By Alex Cravens, Singota Solutions

Demand for small-batch drug product (DP) manufacturing — from formulation to sterile fill/finish — is rising as drugs for precision medicine and large-molecule biologics gain in prominence. However, traditional fill/finish providers may consider small batch sizes as lacking economic feasibility. They may offer only rigid, far-in-the-future manufacturing dates or lack the equipment, expertise, and/or manufacturing slots to produce small batches.

Singota has distinguished itself as an end-to-end, small-batch parenteral manufacturing CDMO that does not just accommodate modest volumes but welcomes and specializes in them. While we typically produce GMP batches of less-than 10,000 units, we understand that batch size is specific based on various customer needs, including total amount for clinical testing, QC testing, retained samples, etc. Singota can help guide small or emerging developers through manufacturing, documentation, QA, or regulatory matters.

For many of our clients, resources are limited: Active pharmaceutical ingredients (APIs) often are very expensive and the customer’s capital may be tied up in a few make-or-break batches. Moreover, they require rapid turnaround times. Singota helps its customers meet their goals through a combination of fit-for-purpose equipment, flexible processes, and expertise that accelerates critical decision-making. We also draw on deep experience working with a variety of molecule types (e.g., an understanding of pump and fill rates, tubing sizes to accommodate the larger viral particles or cells, and different methods of sterilization).

Our partnerships begin with standardized forms that outline the project at a high level: number of units, formulation conditions, safety concerns associated with the molecule, delivery format (e.g., vials, cartridges, syringes), and stable storage conditions. We walk each customer through those steps, discuss any possible hurdles, and explain exactly what can be expected at each step of the process.

Production estimates are a critical part of these initial discussions, since almost all customers ask, “How low can you go?” (in terms of batch size) and seek insight into Acceptable Quality Limit (AQL) sampling levels (i.e., how many samples they may need in terms of overage above those levels). We also frequently are asked about our processes — specifically, formulation and filling — and our utilization of single-use components to use/lose the smallest appropriate amount of product.

Customers receive a dedicated project manager with whom they usually speak daily, and commonly have weekly (or more frequent) discussions with individuals directly involved in their process. Larger organizations often are siloed and cannot offer that constant feedback loop. As a single-site manufacturer, Singota focuses on a collaborative work environment, eliminating the bureaucracy that can delay critical decision-making in larger organizations, in addition to providing customers greater access to our personnel and insight into their project.

Again, efficient use of materials is at the center of our operations. We strive to minimize product line loss through a combination of precise workflows and purpose-made equipment (e.g., the Cytiva (formerly Vanrx) SA25 Aseptic Filling Workcell). Singota also applies smaller sterilizing filters, shorter fill lines, a single dosing needle, and/or a single flow path — all appropriately sized to keep the process economically viable for the customer. While line loss and filter retention are difficult to quantify, Singota has consistently achieved loss in the flow paths as low as ~20 grams per batch. Operations utilizing larger components inherently suffer greater product loss by their use of larger vessels, filters, tubing, etc. A commercial operation might lose 100+ grams per batch.

Additionally, while drug developers often source their own raw materials early in development, they require a more robust supply chain as they push into clinical trials. Singota stands out for its aptitude in end-to-end supply chain management and can guide customers through all its elements, including cold chain storage, shipping conditions, labeling, and optimal packaging. Some clients seek only manufacturing, some only supply chain, but many take advantage of our capability in both.

Singota’s combination of capacity and capability is supported by deep regulatory knowledge. Clinical focus is a different sphere than commercial, and our familiarity with the regulatory process in that respect eliminates a time-consuming variable from our partnerships. We also have proven expertise in tech transfer for large-scale clinical needs and commercial manufacturing, to ensuring a smooth transition of validation of both manufacturing and analytical methods when our partners grow beyond us.

Conclusions

Singota combines small-batch capability and expertise with a wide-ranging knowledge of delivery formats (often, manufacturers specialize in only one or two formats). This gives our customers great flexibility and we aim to honestly guide prospective clients along the optimal path forward, even if the project is not suited to our capability.

While this discussion is seemingly more business development-oriented, those conversations rely on input from our operations and supply chain experts to accurately portray how a project might be executed. Thus, we are able to tailor not only our services, but our communications, to each client’s needs.

To learn more, visit us at https://singota.com/ and on LinkedIn.

About Singota Solutions

Singota Solutions is a contract development and manufacturing organization (CDMO) focused on helping clients in the pharmaceutical, animal health, and biotechnology industries move their products through the drug development pipeline faster by being agile, accountable, and transparent.