Building Quality into Biologic Production to Meet Regulations

Quality control is the foundation of biopharmaceutical production, ensuring that all drug products (DPs) are reliably produced to meet the required safety and quality standards. These measures are outlined by the good manufacturing practice (GMP) and are highly regulated to ensure that products remain safe for patients.

These regulations are becoming more stringent as the biopharma industry moves toward complex biologics such as cell and gene therapies. As a result of the increasing demand for biologics, aseptic processing is becoming more commonplace across the industry, with expected growth from $77.2 billion in 2023 to $94.57 billion by 2027.¹

Biologic materials are highly sensitive, so their administration is limited to parenteral methods. Traditional routes of delivery, such as oral drugs, would lead to DP degradation or damage as the drug would have to pass through the gastrointestinal (GI) tract. Here, the biologic would be exposed to harsh conditions (such as acidic pH) and stress, which could lead to loss of therapeutic activity. When administered via injection, the drug bypasses the body’s natural defenses and is absorbed directly into the bloodstream. As a result, biologic products must be sterile, assuring the absence of any particulate contamination or bioburden for patient safety.

Building Quality Through GMPs

Aseptic processing aims to minimize the risk of particulate- and cross-contamination throughout production, ensuring a product is safe for administration to patients. The sensitivity of biologics means that terminal sterilization is not an option as they can be degraded during the process, which could again result in the loss of therapeutic properties. This means that aseptic processing approaches are the only viable route to produce safe and efficacious DPs.

In the US, the GMP guidelines are outlined by the Food and Drug Administration’s (FDA) 21 Code of Federal Regulations (CFR), parts 210 and 211. This should be followed when manufacturing sterile drugs and biologic products. Effective, compliant aseptic processing incorporates²:

It can be complex to maintain all cleanroom components and make sure that they meet the defined regulatory standards. Proof of GMP adherence must be provided in any new drug application (NDA) or biologic license application (BLA). In-process controls and monitoring combined with batch-release testing ensure QC standards are met and the final DP is safe and efficacious. Completing risk assessments can help to identify potential risks and employ preventative measures for risk mitigation.

Using Transfer Technology

Building sterility into biologic production is essential. From early processes such as the transfer of media powder into large bioreactors to handling lyophilized DPs, implementing solutions to ensure sterility, ease transfer, and streamline production is critical.

Chargebags are designed to help assure product sterility and reduce production risks (courtesy of ChargePoint Technology)

DP materials are at the highest risk of contamination when transferred between different processing lines. Harnessing specialist equipment throughout manufacture, such as split butterfly valves (SBVs), chargebags and chargebottles, can help assure product sterility and reduce production risks. By utilizing transfer systems, the DP is held, processed and transferred through a closed system, allowing for robust and efficient processing of powdered materials without exposure to the outside environment.    

Split butterfly valves (SBVs) facilitate seamless and contamination-free powder transfer, preventing direct contact with the surrounding environment or operators (courtesy of ChargePoint Technology)

Leveraging SUT for Added Protection

Single-use technology (SUT) transfer systems are designed for easy integration into current processing lines, minimizing production risks by creating a closed filling line. Providing the same quality assurance as steel-built equipment (such as SBVs and chargebottles) without the need for validated cleaning procedures, these systems significantly minimize the risk of particulate and bioburden contamination to meet safety regulations as they are disposed of after use. Therefore, cleaning and validation processes are no longer necessary, which streamlines production, saving time and costs. Cross-contamination risks are also removed as a result.

Meeting Industry Needs with a Specialist Supplier

The industry is continuing to shift to biologic products to treat chronic and rare diseases. With this shift comes changing demands for capacity. Traditional SUT caters to small-volume manufacturing, but as capacity needs increase, these systems will have to respond and adapt. An example of this is the transfer of large volumes of media powder, which is dissolved to form media in which biologic components are cultured. Transfer of this powder into larger bioreactors is a critical step, and increasing the capacity of SUT to handle steps such as this can help integrate closed processing techniques from early in the production process, adhering to GMP guidelines and further streamlining processing lines.

Customer-driven innovation is aiding this transformation, allowing for specially designed and modified alternative solutions that are helping drive increasingly diverse off-the-shelf options. This is made possible by the flexibility provided by SUT solutions, which seamlessly transform and better address customer needs.

A specialist supplier can help provide solutions in line with changing industry demands. Helping to navigate the complexity of aseptic processing and meet regulations, partnerships can foster innovation and provide novel strategies to further assure compliance.

Ben Wylie is head of product management and marketing at ChargePoint Technology, Forked River, NJ. For more information, call 609-549-6165, email [email protected], or visit www.thechargepoint.com.

References

1. Aseptic Processing Global Market Report 2023. Retrieved August 18, 2023 from https://www.researchandmarkets.com/reports/5751563/aseptic-processing-global-market-report

2. Sterile Drug Products Produced by Aseptic Processing. Retrieved August 18, 2023, from https://www.fda.gov/regulatory-information/search-fda-guidance-documents/sterile-drug-products-produced-aseptic-processing-current-good-manufacturing-practice