cGMP for Ancillary Materials: Gaining Clarity as We Advance

We as a community have long used the term “current good manufacturing practices,” or cGMP, to describe a class of ancillary materials – or raw materials in certain geographies – produced in accordance with rigorous quality standards. We have done this to assure our clients, often the developers of advanced therapeutic medicinal products (ATMPs), that the materials embedded in their products are verifiably safe. The problem is that cGMP means different things to different people in the world of ancillary materials. To reclaim the term and further benefit from a clear definition as an industry, we need to understand its history.

The term itself has a long history, although it has traditionally been applied to the production of conventional pharmaceuticals. In the United States, it is outlined in Title 21 of the Code of Federal Regulations (CFR). While several countries have their own frameworks and definitions, there have been efforts aimed at driving regulatory harmonization in forums like the International Conference on Harmonization (ICH). These efforts to ensure drug safety through rigorous quality standards have provided clarity for drug developers regarding the minimum standards that must be met in the manufacturing process for products to be deemed safe for human use.

Regardless of the differences in route of therapeutic administration and material complexity, the concept of cGMP came to be adopted by ancillary materials manufacturers serving ATMP developers. This class of products never previously had a dedicated regulatory category, being defined most commonly as for ‘Research Use Only’ (ROU). In recent years, our community has generated publications, driven standards, organized meetings, and created forums in order to define how our materials should be produced. Why is this important? In our world, the final drug product cannot be sterilized. As this is the case, it is critical to ensure that all products entering the cleanroom environment or closed manufacturing system, and therein potentially the patient (albeit indirectly), are sterile.

Regulatory agencies may have different interpretations of what constitutes cGMP in the world of ancillary materials. It is incumbent upon organizations like the Standards Coordinating Body (SCB), the International Organization for Standardization (ISO), and the Parenteral Drug Association (PDA) among others to foster international harmonization in a way that is both relevant and appropriate to this space. We need to focus on the controlled environment, process validation, concurrent stability, and rigorous documentation practices as well as on robust analytical packages that include sterility, endotoxin, mycoplasma, identity, purity, and potency.

The discussions at Phacilitate last week regarding standards and quality of ancillary materials are part of an important, ongoing process. As my fellow panelist Dr. Stephen Oh, FDA CBER Deputy Director, stated, “Start with quality early on in the process, preclinical animal studies should be conducted using the product manufactured like it will be used in the clinic.”

The message is clear. We need to ensure the safety of our ancillary materials. Since the final product cannot be sterilized, all culture components – the media, media supplements, cytokines, cryopreservative agents, and other consumables – must be sterile.

Dr. Oh also emphasized that “while following cGMPs may improve the product itself, they are actually meant to enable our control of product quality and safety, and to help ensure manufacturing consistency. Following cGMPs cannot prevent manufacturing errors from happening, but it can help ensure that controls are in place to catch them and so that we can take appropriate corrective actions.”

Our industry is creating standards to foster greater consistency and traceability. However, we all recognize that increased degrees of regulatory compliance imply higher costs. Without question, cGMP-compliant materials come at a higher price. Our challenge as ancillary materials manufacturers is to meet our partners where they are; to support ATMP developers early on to ensure they start off on the right foot and to scale up alongside them as they inch through the clinical pipeline towards commercialization. We need to be able to offer them consistency of product throughout their development cycle and enable them to take their best shot at success. The ability to trust the integrity of ancillary materials is paramount. We must continue to scale alongside our partners without compromising on quality.

Absent the opportunity to sterilize the final drug product, we must strive to improve the quality of our ancillary materials. First, we must strive for greater consensus regarding what constitutes cGMP in the world of ancillary materials. We need to converse more with one another, with our customers, with our respective regulatory authorities, and with international organizations. Second, we need to start working with our customers earlier on. As Dr. Oh made clear in his remarks at Phacilitate, it is critical to introduce high-quality ancillary materials as early as possible to ensure effective translation and improve safety. Third, we need to adapt our business models and technologies to make the early adoption of cGMP ancillary materials feasible and seamless.

Akron is committed to working with its partners, its clients, and the community at large to foster a stronger regenerative medicine industry. We must make a collective commitment to quality, starting with our ancillary materials, as we continue to bring these live-saving treatments to patients and work to transform the practice of medicine.

Learn more about Akron’s commitment to quality.