What the manufacturing and control package has to say before a cmc clinical trial application is filed: why the chemistry, manufacturing and control section is phase appropriate rather than complete, what stability testing pharmaceutical products require and how a stability testing of pharmaceutical products programme is designed to support a shelf life claim, where accelerated shelf life testing supports and does not replace real time data, what bioanalytical method development and validation has to deliver into the study file, how clinical trial patient enrollment and site readiness interact with supply, and what a sponsor should have on file before the first patient

Building the package

1. Scale the package to the phase. Early phase needs identity, purity, potency, safety related impurities and enough stability to cover the study. Later phases add validated methods, process characterisation and a full stability programme.
2. Start real time stability early. A shelf life claim rests on real time data at the labelled condition. Accelerated data supports it and cannot replace it, so the clock has to start as soon as representative material exists.
3. Validate the bioanalytical methods to the use. Methods supporting clinical samples need documented accuracy, precision, selectivity, stability and a defined range before the samples arrive, not afterwards.
4. Align supply with enrolment. Batch size, shelf life and release timing have to match the enrolment plan. A slow site and a short shelf life together waste material; a fast site outruns supply.
5. Keep comparability in mind at every change. Any change of site, scale or process raises the question of whether the product is the same. Making changes early, while there is little clinical material, is far cheaper than later.
6. Document the reasoning, not just the results. Why a specification was set where it was, and what data supports it, is what a reviewer asks about. Recording it as decisions are made is much easier than reconstructing it.

Stability is the item with the longest clock

Every other part of the package can be accelerated by adding people. Real time stability cannot, because it takes the time it takes, and a shelf life claim is bounded by how early the programme started.

Put representative material on stability as soon as it exists, even if the process will change. The data is not wasted and the alternative is a shorter claim.

Specifications are commitments

A specification filed early becomes a commitment that later batches have to meet, and widening one afterwards requires justification. Setting them from too little data is a common and expensive mistake.

Set them wide enough to be met and narrow enough to be meaningful, and record the data and reasoning behind each one.

Common questions

How complete does an early package need to be?

Phase appropriate: enough to establish identity, purity, potency and safety for the study duration. Regulators expect it to grow, and over-filing early commits you to specifications you may want to change.

Can accelerated data support a shelf life?

It supports and does not replace real time data at the labelled condition. Shelf life claims are extended as real time data accumulates, which is why the programme starts as early as possible.

When should bioanalytical methods be validated?

Before clinical samples are analysed. Retrospective validation of a method already used is far weaker and occasionally forces reanalysis of stored samples that may no longer be stable.

Browse by service class

• Compare Gene synthesis on advertised prices