Denise Bowser, Onyx Scientific, looks at the challenges of a development project – from both sides of the coin
Planning a small-scale research or GMP API manufacturing project comes many challenges. For drug developers, it can be a daunting and confusing process. We explore key considerations when planning such a campaign. Alongside the CRO perspective, I’ve enlisted the assistance of Chris Wallis, who runs a consultancy firm that represents the ‘client side’ of the equation.
Firstly, client side . . .
When you need drug substance for an upcoming activity, there is much that needs to be done. Whether it’s your first project or your twentieth, it will never be smooth. I’ve outlined three important elements to consider.
1. Your choice of CRO
Any development or GMP manufacturing project is likely to succeed or fail based on your choice of CRO. This is not a decision to take lightly. Do your research, seek recommendations and references. The challenges you will face will be less stressful if you choose one with the relevant competence. If you’ve dealt with numerous CROs, you can spot a great one from a satisfactory one. If you have not dealt with CROs, do your homework, use your network of contacts for advice, carry out site visits and pick one based on scientific/technical capabilities. Getting this right first time will save you in the long run.
2. Utilise your CRO’s expertise
Having selected our CRO, it’s now time to utilise their experience and technical expertise. A good CRO will evaluate your chemistry and provide comprehensive feedback on its scalability. They will identify potential obstacles and provide alternative strategies to get around these problems. Most importantly they will provide realistic timelines for the project. A good CRO partner will have worked on many similar projects so will have a good feel for potential challenges and how these can be overcome.
3. Establish your key driver
It goes without saying that quality is of paramount importance and should not be compromised, especially in GMP manufacture. The other two are time and cost. It’s unrealistic to expect your CRO to turnaround complex chemistry very quickly and very cheaply. Make it clear from the outset what your key drivers are. Some CROs are better equipped to deal with rapid delivery so if that’s what you need, make sure they can deal with your requirements. In reality, clients will have a combination of needs so whatever these are and however prioritised, ensure your CRO has the capability and flexibility to deal with the speed and economy you need.
The CRO side…
Now let’s look at the challenges from a CRO perspective.
1. A juggling act
When the project is underway, it will require a serious amount of coordination. Alongside core work on the API, you also have to take into account support services like solid state chemistry, validation and analytical method development, which all need to be planned and managed. So it’s important to communicate closely and regularly with your CRO to keep everything on track and ensure nothing is missed.
2. Prepare to change course
With so much going on at once, deviations are likely to occur. Common issues clients face are delays with toxicity results or obtaining raw materials as you are reliant on third party suppliers. In such a situation, the project team needs to adapt quickly. Whatever comes up, you need to plan in advance and it’s wise to build in contingency. Not doing so gives you zero flexibility and no time to deal with unforeseen challenges. One aspect not going to plan can have a knock on affect to everything else, a major challenge when dealing with a tight timeline.
3. Start early
If timelines are tight, development and ordering of long-lead raw materials and production of common intermediates can start ahead of final product selection. However, as final yields are likely to be unknown at this early stage the manufacture carries some risk and it is wise to build in contingency. Facilities and resources can be allocated ahead of time if the full program requirements are communicated to the CRO, including an indication of likely scale up quantities of both non-GMP API and GMP API material. Bulk intermediates can be manufactured from one campaign and split for non-GMP and GMP scale up, giving cost efficiency, especially if GMP API requirements are small.
This will hopefully provide food for thought for companies planning research work and/or GMP manufacturing campaigns. Ultimately, it’s all about planning, choosing the right partner and being aware things don’t always go to plan. Working closely with your CRO in an open way is likely to lead to a successful outcome. Chemistry is never guaranteed to work but give it the best chance by ensuing you pre-empt challenges and have a plan to overcome them in a collaborative manner.