The benefits of Mixed cGMP and Pre-GMP environments for API Manufacturing

Deriving Value from Integrated cGMP and Pre-GMP Manufacturing Operations

By Didier Combis, Commercial Director, Seqens CDMO

Working with Contract Development & Manufacturing Organizations (CDMOs) in Asia has become a popular strategy for European and U.S.-based sponsors because of the associated lower costs to manufacture complex Active Pharmaceutical Ingredients (APIs). Given the high costs and resources required to produce advanced chemicals – combined with the need to rein in rising drug costs – it’s no wonder Chinese CDMOs have seen heightened business demand.

Yet, events such as the recall of heart drug, valsartan or widespread contamination discovered in a Chinese-manufactured vaccine have also put quality concerns in the spotlight. The big  question remains: how can companies manufacture life-saving drugs and other treatments more cost effectively while making quality paramount? There is another alternative, and that is leveraging a mix of GMP and pre-GMP facilities.

Facilities that operate in accordance with current Good Manufacturing Practices (cGMP) adhere to regulations enforced by the U.S. FDA and the European Medicines Agency (EMA) in the proper design, monitoring, and control of manufacturing processes and facilities. Adherence to regulations requires that API manufacturers adequately control manufacturing operations in order to ensure the identity, strict observance of the registered process, quality, and purity of drug substances. This includes establishing strong quality management systems, obtaining appropriate quality raw materials, establishing robust operating procedures, detecting and investigating product quality deviations, and maintaining reliable testing laboratories.

The Four Stages of Drug Manufacturing  

The pharmaceutical manufacturing process is comprised of four key stages of development:  the Regulatory Starting Material (RSM), the drug substance, the formulated drug, and finally the packaged and labeled finished product. The development of the Regulatory Starting Materials is the first compound to be described in a marketing authorization dossier for the API synthesis, essentially the last chemical in the API value chain to not require full cGMP inspection by the FDA or EMA. A starting material is also the point at which the sponsor commits to GMP manufacture of a drug substance.

RSM – The Frontier Between GMP and PreGMP

Following strict Standard Operating Procedures (SOPs) for quality control, yet avoiding the costly and unnecessary infrastructure required for GMP, the ability to produce APIs in FDA inspected facilities in a strict cGMP environment and the RSMs in a pre-GMP facility  brings a lot of value to pharmaceutical customers. Consider the following benefits:

• Control of impurities. CDMOs that provide a blend of cGMP and pre-GMP facilities not only offer greater value in the manufacture of APIs and other New Chemical Entities (NCEs) without compromising quality, but they also can ensure better control of the carry-over of impurities that could come from another CDMO. This is especially true with the increasing complexity of the new API chemical structure.  

• Speed in development. When an API is developed under compressed timelines, for example on a fast-track status NCE program, two process development teams can work in parallel at the same site to ensure faster completion, as well as greater collaboration to ensure improvements in the GMP synthesis.

• Cost control. It can be difficult to have a reliable long-term commitment from Asia in terms of pricing, but by keeping production of critical RSMs in-house, CDMOs can have better control of cost evolution. They also can avoid the costs associated with delays or drug denials because of chemical impurities or other issues.

Seqens, as a global drug substance CDMO, provides the benefits of mixed pre-GMP and cGMP environments. We currently operate six cGMP sites in Europe and the U.S. for the production of APIs, including one site for potent APIs with Occupational Exposure Limits (OELs) down to 100 ng/ m³. We also can offer more agile and value-focused pre-GMP capabilities from International Standards Organization (ISO)-certified sites in France in Couterne in the Normandie region and Bourgoin-Jallieu, near Lyon.  These sites, along with our Lahr, Germany and Newburyport, Massachusetts site in the U.S., are particularly attractive for the production of complex pre-GMP intermediates and RSMs.

In today’s sophisticated API manufacturing environment, where quality control is of critical importance, despite rising costs and regulatory controls, the availability of mixed environments of both cGMP and pre-GMP capabilities with the same CDMO can provide the perfect balance, enabling the safe, yet value-driven delivery of critical molecules without sacrificing quality.

For more Seqens insights into the evolution of chemical manufacturing please read: When does it make sense to use a CDMO for API Manufacturing; or  Phasing Forward with Seqens.