July 2025

Escalating onto a rising curve

What the published pharmacokinetics permit, what the labels state, and where the two diverge.

What the GIP receptor adds: reading orforglipron as two drugs in one sequence

The glucagon arm raises energy expenditure and also raises hepatic glucose output. Balancing those is the whole engineering…

The tolerability data everybody quotes and nobody reads

Severity in these tables is graded by interference with activity, not by how unpleasant the experience was. Those are different…

The steps get smaller as the ladder gets higher, and that is deliberate

What the published pharmacokinetics permit, what the labels state, and where the two diverge.

Three receptors, one peptide: the design problem behind triple agonism

What adding GIP activity does, on the current evidence, and what remains unresolved.

Is liraglutide better than mazdutide, or differently balanced?

What adding GIP activity does, on the current evidence, and what remains unresolved.

Antiemetics, laxatives and the thin literature underneath them

Constipation is the most tractable of the effects and the most consistently under-managed.

The mechanism behind the mechanism

The receptor populations that produce satiety and the ones that produce nausea overlap substantially. That is why the ceiling of…

We asked four laboratories for a sterility test. Here is what came back.

A compendial sterility test takes fourteen days of incubation and consumes the containers tested. That timescale is incompatible…

The certificate says 2025. The vial in your hand does not say anything.

The interval between manufacture and analysis is the most under-read figure on the page, and the one most likely to matter by…

Custody, condition and the temperature nobody logged

What a laboratory can and cannot know about the provenance, storage history and representativeness of what lands on its bench.

LAL, kinetic chromogenic, recombinant factor C: three ways to the same figure

We submitted vials for endotoxin determination and report the results, the method and the laboratory, because a pyrogen figure…

What twenty companies say about storage, and what they have measured

A stability programme needs a protocol, defined conditions, a stability-indicating method and time. Time is the ingredient no…

A tested vial is evidence about a vial

A result on one vial generalises to a batch only if the vial was drawn in a way that makes it representative — and nobody…

What twenty companies say about storage, and what they have measured

A stability programme needs a protocol, defined conditions, a stability-indicating method and time. Time is the ingredient no…

Why a dead-clean sterile filter can pass pyrogen straight through

Bacterial endotoxin is a heat-stable lipopolysaccharide from the outer membrane of Gram-negative organisms. It survives…

Why "muscle-sparing" is a marketing term and not a measurement

Grading six widely repeated claims against the studies actually behind them.

Thiamine and the vomiting patient

Reduced intake is a plausible mechanism for deficiency. Reduced absorption is not, and the two are conflated in most of the…

The advice is mostly reasonable. The certainty is not earned.

The gap between a defensible recommendation and a confident one is where most of the harm in this subject lives.

The advice is mostly reasonable. The certainty is not earned.

The gap between a defensible recommendation and a confident one is where most of the harm in this subject lives.

Grams per kilogram of what? The denominator problem in protein guidance

A survey of what the meta-analyses support, with the populations named.

The out-of-range flag is a statistical convention with a printer attached

A flag is a probability statement about a population. It is not a statement about the person holding the printout.

Percentage of loss, absolute kilograms, and the sleight of hand between them

What was pre-specified, what was exploratory, and what was calculated afterwards by people who did not run the trial.

A named analyst is the cheapest quality signal in this trade

Two signatures — one who performed the work, one who approved its release — are the ordinary regulated convention and are almost…

What twenty companies say about storage, and what they have measured

Storage instructions in this market are close to uniform and almost never accompanied by the study that would justify them.…

The fourteen-day problem, and what it does to a commercial testing model

The absence of microbiological capability in this market is a commercial fact with a straightforward explanation, and it is…

Who signed this, and what did they undertake by signing it

Two signatures — one who performed the work, one who approved its release — are the ordinary regulated convention and are almost…

The badge is about a sample. The listing is about a product.

A badge asserts that something was tested. It does not assert what, when, on whose sample, by what method, or whether the lot on…

Six words a verification badge would need to mean anything

What a verification mark would have to carry to be checkable: a date, a lot, a method, a submitter and a link to the report.

The certificate of analysis, line by line

The purity figure is the least informative line on a well-constructed certificate and the only line most buyers read.

The mechanism behind the mechanism

The clinical effect profile is almost fully predictable from where the receptor is expressed, which is unusual and useful.

The supply gap as a clinical event

Why the reason for stopping changes what happens afterwards.

What a 1 mL syringe does that a 0.3 mL syringe does not

A unit is a volume. A dose is a mass. The bridge between them is concentration, and concentration is a number somebody has to…

The dose that got you here and the dose that keeps you here

Every withdrawal trial compared full dose against nothing. The clinically interesting comparison — full dose against a reduced…

Percentage of loss, absolute kilograms, and the sleight of hand between them

The trials measured mass. Nobody measured whether the participants got weaker.

A unit is not a dose, and it never was

The graduation interval differs between barrel sizes, and a 1 mL barrel is frequently marked in two-unit steps. Reading one as…

The imaging substudy is an afterthought in the protocol and the centrepiece of the debate

The trials measured mass. Nobody measured whether the participants got weaker.

Maintenance dosing: what is licensed, what is practised, and what is evidenced

A survey of the maintenance evidence, which is shorter than the survey of the withdrawal evidence.

What a split-sample exercise can establish, and what it cannot

The Journal submitted split samples from single lots to three assay services, under names unconnected to this publication, and…

The named comparison we promised two years ago

The Journal submitted split samples from single lots to three assay services, under names unconnected to this publication, and…

Custody, condition and the temperature nobody logged

The condition on arrival is recorded by some services and not others, and it is one of the more informative lines in a report.

STEP 2 was built to answer the stopping question, and it did

A withdrawal trial answers a narrower question than it appears to. This piece states which question.

What a laboratory knows about the material it receives

A result on one vial generalises to a batch only if the vial was drawn in a way that makes it representative — and nobody…

The dose that got you here and the dose that keeps you here

Every withdrawal trial compared full dose against nothing. The clinically interesting comparison — full dose against a reduced…

What happens to a stopper after the fourth needle

Multiple-dose vials are designed for a defined number of punctures. Nobody counts, and the elastomer does not care whether…

Bone density during rapid weight loss: what is known, which is less than you would hope

What the Journal would want measured before treating this as settled in either direction.

Sterility is not a percentage, which is the whole difficulty

Every certificate circulating in this market answers a question about molecules. Almost none answers a question about organisms,…

What column temperature does to selectivity

A shallow gradient resolves impurities that a steep one runs into the parent peak. Both methods are legitimate; only one of them…

The out-of-range flag is a statistical convention with a printer attached

A twelve-analyte panel in a perfectly healthy person has roughly even odds of producing at least one flagged result.

How to read the silence on a certificate you already hold

Our position is about documentation practice. It is not an allegation about anybody’s honesty, and we are explicit about the…

What a diode array adds, and why the certificate never shows it

A diode-array detector records the whole spectrum at every time point and can confirm that a peak is spectrally homogeneous.…

Which results should be repeated before they are investigated

What the pivotal programmes measured and how often, which is a more defensible template than most published monitoring schedules.

A supply gap is a pharmacological event

One omitted dose is a labelling question. Four omitted doses is a clinical one. The two are routinely conflated.

The software decides what counts as a peak

Baseline placement under a tailing peak is a judgement call with a direct effect on the area. It is one of the few places where…

The eighteenth month, and the conversation that should have happened in the third

What the trials measured was continuation against withdrawal. What patients want to know is continuation at a lower dose, and…

Gauge, pain and flow rate

Skin thickness at the standard injection sites is approximately two millimetres in adults and varies remarkably little with body…

How a correct calculation becomes a wrong dose

Almost every case involves a change — a new vial, a new syringe size, a new supplier — carried forward with an old number.

Retained gastric contents, and how a small finding became a large argument

A drug that delays gastric emptying complicates the assumption behind every fasting instruction in perioperative medicine. The…

Escalating onto a rising curve

What the published pharmacokinetics permit, what the labels state, and where the two diverge.

Electrospray, MALDI, and the choice that shapes every spectrum after it

The two ionisation techniques in general use produce different charge distributions, different adducts and different failure…