• PFS MANUFACTURING – Prefilled Syringes & Biologics: The Perfect Partnership of Medicine & Delivery


    The following charts the twin rise of biologics and PFS and outlines some of the common challenges associated with filling and dispensing. It also discusses how a patient-centric partnership approach, based on a culture of collaboration and communication, can help biopharmaceutical companies shorten the development pathway and ensure a reliable supply of safe, effective medicines for the people who need them. BIOLOGICS: THE MEDICINES OF THE FUTURE Recent years have seen some of the biggest leaps in medical science in history. Researchers, driven by rapidly evolving technology and an ever-greater understanding of the underlying mechanisms of disease, have developed a growing number of products that have proved to be nothing short of life-changing. Much of this progress can be attributed to the rise of biologics, or drug products derived from the components of living organisms. Molecular biologists have been able to isolate and purify naturally occurring proteins, such as hormones and antibodies, and then administer them to those whose bodies lack them. The first genetically engineered form of insulin, which replicated the form of the protein found in the human body, was approved in 1982.1 By the mid-1990s, scientists had improved upon this early insulin by altering the protein’s amino acid sequence and changing its properties.1 The first genetically engineered form of insulin, which replicated the form of the protein found in the human body, was approved in 1982.1 By the mid-1990s, scientists had improved upon this early insulin by altering the protein’s amino acid sequence and changing its properties.1 Around this same time, the first antibodies were approved for use in humans, opening the door to the possibility of new drug products that could block the function of specific proteins. Since then, progress has been swift and, today, antibody-based drug products are common in the treatment of several long-term conditions. The previously untreatable progressive neurological condition multiple sclerosis (MS) is one such example. While scientists have yet to find a cure for the condition, disease-modifying drugs, many of which are biologics, are routinely used to slow the progression of the disease and reduce relapse rates, allowing patients to remain active longer than originally anticipated.2 We are now set for the next giant leap, as the tremendous promise of next-generation gene and cell therapies begin to bear fruit. Clinical trials have suggested that cell therapies could play a revolutionary role in cancer treatments, and that gene editing could even reverse blindness caused by specific genetic mutations. In 2018, the FDA had 500 active investigational new drug applications involving gene therapy products, and $2.3 billion in funding has been pumped into private gene therapy companies throughout the past 10 years.3 As many “first-wave” biological products reach the end of their patent period, biosimilars are becoming increasingly common – approximately 50 have been launched since 2010, and many more are in the pipeline.4 Their development highlights their complexity. Biosimilars, or follow-on biologics, are not generics. Every batch of a biologic medicine, whether it is a vaccine, blood component, allergenic, somatic cell, gene therapy, or recombinant therapeutic protein, is biologically different to the one that came before. Simply recreating it, as would be seen in traditional, large molecule drug production, is not an option. In the US and European Union, manufacturers must demonstrate that there are no clinically meaningful differences in terms of quality, safety, and effectiveness between their product and the reference product.5 This involves a robust testing process. The success of biological products overall is demonstrated in the data. Since the first genetically engineered insulin was marketed in 1982, almost 300 biologic drugs have been developed, patented and approved.4 In 2018, the biopharmaceutical industry was worth $210 billion, and an estimated 60% to 70% of drugs currently in development are biological products.4,6 All this makes for a fiercely competitive marketplace, but the drugs themselves are not the sole marker of success. Far from being an afterthought, delivery systems are an integral component of the biological drug development pathway. PFS: THE DELIVERY SYSTEM OF THE FUTURE While it is fair to say that biologics have driven, and continue to drive personalized care, administering these medicines presents a challenge. They are complex products that require complex delivery systems. Tablets, capsules, and pills, the mainstay of traditional, small molecule medicine, are not suitable for biological medications due to high levels of degradation in the gut. This class of medicine must be delivered parenterally, usually intravenously, subcutaneously, or intramuscularly. When compared with needle and vial systems, PFS has emerged as the preferred delivery method for biologics for a variety of reasons. Delivery via PFS is better suited to emergency situations and remote areas and is ideal for the self-administration required for the delivery of many monoclonal antibodies used in, for example, long-term conditions. They also can reduce dosing errors by facilitating the provision of exact doses. In addition to the obvious compliance and safety benefits, this also plays into cost considerations. Multi- and single-dose vials typically have a drug overfill of between 20% and 25% to account for human error — a significant cost implication when manufacturing large quantities of expensive proteins and peptides.7 What’s more, the high viscosity of biological products, and therefore the pressure needed to inject them, makes the use of traditional vial-based syringes extremely challenging. This is particularly pertinent when the medication is being used at home by someone with a condition that can affect dexterity, such as MS. As the number and range of biological treatments have grown, so has the utilization of PFS as an effective delivery system. As of 2017, nine of the top 10 PFS-delivered drug products were biologics, a trend that is expected to increase as next-generation gene and cell therapies come online.8 CHALLENGES: PREFILLED, NOT EASILY FILLED The synergy in the rise of biological medicines and PFS is clear, but the relationship between product and delivery system isn’t without its challenges. Simply put, prefilled does not mean easily filled. Each complex protein or peptide medication is unique in its formulation, use, and safety profile, necessitating bespoke manufacturing, sterilization, filling, and compliance procedures. To build such processes, PFS manufacturers need to consider all factors, including efficacy, active pharmaceutical ingredients (APIs), the product’s characteristics and safety profile, and the preferences of the end-user. Ironically, one of the most widely discussed challenges in formulating and filling PFS with biologics centers around one of the primary reasons they are so compatible – product viscosity. The high-dose requirements of many monoclonal antibodies (MAbs), for instance, mean they must be formulated at high concentrations, increasing their viscosity. A major challenge with filling such a highly viscous product is being able to cleanly dispense the product into the syringes. The solution will often stick to the tip of the filling needle, creating a trail of product along the syringe as the needle withdraws after dispensing. A common method to overcome this problem is reducing viscosity through heat. However, this is not valid for many biologics, including MAbs of which solution stability is temperature dependent. Other approaches have looked at fill needle movement. Some use a short, quick downward motion before needle retraction to break surface tension. However, this approach is problematic when filling products over 1,000 centipoise into polymer syringes. AMRI’s own solution involves using a high-speed camera to film the needle motion, then aligning the retracting motion of the needles to the velocity of the pump motion dispensing of product. This process, which implements a short pause above the final liquid level, ensures the remaining product disconnects from the needle tip. It’s an effective method, but it must be adapted to suit each medicine we work with. Another PFS consideration is the choice between glass or plastic syringes, which are typically made from either cyclo olefin polymer (COP) and cyclo olefin copolymer (COC). Plastic has become increasingly common in recent years – not least in biologics of which viscosity means products need to be stored in packaging that allows for a consistent gliding force during administration. However, it is not always the right solution for the product. Several factors need to be considered, and drug and PFS manufacturers will often work together to holistically assess the three Ps: Product, Process, and Patient. The importance of design flexibility, tighter tolerance, and break resistance, whether the PFS will be integrated with a safety device or autoinjector, and patient comfort will all be considered. Where polymer is the preferred route, filling can be difficult. Improperly programmed machine movements or even minor equipment defects can cause scratches and increase the unit rejection rate. Much of the industry attempts to overcome this with vacuum stoppering, though it is important to note that this solution doesn’t work with all products or container closure systems. Instead, AMRI has developed expertise to assess each case across a variety of syringe sizes and implement custom solutions. AMRI has also developed custom tools that verify all critical components are mechanically aligned before each filling campaign, which minimizes scratching. Extractables and leachables (E&Ls), which can interfere with the drug molecules and compromise the product’s effectiveness, present another challenge to the pairing of biological medications and PFS. Whereas products in vials only come into contact with glass and rubber, those provided in PFS are exposed to most of the delivery system’s materials and components, multiplying the likelihood of interactions. Hence, the PFS market is heavily regulated, with the FDA and EMA, representing the world’s two biggest markets for biologics, setting strict guidelines on the filling and dispensing of PFS to enforce risk reduction. It is another example of how there is no off-the-shelf solution to PFS. The selection of materials and components involves a detailed assessment of biocompatibility, formulations and risk profiles, as well as an encyclopaedic knowledge of the relevant compliance processes. AMRI’s in-house analytical team’s expertise in extractables and leachables, container testing, and heavy metal detection significantly aids in optimizing container closure design for any given product, and is a valuable resource for our clients. THE VALUE OF PARTNERSHIP IN A PATIENT-DRIVEN WORLD Overcoming the multitude of manufacturing and process challenges associated with biologics and PFS – and fulfilling the potential of this product/delivery system coupling – requires partnership. The biological medicines marketplace is fiercely competitive, and with the average drug development pathway taking 10 years and costing $2.6 billion, there is little room for error.9 Quite simply, there is no point to developing an innovative, life-changing drug if people cannot use it. Combining pharmaceutical and drug delivery expertise as early on in the development process as possible can help speed up the pathway, while ensuring new medicines are safe, effective, easy to use, and tackle unmet patient needs. There is no one-size-fits-all solution. Every product is unique, requiring custom mechanical, technical, and compliance processes. Industry-leading CDMOs can take a more agile approach that adapts to the needs of each product and its end users. Every patient group will have differing requirements of both the product itself and the packaging it is supplied in. Therefore, the PFS design and development must evolve in parallel to product design and development. Indeed, many drug developers work with their chosen PFS supplier as early as Phase 1 to ensure the end result meets the needs of the product and patient. The formulation of some solutions, for example, requires the addition of several kilograms of excipients in a low oxygen environment. The whole process, including weighing and transfer, must be conducted within an active nitrogen overlay with low oxygen permeability. Rather than spend a huge amount on a complicated, automated system that would result in significant residual powder losses, AMRI worked with Solo Containment Ltd and Servolift LLC to engineer a custom solution for our clients. The resulting system features an isolator unit with docking station for split butterfly valves and powder containment bags. It allows for large amounts of powder to be moved from isolator to tank in a low-oxygen environment, facilitating the precise addition of the powders to the formulation vessel, and minimizing product loss. SUMMARY The rise of biologic medicines plays a major role in the growth of the PFS market. These cutting-edge treatments have necessitated a shift from oral to parenteral administration, creating a need for state-of-the-art, innovative delivery systems, and the trend is set to continue as more biosimilars, and next-generation gene and cell therapies, come online. However, dispensing highly viscous solutions, minimizing E&Ls, and ensuring biocompatibility, all while developing delivery systems that suit individual patient groups, presents unique manufacturing, compliance, filling, and dispensing challenges. CDMOs with integrated expertise streamline product development and optimization. Close working relationships, both within the organization and with partners and clients, speed up problem-solving and facilitate the creation of bespoke solutions. By partnering with PFS CDMOs, biopharmaceutical companies can benefit from specialized expertise and expect shorter, smoother development pathways. These strong partnerships, working together to develop custom solutions, are the best way to ensure that innovative biologic treatments are delivered effectively, fulfil their potential and, ultimately, save lives. REFERENCES Rise of the biologics by Derek Lowe. Published by MedChemComm, 2018. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6071940/. Drug therapy for multiple sclerosis by Eleonora Tavazzi et al. Published by CMAJ JAMC, 2014. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4119143/. Delivering cellular and gene therapies to patients: solutions for realizing the potential of the next generation of medicine by Kris Elverum and Maria Whitman. Published by Nature, 2019. https://www.nature.com/articles/s41434-019-0074-7. Current perspectives on biosimilars by Frank Agbogbo et al. Published by Fermentation, Cell Culture and Bioengineering Review, 2019. https://link.springer.com/article/10.1007/s10295-019-02216-z. Regulatory explainer: Everything you need to know about biosimilars by Zachary Brennon. Published by Regulatory Focus, 2018. Regulatory Explainer: Everything You Need to Know About Biosimilars. The new administration – prefilled syringes and auto-injectors by NS Healthcare Staff Writer. Published by NS Healthcare, 2014. https://www.nshealthcare.com/analysis/the-new-administration-prefilled-s.... Pre-filled syringes: Getting to the point by Chris Lo. Published by Pharmaceutical Technology, 2011. https://www.pharmaceutical-technology.com/features/featureprefilled-syri.... Impact of PFS and filling process selection on biologic product stability by Wendy Saffell-Clemmer. Published by BioPharm International, 2017. http://www.biopharminternational.com/impact-pfs-and-filling-process-sele.... Biopharmaceutical research and development by PhRMA. Published by PhRMA, 2015. http://phrmadocs.phrma.org/sites/default/files/pdf/rd_brochure_022307.pdf. To view this issue and all back issues online, please visit www.drug-dev.com. Anish Parikh, AMRI’s Vice President, Drug Product Sales & Marketing, has more than 25 years of R&D, sales, and marketing experience in the pharmaceutical industry. He earned his Bachelor’s degrees in Molecular Biology and Biochemistry (MBB) as well as Psychology from Rutgers College at Rutgers University in New Brunswick, NJ.

  • COVID-19: Information on the availability and protective measures at KURZ


    Production is maintained in all of our 9 factories worldwide. In the KURZ plants and in our 25 sales branches all over the world, we can react quickly to regional fluctuations. The security and flexibility of raw material supply are also guaranteed thanks to our well-organized supplier network. We therefore currently see no restriction in our customers' delivery. At all of our locations, we have strengthened existing hygiene measures and regulations and made additional protective products such as disinfectants available. Our employees are instructed to comply with international standards. Furthermore, all trips to and from high-risk areas are discontinued, and trips to other areas are severely restricted or completely canceled. Employees who are able to work mobile are instructed to take advantage of this option. Areas in which remote working is not possible have been spatially rectified as much as possible in order to maintain the prescribed minimum distance. As a company KURZ, we keep a close eye on current developments and take any further steps that may be necessary. We hope that the global situation will improve as soon as possible and keep you informed about further measures at LEONHARD KURZ. Kind regards - and stay healthy! Walter Kurz, Peter Kurz and the management

  • Latest data support continued use of ACE inhibitors and ARB medicines during COVID-19 pandemic

    Recent observational studies of angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs, also called sartans) have not shown an effect of these medicines on the risk of becoming infected with severe acute respiratory syndrome coronavirus 2 (the virus causing COVID-19) and do not indicate a negative impact on the outcome for patients with COVID-19 disease.
  • Drinks bottler turns production to hand sanitiser in glass bottles from Ardagh Group

    Ardagh Group in Dongen, Netherlands has supplied Belgium-based drinks packager, Konings, for 25 years with glass bottles for well-known beverage brands across Europe. As suppliers to the essential food and beverage industry, both companies have continued to work during Covid-19, to ensure supplies continue to reach retail shelves. In response to the shortage of supply during the Covid-19 pandemic, Konings converted one production line to filling hand sanitiser in Ardagh’s 500ml bottles, for the health sector.

  • Why You Need Sanitizer Packaging?


    Brands and business should realize as quickly as possible that the ruling authority is in the customer’s hand. You know the amount of effort, ideas, vision, hard word, creativity, innovation and thoughts that you try to put into a product as a business entity. You do all of that just to let the customers decide its fate at the end of the day. Ultimately, it’s the buyer that is going to decide if you a product that is worthy of their purchase. They will decide if they feel like investing in your business or not. The customers will never ever know about the tiring journey, the efforts, hard word, the trails that simply went into the whole designing and manufacturing of your product. On the other hand, for the customer it’s only a matter of few seconds for it to decide if your product has what it takes, if it is meeting its demands and standards. Therefore, it would be best for you to not give them any reason to reject your product. For this, you need to have the perfect packaging for your product. You need to have an ideally beautiful Sanitizer Packaging choice for your product that can hit the market by the storm.

    You Need To Work on Your Customization

    Brand manufacturers know they are up against a tight competition in the market because it’s full of variations of the same goods. These variations further make it hard for the buyers to make any decision because they are in a fix. They do not know which brand to choose. They definitely know the product they want to buy, but it all comes down to the brand they will go after. Because there are numerous number of brands that offer more or less similar goods in the market. The only thing, one product may be slightly better than the other one. This is the reason why making a sound call for the customers is not an easy thing. Manufacturers first need to try hard as possible to attract the customers to their products. Only after they have done that successfully will the customers be able to decide than the one they are about to opt for is good for them – yours in other words. Given this reason, the customized choices are simply mandate in such instances. But in saying that, ever wonder why this reason? Well, we are here to explain everything to you. Let us tell you why we consider this particular one element has the tendency to give your goods the needed nudge that can simply take your products to the next level. When you have these choices wrapped around your product, they simply add a hint of innovation, creativity, and uniqueness to the goods; products that otherwise could be simply basic things. Or in other words, these would be more or less the exact same of similar nature as the all the rest in the market that customers might come across. In order to gain the customer’s attention and simply hold it, manufacturers need to employ all these methods and techniques that are a cinch to win them the needed customer base. Manufacturers need to understand the psychology of buying. They need to know that this is perhaps a psychological game that they need to play with the buyers and master it at the same time. In the current world, most of the manufacturers are in constant search of diversified needs and preferences of the buyers. Only by knowing these needs and preferences will the manufacturers be able to cater to the varied options and choices of the customers. Considering this very factor in mind, it seems as if the customized choices are perhaps the most efficient consumption of all the available resources. The best part, there is a minimum chance of depletion in this regard.

    Customization with Its Various Benefits

    You need to realize as a manufacturer that customization of packaging choices have unique benefits of its own. You get to promote your business with the help of these choices, and that too quite efficiently and effectively. At the same time, you are giving the customers an easy reason to identity you. They will easily know yours is the product they need and will have the peace of mind that they are buying from you. However, just as the buyers need to make a selection from all the brands and/or products from all those countless simply scattered all in front of them, the brands on the other hand to go through the same dilemma when they need to select a Kraft option that is going to represent your business and manufactured goods. The brands too need to face that horrid and dreaded decision making factor. They need to ensure they are making the right selection and choice. They need to be accurate in every decision that they make from selecting the right material for packaging, the colors, shape, the packaging size, style, and design to the printing options being the best in line. These are all the selections they need to make. It can all be a little too complicated for them. However, when this decision is made accurately, you need to trust us on this one, this final word will never be regretted. A packaging company will definitely have its limits and creativity tested when it’s about designing the choices. However, they are experts in them and they know how to sort out the best Custom Packaging solutions that can be available in the market for the packaging process. These companies have the means and technology that will allow them to achieve targets quite easily and do the unthinkable. Having said that, the only thing that needs to be done accurately is selecting the best choices out of a numerous. This is for their own good at the end.

  • Temperature and tampering technology for COVID-19 drugs

    As the world’s scientists rush to find vaccines and therapeutics to treat COVID-19, there’s another group of scientists who are working just as hard to protect the drugs and safely deliver them to patients and - - in addition - - fight counterfeiters, the companies explain. “Once a COVID-19 vaccine is produced, it needs to be safely distributed throughout the world and must survive the risks of freezing, heat abuse, sun (UV) damage, tampering and counterfeiting.” said Lyle Small, CTI’s CEO. “The world is throwing money at beating the coronavirus in a compressed timeline. This just amplifies the risk but CTI has simple solutions for all of these related efficacy challenges,” he added. According to the World Health Organization, seven of the 10 top-selling drugs in the world are damaged by freezing temperatures, including vaccines for influenza and pneumonia. “ATI is already working with dozens of pharmaceutical companies and we are diligently launching this program to support all of their COVID-19 R&D and launch efforts,” said Randall Lane, CEO of ATI. CTI and ATI’s goals are to protect at least 100 million units of drugs being distributed to health care officials. The CTI donation has an equivalent value of US$5 million. Pharmaceutical companies can request samples or place orders via CTI Inks. CTI claims to be the world’s largest supplier of smart, specialty, colour-changing technology that responds to temperature, light and pressure, exporting to 55 countries. American Thermal Instruments produces custom temperature monitoring solutions for industries that require accurate and measurable systems including pharmaceutical, medical, food, beverage and industrial sectors.
  • Aptar Pharma’s PureHale™ Respiratory Device Launches with Blairex Laboratories’ Breathe Free® Essentials Brand

    This marks the first commercial launch worldwide of a brand using Aptar Pharma’s innovative PureHale™ respiratory technology. Breathe Free® Essentials is formulated with moisturizing saline and 100% natural essential oils, and is available in three blends – Soothing, Relaxing and Clarity. Each Breathe Free® Essentials kit comes with a personal face mask and adapter for effortless, on-the-go delivery for today’s in-demand lifestyle. Aptar Pharma’s PureHale™ is a portable and ready-to-use delivery solution designed for upper respiratory care. An alternative to traditional nebulizer technology, PureHale™, when used with saline and other natural ingredients, distributes a fine, gentle mist to cleanse, moisturize and soothe the upper respiratory tract, in turn helping to reduce any irritations caused by coughs, colds, allergies, respiratory problems and dry nose/throat issues. PureHale’s user-friendly system is based on Aptar Pharma’s well-established Bag-on-Valve technology which, when actuated, delivers a continuous mist with fine particles of approximately 20µm optimized for targeted deposition to the upper airways. Unlike traditional nebulizers, the PureHale™ system does not require batteries or the prefilling of a reservoir. Both quiet and lightweight, the device can be used with or without a mask, offering adaptable treatment options. Jeffrey Logston, President, Blairex Laboratories, Inc., “Blairex Laboratories has a history of offering products in innovative packaging and delivery systems. Breathe Free® Essentials continues that legacy. We designed Breathe Free® Essentials to create an on-the-go personal retreat, and hope to provide our customers with a much needed moment to breathe.” “We are pleased to partner with Blairex on this first launch of our PureHale™ device with Breathe Free® Essentials,” commented Gael Touya, President of Aptar Pharma. “PureHale’s innovative technology is meeting a new need in the marketplace for portable, on-the-go respiratory support. We look forward to this and future launches using PureHale™.”
  • EU actions to support availability of medicines during COVID-19 pandemic – update #7

    The EU Executive Steering Group on Shortages of Medicines Caused by Major Events held a virtual meeting on 3 June 2020. Regular participation in the meeting of the steering group was extended to all the heads of the national competent authorities (NCAs) of the EU Member States to discuss the measures taken by EU authorities to ensure the continued availability of medicines in Europe during the ongoing COVID-19 pandemic.
  • Abrasion-Resistant and Award-Winning: TEVA Relies on Schreiner MediPharm for Novel Adrenaline Injector Label

    Oberschleissheim, June 8, 2020 – Patients suffering from life-threatening allergies always carry a life-saving companion with them: an adrenaline autoinjector in order to immediately inject themselves in the event of an anaphylactic shock and to thus counter an allergic reaction.

  • LC Packaging COVID-19 Update


    we would like to further inform our customers about how we are securing our supplies and services and what precautions we have taken and will continue to take to ensure the health and wellbeing of you and our colleagues. LC Packaging is taking the situation very seriously and we are following all measures recommended by the authorities in the countries where we are present.

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