Clinical GMP manufacturing and release of biopharmaceutical products are two of the most sought-after outsourcing demands in life sciences. These activities are needed to allow subsequent testing in human subjects for safety and efficacy. Globally, the market for this outsourcing activity is estimated at about $3 billion annually. Biotech companies account for about 85% of that value, and large biopharmaceutical companies account for the rest.
Reasons for biotech companies to outsource this activity to third party vendors may be apparent, such as the need for specific expertise and facilities. Some examples:
- You need highly trained staff and mature IT infrastructure to meet regulatory requirements for documentation and data retrieval
- Building, maintaining, and operating clean room facilities is expensive. Therefore, such facilities need to run at full occupancy
- The entire manufacturing and release trajectory requires intimate oversight from QA and QC team. They ensure that every step in the process adheres to the strict guidelines. Regulatory organizations, like EMA and FDA. set these guidelines for Europe and the US.
CDMO selection guidelines for clinical GMP manufacturing
When you select a partner for clinical manufacturing, risk mitigation is very important. Here are a few guideline examples to prevent surprises during the execution of the project and release of the batch.
The CDMO’s quality systems and procedures should ensure compliance to applicable FDA and EMA regulatory requirements and standards. Therefore, the QA and QC team, headed by a Qualified Person, should oversee the entire production process. This means that they should be involved from the validation of equipment to the approval of the required documents.
Make sure the company’s culture is to only use manufacturing equipment for GMP manufacturing in line with the equipment to be used for commercial manufacturing. Therefore, it is crucial to first understand the commercial manufacturing process and scale. This will ensure a smooth transition of the candidate product from clinical trials to a commercial manufacturing setting.
Freedom to operate
A thorough and broad understanding of intellectual property restrictions is crucial to guarantee freedom to operate. This should include the used technologies, manufacturing platforms, and raw materials. Freedom to operate of the developed process supports a smooth transition from bench to market.
Many CDMOs have a development department completely separated from the manufacturing department. In that case, they need an internal tech transfer. A system where the experts developing the upstream and downstream processes are also performing the manufacturing in GMP, has benefits over the traditional structure. Reason is, that it eliminates time consuming and error-prone technology transfer processes. Additionally, you should watch for an experienced team that is intimately involved in transferring the manufacturing process to the client’s late stage / commercial manufacturer.
Naturally, the CDMO should have a facility that matches the requirements of your product. Do you require grade A, B or C clean room facilities for the production and purification of your biopharmaceutical? Does the facility have dedicated upstream and downstream suites to avoid the risk of contamination? Is the facility equipped with the right manufacturing platform? Also, if you want the company to do stability studies, temperature controlled storage areas should be available at -80°C, -20°C, 5°C and room temperature. In addition, Drug Substance and Drug Product stability testing require dedicated space. Lastly, you should watch for audits of the facility by authorities and other customers. For example, if the facility is regularly audited by various types of organizations and has never received critical or major observations, this indicates that they maintain high quality standards.
It is highly advised to check whether the CDMO has successfully manufactured and released products for clinical trials, both in Europe and USA. Successful IND and/or IMPD dossier submissions confirm a successful track record for GMP manufacturing and release of clinical products.