CDMO: how can you optimise your pharmaceutical production?

The transition from a laboratory formulation to industrial production relies on a series of technical decisions: choice of process, analytical development, availability of equipment, definition of manufacturing parameters, control strategy, documentation transfer and regulatory organisation.

Where these skills or capabilities are not available in-house, engaging a CDMO allows all or part of the development and manufacturing to be entrusted to a specialised industrial partner. The scope can range from a feasibility study to the production of commercial batches, depending on the maturity of the project.

 

Unither Pharmaceuticals is a CDMO specialising in the development and manufacture of pharmaceutical products, particularly in sterile and non-sterile liquid forms.

 

The acronym CDMO stands for Contract Development and Manufacturing Organisation.

A CDMO can be involved in two complementary areas:

• pharmaceutical development, for example formulation, process development, analytical methods, pilot batches and the studies required to prepare for technology transfer;
• contract manufacturing, from technology transfer through to the production of commercial batches, depending on the scope and responsibilities defined with the client.

This dual focus distinguishes a CDMO from a CMO, or Contract Manufacturing Organisation. A CMO focuses primarily on the manufacture of a product whose formulation and process are already established. A CDMO may also be involved in activities that precede industrial production.

 

Depending on the stage of the programme, collaboration with a CDMO may involve:

• the feasibility of a formulation or packaging;
• the development or adaptation of a process;
• the production of prototypes and pilot batches;
• the manufacture of clinical batches;
• the development and transfer of analytical methods;
• technology transfer to an industrial site;
• the production of commercial batches;
• certain regulatory and documentation activities;
• support for changes throughout the product lifecycle.

Unither Pharmaceuticals offers development services from the early stages through to prototypes, pilot batches, clinical batches and commercial batches of varying sizes.

 

Why use a CDMO?

 

Incorporating industrial constraints at an earlier stage

A formulation that performs satisfactorily at laboratory scale cannot automatically be scaled up to industrial scale. The transition to production requires an assessment of the product’s compatibility with equipment, primary packaging, process parameters and the analytical strategy.

Involving a CDMO at an early stage enables these constraints to be addressed during development. This approach facilitates the identification of missing data and the preparation of the transfer and qualification stages.

It does not guarantee a specific timetable. However, it does enable the creation of a development programme that is consistent with the envisaged production conditions.

Gaining access to a combination of skills

A pharmaceutical project draws on a range of specialist areas:

• formulation and pre-formulation;
• process development;
• analytical development;
• stability studies;
• pilot batch production;
• technology transfer;
• quality;
• CMC documentation;
• preparation for industrial manufacture.

Using a CDMO makes it possible to bring together some of these areas of expertise within a single project organisation. The level of integration must be defined according to the client’s actual needs and the responsibilities they wish to retain.

Deploy technology tailored to the product

The choice of technology depends on the formulation, the route of administration, the volume, the physicochemical properties of the product, the intended device or packaging, and the associated regulatory requirements.

Unither works in particular on the following technologies:

• Blow-Fill-Seal;
• standard multi-dose;
• preservative-free multi-dose;
• liquid stick-packs;
• sprays;
• pharmaceutical bottles.

The mere availability of a technology is not sufficient to determine the feasibility of a project. A technical assessment is still required before defining the development and manufacturing strategy.

Adjust the scope during the development phase

An early-stage company does not have the same needs as a laboratory that already has a product on the market.

An early-stage programme may require an initial formulation, a prototype or a feasibility study. A more advanced programme may involve pilot batches, a stability study, analytical development or preparation for transfer. A product that has already been scaled up for commercial production may require a site transfer or the evaluation of a change.

The collaboration model can therefore be structured in stages, with deliverables and decision criteria defined for each phase.

 

The key stages of a CDMO project

 

1. Analyse the available information

The first stage involves reviewing the information provided by the client:

• product composition and characteristics;
• formulation data;
• existing or proposed process;
• available analytical methods;
• primary packaging;
• stability results;
• batch sizes;
• target markets;
• desired timetable;
• available regulatory documentation.

This review serves to establish the technical scope. It also helps to distinguish between data that can be used directly and data that will need to be supplemented.

2. Assess feasibility

The feasibility study examines the compatibility between the product, the process, the packaging and the proposed equipment.

Depending on the programme, it may include:

• a literature review;
• formulation trials;
• a process evaluation;
• an initial analytical characterisation;
• the production of a prototype or a small batch;
• the identification of technical risks.

The conclusion must specify the assumptions made, the limitations identified and any additional tests that may be necessary.

3. Develop the formulation and process

Whilst the product is still under development, work may focus on:

• the selection or adjustment of the formulation;
• interactions between the product and its packaging;
• the definition of process parameters;
• the development of analytical methods;
• the definition of a testing strategy;
• the preparation of initial stability studies.

Decisions must be documented in order to prepare for the subsequent phases of development, transfer and production.

4. Produce pilot or clinical batches

Pilot batches are used to examine the behaviour of the process under conditions that are more representative of future manufacturing. Depending on the status of the programme, they may be intended, in particular, for stability studies or clinical trials.

In its proposal, Unither outlines support from the initial prototypes through to pilot, clinical and industrial batches.

The intended use of the batches, the production conditions and regulatory responsibilities must be clarified before operations commence.

5. Prepare for technology transfer

Technology transfer involves the transfer of the knowledge required to replicate the process at the industrial site.

The transfer dossier may include, in particular:

• the formulation;
• manufacturing instructions;
• critical parameters;
• raw materials and components;
• equipment;
• analytical methods;
• specifications;
• development results;
• available stability data;
• relevant protocols and reports.

6. Organising commercial production

Prior to the start of commercial production, the parties must define:

• operational responsibilities;
• applicable specifications;
• in-process controls;
• acceptance criteria;
• data review procedures;
• non-conformity management;
• change management;
• release conditions;
• project governance.

Commercial production is thus based on a transferred process, established documentation and methods tailored to product control.

 

What is the role of regulatory support?

 

The formulation, manufacturing process, analytical methods and packaging form the basis of the product’s regulatory documentation. Industrial developments may therefore have implications for the pharmaceutical dossier.

The regulatory support provided as part of Unither’s offering includes, depending on the contracted service and the product’s status, activities relating to CMC documentation, technology transfer, regulatory dossiers and the management of certain variations.

A regulatory expert may be integrated into the project team during development or transfer to identify the necessary information and actions.

The role of the CDMO must, however, remain distinct from that of the marketing authorisation holder. Unither acts as an industrial partner and service provider. The respective regulatory responsibilities must be defined in the contract and the quality agreement.

It is also important to distinguish the status of the product in question. A medicinal product, a medical device or another type of healthcare product is subject to different documentation requirements and a different authorisation framework.

 

How do you choose a CDMO?

 

Compatibility between the product and the equipment

The assessment must go beyond a general list of available technologies. It must verify the actual compatibility between:

• the formulation;
• the process;
• the packaging;
• batch sizes;
• site equipment;
• analytical methods;
• target markets.

Continuity between development and manufacturing

For a product still in development, it is useful to examine the coordination between the formulation, process development, analysis, quality and production teams.

The deliverables, responsibilities and criteria for moving from one phase to the next must be defined at the scoping stage.

Experience in technology transfer

The transfer involves not only data, but also an understanding of the process and its parameters. The assessment of the CDMO may therefore include:

• its transfer organisation;
• its method for reviewing the dossier;
• the management of missing data;
• the procedures for scale-up;
• coordination between the sending site and the receiving site;
• the preparation of protocols and reports.

Project governance

Clear governance sets out:

• the points of contact;
• responsibilities;
• the frequency of reviews;
• deliverables;
• approval deadlines;
• decision-making bodies;
• escalation procedures;
• change management.

 

What risks should we be prepared for?

 

An incomplete transfer dossier

The absence of data on the formulation, process parameters or analytical methods may lead to further investigations or testing. A detailed analysis of the dossier at the start of the project enables this risk to be assessed.

 

A late change to the product

A change to raw materials, suppliers, formulation, methods or packaging may affect development, the timetable, documentation and regulatory status.

Governance must specify the change management procedure and the responsibilities associated with impact analysis.

 

An unaligned analytical strategy

The methods used during development must be aligned with the requirements of stability studies, quality control and industrial transfer.

The development, validation and transfer of methods must therefore be planned in line with the various phases of the programme.

 

Insufficiently defined responsibilities

A lack of clarity regarding the roles of the client, the CDMO, the marketing authorisation holder or the legal manufacturer may delay decisions or lead to discrepancies in documentation.

The contract, the quality agreement and the project plan must specify these responsibilities.

 

Do you have a project?

 

Unither can support you with development, production, scale-up, technology transfer, life-cycle management and certain regulatory services.

Are you preparing a new formulation, a technology transfer or an industrial scale-up?

The teams at Unither Pharmaceuticals can work with you to assess:

• the maturity of the project and the available data;
• the feasibility of the formulation and process;
• the proposed technology and packaging;
• analytical requirements;
• pilot, clinical or commercial batches to be planned;
• the technology transfer strategy;
• the regulatory activities to be included in the scope.

Contact Unither Pharmaceuticals’ team