Drug manufacturing: a long and closely monitored process

Manufacturing a drug is a long process. Sometimes very long! From test tube to pharmacy takes an average of around 15 years... This journey is closely monitored, highly regulated and follows a well-established process.

It all begins with the research phase. This first step, conducted in the laboratory, explores numerous alternatives and targets thousands of active ingredients before launching pre-clinical trials. At this stage, the researchers will assess the potential of the various active ingredients, firstly “in vitro”, meaning on cells in culture. Once this step has been validated, potential future drugs will be tested “in vivo” (editor’s note: on living organisms), mimicking real-life conditions as closely as possible. In practice, this initial data-gathering exercise aims to establish the active ingredient’s “résumé” and to “profile” its behavior, including rate of diffusion in the organism, toxicity, elimination, etc. During this phase, numerous alternatives will be ruled out due to a failure to meet applicable pharmacological or toxicological criteria.

For the selected drug candidates, however, the journey will continue, moving on to the clinical phase – i.e. with trials involving healthy human volunteers, as well as sick patients. The objective at this stage is to assess the product’s safety, then its therapeutic efficacy and, finally, the benefits of the potential treatment. If the benefits are considered to outweigh the risks, then the laboratory may apply for a Marketing Authorization (MA) from the drug regulatory authority in the country (or countries) where it wants to distribute its drug. That agency grants permission for marketing following a careful assessment of the data.

Materials for clinical trials

Before being marketed, however, the “authorized” drug will undergo a number of production stages. During these stages, it will pass through a complex series of tubes, filters and bags in order to prepare the doses. In other words, the materials chosen are of the utmost importance in ensuring that the drug is as safe as possible.

During this long biopharmaceutical process, industrial groups such as Saint-Gobain provide laboratories with components and consumables they need for the proper functioning of the various equipment, such as final filling machines, for example, which make it possible to fill containers with batches of biopharmaceuticals, vials or syringes for example, from which they will be administered to the patient.

“In the vast majority of cases, we become involved during the latter stages of clinical trials, just before pre-industrialization,” explains Benjamin Le Queré, General Manager of the Bioprocess Solutions BU at Saint-Gobain. “To respond as closely as possible to our customers’ demands, we work together to design the assembly lines and define the best configuration to optimize the bioprocess.” At Saint-Gobain, all assembly lines are therefore custom-built from a wide range of components manufactured internally. We don’t limit ourselves, however. In order to find the best solution for its customers, the group may use components manufactured by external partners. “It opens up a whole range of possibilities!” adds Benjamin Le Queré.

Polymers with a range of powers

In step with this most demanding of markets, the Bioprocess Solutions BU applies standards aligned with those of its customers when manufacturing consumables. Many are therefore designed in clean rooms in a controlled atmosphere, in order to minimize contaminants.

As all biopharmaceutical processes are different, manufacturers, Saint-Gobain included, need to be able to adapt, starting with the choice of materials. For example silicone is used for a wide range of applications in biopharmaceutical processes. Known for its long lifespan in the pump, it offers optimum reliability for fluid transfers. Problems can sometimes arise with certain additives, however, in the case of certain formulations based on insulin for example. Manufacturers therefore opt for fluoropolymer tubes instead, which are very stable and chemically resistant. Whether the tube is to be welded or sealed, an elastomeric thermoplastic such as C-Flex® will then be used.

Sterile and sealed

Choosing the right material is one thing, but it is also necessary to examine the required pump flow, to calculate the diameter necessary for transfer of the fluid, to check the material's pressure and temperature resistance, etc. Like a Swiss clock, everything must be thoroughly and precisely regulated.

Another crucial point is the integrity of the system. This is one of the major risks in the drug manufacturing process, as any breach, however minor, allows contamination of the product by microbes, potentially endangering the patient and compromising the production process. This is especially the case during the final manufacturing phase, when the product is particularly valuable. Just one leak can be a disaster, costing the lab a small fortune. To make joints more secure, Saint-Gobain’s Bioprocess Solutions BU has therefore developed an overmolding process to optimize the sealing of assembly lines, as well as connectors – “BarbLocks®” – used to securely connect tubes.

Designing assembly lines to be ergonomic

As well as eliminating leaks, manufacturers of components and consumables need to consider the ergonomics of solutions, in order to best adapt to the restricted environment in which their customers operate. The approach can be defined in three words: simplicity, ease of use and efficiency. Assembly lines are therefore configured with the end user in mind, components are ergonomically designed to facilitate their handling, etc.

Components used all around the world

Saint-Gobain’s polymer components are currently used in most vaccine manufacturing, including vaccines against Covid-19. Given the numerous health and economic challenges that exist, the Bioprocess Solutions BU is continuing its efforts to develop new products while working closely with its customers. Demand is strong, since many biopharmaceutical laboratories are now turning to single-use technologies, which offer a high level of flexibility and reduce investments and time to market, while maximizing safety for patients and avoiding contamination.

Choice of materials, leak-free assembly lines, ergonomics – from the first tests to packaging, the drug follows a long, highly regulated manufacturing process which meets strict quality standards. The aim is to guarantee patient safety and the production of reliable and effective drugs.
 

Photoq Credits : Numstocker/Shutterstock / FOTOGRIN/Shutterstock