Four Quick Questions: Solid Dosage Research & Development

What pieces of equipment/solutions do you offer that are specialized for oral solid dose (OSD) R&D? At what point in the process do they ‘fit’?

Tomoki Kishi, General Manager for Maruho Hatsujyo Innovations, Inc. (MHI): Maruho Hatsujyo Innovations (MHI) is the U.S. subsidiary of multinational Japan-based healthcare company Maruho Co. Ltd. Among the company’s specialties are blister machines, and our most recent equipment introduction is specifically intended for stability testing and similar small-run applications. Called the Eagle-LP – short for “Lab Pack” – the machine is a reliable, cost-effective solution for development stages, stability testing, and initial small-batch production.

The impetus behind the Eagle-LP is clear: Research and development teams need a blister machine designed with their needs in mind. Too often, they’ve been left choosing among a poor set of options, including purchasing large, expensive equipment or interrupting mass production machinery, which can limit a company’s overall output capacity. The Eagle-LP gives R&D applications the special consideration they deserve.

Jim McKee, Sales Manager, Processing Division for MG America – the U.S. subsidiary of MG2 of Bologna, Italy: For R&D oral solid dose applications, MG America – the US subsidiary of Italy-based MG2 – offers a pair of solutions. One is the new Initia capsule filler, a tabletop unit for laboratories focusing on dosator technology. The module is designed to fill up to 5 capsules in sequence, ranging from size 000 to 5, for both standard and low dosages of powder.

Initia’s by-design flexibility and user-friendliness promote intuitive, error-free action for vital R&D steps. Guided through the process via HMI, the operator can quickly identify the optimal machine parameters for transfer to a wide range of other capsule fillers, whether they be additional pre-production units or those for large-scale production, such as MG2’s PLANETA series.

The second solution is called FlexaLAB, an R&D-level capsule filler named for its dosing versatility – including powders in standard doses, low doses down to 5mg, and micro-doses as minuscule as 0.5mg, as well as pellets, tablets, microtablets, and even liquids. The FlexaLAB can produce up to 3,000 capsules per hour, and its process is scalable for transfer to production-level machines.

Uwe Braun, Senior Business Development Manager, Medication Adherence Monitoring Solutions at Schreiner MediPharm: Schreiner MediPharm offers smart blister packs for oral solid dose applications. By integrating conductive lines and an electronic sensing unit in blister wallets, digital therapy control and monitoring of the patient’s medication adherence are enabled.

The smart blister packs are used in clinical trials to automatically track medication intake. For instance, the latest solution of Schreiner MediPharm’s Smart Blister Wallet is extendable to 64 cavities that can be individually tracked electronically. It seamlessly integrates with all blister designs, even accommodating two- or multiple-fold blisters.

Schreiner MediPharm provides the complete package, supplying the cardboard box equipped with integrated conductive lines and printed circuit boards to pharmaceutical manufacturers or contract manufacturing organizations (CMOs). They can process the smart packaging as usual and fill it with the respective tablet blister.

How does this equipment/solution differ from ‘conventional’ pieces?

Kishi: The Eagle-LP addresses two longstanding challenges in early-stage blister packaging: affordability and floor space. Many pharmaceutical manufacturers have faced challenges finding blister units for stability testing, clinical trials, and small batch runs that aren’t onerously expensive and unnecessarily lengthy or bulky. With this in mind, the modestly priced Eagle LP measures just 1.8 meters in both length and height and just .9 meters in width.

Despite a healthy blister cavity depth of up to 20mm, the unit’s small tooling size allows it to recreate the work of multiple smaller units.

McKee: The major difference between the FlexaLAB and production-level equipment is its footprint – which is small and suitable for the tight spaces typical of R&D environments – and of course the production speed. The FlexaLAB is also ergonomically designed to optimize cleaning, changeover, and maintenance. Also, the FlexaLAB is supplied on wheels for easy intra-facility transport.

Notably, FlexaLAB operates via continuous motion, which eliminates potential alignment problems and any risk of product spillage. Continuous motion also affords enhanced dosing accuracy and requires less maintenance.

Braun: In contrast to conventional blister packs, Schreiner MediPharm’s smart packaging solutions enable the digitalization of processes in clinical trials. Once the patient pushes tablets out of a cavity, data is automatically generated in real-time. This includes the exact time the tablet was removed, the respective cavity, and its dosage. Optionally, temperature tracking of sensitive substances is possible as well.

The data is stored in the smart package and sent to a database, either by a smartphone app or reader using NFC or Bluetooth. Specialized software subsequently serves to analyze the data obtained. For clinical research, Schreiner MediPharm’s digital Smart Blister Wallet provides key benefits. It ensures better and more reliable data quality, which is fundamental for maintaining the integrity of study results. Furthermore, it contributes to a lower failure rate by addressing the issue of non-adherence, thus enhancing the overall success of clinical trials.

Additionally, the smart solution promotes a faster time-to-market by enabling shorter trial periods, leading to reduced costs and an accelerated approval process for new drugs. Ultimately, it streamlines research processes by reducing or eliminating labor-intensive tasks such as manual documentation and the counting of pills.

What sorts of adaptations or engineering innovations did the company need to make to produce this equipment?

Kishi: Our focus for the Eagle-LP was creating a testing unit segregated from mainstream production. It is among the first such units to be dedicated solely to such R&D and pre-production processes – testing, sampling, prototyping, etc.

Another consideration was the increasing desire to incorporate more sustainable blister films into OSD packaging. The Eagle LP is designed to accommodate a newer generation of more sustainable blister film substrates – ones that are typically more difficult to form and seal. The unit can easily accommodate PVC, PVDC, PET, ACLAR, ALU, and PP.

McKee: MG2 was able to adapt its innovative MultiNETT weight control system to the FlexaLAB capsule filler. MultiNETT is a 100% weight control system designed to measure the net weight of each single component dosed for every capsule produced in a batch. MultiNETT is also suitable to measure the powder in low-dosage applications, such as 5mg capsules for inhalation.

Another special feature of the FlexaLAB is the ability to “micro” dose powder into a capsule, meaning, dosages as low as 0.5 mg are particularly useful for AIC (API in Capsules) applications.

Braun: There were some challenges Schreiner MediPharm had to address when developing its Smart Blister Wallet solutions. The technology – i.e., the conductive lines and electronic unit – must be integrated inconspicuously into packaging designs. The conductive lines must be precisely positioned around each blister cavity to allow easy push-through while ensuring reliable technical functionality.

The smart cardboard wallets also must allow reliable heat sealability at the pharma manufacturer or CMO, ensuring product integrity. Continuous testing along the entire supply chain ensures a high quality and reliable functionality of the smart packaging. Moreover, highly customized packaging designs can be realized. Also, due to scalable production capacities via roll-to-roll processes, higher volume demands of pharma customers can be flexibly adapted at a high-quality level.

How is the “user experience” different with the R&D equipment versus full-size/larger capacity versions?

Kishi: The user experience is far simpler with the R&D unit than with traditional, production-level blister machines. Free of upstream or downstream connectivity and product flow considerations, the Eagle-LP can be operated manually for most key actions. And of course, R&D applications operate at lower speeds and produce smaller volumes, further simplifying the operation process.

McKee: As mentioned above, the major differences between FlexaLAB and production equipment are reduced footprint, reduced production speed, and ergonomic design. In particular, the reduced speed is obtained by using just one dosing element instead of multiple elements. Having just one dosing element also minimizes the number of overall capsule handling components, allowing for expedient setup and product changes for operators. This speed and efficiencyares crucial when producing batches in very small sizes, which invariably leads to more changeover than production-level machinery.

The same concept also applies to the Initia capsule filler, which occupies minimal floor space and is ergonomically designed to let operators work expediently and effectively.

Braun: Benefits for the user include active support for medication intake. Easy self-monitoring of the medication regimen is facilitated through an automatically generated eDiary, simplifying tracking. A convenient reminder function via an app enhances adherence. In addition, central digital monitoring offers the potential for physicians to adjust therapy plans for all patients, ensuring optimal treatment.

Automatic documentation of medication intake streamlines the process, while the user-friendly smart packaging design ensures a seamless experience. The push-through force and general application of the pill or capsule blister remain unchanged, maintaining familiarity and comfort. Ultimately, digital medication adherence monitoring tools enabled by smart blister packaging support therapy success and increase patient safety.

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