Bai Xiaobai delivers its first GMP-compliant, high-capacity vial-specific cleaning machine.

As the name suggests, laboratory washers are generally used for cleaning laboratory glassware and can be widely applied in laboratories across various fields, including pharmaceuticals, food, cosmetics, universities, and scientific research. It’s relatively rare to see them used in pharmaceutical canning production lines, and even more challenging when it comes to canning ampoules. Recently, Bai Xiaobai successfully completed the delivery of this seemingly improbable application.

Drug safety is a matter of great importance to people's livelihoods and directly affects the lives and well-being of those who use medications. The state has established stringent regulatory standards and requirements for drug production to ensure the quality and safety of pharmaceutical products. Consequently, pharmaceutical canning production lines have strict requirements for cleaning canning containers. At the same time, the unique characteristics of ampoules themselves pose numerous challenges in the development of specialized cleaning equipment for this purpose.

Customer needs

In the liquid oral dosage form workshop, we are producing isopentyl nitrite inhalation agents. We have added a new ampoule washer-dryer integrated machine, which is used to clean and dry 1 ml ampoules.

Canning Workshop Process Flow (For Reference Only)

Regulatory and standard requirements

The equipment is used for the packaging and production of pharmaceutical products and must therefore comply with the following relevant standards/requirements: China’s “Good Manufacturing Practice for Pharmaceutical Products (Revised in 2010),” TJ36-79 Hygienic Standards for Industrial Enterprise Design, GB-52261-2002 Safety of Machinery—Part 1: General Technical Conditions for Mechanical and Electrical Equipment, GB-8196-87 Safety Requirements for Machine Guards in Mechanical Design, and GB-12265-90 Safety Requirements for Machine Guarding.

Process Performance Requirements

The equipment is capable of washing and drying 1 ml ampoules with a diameter of Ø10 mm, an inner mouth diameter of Ø4 mm, and a height of 60 mm. It can meet the requirements for continuous three-shift production, with a washing and drying capacity of ≥1300 bottles per cabinet. The processing time per cabinet shall not exceed 1 hour. The pass rate for intact and qualified washed and dried ampoules shall be greater than 99.9%. The equipment is located in the filling area within the clean zone (Class D area), and the bottle-loading method is manual loading of entire trays.

Continuous operation requirements

It should have the capability for long-term continuous operation and ensure stable equipment performance.

Mechanical Requirements (Partial)

The materials used for components of the equipment that come into contact with products/pharmaceutical bottles are 316L stainless steel. Components such as flexible connectors and gaskets shall be made of materials—including silicone, PTFE, and EPDM—that meet GMP requirements. Other parts shall be made of other materials meeting GMP requirements (with stainless steel being at least grade 304), and relevant material certificates must be provided. The inner walls of the equipment shall have a mirror-polished finish with a surface roughness Ra < 0.65 μm. Welded joints must be accompanied by relevant welding certificates or records. All accessories shall be designed and manufactured in compliance with GMP environmental requirements, ensuring they are free from contamination, rust-free, and easy to clean.

Project Challenges and Implementation

After comprehensively considering key factors such as GMP compliance, total cost, delivery time, and various technical specifications, the Baixiaobai R&D team decided to carry out a specialized development of a dedicated cleaning machine for ampoule filling lines, based on the existing pharmaceutical laboratory washer BS580D. This approach not only enables delivery in the shortest possible time but also helps customers save on economic costs, making it the optimal choice.

BS580D appearance diagram

The Bai Xiaobai BS series laboratory washer has undergone compliance testing and certification by SGS, a recognized testing, inspection, and certification body. It has also passed the IEC60068 operational stability test standard, demonstrating its capability for long-term, continuous, and stable operation. The BS580D is a laboratory washer specifically developed for the pharmaceutical industry, with all design elements fully aligned with GMP compliance requirements. The chamber is constructed from 316L mirror-finish stainless steel, featuring a surface roughness Ra < 0.2 μm and manufactured using laser welding technology. The flatness and surface roughness can be visually inspected and verified via wireless non-destructive testing instruments. The tubing materials meet both medical-grade and food-grade standards and are accompanied by corresponding certification certificates. The device incorporates a built-in compliance module that includes audit trail functionality, access control, and data statistics, fully complying with the requirements of FDA Regulation 21 CFR Part 11.

The aforementioned hardware and software configuration of the existing model has laid a solid foundation for the development of an ampoule filling-line cleaning machine that meets GMP requirements. The primary challenge now lies in satisfying the requirements for process performance. The cleaning target is 1 ml ampoules with an inner diameter as small as 4 mm, particularly near the bottle mouth. The machine must be capable of handling at least 1,300 ampoules simultaneously, completing both cleaning and drying within one hour, with a pass rate exceeding 99.9%. These seemingly simple figures have, in practice, presented developers with significant difficulties and challenges.

Difficulty 1: Design of a Cleaning Basket Rack for 1,728 Ampoules

The existing model is designed for laboratory applications and does not come with a dedicated basket rack for washing ampoules, so a completely new design and development process is required. Based on the spatial capacity of the current chamber, engineers have calculated that the structural design can accommodate up to 1,728 ampoules per cycle—far exceeding the customer’s requirement of 1,300 ampoules. This result is undoubtedly exciting; however, the greater the number of ampoules to be processed, the more existing balances need to be disrupted, which in turn means higher development complexity. The existing equipment’s current capacity allows it to clean and dry just over 400 ampoules. Increasing this capacity to 1,728 would clearly be like using a small horse to pull a large cart, and the difficulty of making systemic improvements is easy to imagine. After careful consideration and deliberation, the R&D team decided to take on this highly challenging task. By doing so, we can significantly enhance cleaning efficiency for our customers—a result that the engineers are eager to achieve.

After the general direction was confirmed, the experienced engineers quickly designed the first prototype of the ampoule cleaning basket and promptly proceeded with mold making and machining. However, once the machine testing was completed, everyone lost their initial enthusiasm. The cleaning performance fell far short of the actual requirements—far beyond what had been anticipated. What should they do now? With the project schedule already tight, the engineers suddenly found themselves under immense pressure. After repeated research and discussions, they finally pinpointed the root cause of the problem.

The total number of cleaning ports on laboratory washers typically does not exceed 600; the current model, BS580D, has a maximum capacity of just over 400. At the same time, it can clean 1,728 ampoules, which requires matching 1,728 spray nozzles and drainage ports. Looking at the entire industry, it’s extremely rare to find precedents for such a setup, and naturally, the challenges encountered are unprecedented as well. Under the same chamber volume conditions, the dramatic increase in the number of ports leads to a significant rise in the “air hold-up rate.” The higher the air hold-up rate, the greater the resistance the fluid encounters during its flow, making it increasingly difficult for the cleaning water to circulate effectively through the spray nozzles. This directly results in an imbalance in fluid distribution, severely disrupting the existing equilibrium in water consumption. As a consequence, a comprehensive redesign of the water circuit system becomes necessary (since a systemic overhaul would be overly complex, we’ll skip further details here—same applies below). It truly is a case of “one move affecting the whole system.” From the perspective of the basket design, constrained by the inner diameter of the ampoules at 4 mm, the inner diameter of the spray nozzles is essentially fixed, leaving virtually no room for adjustment. Consequently, engineers shifted their focus to optimizing the structure of the water reservoir at the bottom of the basket—specifically, the reservoir’s capacity and overall shape. After numerous calculations and iterative adjustments, they finally struck a new balance, successfully resolving the spray imbalance caused by the dramatic increase in air hold-up rate. Particularly noteworthy is that the engineers broke away from conventional thinking and adopted a sloped design configuration, which ultimately became the key factor behind their success.

Difficulty 2: Achieve cleaning and drying within 1 hour.

If you take a close look at the structure of an ampoule, you’ll notice its distinctive feature: a narrow, elongated neck. This structural characteristic makes it difficult for the liquid inside to flow out easily. The narrower opening increases the surface tension of the liquid, forming a tension film at the mouth of the ampoule that effectively blocks the liquid from escaping. Simple tests have shown that it’s virtually impossible to pour the liquid out of an ampoule by simply tilting it—some external force is required to make it happen. Therefore, it’s not hard to conclude that cleaning and drying ultra-narrow-necked ampoules are extremely challenging. In particular, the drying process has nearly driven engineers to the brink of despair.

To ensure cleanliness, the engineers opted for the most challenging injection-type cleaning method—and with it came a host of challenges. When the spray nozzles were positioned close to the bottom of the bottles, it facilitated drying of the lower half of the bottles, but moisture in the neck area proved extremely difficult to dry completely. Conversely, if the nozzles were positioned slightly farther from the bottom, the effect was just the opposite. After repeated testing, the engineers finally adjusted the nozzle positions to an optimal distance. It would have been ideal to stop there—but the problems didn't end there by any means.

Achieving cleaning and drying within just one hour places extremely high demands on drying efficiency under the current conditions. To ensure that as much water as possible flows out of the bottles quickly and efficiently, the engineers introduced a “pulsed” drying design. To further enhance drying efficiency, they also added an auxiliary external drying system. However, despite these efforts, the completion rate only improved from around 70% to about 85%, still falling far short of the target. Where exactly did the problem lie? After repeated testing, the engineers discovered that as the number of air pathways increased, the completion rate not only failed to improve—it actually declined! Such an unexpected outcome had to have a specific cause, so the engineers decided to dig deeper. At this point, the delivery deadline was fast approaching, and the engineers were already so anxious that they could hardly sleep at night. This was precisely the critical moment to test their patience—and it was precisely during times like these that true resilience would be put to the test. They made bold assumptions but proceeded with careful verification. By systematically examining each factor one by one, they eventually pinpointed the core issue: As the airflow volume doubled past a certain critical threshold, the pressure inside the chamber began to rise, obstructing air flow and disrupting the original balance between incoming and outgoing air. As a result, the air inside couldn’t escape, while the air outside couldn’t enter smoothly. With the efficiency of air circulation plummeting, the drying efficiency naturally suffered as well. Once they identified the root cause of the problem, the engineers immediately carried out a systematic overhaul of the air-flow system. Thanks to their efforts, this seemingly intractable challenge was successfully resolved right before the delivery date.

Difficulty 3: Filtration accuracy of circulating water—200 mesh

The production of pharmaceutical packaging must comply with the requirements of China’s “Good Manufacturing Practice for Pharmaceutical Products (Revised in 2010).” Accordingly, the filtration accuracy of the specialized washing machines used for ampoules must reach 200 mesh—meaning they can effectively remove tiny particles and suspended solids that are difficult to distinguish with the naked eye from the wash water—thus ensuring that residual contaminants in the wash water meet the required standards. The mesh count of a water filter refers to the number of mesh openings per inch of filter length. It is a standard used to measure the size of the filter’s pore openings. Generally speaking, the higher the mesh count, the smaller the pore size, the greater the filtration accuracy, the purer the filtered water, and the lower the efficiency with which water passes through the filter. A mesh count of 200 represents twice the filtration accuracy of existing equipment; this change has also disrupted the balance of current water filtration systems. As the mesh count increases, the flow rate of water drops dramatically, making it impossible for the wash water to circulate at the required speed and thus disrupting the normal operation of the cleaning process. To ensure the proper functioning of the water circulation system, it is essential to improve the efficiency with which water passes through the filter.

As the pores of the filter become smaller, the water above forms surface tension, blocking the air beneath the filter and causing the air pressure below to rise. This makes it increasingly difficult for the water above the filter to flow downward. It’s just like the experience we often have when brewing tea in a teacup equipped with a filter—when the filter mesh is too fine, it becomes very hard for the water to pour into the cup. Moreover, once the blocked air enters the pump, it can generate a large number of bubbles, leading to cavitation. This phenomenon can cause varying degrees of damage to components such as the pump’s impeller and blades, posing a significant hazard.

Solving this problem within a cabin space with relatively good sealing performance is extremely challenging. An obvious approach would be to increase the suction power of the water pump—using external force to draw water upward from below and thereby improve the efficiency of water flow. However, this alone falls far short of meeting the requirements. This is precisely the moment when engineers’ ingenuity comes into play once again. They adopted a reverse approach: they created an air hole in the filter screen. Of course, this wasn’t just any ordinary air hole—it had to ensure that impurities in the cleaning water wouldn’t leak through the filter screen while also enhancing airflow beneath the screen. After careful design and meticulous refinement, a superior solution was finally developed, enabling us to overcome this difficult challenge smoothly.

Summary of Difficulties

The cleaning machine is a relatively complex cleaning system composed of multiple subsystems. It accomplishes the entire cleaning task through close, interlinked coordination among these subsystems. Therefore, modifying even a single component can trigger a cascade of interconnected changes—impacting not just one element but an entire network or even an entire system. During the actual R&D process of this project, we encountered numerous small yet challenging hurdles that space constraints prevent us from listing here in detail. We’re sharing only the three key challenges mentioned above as typical examples of our efforts to overcome them. We hope this will give everyone a deeper understanding of the work carried out by equipment manufacturers. We also sincerely hope that, with your continued support and encouragement, our engineers will be able to fully leverage their expertise, refine more outstanding products, and expand the scope and depth of cleaning equipment services, thereby making greater contributions to society and better serving the community.

Acceptance and Delivery

Factory acceptance

After two months of painstaking and relentless efforts, the newly developed cleaning machine specifically designed for the ampoule filling line of the inhaled medication has finally reached the stage of on-site acceptance by the customer. On the day of acceptance, the head of R&D and all the engineers were brimming with confidence—just like soldiers returning from the battlefield after a hard-fought victory, eagerly awaiting the triumphal review. Although exhausted, they felt deeply joyful inside, knowing full well that every single challenge had been successfully overcome. The outcome was beyond doubt: the machine smoothly passed the customer’s factory acceptance and received high praise.

Delivery and installation

Subsequently, the installation engineers arrived at the customer’s pharmaceutical plant and completed the installation and commissioning of the equipment. With this, the specialized cleaning machine for the ampoule filling line of Baixiaobai inhalation spray has been successfully delivered. Baixiaobai’s R&D capabilities have been further enhanced and recognized.

Since last year, Shanghai Hanyao has become Bai Xiaobai. Shanghai, Zhejiang, Jiangsu Regional general agent for the pharmaceutical industry. Han Yao has consistently focused on providing high-quality products and technical services to users in China’s biopharmaceutical, food, and chemical laboratory sectors. Adhering to our longstanding service philosophy and putting into practice the values of “integrity, altruism, and gratitude,” we prioritize customer satisfaction and offer meticulous, attentive service. While growing together with our customers and partners, we strive to create greater value for society.