Avive’s personalized, multi-medication 30-day dosing system won the 2012 Compliance Package of the Year award in an annual competition organized by the Healthcare Compliance Packaging Council (HCPC). HCPC also recognized a pharmacy seal pack from Information Mediary Corp. as first runner-up, and a 30-day dose pack from Eli Lilly as second runner-up. Awards were presented at the association’s RxAdherence 2013 meeting, on March 12, 2013, in Florham Park, New Jersey.

The winning Avive package was developed by MWV Healthcare and LTCPCMS, its pharmacy innovation partner, with input from patients and pharmacists.  Each Avive package features a month’s supply of prefilled medication packets, labeled with medication names and dosing instructions. The container also holds patient education information. The Avive service is designed to increase medication adherence and consumer convenience, allow more time for pharmacist–customer counseling, and reduce medication errors.

The Avive system synchronizes a person’s medications, so all prescriptions are picked up on the same day each month from one pharmacy. The system also creates a customized regimen, which consolidates dosing times consistent with universal medication schedules and aligns with the consumer’s daily habits. A central-fill location dispenses medications via a robotic system and pharmacist oversight. At the local pharmacy, the pharmacist makes a final inspection prior to pickup. 

The multi-medication packaging format delighted the judging panel. One judge noted the Avive dosing system “truly brings us to a personalized medication approach.” Another judge commented that the dosing system “…seems to be tailor-made for elderly patients, who often have multiple drugs to take, while assisting them in maintaining compliance.” 

The first runner-up in the competition, the Med-ic 21 Dose Multi-Med Pharmacy Seal Pack from Information Mediary Corp., was initially developed for a study to monitor Hepatitis C. The package provides large blisters for multiple dosages, is easily filled at the pharmacy, and can be heat- or cold-sealed. An electronic content monitor (ECM) and grid hidden inside the paperboard records when the patient breaks through the package. This information is stored on the ECM tag and can be read when the empty package is returned to the pharmacy. It also can be read via Smartphone, near-field communication terminal, or radio-frequency identification reader.

One judge commented, “This package is quite unique—especially with a way to transmit information about adherence to the pharmacist straight from the packaging. The ECM tag is a great feature that does not require a patient report of behavior….The blister packs are easy to push through, which is good for individuals with arthritis. This can allow pharmacies to send a reminder call or text and interact with the patient to figure out ways to improve adherence. This design also allows for pharmacists to package multiple medications per day in one blister pack for the patient.”

Second runner-up honors were earned by a MWV Dosepak for an Eli Lilly Strattera Physician Sample, copacked by AndersonBrecon. Eli Lilly Strattera treats attention-deficit/hyperactivity disorder in children, teens, and adults and is prescribed (based on the weight of the patient) in a titrating regimen to reach the target dose. The 30-day Strattera Physician Sample Dosepak features a color-coded, calendarized format that identifies the starting dose of 18 mg for the first five days of therapy and progresses to 25 mg for the second five days, 40 mg for the third five days, and 60 mg for the remaining 15 days. Other versions present 10/18/25/40 mg or 25/40/60/80 mg regimens. 

To further support patient compliance, the Strattera design incorporates dosing instructions that include tips to avoid side effects. The pack also directs patients to a supporting website for further information and possible discounts. A patient medication guide is included in the cover panel of the Dosepak sleeve.

“This package is ideal for individuals beginning a new medication regimen,” noted one judge, adding, “The color-coded sections for each increasing titration of medication helps the patient know what they are taking and also be able to pinpoint side effects to specific dosages. The opening design is great for preventing medication overdose and child resistance. Additional pluses are the easy-to-read instructions included on the inside panel.”


Hallie Forcinio is Pharmaceutical Technology's packaging editor, 

Articles

Packaging

An annual Healthcare Compliance Packaging Council competition recognizes innovative pharmaceutical packages designed to improve patient adherence.

Thirty-Day Dosing System Wins Packaging Award

Axiom Analytical
 Shielded and self-cleaning near-infrared probes are designed for on-line analysis

 Axiom added shielded and self-cleaning near-infrared (NIR) probes to its line of robust probes designed for on-line spectroscopic analysis. The FPT-850SJ NIR transmission probe includes an integral steam jacket that facilitates the elimination of condensed sample material without requiring probe removal. The FDR-825 non-contact NIR diffuse-reflectance probe uses a vortex flushing system that allows the objective optics to be effectively cleaned while in place on the process line. The on-line probes have a robust seal around the viewing window that is resistant to extreme conditions of temperature, pressure, and chemical reactivity. 

I Holland
 Tablet-design software aids in design of tablet parameters and performs stress analysis for tool tips

 I Holland’s iTAB tablet-design software calculates tablet parameters and performs stress analysis to help users design pharmaceutical tablets. The software first calculates tablet-design parameters (e.g., volume, mass, density, and surface area) as the user modifies tablet dimensions (e.g., diameter, cup depth, and radii). The software next runs a real-time, integrated finite element analysis (FEA) simulation against the design and calculates a punch-tip maximum force. Using this analysis in the design step helps eliminate problems such as punch-tip breakage. The software produces a two-dimensional drawing and generates a design report that can be emailed to I Holland for further analysis, design work, and tooling production.

Products from Axiom Analytical and I Holland.

April 2013 Editor's Picks: Products from Axiom Analytical and I Holland

The conference schedule at INTERPHEX 2013 covers a wide range of topics, including facility and process design, product development, and regulatory quality assurance. 

 interviewed some of the speakers to get a preview of their presentations. Access the podcasts using the links below.


 Modularization has been used by other industries for decades and, over the last few years, has been more accepted by the bio/pharmaceutical industry. Modularization is fast becoming an essential component of bio/pharmaceutical facility design. Use of modularization is growing because it meets industry needs for reduced cost, accelerated construction schedules, and quality construction. The need for offsite skilled labor to construct hygienic components in a controlled, quality location is increasing, notes Craig Sandstrom, director of process engineering at Fluor, driven in part by the growth of construction in locations such as Asia or South America where local trades aren’t as mature as in North America and Europe. 

The concept of “standardization” in modularization is often misunderstood, comments Par Almhem, president of ModWave and Modular Partners. He explains that a process can be divided into discrete operations with defined inputs and outputs, and a variety of systems can then be made from these standard building blocks (i.e., modules). In the future, modules will be used more widely as a more efficient way of building anything, whether it is a physical building, a software system, or a bio/pharmaceutical process, predicts Almhem.

Sandra Leuken from Baxter Pharmaceuticals, Par Almhen from Modular Partners, Detlef Kehm from Grifols, and Craig Sandstrom from Fluor are part of a panel discussion, “Getting Excited about the Modular Experience” (1:30-3:00 pm Wednesday, April 24).  Par’s presentation is on “Advances in modularization: standardization, modular unit operations, and global deployment,” and Craig’s presentation is titled, “Modularization overview and implementation strategies.”

Single-use Systems in Traditional Stainless-Steel Facilities


 Advantages of single-use systems are well known. These include reducing cleaning costs, floor space requirements, and classified-space requirements. One of the biggest advantages, says Jeff Odum, director of operations at IPS–Integrated Project Services, is flexibility, particularly related to process changes in early-stage development. He explains that there are several types of companies that can benefit from the flexibility of single-use systems. These include contract manufacturing organizations (CMOs), research-driven organizations doing high-level development work, and companies focused on pandemic response, all of which need to adapt to new technologies. Academic institutions can benefit from the lower capital requirements. “Any manufacturing organization should explore the potential advantages of this technology,” says Odum. 

The IPS presentation, “Implementing Single-Use Biomanufacturing Systems into Traditional Stainless Steel-based Facilities,” will be held on Tuesday, April 23 from 2:45-3:45 pm.


 The International Conference on Harmonisation (ICH) guidance for industry, Q8(R2) 

Guidance for Industry Process Validation: General Principles and Practices 

describe approaches for development and validation of pharmaceutical processes (1, 2). These concepts can also provide a scientific basis for the development and validation of cleaning processes, says Keith Bader, senior director of technology at Hyde Engineering + Consulting. Cleaning processes have traditionally been developed on full-scale manufacturing equipment using general industry information without real regard for the nature of actual residues and their removal. Validation of cleaning processes, likewise, has in the past relied only on monitoring critical process parameters, such as temperature and concentration of cleaning solution, and using a fixed cycle time rather than using forward-processing criteria to indicate when the cleaning process is complete. Moving forward, however, process analytical technology and better understanding of the cleaning process design space can improve decision making and result in more efficient cleaning, explains Bader. 

Keith’s presentation, “Establishing a design space: cleaning process development and validation,” will be held on Tuesday, April 23, from 11:30 am to 12:30 pm. 

Keith Bader, Hyde Engineering + Consulting

Each company must implement its own continuous validation program (CVP) for its systems based on current FDA guidelines (2). Defining a CVP helps plan and prioritize validation projects and determine personnel requirements and budgets, notes Victor Hernandez, senior process validation engineer, project engineer III, in the Sustainable Engineering department at EMD Millipore in Jaffrey, New Hampshire.  Procedures and policies must be transferred from the corporate level to the division level and to specific sites, where they must be applied to specific manufacturing processes. In his case-study presentation, Hernandez describes how the EMD Millipore Jaffrey site helped bring Merck’s CVP in line with current trends and apply it to EMD Millipore Corporate division and to EMD Millipore separation and filtration device-system manufacturing processes at various sites, following Millipore’s acquisition by Merck KGaA. 
  
 Victor’s presentation, “Current continuous process validation program: following FDA current guidelines,” will be held on Wednesday, April 24 from 1:30-2:30 pm. 


 A panel discussion moderated by Pharmaceutical Technology will examine the lessons learned, successes achieved, and ongoing challenges of implementing QbD in pharmaceutical manufacturing.  Dr. John Lepore, senior director of Chemical Process Development and Commercialization for Global Pharmaceutical Commercialization at Merck and Co., will provide expertise on application of design space and control strategies for API manufacturing. Dr. Chris Moreton of FinnBrit Consulting will share his expertise in how to incorporate excipients into the design space. Jonathon Thompson, senior manager of Compliance Services Consulting at Invensys Operations Management will use his experience to discuss challenges in adapting the manufacturing process from a control perspective, including the feasibility of real time release. Together, the panel will consider the benefits of adapting QbD and the challenges yet to be addressed. 

The panel discussion, “Lessons Learned: Successes and Challenges in Implementing Quality by Design,” will be held on Wednesday, April 24, from 10:15-11:15 am. 

Guidance for Industry, Process Validation: General Principles and Practices

INTERPHEX Preview

Speakers discuss modularization, single-use systems, and process validation in a series of podcasts available on the Pharmaceutical Technology website.

Experts Give "Sneak Peeks" into INTERPHEX 2013 Conference Presentations

 annual equipment and manufacturing survey gained the industry’s perspectives on trends in finished drug-product manufacturing and equipment. Respondents in both solid dosage and parenteral drug manufacturing were generally satisfied with the utility of existing equipment and the pace of innovation in meeting manufacturing needs. Most employ quality by design (QbD) to some extent, but respondents identified a range of challenges in implementing QbD. This article is excerpted from an article in the April 2013 issue of 

, which further details trends in high-potency/high-containment manufacturing, process analytical technology (PAT), and continuous manufacturing.

Solid-dosage equipment
The survey showed that existing solid-dosage equipment is generally meeting needs. Areas noted by more than 20% of respondents as needing significant improvement, however, included process control/automation, powder transfer/materials handling, and feeding/dispensing (see Figure 1). When asked if innovation is keeping pace with current and future needs, responses were similar, with the same three areas indicated as lacking solutions by 20% or more of respondents. Tablet compression stood out as a strongly innovative area, with 96% of respondents indicating that innovation is “excellent” or “good” for this equipment.

 Users of parenteral equipment, likewise, are generally satisfied with existing equipment, as shown in
Figure 2. Process control/automation and vials/cartridges fill–finish equipment, however, were two areas noted by 20% or more of respondents as needing significant improvement. In all segments, nearly 80–90% of respondents said that the pace of innovation was “good” or “excellent”.

QbD
Almost half of respondents indicated that their company applies QbD principles for both new and legacy products, and another 32% apply QbD to all or select new products (see Figure 3). Only 22% of respondents do not apply QbD at all. Approximately 72% identified better process understanding as a benefit of QbD. Participants were invited to choose all answers that applied, and they indicated other benefits of QbD as increased 

efficiency/reduced waste (48%), reduced costs (44%), shorter process times (35%), streamlining regulatory review (32%), and improved ease of making changes (29%). Only 6% of respondents felt that there are no challenges or barriers to implementing QbD. More than half noted lack of knowledge and training as a problem.

 Equipment and Manufacturing Survey targeted individuals in production and engineering. The survey was conducted by email in February 2013 and had 193 respondents. Nearly 30% were from innovator pharmaceutical companies, 28% from generic-drug companies, 20% from contract manufacturers, and 10% from consumer healthcare companies making over-the-counter products. The remaining respondents included excipient and raw material suppliers (7%) and equipment or machinery vendors (5%). About half of the respondents were involved with solid-dosage manufacturing and the other half in parenteral drug manufacturing. The majority of respondents (79%) were from companies with under $1 billion in revenue. Nearly 7% were from companies with between $1 billion to 10 billion in revenue, almost 7% were from companies with $10 billion to 50 billion in revenue, and the remainder (8%) were from companies with over $50 billion in revenue.

Production Trends

Pharmaceutical Technology's survey of manufacturing equipment and trends shows satisfaction with utility and innovation in most solid-dosage and parenteral drug-manufacturing equipment.

Equipment and Processing Report-04-17-2013

Thirty-Day Dosing System Wins Packaging Award

April 2013 Editor's Picks: Products from Axiom Analytical and I Holland

Experts Give "Sneak Peeks" into INTERPHEX 2013 Conference Presentations

Evaluating Equipment Utility and Innovation