An area often overlooked in considering the final product container is the issue of filling validation. If the clinical trial
material is to be supplied by the CMO in its final dosage form, then the CMO must undertake a filling validation to provide
assurance that it is able to fill the requisite number of containers in an aseptic manner. The validation must also demonstrate
that the correct volume of product is dispensed into each container, within an agreed and defined tolerance level.
Conflicting Demands of Robustness and Speed
There are always lively discussions between process development professionals and those on the business side who are overseeing
the clinical development. It is understandable that the sponsoring company will be anxious to deliver the clinical trial material
to the clinic as fast as possible. Many biopharmaceutical companies' entire business model is based on speeding a therapeutic
candidate into the clinic as quickly as possible to establish the safety of the product and to confirm proof of principle,
with the intention of partnering with a larger pharmaceutical organization to take the candidate forward into later-phase
clinical trials (and hopefully through to commercial manufacture).
Compounding this need for speed is the fact that regulatory authorities do not insist on manufacturing early-phase clinical
trial material using a fully validated manufacturing method. Everyone knows that validation will need to be performed for
later-phase clinical trials (and certainly for commercial manufacture), but it can be tempting to avoid any extraneous expense
and time in process development for a Phase 1 clinical trial.
The antidote is to use the services of the Qualified Person (QP) within the CMO to prepare for a clinical trial. The QP will
help ensure that compliance is built into the manufacturing process for clinical trial material and avoid any nasty surprises
with the regulators. The QP can advise on whether the proposed manufacturing strategy and proposed design of the clinical
trial will be likely to be acceptable to the regulatory authorities.
Working with a QP will ensure that the trial design and manufacturing are appropriate for the stage that the therapeutic candidate
has reached. The payoff is that you avoid any nightmare scenarios in which a sponsor has gone through cGMP manufacture of
clinical trial material, but regulators have picked up some issue with regard to manufacturing, testing, or packaging that
cannot be resolved. In the worst case, this could lead to the need to remanufacture the whole clinical trial investigational
medicinal drug product, which would be a catastrophic waste of money and time.
Susan Cameron is a commercial scientist at BioReliance, Ltd., Glasgow, UK, +44.(0).141.579.3265, firstname.lastname@example.org
1. Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of the laws, regulations
and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct
of clinical trials on medicinal products for human use. Official J Eur Communities 2001 Jan 5; L121:34-44.