Low-profile models in Volkmann’s pneumatic pharmaceutical conveyor series (PPCVS) feature a low-profile vacuum pump and reverse-jet shock tank to convey tablets and capsules in restricted height areas. All Volkmann PPCVS units feature a one-piece, gap-free design with a smooth, polished stainless-steel surface. A modular, quick-release, cGMP design allows for no-tools cleaning. The units feature a patented QX filter system with a unique connection to the filter plate. In this design, a double seal replaces the commonly used felt seal or O-ring seal and ensures complete isolation of the process down to 0.3 micron. 

Articles

A low-profile pneumatic pharmaceutical conveyor moves tablets and capsules in restricted height areas.

Volkmann Introduces Low-Profile Pneumatic Conveyor

Accelrys Materials Studio 7.0 modeling and simulation environment contains enhancements in quantum mechanics, classical simulation, usability, visualization, and collaboration to enable scientists to engineer better performing and more cost-effective materials. The software enables scientists to perform highly complex materials research using multi-scale simulation methods to construct, manipulate, and view models of molecules, crystalline materials, surfaces, polymers, and mesoscale structures. An improved solubility-property prediction provides better understanding of solvation properties. By understanding and predicting the relationships between a material's atomic and molecular structure and its properties and behaviors, materials scientists can develop better performing materials of all types faster and more efficiently than with test and experimentation alone. 

New simulation software improves modeling for chemists and materials scientists.

Accelrys Materials Studio Enhances Modeling and Simulation

In a recent survey of current trends and practices in biopharmaceutical manufacturing, 

 readers revealed a preference for disposable systems, identified challenges for different therapies, and suggested technology enhancements to improve process efficiencies (1).

Survey respondents represented research, development, formulation, and process development functions, as well as quality control/assurance, validation, and laboratory management titles at branded and generic-drug companies in the United States, Europe, and Asia. More than half of the respondents work for organizations that produce both small- and large-molecule drugs; 25% added a biopharmaceutical-manufacturing program in the past year. 

The responses indicate some signs of manufacturing growth. More than half of all respondents said their companies increased biomanufacturing capacity in 2013. Less than 3% reported a drop in production. Only 8.1% said their companies decreased spending for biopharmaceutical equipment and services in 2013 compared to 2012; 37.8% reported increased spending; spending was flat for 33.8% of respondents. Nearly 40% expect spending to increase in 2014 compared to 2013; only 5.4% expect a decrease.

The top reasons for increased capacity were the addition of new products and increased production of existing products. More than 40% of respondents said that internal development of new products spurred the need for additional capacity. About 20% said capacity was added due to the acquisition of another company or in-licensing of a drug product

Almost 45% of the respondents reported that their organizations manufacture therapeutic monoclonal antibodies (mAbs); more than 55% of those surveyed said they manufacture protein-based drugs other than mAbs. More than 40% of the respondents said their companies manufacture vaccines; 17.7% develop cells for tissue and/or cell therapies; 10.4% manufacture nucleic-acid based drugs.

. Facilities that manufacture protein-based drugs reported use of multiple purification technologies. Ion-exchange chromatography was the most frequently reported (71.6%) followed by chromatography with other resins (62.7%), chromatography with Protein A (56.7%), and membrane-based filters (53.7%).

Protein stability led the list of reported technical challenges, cited by 53.7% of the respondents. Producing sufficiently high product yields was a close second at 52.2%; purifying high product yields was the third most frequently cited at 49.3%. Protein aggregates, formulation issues, creating/cloning cell lines, regulatory issues, and analytics were mentioned by more than 25% of the respondents (see 

. Although they represented a smaller subset of the respondents, those that manufacture nucleic-acid based drugs reported multiple manufacturing challenges. Purification (reported by 45.5%), stability (36.4%), drug delivery (31.8%), and scale up (27.3%) led the list (see 

. Process development for cells for tissue- or cell-based therapies created technical challenges for half of the respondents. Scale up (35.7%), cell viability (31%), and cell stability (28.6%) were also listed as top technical issues. Regulatory issues, costs, analytics, and inadequate bioreactor volumes were other challenges (see 


  More than half of the respondents reported using process analytical technology (PAT) in manufacturing operations. High-performance liquid chromatography was the clear leader, used by 71.7% of those that implement PAT. Use of Fourier transform infrared spectroscopy was reported by 41.3%; almost one-third use near-infrared spectroscopy. More than one-quarter use disposable sensors


  Hybrid manufacturing systems, which feature traditional stainless steel and disposable, single-use equipment, were used by almost three-quarters (74.4%) of the respondents; 16.3% use all stainless; 9.5% use all disposable.

All respondents, those who used and did not use disposables, shared perceptions about the value of single-use systems. Nearly 70% cited reduced contamination as an advantage. Time savings, ease of use, and flexibility for multiproduct manufacturing were identified as advantages by more that half of the respondents (

). While 38.1% said disposables offered cost savings, 55.6% said high cost was a challenge to using a disposable system. Other challenges were limitations on size and leaching of the disposable material into the product (


  Improved process understanding (68.4%), improved product quality (66.7%), and reduced variability in product quality (57.9%) were the top advantages identified by the respondents who have implemented quality-by-design (QbD) principles in their biopharmaceutical manufacturing operations. Nearly half reported improved manufacturing efficiency as a result. However, almost 32% of the respondents have not implemented QbD. Reasons cited for not implementing QbD include a lack of guidance and direction from regulatory agencies (46.2%), no process or quality advantage to be gained (30.8%), a lack of understanding of the QbD initiative (23.2%), or it is too costly.


  Respondents revealed insight about recent innovations that have improved process efficiencies.  Equipment and products related to disposable systems were most frequently mentioned. 

There is, however, room for improvement. Better disposable systems, including bags that do not leak, reduced leaching, larger bioreactors and fermenters, and disposable sensors were identified as desired new technologies to improve process efficiencies. Better filtration, chromatography columns, automation, and process analytical technologies also were identified as ways to improve manufacturing efficiencies.
  an Alternative:


  Outsourced manufacturing plays a prominent role among the companies represented in the survey. Almost 40% reported outsourcing of some component of biopharmaceutical manufacturing. Leading outsourced function, are drug substance manufacturing, API and finished products manufacturing, and clinical trial-materials manufacturing. More than one-third of the companies outsource full-scale commercial manufacturing. Limited internal manufacturing capabilities and cost-effectiveness were the leading reasons cited for outsourcing different functions in biopharmaceutical manufacturing.

BioPharm International Manufacturing Trends 2014 Survey

Production Trends

A survey of BioPharm International readers found that single-use systems and other technologies are driving process efficiencies in biomanufacturing, but there is room for improvement.

2014 Manufacturing Trends and Outlook

"Best Practices In Adopting Single-Use Systems"

Bioprocessors have successfully deployed single-use equipment at nearly every conceivable production scale. Yet, the decision to “go disposable” is significant. It involves considering the product, scale, process, and corporate objectives that include the value of legacy stainless-steel equipment. Decisions made early in process development and scaleup will affect the trajectory of manufacturing at successive production scales. Employing best practices when selecting single-use products during process development can ease the transition from clinical to commercial production and maximize the overall benefit of single-use systems. Based on shared and observed experiences in single-use bioprocessing, the principal factors to consider when embarking on a new single-use deployment include materials of construction, components, system design, and vendor support. Neglecting these considerations can result in costly delays and an uncertain pathway to commercial scale-up.
  
  


  Materials of construction constitute a principal factor when specifying single-use bioprocess equipment. At the most basic level, materials must meet stringent biological and chemical guidelines. Bioprocessors should settle for nothing less than fully compliant materials from proven suppliers with established reputations. 
  
  Consistency and availability of materials of construction directly affect the quality and supply of single-use products. End-users should expect availability of the same or equivalent materials of construction, of equal or higher quality, for the duration of a development and/or manufacturing campaign. To meet these requirements, suppliers should maintain a redundant or backup supply chain for their raw materials. Customers should inquire about a vendor’s contingency plan in the event of a supply interruption.

Frequent change notices from single-use system suppliers altering materials of construction carry potential quality implications that may delay program timelines and add to quality assurance costs. Consider the frequency of a vendor’s change notices, or whether the vendor is providing notifications at all. New materials introduced to existing systems can lead to validation issues and delay a product’s time-to-market.
  



  Components are the building blocks of single-use systems that are, in essence, only as robust as their weakest link. Users should specify components that are consistent with overall facility practices. For example, if commercial production relies on sterile welders and sealers, users should specify compatible tubing that meets material requirements. 
  
  Proprietary components not generally available to the market at competitive prices will almost certainly add to cost and reduce customer choice. Bioprocessors can strengthen their long-term supply position by specifying components from suppliers that trade freely with other single-use system assemblers. Only by evaluating both performance and marketing practices can a user make the best selection decisions. Also important is the component supplier’s reliability and delivery history. 

Delaying a development program or manufacturing campaign due to an unreliable supplier can be a real issue. Delays occur when a crucial component of a single-use system has a very long lead time. Because the assembler cannot produce the system without this component, system delivery times will be dictated by the long-lead item. To avoid this pitfall, assess potential suppliers by the experience of users who have previously worked with them. 

Bioprocessors will commonly use any component on hand during preclinical development. By the time a product reaches clinical testing, processors will have a much better idea of what the process looks like. By Phase III, the process becomes “locked.” As integral components of manufacturing processes, single-use components and systems should parallel biopharmaceutical development in terms of maturity. When processes become established, so should the components. 
  
  


  The decision to replace a multi-use unit operation with its single-use equivalent depends on the product, the process, and the organization’s business objectives. Some reasons include the need to eliminate a processing bottleneck (e.g., cleaning and cleaning validation), process issues such as frequent contamination failures, or to realize the calculated benefits that stem from cost, time, and product quality. 
  
  Best-in-class single-use system suppliers possess expertise that customers can use to help select components and systems most suitable to their business needs. The best designs are often minimal in terms of materials and accessories. Products such as single-use bags with unused ports, tubing, and fittings, which are commonly found in off-the-shelf systems, add nothing but excess cost and waste, thus reducing the advantages of single-use systems. 

The vendor’s job is to produce and ship precisely the system a bioprocessor requires. The system should arrive with the required regulatory documentation, ready to use. At one time, bioprocessors made routine modifications to single-use systems at their facilities. These days, it is best to avoid changes at a facility, particularly those that might compromise sterility.
  


  Because the business relationship between supplier and customer may last many years, vendor qualification is crucial. Top vendors view customer interactions as opportunities to improve their products and services. Conversely, a vendor’s lack of expertise, poor communication, or reluctance to collaborate with or on behalf of the customer can limit the benefits of single-use bioprocesses. 
  
  Suppliers should be prepared to play an ongoing support role for every single-use system sale and for the product’s entire lifecycle. End-users should ask for specific examples of a proposed vendor’s ability and willingness to provide support, process expertise, and technical advice that add value to the business relationship. 

The customer-vendor relationship should be capable of feedback that results in system optimization, thus, creating significant value for both parties. Because flexibility and ease of modification are key advantages of single-use systems, end-users should seek vendors that are adept at maximizing these advantages.

Customers must assess the value associated with every aspect of vendor contact. This process need not be difficult. If the vendor consistently assists in problem-solving, improving processes, and educating their clients, then the time is well spent. Vendors should demonstrate competence in their clients’ bioprocessing niche, and be eager to point out how changes in equipment or operations will improve the process. Suppliers who do not provide this level of value should be avoided as time spent with them offers no tangible return. 
  
  

After determining the suitability of single use, bioprocess organizations must consider the practical aspects of “going disposable.” Examining the impact of materials, components, systems, and the vendor relationship at each stage and at every level will help customers make good decisions. Value should always be the bottom line: Does deploying a single-use device improve your process, and thereby your product? Will adoption drive key business objectives such as improved quality, shorter timelines, and cost savings in a concrete, quantifiable way? Will your relationship with your supplier be a two-way street, supportive, and mutually value-driven, or does the vendor’s responsibility end with the sale? Bioprocessors who follow the decision process outlined here are in the best position to benefit from the considerable promise of single-use systems.

John Schmitz, director of strategy and business development, life sciences, Saint-Gobain Performance Plastics.

Troubleshooting

Consider these best practices when deciding to implement single-use components.

Selecting Single-Use Systems for Biopharmaceutical Manufacturing

A “track-and-trace” bill, the Drug Quality and Security Act, was recently passed by the US Congress as part of the government’s effort to deal with counterfeiting of pharmaceutical products by requiring a tracking system (i.e., serialization). Ian Parsonage, director of serialization at Packaging Coordinators, Inc. (PCI), discussed issues that pharmaceutical manufacturers should understand about serialization with 

 What is required from the pharmaceutical industry as a result of the track-and-trace bill, and when will these requirements take effect?
  
  

 HR 3204 is complex. There is a requirement, as of Jan. 1, 2015, for manufacturers to pass transaction records (i.e., bills of sale in either electronic or paper format) to the FDA. Three years after enactment, serialization at both saleable unit and case becomes mandatory; after 10 years, full supply-chain traceability will be required. The first requirement for serializing the case and the saleable unit does not explicitly state that the codes must be related, but all of the primary distributors in the US are requiring this of their goods, thus there is a need to aggregate. The federal law has preempted the California law, which required that 50% of products sold must be serialized before Jan. 1, 2015 and 100% by Jan. 1, 2016. The new deadline is three years after the federal act was signed into law.

 What are some of the primary challenges in implementing a serialization system?
  
  

 There are many significant challenges. One is having space on the artwork to carry the two-dimensional datamatrix code and the mandatory human readable information together with all of the required product and dosage data plus the national drug code (NDC) and other branding elements. Because of the variability of sizes of product packaging, serialization equipment needs to be custom configured for each package size and coding location. To facilitate aggregation, the serial code must be visible throughout the entire packaging process; dummy codes may be needed to help with this.

The volume of data and the reliance on information technology (IT) networks is a level never before encountered in most pharmaceutical plants, which forces the production network to move out of the domain of engineering into the IT realm. Another challenge is that business-to-business information must be shared in a near real-time fashion to facilitate the requesting, receipt, and commissioning of serial numbers together with their post-production status and aggregation detail.

What is a typical timeframe for implementing a serialization system? 
  
  

 The longest component of the leadtime is the provision of serialization equipment, which can be anything between 10 and 15 weeks depending on the complexity. Before purchasing serialization equipment, a company needs two to four months to review the product, artwork, and current packaging process and decide the way forward. After receiving equipment, a company needs three to four months to cover installation, commissioning, validation, and trialing. All in all, a company may need anything between 6 and 11 months from review to implementation. 

 What are some of the benefits companies can gain from serialization, outside of compliance with the law and avoiding counterfeiting?

 Serialization can help manufacturers track their own product. Aggregating to a pallet level, for example, can enable a manufacturer to know exactly which packs of product were shipped to a particular customer or wholesaler. This, coupled with knowing the exact sequence of manufacture, can ease the investigation of a potential quality issue and lessen the market impact of any problem. It should, at least in theory, be possible to avoid a mass recall in the cases where a known portion of a production run is found to have a defect.The equipment used for producing the serialized packs can also collect a huge amount of data about the efficiency of a production line. These data can offer insights into where a line needs to be updated or processes need to be changed in order to increase efficiency and reduce costs.

Packaging

PCI discusses the challenges and benefits of serialization in light of the new US track-and-trace legislation.

Equipment and Processing Report-01-15-2014

Volkmann Introduces Low-Profile Pneumatic Conveyor

Accelrys Materials Studio Enhances Modeling and Simulation

2014 Manufacturing Trends and Outlook

Selecting Single-Use Systems for Biopharmaceutical Manufacturing

Preparing for Serialization: A Q&A with Packaging Coordinators, Inc.