What is aseptic drug manufacturing?

Aseptic Manufacturing and Sterile Fill-Finish is a process in which the drug product, container, and container closure are first sterilized separately and then brought together. The step of combining the product, container and closure is done in a clean room and often uses special equipment that is self-contained in a sterile environment. The aseptic, sterile fill-finish process is challenging and complex.

What does aseptic mean?

Aseptic means that the product, delivery devices, and containers are free from contamination caused by harmful bacteria, viruses, or other microorganisms.

When is a sterile fill-finish pharmaceutical manufacturing process used?

A sterile manufacturing process is used for parenteral medicines—those that are injected into the body intravenously, intramuscularly, or subcutaneously—because these products bypass the bodies natural defenses against harmful bacteria and viruses. Drugs delivered by ophthalmic, inhaled, or otic routes also present an increased risk of infection or harm and are produced by sterile processes as well.

What is the difference between terminal sterility and aseptic manufacturing processes?

Terminal sterility is done after a drug has been manufactured and uses heat, radiation, and/or filtration, but this is not always feasible and can have a detrimental effect on the product and its container. When terminal sterility cannot be done, an aseptic manufacturing process is the preferred method. Aseptic Manufacturing and Sterile Fill-Finish is a process in which the drug product, container, and container closure are first sterilized separately and then brought together. The step of combining the product, container and closure is done in a clean room and often uses special equipment that is self-contained in a sterile environment.

Why is aseptic stability testing done?

Stability testing provides evidence on how the quality of a drug substance or product varies over a given time and under the influence of environmental factors including temperature, humidity, and light. All drug products must undergo stability testing.

Why is lyophilization used when producing parenteral drugs?

As the number of complex drug products that pose stability issues become more common and a liquid dosage form is not possible, drug developers turn to sterile lyophilization. An effectively developed sterile lyophilization cycle can deliver stability for parenteral drugs over time and under a variety of environmental conditions during storage and transport.

What makes aseptic drug manufacturing so challenging?

Aseptic processing requires special equipment, highly trained, experienced people, and detailed planning and execution. The risks are significant for both the patient and production staff. The outcome for the process is to eliminate contamination completely from the drug product, personnel, equipment, and facilities.

What regulatory guidance exists for sterile manufacturing?

In the US, the FDA’s Sterile Drug Products Produced by Aseptic Processing – Current Good Manufacturing Practices is the guidance to help manufacturers meet the FDA’s requirements. In Europe, EMA’s Guideline on the sterilization of the medicinal product, active substance, excipient and primary container is the guidance on the selection of appropriate methods of sterilization for sterile products.

What are the cGMP requirements for pharmaceutical aseptic manufacturing?

The cGMP regulations for drugs contain the minimum requirements for the methods, facilities, and controls used in manufacturing, processing, and packing of a drug product. The regulations make sure that a product is safe for use, and that it has the ingredients and strength it claims to have.

Do you have R&D capabilities in the event we need them?

When conducting an aseptic process tech transfer, we clearly define each critical quality attribute (CQA) for your product and will test each to failure before we begin production. If issues arise, we have vertically integrated analytical capabilities in our campus facilities to quickly develop solutions.

Can you conduct aseptic processing for biologics?

We can handle manufactured biologic drug products in our facilities and aseptically fill vials, syringes, and cartridges.  We do not currently have the capabilities to produce biologics.

Meet an Aseptic Sterile R&D Expert

When clients with aseptic pharmaceutical projects reach out to Pharmaceutics International (Pii) for development support, they typically meet Bryan Braxton, and soon after, they get the feeling of confidence that comes with choosing the right contract developer.

The first thing one notices about Bryan is his friendly, grounded demeanor, something for which he gives credit to his parents and his blue-collar, Midwestern upbringing. Underneath that friendliness is a scientific mind that creates solutions for our most complex aseptic development projects. But how did these two traits combine in the same person?

When describing his role, he says, “it is all about relationships” and understanding the dosage form objectives of the drug sponsor.  As a senior director of Aseptic R&D in a CDMO, the relationship with the drug sponsor is critically important. However, when engaged in the hard work of R&D, the important relationship is that between the science and the patient.

MeetDr.BrianBraxton

Dr. Brian Braxton