	Serialization implementation can become easier, faster, and less expensive with the Open Serialization Communication Standard Group’s (Open-SCS) Packaging Serialization Standard (PSS 1.0). Nine vendors and one end user conducted pilot tests to evaluate the standard, and the validated PSS 1.0 was officially released in November 2017.

	The standard is expected to reduce integration costs, which can run into the hundreds of thousands of dollars, by 50 percent, said Adriano Fusco, Open-SCS’s marketing director, and strategy & development director for Antares Vision. Fusco made the remark during a press conference held by the group on Sept. 25, 2017, at PACK EXPO Las Vegas (Sept. 25-27, 2017, Las Vegas Convention Center). Adoption of the PSS 1.0 minimizes customization of plant-to-enterprise interfaces (Levels 3 and 4), thereby shortening the integration process by months and improving scalability and repeatability.  

	The culmination of more than two years of work by the Open-SCS Group, the PSS 1.0 covers four use cases involving typical communication between onsite servers (Level 3) and corporate repositories (Level 4). It also defines best practices for serial number provisioning, serialization report transmission, batch and master data repository, and unused serial number return (1).

	Serialization requires an exchange of data on multiple levels. However, communication is difficult and requires spending a lot of effort on interfaces, Fusco said. Standardization with its common language and templates benefits end users and vendors by dramatically reducing the amount of customization needed. Quicker and easier integration across vendors and facilities expedites compliance with anticounterfeiting regulations worldwide.

	Vendor and end-user members of the Open-SCS Group started with the goal of developing functional interoperability of packaging solutions to seamlessly integrate the serialization process. Fusco, added, “Competitors have come together to do what’s right for industry. We have made our knowhow public. In the medium and longer range …we will all benefit-vendors and end users.” Seamless information technology (IT) connections and elimination of customized interfaces not only benefit serialization newcomers, but also serialization veterans who will eventually need to upgrade their IT infrastructure and equipment (2).

Abbott
					Pfizer
					Roche
					Teva Pharmaceuticals Industries


					ACG Pharma Technologies
					Adents
					Advanco
					Antares Vision
					Arvato Systems
					facilityboss
					Giesecke & Devrient
					Laetus
					Omron
					Optel Vision
					Rockwell Automation
					SAP
					Systech
					TraceLink
					Tradeticity
					Uhlmann Packaging Systems
					Vantage Consulting Group,
					Werum IT Solutions
					WIPOTEC-OCS

	Since its founding by 11 firms, the Open-SCS Group has seen its membership more than double. As work continues, Fusco expects membership to continue to grow. In order to streamline the standard development process, the Open-SCS Group works under the auspices of the OPC Foundation, an organization focused on interoperability standards for secure and reliable data exchange for industrial automation. It also collaborates with other organizations such as the International Society of Automation, the International Society for Pharmaceutical Engineering, and GS1.

	With official release of the validated PSS 1.0, the Group plans to introduce an OPC-standardized certification process in 2018, which will define what vendors must do to show that their products conform with the PSS 1.0, and how testing must be performed. Although no certifications have been granted yet, Fusco predicted, that most vendors will be able to deliver compliant product “within months.”

	Next steps for the Open-SCS Group involve work on Level 2 and Level 3 interfaces. The forthcoming PSS 2.0, targeted for release by the end of the second quarter of 2018, will address nine exchange use cases between Level 3 (site serialization manager) and Level 2 (line serialization controllers and smart devices). “We need funding for subject matter experts,” noted Fusco, adding, “We are looking for more companies to participate.” Work also is proceeding on developing a business model that will help to ensure faster adoption of the standard worldwide.

	1. Open-SCS Group, “First Packaging Serialization Standard from Open-SCS Group Showcased at Pack Expo; Release of Validated Standard Planned for November 2017,” News Release, Sept. 29, 2017.

	2. Open-SCS Group, “At Pack Expo, Open Serialization Communication Standard Group (Open-SCS) to Announce Major Milestone,” News Release, Sept. 22, 2017.

	3. Open-SCS Working Group, https://opcfoundation.org/markets-collaboration/open-scs-working-group/, accessed Oct. 31, 2017.

Articles

Feature

Implementation of the Packaging Serialization Standard cuts serialization costs, shortens deployment time, and expedites compliance with anticounterfeiting regulations. 

Standardizing Serialization

	Orbis Biosciences’ Optimµm Platform, an encapsulation technology developed for oral drug products, won the 2017 CPhI Pharma Award for Excellence in Pharma: Formulation. In an interview with 

, Nathan H. Dormer, vice-president of Research & Development, Orbis Biosciences, shares insights on the challenges in manufacturing controlled-release drug-delivery systems, the limitations of traditional methods used to coat microparticles, and the innovation behind Orbis’ Optimµm Platform.

What are the challenges in manufacturing controlled-release microparticle drug delivery systems? 

Micro- and nanoparticulate powders are manufactured with a myriad of processes, but the primary motivation is integration of controlled-release mechanisms to govern particle disintegration and API dissolution. The requirement of achieving controlled release universally relies on physical sequestration of the API via one or more physicochemical mechanisms, which typically requires multiple steps. A powder form, however, can present unique challenges to achieving controlled-release coatings due to the high surface area of the particles, the irregular sizes of particles within the powder, and the number of process steps required to ensure predictable performance and reasonable quality of the final product. Nonetheless, taste-masking can still be achieved with powders when a coating or other chemical modification is applied.

 What are the different steps involved in coating microparticles?

The most straightforward method for achieving taste-masking and controlled release with coated powders involves a two-step process in which a precursor particle is manufactured by various means, then coated with one or more layers containing controlled-release materials. Precursor particles can either be finely-milled API crystals, crystalline or amorphous API co-mixed with inert bases or controlled-release materials, or an entirely inert core without API. These three types of precursors can be manufactured by one or more means, which include traditional vibratory methods, congealing/spinning disk atomization, prilling, hot-melt extrusion (HME) and spheronization, aqueous dispersion, blending/bulking, electrohydrodynamic spraying (EHDS), spray drying, or ion exchange resins. Material selection for the precursor particle relies on process capabilities, the desired end-product controlled-release properties, API thermal and oxidative stability, and the desired physical properties (such as surface features, density, friability, and hardness, among others). Once the precursor microparticulate is manufactured, the product is then sieved to remove out-of-specification particles and coated for taste-masking, delayed-release, or stability-enabling properties. The precursor particle advances to subsequent traditional coating steps using fluidized beds, Würster coaters, dry polymer coating, spray coating, pan coating, or coacervation. The materials of choice for the secondary coating steps are selected for reasons commensurate with the precursor particles (i.e., material compatibility, controlled-release behavior, and stability). The final dosage form can then be bottled for resuspension at time of use, packaged in sachets or sprinkle capsules, placed in dissolving tongue strips, co-lyophilized with other materials for orally-disintegrating tablets (ODTs), or reconstituted in syrup if liquid stability is not an issue. 

 What are the limitations of traditional technologies? 

The approach of manufacturing controlled-release powders by adding multiple coating steps to API-rich precursor particles is an accepted method for powder dosage forms. These techniques are, however, divergent from state-of-the art approaches that focus on chemical modification or comlexation of the API and/or substrate using ion-exchange resins. The main advantages that ion exchange resins can yield are liquid stability and deterring abuse of scheduled APIs, such as opiates and amphetamines. Although it is innovative, drug complexation involves a number of manufacturing steps and quality control aspects that far surpass that of simple bead layering, and it still usually includes a final coating step. The major criticisms of all traditional methods, however, focus on the sheer number of process steps to achieve particle size distributions that contain a considerable amount of fine and large out-of-specification particle sizes.   

Can you tell us more about Orbis’ Optimµm Platform? What challenges does it solve and what makes the technology unique?

Orbis’ Optimµm Platform leverages its Precision Particle Fabrication technology to deliver oral pharmaceutical products that have both controlled release and taste-masked attributes. Orbis’ controlled-release capabilities are unique in that they are achieved in a single manufacturing step and do not require additional coating steps to achieve taste-masking, extended release, or modified release. Optimµm technology incorporates vibration with a scalable nozzle approach to create both microspheres and microcapsules in a single manufacturing step. The Optimµm technology produces uniform microspheres or microcapsules exhibiting a narrow size distribution, offering precise control over particle morphology (e.g., porosity, coating thickness, etc.) and therefore precise control over the release kinetics. These release kinetics can include extended or modified release options. The flexibility of Optimµm technology allows for production of a wide range of particle materials, sizes, and desired characteristics in a single-step process that scales linearly by simply adding additional nozzle heads. Scale-up has been successfully validated with the commissioning of Orbis’ cGMP compliant manufacturing system, which has a minimum of 60 times more throughput than a laboratory-scale unit.

Can you provide some examples of how the Optimµm Platform was used to address key formulation or manufacturing challenges?

In one example, Orbis used its novel core-shell technology to enable modified-release options such as enteric or reverse-enteric delivery in a format-flexible powder. Specifically, Orbis created an enteric-coated bead with a pure ibuprofen core.

dissolution shows that API release is limited to less than 10% for two hours in gastric conditions with immediate release when exposed to neutral pH similar to the small intestine. This modified-release approach is accomplished by fabricating a microcapsule with an engineered shell of uniform thickness designed for targeted release specifications. Efficiencies are gained using the Orbis process by eliminating the secondary coating step for applying the enteric coating.

	In another example, Orbis used its Optimµm technology to create an immediate-release, taste-masked, microcapsule-based powder, which contained the very bitter drug, prednisone. The prednisone powder was found preferable over the traditional pill in taste testing, and had similar taste to a placebo microsphere powder with no encapsulated drug. Additionally, the powder provided equivalent total body exposure of prednisone and active metabolite, prednisolone, in a randomized, open-label, two-product, two-period, crossover study in a fasted state comparing 10-mg prednisone taste-masked microspheres to a 10-mg prednisone tablet.

Orbis Biosciences’ Optimµm Platform delivers microparticulate dosage forms with controlled-release and taste-masked properties in a single manufacturing step. 

Equipment and Processing Report-12-20-2017

Standardizing Serialization

Manufacturing Microparticles in a Single Step