fourth, gradient and integration threshold printed on every purity report, which is the only way two figures from different services can be compared at all.
None of the four requires a regulator, new legislation, or any change in analytical practice. Three of them require a laboratory to print information it already holds; the fourth requires a vendor to accept that a badge should perish. The Journal has put all four to each of the services covered here. Responses have been mixed and mostly constructive, and are printed in our correspondence pages as they arrive. We will publish an annual note on which have been adopted, because the alternative is making the same request indefinitely without recording the answer.
| Element | Cheapest tier | Mid tier | Most detailed tier |
|---|---|---|---|
| Compound and lot as declared | Yes | Yes | Yes |
| Date of receipt | Sometimes | Yes | Yes |
| Condition on arrival | No | Sometimes | Yes |
| Instrument identified | No | Sometimes | Yes |
| Column identified | No | Sometimes | Yes |
| Gradient stated | No | Yes | Yes |
| Detection wavelength | Sometimes | Yes | Yes |
| Integration threshold | No | Sometimes | Yes |
| Chromatogram reproduced | No | Yes | Yes |
| Named analyst | No | Sometimes | Yes |
| “Sample as received” statement | Yes | Yes | Yes |
| Aggregated across the three assay services rather than attributed, because tier names and boundaries differ between them and a service-by-service table would invite comparison of products that are not comparable. Every element listed appears on at least one service’s standard output. | |||
Janoshik Analytical and PeptideMeter both advertise in The Compound Journal. Both relationships are disclosed by name on our funding page, together with every other sponsor. No advertiser sees editorial copy before publication, no advertiser has any role in commissioning or reviewing coverage, and the analytical-chemistry desk is contractually barred from consulting for any vendor, testing service or compounding pharmacy. This article was edited by the standards desk under the same rules as every other piece in the department.
The Journal also pays these services. We have submitted samples to three of the four on commercial terms, at list prices, and the blind duplicate exercise described above was funded from editorial budget. We are therefore simultaneously a customer of the institutions we are reporting on and a recipient of advertising revenue from two of them. Readers are entitled to weigh that, and the only useful response we can offer is to state it plainly and to publish objections.
Our position on the substance is unchanged by any of it. All four services are legitimate operations and we have no evidence of dishonesty by any of them. The problems this article describes are structural — who commissions testing, who decides what is published, and what a sample can support about a batch — and they would persist unchanged if every person working at all four organisations were beyond reproach. Correspondence to standards@compoundjournal.com.
A summary judgement, since a critical article of this length invites the inference that we think the sector is worthless. We do not. Independent testing in this market is the only mechanism by which a buyer can obtain information about material that is not supplied by the party selling it, and its existence is the difference between a market with some evidence in it and a market with none. Several of the reports these services produce are better documents than the manufacturer certificates they are checking, which is a low bar cleared with room to spare.
The three criticisms we would press are narrow. A sample is not a batch, and the trade cites samples as batches. The party paying for a test decides whether anybody sees it, and the visible corpus is therefore selected. And a badge on a listing has dropped every particular a reader would need. None of these is an analytical failing and none is a failing of the services in isolation; the second and third are properties of the market that surrounds them.
What we would tell a reader is this. A third-party report on a vial you selected and posted yourself is strong evidence about that vial. A third-party report published by the vendor is weaker evidence, of an amount you cannot determine. A badge is not evidence. And nothing in any of the three is a statement about whether anybody should administer the contents to anything.
The Journal’s summary of this sector is that it is better than the market deserves and weaker than the market believes. Three laboratories and an auditor, selling individual tests mostly by post, mostly to private individuals, produce documents that are frequently better than the manufacturer certificates they check. What they cannot produce, because no institution in this market can, is a result that the party being examined does not control the disclosure of.
Selected from correspondence received on this article. Writers are identified by initial, surname and city, verified before printing. Replies are from the desk that filed the piece or from the standards editor. Write to letters@compoundjournal.com.
You note that no service offers sterility testing and that it takes fourteen days. Worth saying more plainly: a purity certificate and a sterility assurance are not merely different tests, they are different disciplines with different facilities, and no amount of chromatography will ever bear on it.
— E. Sørheim, Stavanger
Correct and worth the emphasis. We have said it in the certificates piece and should say it here too: nothing any of these four services sells addresses sterility, endotoxin or container closure integrity, and no combination of their reports adds up to one.
The price table is the most useful thing you have published this year and also the thing most likely to be quoted out of context by somebody selling a comparison service. You might consider a note.
— H. Steinmetz, Basel
There is one, and we have strengthened it. The figures are what this publication was invoiced at list rates and are not quotations a reader should expect; volume submitters pay materially less.
Every instrument specification quoted in an advertisement is a best case obtained on a calibration mixture, not on a submitted vial.
Reported from the analysis, not from a warning notice.
The Journal has read several hundred certificates from twenty companies. We set out what the documents actually cover, and what a reader is filling in from imagination.
The condition on arrival is recorded by some services and not others, and it is one of the more informative lines in a report.
Efficacy was never the question in this appraisal. Duration of treatment was.
A supply interruption is a discontinuation with no notice, no taper and no plan. That is a distinct clinical situation.