Taking the trial out of clinical packaging
Contracting out clinical trials packaging is an increasingly popular option, but how do you get the best out of the relationship? Sue Price* outlines the key criteria for establishing a successful clinical packaging contract
Contracting out clinical trials packaging is an increasingly popular option, but how do you get the best out of the relationship? Sue Price* outlines the key criteria for establishing a successful clinical packaging contract
Increasing numbers of pharmaceutical and biotechnology companies are contracting out clinical trial packaging. This may be for a number of reasons, including a lack of in-house expertise or capacity, or because there are specific technical requirements which the company does not have the ability to fulfil.
For those with a need to pack within the EC specifically for European study sites, a new EC Directive — currently in draft form — will also further stoke demand for specialist services, as this states that release of the packaged trials must be carried out by a Qualified Person.
Often when a client approaches a contract packaging organisation, the initial contract takes some time to establish, but there are ways of easing the process and this article outlines the key criteria for establishing a successful partnership with your contractor.
Information requirements: Firstly, when looking for a contract packaging company it is prudent to approach the contractor with a consistent set of information so that the basis of any costing can be clearly understood. This is especially important when several contractors are being approached and meaningful comparisons are to be drawn between quotations thus facilitating contractor selection.
When considering the information requirements, a few general concepts should be borne in mind:
Planning: The length of time taken to complete a clinical packaging cycle can vary considerably depending upon the exact scope of the project. This should be negotiated early with the contractor as part of the project set-up.
In general terms, a simple study, for example a placebo controlled, parallel group of less than 50 patients, takes at least four weeks to pack. Larger, more complicated studies take considerably longer, especially where multiple languages and printed components are needed for the packs.
updated packaging schedule
A mechanism should be agreed and implemented whereby the contractor is responsible for regular updates of the packaging schedule to the client. Any changes in the critical path for the project should be flagged to all parties so that the underlying issues can be addressed.
Packaging materials: The specification of packaging materials is important. Drug products should only be presented to patients in packs for which there is an adequate stability database.
In the case of comparators to be re-packaged, for example for blinding purposes, it is best practice to duplicate the manufacturer's packaging materials as far as possible. The responsibility for supply of packaging components should also be defined, that is, which party — client or contractor — is to supply which material.
When the contractor is to supply printed components these are generally handled in the same way as labels, with client approval being an important key step in the process.
Pack design: The pack design for a clinical study is usually outlined in the clinical trial protocol. This section of the protocol is often open to interpretation and allows for flexibility in pack design.
The expertise of the contractor should be fully utilised with regard to pack design, as there may be quality, cost or lead-time implications with some suggested clinical packs, and contractors will know what works best in their organisation.
Labelling: Label and pack design go hand-in-hand. It is important to define the type of labels to be used and where they are to be applied. Features to consider include:
“In the case of comparators to be re-packaged, for example for blinding purposes, it is best practice to duplicate the manufacturer's packaging materials as far as possible, and the responsibility for supply of packaging components should also be defined |
It is usual practice to have the client perform final approval of the labels which should be reviewed to ensure that they are compliant with specific study requirements, EC GMP requirements (see Annex 13) and any additional local regulatory needs.
Number of packs to be produced: The number of packs required and their configuration requires careful consideration. It is usual practice to allow an 'overage' of packs to cover patient recruitment difficulties, damage in transit and at site, and so on. In the case of studies with a placebo run-in phase it is usual to pack a large excess of run-in packs (up to 200%) and a smaller excess of treatment packs (120% to 150%). The exact overage is very much dependent upon the nature and duration of the clinical study and the disease state of interest.
Dummy packs: Dummy packs are empty packs provided to the client for demonstration and/or sample purposes. These are often produced separately from the main packaging run, so as to avoid the potential for mix-ups. It is important to define what is needed before packaging begins.
Drug products: The provision of drug products should be defined. Who will supply each component, how many batches of drug will be supplied, how many formulations are to be expected? Provision of multiple batches of drug product can cause problems to contractors who must provide traceability throughout the packaging process.
If a comparator is purchased by the contractor, information should be given relating to the source, including the product licence number and place of origin, for example UK, EC, ex-EC.
Analytical testing: Most contract packaging companies can now offer a seamless analytical service. If the contractor sub-contracts this work to an analytical laboratory it is important that all involved know where their responsibilities lie.
clinical supplies directive
With the imminent implementation of the new EC directive for clinical supplies it is likely that any materials being supplied from outside of the EC will require analytical testing at the point of importation. The requirements for this should be defined in the contract, laying out clearly what test methods and laboratories are to be used. Import analysis for non-EC materials is closely linked to the QP release process and the relevant QP should be involved in defining the exact process and requirements.
If comparator drug products are being processed, for example, over-encapsulated and/or re-packed, it is usually necessary to arrange analysis to prove that the dissolution and stability profiles of the drug have not been significantly changed by the processing operations.
It should also be noted that post-packaging identification testing is being requested more frequently, mainly to provide evidence that the packaging procedures have been performed in accordance with the agreed contract.
Randomisation: The majority of clinical studies require randomisation and blinding. The important points to consider are:
“Health and safety legislation requires provision of a material safety data sheet to the contractor. It is helpful if this can be received early in the project, especially for novel, toxic or potent compounds where special handling procedures are required |
randomisation schedule
If the client provides the randomisation, will the format be hard copy, electronic, spreadsheet or database and who will provide it, for example, the client's biostatistician or a third party?
When the contractor provides the randomisation schedule the format should be agreed. Inevitably the client will require a copy of the randomisation so that the study results can be interpreted and the means of communicating this information between the parties needs to be defined in the contract.
Blinding parameters: Blinding parameters should be specified, because if a trial is blinded the levels at which checks are to be performed should be documented, for example, individual dosage units (tablets, capsules), primary packs (bottles, blisters) and secondary packs (cartons).
Retention samples: Increasingly clients request that representative samples from each packaging run are taken for retention purposes. These can either be returned to the client or held at the contractor's site on their behalf.
Storage, handling and distribution: Any special storage requirements for the drug products should be defined. This can range from shipment of the entire supply to the client to individual despatches to clinical sites. If cold chain storage is needed this should also be defined. For cold chain products, the length of time the product is allowed out of cold storage conditions must be supplied to the contractor and shipment must also be considered, including validation of insulated shipping systems.
The procedure for approval/release of shipments which have been delivered outside of the validation criteria must be documented in the contract.
Health and safety legislation requires provision of a material safety data sheet to the contractor. It is helpful if this can be received early in the project, especially for novel, toxic or potent compounds where special handling is required, such as b-lactams. It is vital the contractor is notified in advance if the compound in question belongs to one of these classes. Special care must also be taken with controlled substances.
If an interactive voice response telephone system is to be used as a part of the trial, there may be design implications for the clinical supply. If any assembly or labelling is required at the point of despatch, then this should be agreed as a part of the overall project.
Documentation review and release: A variety of options for documentation review and release are generally available:
avoiding misunderstandings
There may well be criteria individual to the project undertaken which must also be taken into account, but following these guidelines will, at the very at least, avoid basic misunderstandings and problems which could occur.
Finally, as outsourcing becomes part of a strategic plan, rather than an emergency measure, so it is increasingly important to view your contractors as long-term business partners as opposed to 'hired help'. A sound, two-way, relationship with a company which has established its expertise in a chosen field can provide added value to your business way beyond the simple fulfilment of the tasks contracted out.