Autonomous Delivery of Materials to Grade-D Biopharmaceutical Production Areas: Two Scenarios for Consideration

According to a 2023 report, the market size for warehouse automation is expected to grow from US$22.15 billion in 2023 to $46.93 billion by 2028 at a compound annual growth rate (CAGR) of 16.20% (1). The report adds that warehouses using conveyors, sorters, and pick-and-place solutions accounted for 15% of all warehouses in 2023 (1). Manufacturing industries certainly are trending toward logistics automation. That trend raises a question: Why hasn’t the biopharmaceutical sector adopted logistics automation more broadly than it has?

The first two milestones in BioPhorum’s 2022 Robotics Technology Biomanufacturing Roadmap to 2030 focus on addressing the adoption problem (2, 3). But in modern biopharmaceutical facilities, moving material from nonclassified (NC or “black”) goods-in spaces to production areas remains time-consuming for warehouse, operations, and quality assurance/control (QA/QC) personnel. Here, we put forward two scenarios in which warehouse items are delivered — “on demand” or according to a schedule — into grade-D production areas with minimal human intervention.

_{Figure 1: A high-level illustration of our proposals for transport of materials received in a nonclassified (NC) area into a controlled, nonclassified (CNC) area and then a grade-D area within a biopharmaceutical facility; major stages are shown in blue font, and the general process flow is indicated by blue arrows; icons in the figure represent steps for material inspection, wipe-down, air-showering, and ultraviolet (UV)-light sterilization. (ASRS = automated storage and retrieval systems).}

Although human movement has no inherent advantage over robotic movement in manufacturing contexts, use of autonomous mobile robots (AMRs) remains limited to warehouse areas. Implementing our scenarios would make AMRs a common sight in production areas.

Another consideration is that wiping down materials transported from controlled, nonclassified (CNC) areas into airlocks and grade-D areas is a time-consuming and variably effective process that pulls operations staff away from production processes. Our secondary aim in this article is to propose a solution for full automation in material airlocks (MALs).

High-Level Summary: Achieving full automation of the transportation process requires removal of the wipe-down step in an MAL, along with streamlining of the broader process (Figure 1). We envision a wooden or plastic pallet arriving in a warehouse. An initial inspection occurs to identify and remove visible dirt. The pallet is moved and stored in the warehouse as required. Then, cardboard packaging is removed, and material passes into a CNC kitting area through an air shower to remove particulates. The items undergo another inspection in an ergonomically designed kitting area, then are wiped with a disinfectant and placed in a smooth kitting container that is compatible with ultraviolet (UV)-light treatment. All those activities occur under laminar air flow. Finally, kitted material is stored in a clean miniloader/paternoster and loaded onto autonomous vehicles as required during a production process.

_{Figure 2: Scenario 1 for pharmaceutical manufacturers that perform kitting activities in house, with material flows shown by faint gray arrows (NC = nonclassified; CNC = controlled, nonclassified; QC = quality control).}

_{A = goods-in area, B = pallet-exchange area, C = high-bay warehouse space, D = cold-storage area, E = miniloader, F = cardboard-removal area, G = waste area, H = large-item black-CNC clean-down airlock, I = kitting area, J/K = CNC-area miniloader with clean kits, L = dispensary unit, M = sampling-area unit, N = CNC corridor, O = automated airlock leading into grade-D area, Q = quarantine area.}

Scenario 1: In-House Kitting

Our first scenario applies to pharmaceutical manufacturers that perform kitting activities internally. Figure 2 provides an example facility layout with the following areas labeled.

Goods-In Area (A): Material enters a facility on either wooden or plastic pallets. Warehouse staff remove outer wrapping, then log packaged contents into the company’s enterprise resource planning (ERP) system.

Pallet-Exchange Space (B): Wooden pallets can bring mold into a warehouse and can shed significant amounts of particulates, especially when transported on conveyors. Thus, in our scenario, warehouse staff exchange wooden pallets for plastic ones before placing material on a conveyor. In preparation for high-bay storage (C), staff members check the loaded materials and new pallet for visible dirt, performing wipe-downs as needed. We recommend consulting relevant regulatory guidances — e.g., the EU Annex 1 guidance on Manufacture of Sterile Medicinal Products, especially sections 4 (“Premises”) and 5 (“Equipment”) — to help determine suitable cleaning agents. Note that plastic pallets can have embedded radio-frequency identification (RFID) tags to aid tracking of stock-keeping units (SKUs).

High-Bay Storage (C): In a recent article about trends in warehouse automation, Ganesh calls attention to automated storage and retrieval systems (ASRS), which are computer-controlled systems that “keep goods in a small area and recover them quickly when required. These devices assist warehouses in maximizing vertical and horizontal area,” especially because they can extend storage “to heights beyond the grasp of humans” (4). The small dimensions of ASRS also enable compact container storage (4).

High-bay warehouses provide storage of material on plastic pallets. Such facilities depend on conveyor systems. In this first scenario, those conveyors feed into and are fed by warehouse-forklift AMRs. Pallets are scanned in and out of the system automatically. Outlet conveyors either load an AMR or transport a pallet directly to a depalletizing robot.

Cold-Storage Space (D): Biologics facilities often require cold storage of media and feed solutions. Depending on the number of SKUs, such storage areas might or might not require automation.

Black-Area Miniloader with ASRS (E): A miniloader stores cardboard boxes that have been removed from a pallet or that have arrived separately. In this scenario, a depalletizing robot or warehouse employee feeds the incoming conveyor. Boxes are scanned in and out automatically.

Cardboard-Removal Area (F): Cardboard must be removed before material can enter a CNC kitting area (I). In this scenario, material is unpackaged from a miniloader and passed along a conveyor tunnel with an air shower into a kitting area. Cardboard is transferred to an adjacent waste area (G). Materials that arrive with certificates are logged into a company’s QA system at this point.

Waste Area (G): The waste area is accessible by the cardboard-removal area (F) and CNC corridor (N). Warehouse teams should consider automated compactor loading depending on throughput needs. Biohazardous waste requires special attention.

Black-to-CNC Airlock for Large Items (H): Large material enters the kitting area through a black-to-CNC MAL. There, items undergo wipe-down and inspection before transferral to the CNC corridor (N) or dispensing/sampling area (L and M, respectively).

_{Figure 3: Scenario 2 (outsourced kitting) at a pharmaceutical company’s warehouse, with material flows shown by faint gray arrows (NC = nonclassified; CNC = controlled, nonclassified; QC = quality control).}

_{A = goods-in area, B = airlock and pallet-exchange area, C = cold storage, D = high-bay storage for nonkitted material, E = black-to-CNC airlock, F = waste area, G = clean kits in miniloader, H = CNC corridor, I = automated airlock.}

Modular Kitting Area (I): In both scenarios, we propose operating kit areas without robotics. Our reasons relate primarily to pickability (see the “Characteristics” box on the previous page) (5). Many kinds of items enter a biologics facility, from single-use assemblies to code-7 filters. Picking robots currently cannot handle such variability, especially because items of a given type can come in irregular shapes, with transparent packaging, with moving centers of gravity, and so on. Thus, we advise keeping a kitting area staffed during typical work hours.

Kitting-Area Procedures: Because the inside surfaces of transported boxes will be exposed to a grade-D environment when opened, we suggest that CNC kitting areas have down-flow filters. Staff enter through a manufacturing changing area rather than the warehouse, wearing at minimum low-shedding laboratory coats, hair nets, and disposable gloves.

Warehouse material comes into the kitting area through an air shower. Then, material either is wiped and placed directly into a kitting box or moved into a CNC miniloader (J) for storage. Our scheme assumes use of cleanable kitting boxes with embedded RFID chips. Once a box is completed, the lid is fitted, the outer surfaces are wiped, and the kit goes by conveyor to the CNC miniloader. We suggest performing kitting in standardized, modular cleanrooms that can be fabricated off site and placed in a required area.

CNC Miniloader with ASRS (J): This miniloader serves several functions, including storage of clean, empty kitting containers; assembled kits; and parts that have been removed from cardboard secondary packaging but not yet placed into kits (K). For an extra level of safety, a miniloader could be provisioned with filtered air to prevent dust contamination during storage.

_{Figure 4: Facility layout for Scenario 2 (outsourced kitting) at a subcontractor’s warehouse, with material flows shown by faint gray arrows (NC = nonclassified; CNC = controlled, nonclassified).}

_{A = goods-in area, B = airlock, C = pallet-exchange area, D = high-bay warehouse space, E = cold-storage area, F = miniloader, G = cardboard-removal area, H = waste area, I = black-to-CNC airlock, J = kitting area, K = clean kits in miniloader, L = dispensary area, M = sampling area, N = CNC corridor, O = exit airlock.}

Dispensary- (L) and Sampling-Area Pods (M): Powders are handled in the dispensary and sampling areas. Full automation currently is not possible in those areas; however, transport to and from them can and should be automated. Note that robot-enabling sample containers (barcoded and with a robot-compatible lid) would facilitate automated processing in the QA/QC laboratory. AMRs already are used to transfer such containers to automated storage systems.

CNC Corridor (N): When an operations team requires a kit, one is delivered by conveyor from a miniloader to a box-lifting robot. That enables kit delivery to a grade-D airlock (O) either by clean pallet or by mini-AMR via the CNC corridor.

Automated CNC-to-Grade-D Airlock (O): Because boxes have been cleaned inside and out in the kitting area, all that is required in the airlock is to

• remove dust acquired during storage in the miniloader and transport down the CNC corridor

• sanitize the outside of the boxes with UV light.

A CNC-dedicated AMR places a pallet with kitting boxes into an automated decontamination system, which performs a blow-down on those items and then exposes them to UV. Next, a grade-D–dedicated AMR enters the airlock and takes sanitized items to the production area.

Scenario 2: Outsourced Kitting — Pharmaceutical-Company Warehouse

Goods-In Area (A) and Airlock (B): When kits come to a pharmaceutical facility preassembled, material can enter on RFID-tagged plastic pallets into an MAL (B); no wooden pallets can enter (Figure 3). That airlock serves to prevent pests from entering the warehouse. Outer wrappings are removed, and materials are logged automatically into the drug company’s ERP system. Kitting suppliers also must be part of the ERP and quality systems.

“Just-in-Time” Warehouse (C and D): Nonkitted material is kept in cold (C) or high-bay storage (D) before entering the airlock to the next area.

Airlock for Nonkitted Material (E): Material is wiped with disinfectant before entering a CNC area.

Waste Area (F): Because most cardboard is removed before delivery, this area is reserved mainly for waste generated within the facility.

Clean-Area Miniloader (ASRS) (G): Robot arms depalletize kits and place them on a conveyer. Those boxes pass through a UV tunnel and air shower to enter the CNC area. Then, the conveyor loads material into a clean-area miniloader.

CNC Corridor and Automated MAL (H and I): These features are identical to those described in Scenario 1.

Scenario 2: Outsourced Kitting — Contractor Warehouse and Kitting Area

As shown in Figure 4, a subcontractor’s warehouse and kitting area resemble those shown in Scenario 1 (Figure 2) but differ in scale depending on how many pharmaceutical manufacturers and/or facilities the kitting company supplies. Our design in Figure 4 accounts for high-volume sampling and dispensing

(L and M) requirements, placing those areas closer to a cold-storage area (E) and thus decreasing the amount of space and number of employees needed for such tasks. Note that an extra airlock/sealed dock is required to load smaller delivery trucks and that the vehicles’ interiors must be kept clean.

Conclusion

Pharmaceutical companies must take a holistic approach to automate material delivery and warehouse activities in their facilities. Such an approach involves working with consumables suppliers, technology integrators, and engineering companies. Some tasks such as kitting and raw-materials sample testing are difficult to automate with current technology; however, preparatory work is feasible.

Regarding subcontracted kitting, having clusters of companies in the same area would be a distinct advantage to involved parties, providing economies of scale and potential for a better return on investment (RoI) for automation that becomes available.

References

1 Warehouse Automation Market Size & Share Analysis — Growth Trends & Forecasts (2023–2028). Mordor Intelligence: Hyderabad, India, September 2023.

2 Technology Roadmapping Robotics Group. Robotics Technology Biomanufacturing Roadmap to 2030. BioPhorum: Sheffield, UK, 5 July 2022; https://www.biophorum.com/download/automation-and-the-road-to-lights-out-manufacture-in-biopharmaceuticals.

3 Wolton D, Coulon C-H. Robots in Biomanufacturing: A Road Map for Automation of Biopharmaceutical Operations. BioProcess Int. 20(6) 2022: 32–36; https://www.bioprocessintl.com/information-technology/robots-in-biomanufacturing-a-road-map-for-automation-of-biopharmaceutical-operations.

4 Ganesh S. Top 10 Trends in Robotic Warehouse Automation 2.0 in 2023. Analytics Insight 22 March 2023; https://www.analyticsinsight.net/top-10-trends-in-robotic-warehouse-automation-2-0-in-2023.

5 How To Determine Whether Your Warehouse Could Benefit from Automated Item Picking. Swisslog: Buchs, Switzerland, May 2022; https://www.swisslog.com/en-us/case-studies-and-resources/white-papers.

Based in Zurich, Switzerland, David Wolton is a biologics operations consultant and owner of Defined Tubing Routing ([email protected]). Alan Kelly is a subject-matter expert in aseptic fill–finish at PM Group; [email protected].