Tag: OsoBio

Albuquerque, NM Nov 8, 2012 – Milton Boyer, president of OsoBio, has been appointed to the executive committee of the Drug, Chemical and Associated Technologies Association (DCAT).
Boyer – whose term began Nov. 1 – will represent the contract formulation, fill, finish, and contract packaging industry as segment vice president. Boyer joined the DCAT board of directors last year.
Founded in 1891, DCAT is the premier business development association whose membership consists of companies that manufacture, distribute or provide services to the pharmaceutical, chemical and related industries. More than 300 corporate members belong to DCAT.
“DCAT is one of the most unique trade organizations in our industry. Because it is truly member-run, each individual has an opportunity to make a distinctive impact, and new initiatives continue to increase the organization’s value proposition,” Boyer said. “I am honored to be selected for this position by my industry peers and look forward to serving in my new role.”
In addition to his board membership at DCAT, Boyer is a member of the International Society of Pharmaceutical Engineers (ISPE) and the American Association of Pharmaceutical Scientists (AAPS).
OSO BioPharmaceuticals Manufacturing LLC – OsoBio for short – is a contract manufacturing organization (CMO) that specializes in delivering injectable sterile liquid, suspension and lyophilized biologic and pharmaceutical products to the pharmaceutical industry. The company offers significant knowledge and experience in late-phase clinical products and successfully taking them to commercialization.
In the history of its Albuquerque, N.M., facility, OsoBio has manufactured more than 250 distinct commercial presentations in every major therapeutic category. The U.S. Drug Enforcement Administration (DEA) has granted OsoBio registrations for Schedule II through V controlled substances.

Albuquerque, NM Oct 3, 2012 – OSO BioPharmaceuticals Manufacturing, LLC, has appointed Alan P. Heim as vice president of human resources.
In his capacity, Heim administers all policies and programs that affect personnel at OsoBio, including issues such as organizational planning; recruitment, hiring and training; employee compensation, performance and benefits; information technology; and labor-related government regulations.
Heim – who has a strong background in organizational leadership and change – brings to OsoBio tremendous experience managing people.
He served for more than 20 years in the U.S. Marine Corps, advancing to the rank of colonel. Among his many tours of duty worldwide included a two-time assignment to the Washington, D.C.-based Joint Operations Staff functioning under then-chairman Gen. Colin Powell.
Upon retiring from the Marines, Heim joined ICN Pharmaceuticals Inc. – now Valeant Pharmaceuticals – as director of organizational planning and development. In 2000, he co-founded Lathian Systems Inc., a software and marketing solutions company for the life-science industry. While there, he helped raise $17 million in venture capital funding, contributed to the company’s profitability and grew it to 40 employees. Most recently, Heim served as vice president of human resources for Directed Electronics.
“OsoBio is growing in large part because of the knowledge, expertise, flexibility and responsiveness of our employees,” said Milton Boyer, president. “Alan has been key in identifying and recruiting people who embrace and exemplify OsoBio’s entrepreneurial culture.”
Heim completed a research fellowship at Harvard University, where he studied and wrote about organizational leadership and change. He earned his master’s degree in human-resource management from Pepperdine University, and was certified as a Senior Professional of Human Resources.

Albuquerque, NM Sep 18, 2012 – Robert “Bob” Cashman has been promoted to vice president of business development at OSO BioPharmaceuticals Manufacturing, LLC.
In his new role, Cashman is responsible for developing and executing strategies to expand the company’s injectable pharmaceutical contract manufacturing business. He also will oversee existing and potential customer relationships, manage pricing structures, and direct strategic corporate alliances.
Cashman, who joined OsoBio in 2009, previously served as director of new business development for the company’s East Coast market. He steps into a position vacated by Milton Boyer, who was appointed president of OsoBio in February.
“Bob has consistently demonstrated a keen ability to foster existing and new client opportunities for OsoBio,” Boyer said. “As OsoBio continues to successfully grow as a CMO renowned for world-class customer care, project management and regulatory compliance, I know Bob will help us achieve the goals we’ve set for ourselves.”
With more than 20 years of experience in contract pharmaceutical and biotechnology manufacturing, Cashman is a board member of the Philadelphia Drug Exchange, the oldest continually active trade organization in the United States. A member of the Parenteral Drug Association, he also heads the scholarship committee for the Drug, Chemical and Associated Technologies Association (DCAT). Cashman holds a bachelor’s degree in business administration from Villanova University.

Albuquerque, NM Apr 30, 2012 – OSO BioPharmaceuticals Manufacturing LLC is investing more than $5 million in equipment and infrastructural improvements that include a new Grade A aseptic filling suite for liquid, suspension and lyophilized products.
The rolling diaphragm pump filling suite, manufactured by Bosch, comes equipped with optional rotary piston and peristaltic pumps. It will function at 115 percent of the previous line’s capacity, increasing the speed and efficiency with which OsoBio can deliver drug products to clients.
Thanks to its ability to conduct non-destructive online weight tests, the new line will deliver greater precision and yield. And its restricted access barrier system will minimize risk of cross-contamination and diminish potential occupational exposure.
OsoBio is a contract manufacturing organization (CMO) that produces injectable sterile liquids, suspension and lyophilized biologic and pharmaceutical products for the pharmaceutical industry.
“This state-of-the-art filling suite represents a substantial investment in the future – the future of OsoBio, as well as the futures of the pharmaceutical clients we serve,” said Milton Boyer, president. “It allows OsoBio to manufacture drugs in a better, smarter and faster manner, while ensuring high-quality product and the safety of patients and employees alike. This is an exciting new addition to OsoBio’s facility.”
In preparation for the new line, OsoBio extensively remodeled its facility, making infrastructural enhancements that included installing welded PVC walls throughout controlled and classified areas to further secure the sterile environment and improve durability, ease of use and maintenance. OsoBio also installed poured epoxy floors throughout its facility to support its strong record of industrial safety.
The new line produces sterile liquid, suspension and lyophilized formulations in vial sizes ranging from 2cc to 100cc. The Bosch equipment includes:

• An RRU 3084/44 high-performance container washing machine, which uses intensive flooding, ultrasonic and spraying techniques to reliably clean vials inside and out in a continuous process,

• An HQL 4480S drying and sterilization tunnel with laminar flow for depyrogenization and cooling of glass vials,

• An FLC 3080 filling and closing machine designed to fill, sample check- weigh and stopper vials in a continuous motion process in compliance with International Organization for Standardization requirements,

• A GLT 4040 tray loader with 100-percent vial counting accuracy, and

• A TRL 1030 tray loader designed to automatically load vials at high speed in cleanroom applications, requiring minimal interaction and maintaining Good Manufacturing Practices (GMP) standards.

OsoBio’s new filling suite should be installed, fully validated and operational by late August.
Headquartered in Albuquerque, N.M., OsoBio specializes in products requiring complex handling, including highly potent compounds. Responsiveness, attention to detail and clear communication are the hallmarks of our client care.

Albuquerque, NM Feb 21, 2012 – Dr. Marian Meyer has been named director of laboratories at OSO BioPharmaceuticals Manufacturing, LLC.
In her role, Meyer manages the company’s chemistry and microbiology labs, which are responsible for such quality-control services as materials testing and release, environmental monitoring and analytical methods compliance.
Meyer brings to OsoBio more than 15 years of pharmaceutical industry experience in sterile injectables manufacturing, contract steriles, biologics, and tablets and capsules manufacturing. Most recently, she served as quality control manager for raw materials, microbiological, stability and compliance for Sandoz in Broomfield, Colo.
Meyer is a member of the Small Molecules 4 expert committee for United States Pharmacopeia (USP), a non-governmental, official public standards-setting authority for prescription and over-the-counter medicines and other health-care products manufactured or sold in the United States. USP standards for quality, purity, strength and consistency are recognized and used in more than 130 countries.
Having received her doctorate in chemistry from Arizona State University, Meyer also holds a master’s degree in business administration from Loyola University.

Albuquerque, NM Feb 13, 2012 – Milton Boyer has been appointed president of OSO BioPharmaceuticals Manufacturing, LLC.
Boyer has been responsible for guiding business strategies and creating new growth opportunities at OsoBio since 2008, most recently as vice president of business development and sales. As part of his promotion, he joins OsoBio’s board of directors.
“Our mission at OsoBio remains focused on building an injectable drug contract manufacturing organization that distinguishes itself with world-class customer service,” said George Aitken-Davies, board member. “Milton has demonstrated continued commitment to this vision by developing strategic customer relationships and driving significantly increased visibility of OsoBio in the market. We are confident that Milton’s leadership skills will help us achieve the bold and ambitious goals we’ve set for 2012 and beyond.”
Boyer said his immediate priorities include continuing to update and expand OsoBio’s operational capabilities, toward which the company is making significant capital investments this year. He also intends to deepen OsoBio’s talent pool and drive operational efficiencies.
Boyer serves on the board of directors at the Drug, Chemical and Associated Technology Association (DCAT), the business development association whose membership is comprised of companies that manufacture, distribute or provide services to the pharmaceutical, chemical and related industries. He also is a member of the International Society of Pharmaceutical Engineers (ISPE) and the American Association of Pharmaceutical Scientists (AAPS).
With more than 20 years of professional experience within fine chemical and pharmaceutical business development, Boyer has developed special expertise in active pharmaceutical ingredients (APIs) and narcotic raw materials. He previously served as director of sales and marketing for Siegfried-USA and Chattem Chemicals Inc.

Albuquerque, NM Nov 1, 2011 – Milton Boyer, vice president of business development at OSO BioPharmaceuticals Manufacturing LLC, has been elected to the board of directors at the Drug, Chemical and Associated Technology Association (DCAT).
Boyer – who is responsible for guiding business strategies and creating new growth opportunities at OsoBio – will serve a three-year term on the board.
Founded in 1891, DCAT is the premier business development association whose membership is comprised of companies that manufacture, distribute or provide services to the pharmaceutical, chemical and related industries. More than 300 corporate members belong to DCAT.
“We are delighted to have Mr. Boyer join the organization’s leadership,” said Margaret Timony, executive director. “He brings unique qualifications and experiences to his role that will help shape and support the organization’s programs and projects.”
OsoBio – a contract manufacturing organization specializing in injectable products – manufactures sterile liquid, suspended and lyophilized biologic and pharmaceutical products for the pharmaceutical industry. The company is renowned for its expertise in difficult-to-manufacture, demanding or highly potent products.
After working more than 20 years in fine chemical and pharmaceutical business development, Boyer has developed special expertise in active pharmaceutical ingredients (APIs) and narcotic raw materials. He previously served as director of sales and marketing for Siegfried-USA and Chattem Chemicals Inc.
In addition to his board membership at DCAT, Boyer is a member of the International Society of Pharmaceutical Engineers (ISPE) and the American Association of Pharmaceutical Scientists (AAPS).

Albuquerque, NM Jul 28, 2011 – A microbiology laboratory manager at OSO BioPharmaceuticals Manufacturing, LLC, has authored a chapter on environmental monitoring trends for an industry reference manual.
Kim Van Antwerpen wrote a chapter for “Environmental Monitoring: A Comprehensive Handbook (vol. 5)” edited by Jeanne Moldenhauer and being published in September by the Parenteral Drug Association.
Van Antwerpen’s key observation is that aseptic drug manufacturers should closely observe the environmental monitoring trends of their production facilities to ensure regulatory compliance and protect consumer health.
OsoBio, an injectables CMO, manufactures sterile liquid, suspended and lyophilized biologic and pharmaceutical products for the pharmaceutical industry. The company is known for its expertise in difficult–to–manufacture, demanding or highly potent products.
In her chapter, Van Antwerpen wrote that each aseptic drug manufacturer should have a clear understanding of its unique environmental monitoring profile in order to pro–actively execute preventive or corrective steps if an adverse trend is detected.
“The manner in which data are trended influences all stakeholders – both internal and external – and affects resulting opinions of one’s environmental monitoring program, perceptions of control at the production facility, and actions taken to mitigate potential risks,” she stated. “When trends are presented in a concise, thorough and understandable manner, the company gains credibility.”
Van Antwerpen will be a featured speaker at the PDA’s sixth annual Global Conference on Pharmaceutical Microbiology, taking place Oct. 17–19 in Bethesda, Md. She will discuss how to trend environmental data using commonly available software presentation, as well as how best to implement an environmental review board.
Van Antwerpen holds a bachelor’s of science degree in microbiology from the University of Wisconsin–La Crosse and a master’s degree in business administration from the University of Phoenix. A Lean Six Sigma black belt, Van Antwerpen is a member of the Parenteral Drug Association – for which she serves on its program steering committee – and a senior member of the American Society for Quality.

Albuquerque, NM Jun 22, 2011 – OSO BioPharmaceuticals Manufacturing, LLC, has been granted approval for the Researcher registration by the U.S. Drug Enforcement Administration (DEA) for Schedule II through V controlled substances.
OsoBio, an injectables CMO, manufactures sterile liquid, suspended and lyophilized biologic and pharmaceutical products for the pharmaceutical industry. The new DEA registration allows OsoBio to execute the development of manufacturing processes for controlled substances.
Renowned for its expertise in difficult-to-manufacture, demanding or highly potent products, OsoBio is well suited to handle controlled substances, said Dr. Stuart Rose, president and CEO.
“As a highly disciplined organization, OsoBio is comfortable with the processes, controls and documentation required when working with especially sensitive pharmaceutical materials,” he said. “We do the work that’s difficult to do.”
The DEA places strict guidelines on the research, manufacture and distribution of controlled substances to prevent their diversion into illicit markets. The agency categorizes controlled substances according to each one’s respective use in medical treatment, as well as its potential for abuse or causing dependence.
The agency approved OsoBio’s registration application to conduct research related to the potential manufacture of Schedule II through V controlled substances for clients.
“There aren’t many companies in the United States capable of producing injectable controlled drugs, so we’ve already fielded a number of calls from clients who have that need,” Rose said. “As we broaden OsoBio’s capabilities in handling products that demand special attention, we demonstrate our continued confidence that our company will exceed quality assurance and regulatory compliance expectations.”

Jun 6, 2011 – Improved methods for the development, manufacture, and administration of drugs, particularly increasingly complex biologics such as protein and peptide therapeutics, are more in demand than ever and are being met with advanced drug delivery options. Expansion of biologics in the marketplace has fostered the exploration of drug delivery methods such as prodrug delivery, and technologies such as Hot-Melt Extrusion. Product life cycle management is also driving drug delivery technologies. With fewer new drugs coming to market, pharmaceutical companies increasingly look to hold onto product revenues of existing drugs through new drug delivery options, reformulations and product line extensions (PLE), aimed at improving either safety, efficacy, patient compliance and ease of use (or all of the above)!
The latest drug delivery trends arise from the impact of current pharma and biopharma R&D. “The drug delivery market is forecasted to grow annually by about 10% until 2013,” said Sheila Dell, Ph.D., vice president of Product Innovation at Catalent Pharma Solutions. “Oral types will remain the largest drug delivery category while parenteral, inhalation and implantable systems will grow the fastest. And eventually, parenteral formulations will surpass oral dosages due to changes in the market trends in the type of molecules that are being discovered and commercialized.” Additionally, self-administered injectable devices are gaining in popularity amidst chronic diseases and the changing healthcare environment. Inhaled drug delivery formats are expanding to accommodate everything from pain medications to autoimmune disease targets and vaccines, and drug formulation strategies are taking on the challenges that lurk between API and administration.
R&D’s Impact on Drug Delivery
With the increasing complexity of drug candidates in development and shifts in drug research strategies and methodologies, how are drug delivery technologies being impacted by current pharma/biopharma R&D? According to Mike Marek, technical project manager at OSO BioPharmaceuticals Manufacturing, LLC, “It is through increased efficacy, reduced side effects, continuous dosing (sustained release) and increased compliance, among other attributes, that drug delivery technologies are impacted by current pharma/biopharma R&D. Drug companies — from start-ups to biotech to big pharma — are involved in developing novel drug delivery systems resulting in a number of approvals.” He noted that approved dosage forms range from Vivitrol (sustained release naltrexone) indicated for opioid addiction, a microsphere dosage form, to Sylatron (peginterferon-2b) and Cimzia (certolizumab pegol), both pegylated proteins providing longer plasma half life with fewer side effects.
In addition to drug delivery advances that have resulted in improved safety, efficacy, and compliance, challenges have necessitated enhanced collaboration among R&D and drug delivery from formulation to packaging. There are significant formulation challenges with how newly developed APIs are used. According to Jamie Beggs, market development manager at Celanese EVA Performance Polymers, “Limited bioavailability has plagued some of these new APIs, which are inherently less soluble in typical excipients, or there is the challenge of larger, more complicated molecules with biologics. More demand is placed on the formulation strategy, delivery systems, and ultimately, the excipients. Alternative excipients, which can be used in conjunction with novel pharmaceutical combination devices or via different routes of administration, are one way to help researchers avoid discarding promising compounds because they can’t find a way to deliver them effectively. Examples of formulation techniques helping scientists tackle the problem of poor solubility are amorphous solid solutions and dispersions. Hot-melt extrusion, one way to create a solid dispersion, is a processing method that is gaining popularity and acceptance, and it is also a technique that is highly suited for thermoplastic polymer excipients like ethylene vinyl acetate (EVA).”
The development of complex compounds affects all aspects of drug delivery and the roles of formulation and device require an increasingly collaborative effort among drug development and delivery strategies. According to Graham Reynolds, vice president of marketing and innovation at West Pharmaceutical Services, Inc., “New, sensitive biologic products are forcing the industry to deal with packaging and delivery systems much earlier in the process. The traditional container, which has historically been made of glass, has the potential to interact in a negative fashion with these products. For instance, in a vial format, glass delamination is a potential issue. In staked-needle syringe systems, there are considerations such as adhesives, tungsten and silicone oil that can cause interactions.”
The industry is seeking alternative materials in order to get around the issues associated with glass and sensitive biologics. “New materials, including break-resistant cyclic olefin polymers, such as Daikyo Crystal Zenith and unique designs, allow for easier and safer administration,” said Mr. Reynolds. “These systems are not only manufactured from a novel plastic material that reduces the risks of breakage, but the dimensional tolerances, quality standards, and freedom from materials such as silicone oil, tungsten or adhesives, help the systems provide the combined benefits of a plastic with the features necessary to contain a sensitive biopharmaceutical. This also provides significant flexibility in delivery system design, whereby device development is not constrained by the shape and dimensional variability of existing glass containers.”
Trends & Challenges
Drug delivery is playing an increasingly significant role in the quest for new product opportunities as the pharmaceutical industry faces patent and pipeline challenges. Also, growing healthcare costs are shifting in-patient treatments to the home setting. As a result, injection delivery methods are on the rise, particularly for the treatment of chronic conditions. “While oral drug delivery is still the most active in terms of deals being signed, the market has evolved over the past few years with a variety of goals now being sought beyond the more traditional oral extended/controlled release options,” noted Fidelma Callanan, senior director, marketing and communications at Elan Drug Technologies, which was recently acquired by Alkermes. These include targeted site delivery, pulsatile release (intended to deliver a burst of drug at predetermined intervals), and bioavailability enhancement strategies. Beyond oral delivery, one of the most active areas is that of depot injectable delivery. Recent notable approvals include the anti-psychotic Invega Sustenna product, which provides for once-monthly treatment option for patients.
The most effective delivery of biologics to date remains the injection route. “Because biologics are often large molecule products that do not transport well through non-injectable delivery methods, delivery devices such as auto-injectors are often the best choice for administration,” said Mr. Reynolds of West. In the injectable device realm, prefillable syringes, pen injectors, electronic patch injectors and depot injectable delivery methods are all making significant headway in the growing area of home delivery or self-administration. The growth in these home delivery systems can, in part, be attributed to increasingly prevalent illnesses like diabetes and autoimmune diseases that require self-administration of medications. While these delivery methods represent breakthroughs, they are subject to limitations. Factors such as drug volume, dosing schedules, and the symptoms the drug is treating, all come into play with each method.
Prefilled syringes (PFS) highlight the benefits and limitations of various injectable technologies, as pointed out by Mr. Reynolds of West: “Prefillable syringes can aid in patient compliance, but most are still based around conventional glass syringes. Also, newer drugs, including those with high viscosity or that need to be administered in high volume, can present administration challenges. Pen injectors and multidose cartridges, which can be used for those who have frequent needs, are limited to specific therapies such as diabetes and growth hormones. Additionally, easy-to-use auto-injector systems, which are based on prefillable syringes, provide a more convenient method for delivering drug products, especially for patients who may have dexterity or needle phobia issues. There is a growing trend in the industry toward the use of these systems.”
There is another alternative injectable method that mitigates some of the administration roadblocks encountered with the PFS and pen injector. “The electronic patch injector system, which can deliver a large dose over an extended period of time, simplifies administration by automating processes and equipment, and can move drug infusion therapies from hospital-based to home-based settings. Newer systems, such as West’s electronic patch injector, also offer significant benefits through the inclusion of electronic systems to control dose rate, volume and also provide feedback to help compliance,” said Mr. Reynolds. As devices become more and more complex, the concept of downloading information from the drug device is another growing trend. The goal is to not only improve patient compliance, but also to provide precise information about the frequency and the amount of drug delivered.
These injectable devices not only result in ease-of-use for the patient or administrator, but also potentially help manufacturers conserve costly drug product. “Biologics can be very costly and manufacturers are increasingly seeking new ways to minimize waste. PFS, with their premeasured dosage, have the potential to reduce dosing errors and increase patient compliance while potentially saving manufacturers money. Unlike single- or multi-dose vials that may require drug product overfill by as much as 30% to ensure adequate withdrawal, a PFS can virtually eliminate the need for excess overfill. An increase in PFS and delivery systems, as well as auto-injectors, is likely. Additionally, patch-injector systems, which can provide larger doses or multiple doses over a period of time, likely will experience growth, particularly in the oncology area, where lengthy administrations may move from the hospital setting to the clinical or home setting,” added Mr. Reynolds.
Inhalable Systems
In the area of respiratory drug delivery, there have been notable advances to mechanisms such as dry power inhalation (DPI), and pressurized metered dose inhalation (pMDI) systems that have piqued interest in this delivery method and expanded the playing field to include medications that treat a greater variety of illnesses. “Inhaled drug delivery is becoming quite popular as a drug delivery method today. In addition to treating simple ailments such as nasal congestion, the treatment and management of flu, pain, migraine, etc., is seeing increased acceptance with this delivery format. Also, the use of intranasal drug delivery for prophylactic vaccines is projected to grow significantly,” said Dr. Dell at Catalent Pharma Solutions.
“There is considerable interest in delivery systems that administer drugs directly into lungs. Systems such as DPI are gaining momentum. For pMDI systems, new propellants that have minimum adverse impact on environment are also increasingly being considered. Nasal sprays have been shown to be very effective for the delivery of small molecules,” said Vitthal Kulkarni, Ph.D., scientific advisor, Research & Development, DPT Laboratories. Although inhalation devices, such as pMDI and DPI delivery systems, have been associated with complex regulatory compliance and dosing issues, more advanced delivery systems are taking dose content and uniformity out of the hands of the patient.
“For inhalation, we see a continued pressure to reduce dosing variability and increase efficiency,” said Anne Roush, business development manager at 3M Drug Delivery Systems. “Our DPIs are quite efficient at deagglomerating the powder (separating the individual particles from each other) so the drug can reach the intended region of the lung for the maximum therapeutic benefit. Improvements in delivery technologies that aid patient compliance continue to be important. New inhalers now have features such as dose counters and dosing feedback mechanisms that help assure the patient that they’ve received their medication.”
Additionally, advances in inhalable drug delivery devices have impacted formulations in that these systems can expand the range of molecules that can be delivered or enable the device to be more efficient and dose sparing. “One of 3M’s DPIs, for example, doesn’t require a formulation aid such as lactose, thereby potentially eliminating a substantial amount of formulation development work and allowing more drug candidates can be considered for inhalation delivery,” noted Ms. Roush.
Formulation Strategies
Before these increasingly complex drugs reach their destination device, there exists the elaborate matter of formulation. New manufacturing technologies are emerging to resolve some of the common barriers to successful drug delivery. These drug delivery technology trends, according to Mr. Marek of OSO Bio, include prodrugs (activated in vivo, resulting in less toxicity) heat-activated liposomes for targeted drug delivery, nanoparticles, and monoclonal antibodies conjugated to toxins, immune modulators or pegylated.
Poorly soluble compounds and protein and peptide therapeutics present some of the greatest drug delivery challenges. In an effort to get drugs to reach their disease target, a variety of methods are being employed. Also, technologies such as
hot-melt extrusion and pegylation are improving outcomes. Prodrug design, aimed at optimizing drug delivery to minimize undesirable drug properties while retaining the desirable therapeutic activity, has proven an important means of improving drug efficacy. PEGylation, a process by which polyethylene glycol chains are attached to protein and peptide drugs, has helped to resolve degradation issues and improve pharmacokinetics. Also, Hot-Melt Extrusion (HME), the process of pumping materials through a die under elevated temperature into a new uniform product, represents an efficient manufacturing process and also has the potential to improve product quality and efficacy.
“Different strategies can be applied to poorly soluble drug compounds. The use of proper surfactants, combinations of surfactants, use of co-solvents, or lipids will typically improve solubility. There are also newly developed ‘solubility improving’ excipients that may help improve solubility of drug substance in the aqueous phase. Using micronized API in combination with solubilizing agents is also used to improve solubility. Other techniques to improve solubility that are useful for certain drugs include hot-melt extrusion or forming ‘eutectic mixtures’ of API with suitable excipients,” said Dr. Kulkarni of DPT.
According to Mr. Marek, “Peptides and proteins can be pegylated to provide ‘stealth’ properties in order to increase serum half life. Proteins and peptides can also be conjugated to monoclonal antibodies for targeted drug delivery. Additionally, ‘nanotechnology’ — incorporating drugs, proteins and peptides into nanospheres — will likely have an increasing role in drug delivery.”
Ms. Callanan of Elan Drug Technologies noted, “As a consequence of the clear trends emerging from the drug discovery process, it is expected that solubility-limited oral absorption will continue to pose a significant challenge in small-molecule drug development. Several relevant technology approaches, each capable of enhancing drug solubility, are available. They include solid amorphous dispersions, pharmaceutical co-crystals, self-emulsifying and self-microemulsifying drug delivery systems, and from Elan Drug Technologies, the NanoCrystal technology.” This technology boasts five licensed products on the market and more than $2 billion in annual in-market sales, ranking it among the successful technologies available for poorly soluble compounds.
Building on the NanoCrystal technology, EDT is now advancing a new, hybrid particle-engineering approach, called NanOsmotic technology. “The attractiveness of NanOsmotic technology,” according to Ms. Callanan, “arises from its ability to maintain a drug in its original crystalline form until biologically activated.” Following activation, a thermodynamically enhanced form of the drug is delivered and maintained for a period of time sufficient to achieve absorption. Accordingly, NanOsmotic technology offers a number of potential performance advantages over alternative technologies in the poorly water-soluble drug delivery space, noted Ms. Callanan, including enhanced bioavailability, improved chemical and physical stability, higher drug loading and the ability to achieve programmable release of drug for extended periods of time.
The increased focus to create more palatable delivery methods for patients has resulted in more convenient transdermal routes and nasal delivery. However, oral delivery continues to defy research efforts. “While delivery of proteins and peptides orally would seem like an obvious field of study for drug delivery companies, success to date has been very limited. The search for formulation approaches that are stable, bioavailable, and can be readily manufactured and acceptable to the patient, has led to major advances in development of nasal and controlled release technology. And while strides are being made in fundamental research in areas including oral delivery, transdermal delivery, pulsatile and ‘on demand’ delivery of peptides and proteins, it still remains the elusive holy grail of drug delivery,” said Ms. Callanan of EDT.
“3M’s microneedle technology is very conducive to delivery of macromolecules like proteins and peptides, achieving a similar pharmacokinetic profile to IV administration,” said Ms. Roush at 3M. “For certain drugs that require rapid onset of action, the pulsatile profile of MTS might be more effective than subcutaneous or intramuscular injection. For delivery of protein and peptide vaccines, the intradermal route has advantages because the drug is presented to the area with a rich source of immune cells. Additionally, if lung delivery is desired, DPIs may be a viable method for delivery of proteins and peptides.”
Ms. Roush also described how 3M’s MTS technology impacts formulation: “Using 3M’s MTS technology, the barrier of the stratum corneum is eliminated to enable delivery of a wider variety of molecules transdermally (eg, large molecules such as monoclonal antibodies). With solid MTS (sMTS), API is coated and dried on the microneedle, allowing one to deliver solid API through the skin. This feature of sMTS may also eliminate cold chain storage for some drugs and vaccines.”
While major advances have been made to improve drug delivery options for protein and peptide therapeutics, delivering them more and more effectively and with greater ease to patients, remains highly sought after.
Lifecycle Management
The pharmaceutical industry continues to take advantage of drug delivery technologies in its efforts to add years to product revenue streams. Although more traditional approaches are often used in order to improve the likelihood of approval, emerging drug delivery technologies are peeking the interest of drug developers. “While many approaches exist to ‘lifecycle manage’ a product, those pursued using drug delivery approaches have proven more effective than most, particularly where patient/clinical benefits are apparent. New formulation strategies have been shown to deliver the best returns on investment, proving significantly more effective than an OTC/branded generic route, repositioning, or a new indication. A Merrill Lynch industry report found that 87% of ‘switch and grow’ strategies not only sustained the value of the original franchise, but increased its sales following the switch to the improved product. A good example is Ritalin LA, developed by Elan, which grew Novartis’ methylphenidate franchise by 62% in its first year following launch,” said Ms. Callanan.
Improving safety and efficacy tops the list for companies seeking enhanced drug delivery methods for existing products. Also, more efficient drug delivery can lead to cost savings when dealing with expensive API. “One area where we are receiving strong interest from our customers is sustained or controlled release formulations,” commented Ms. Beggs of Celanese. “More specifically, our customers are
looking to create formulations that are delivered over an extended period of time via a mucosal or subcutaneous route. In some cases, they are also seeking to deliver the APIs locally at the specific site of indication versus dosing systemically. Formulators can use these techniques to create products that have improved safety and efficacy profiles through lower dosing with less variation in blood plasma API concentration.
When working with these advanced delivery methods, an emphasis must be placed on designing a formulation that adequately tailors the release profile of the API. This necessitates a strong, open relationship between excipient providers and drug/device formulators.”
“The intradermal delivery area is emerging as a potential way to obtain a desired pharmacokinetic profile with a faster onset or targeting drugs to the lymphatic system,” noted Ms. Roush of 3M. “These PK profiles are difficult to match via other routes of administration. MTS offers the potential for a faster onset of action and a reduction of injection site reactions. Intradermal delivery via MTS has shown improved bioavailability when compared to subcutaneous or intramuscular injection, which may translate to similar efficacy at a reduced dose.” If the API is expensive, comparable efficacy at a reduced dose can have real benefit to both pharmaceutical companies and patients.
Self-administration of injectable medications is a fast growing trend that will likely pick up speed as drugs advance through the pipeline, and to offset healthcare costs associated bringing treatment options for chronic illnesses from the hospital to home setting. Also, the once-insurmountable challenges around poorly soluble compounds are being met with incremental success. While protein and peptide therapeutics hold great potential in the treatment of serious diseases, improved drug delivery methods remain sought after due to their fragile nature, large size, and instability. Establishing advanced drug delivery mechanisms in this area is imperative for the future success of modern medicines.