Category: Long-Acting Injectables

Key Takeaways

• Polymeric microspheres, injectable depots, implants, lipid systems, and nanoparticle-enabled platforms use different mechanisms to control extended drug release.
• Polymer properties, drug loading, internal microstructure, and manufacturing conditions strongly influence burst release and long-term performance.
• Successful long-acting formulations require formulation, device, process development, and analytical testing to be integrated from the start.
• Scale-up and technology transfer must reproduce the release-controlling structure, not just the formulation composition.
• Predictive development depends on better links among material attributes, dosage-form structure, in vitro release, and in vivo performance.

Extended Release Is a Systems-Engineering Problem

Long-acting drug delivery can be pursued by changing how the active ingredient behaves in the body or by placing it within a formulation that controls its release after administration. The first approach includes molecular strategies intended to alter distribution or clearance. The second relies on a dosage form that retains the drug, establishes one or more barriers to transport, and releases the payload gradually. This second category includes crystalline or suspension depots, biodegradable polymer microspheres, in situ–forming depots, preformed implants, lipid-based systems, and hybrid formulations that incorporate nanoparticles within a larger matrix.¹

These platforms differ substantially in their physical structures and release mechanisms. A microsphere formulation distributes a dose across a large population of small particles. An implant concentrates the payload within a defined matrix or reservoir. An in situ–forming formulation is injected as a liquid or flowable material and develops its final structure after contact with tissue fluids. Lipid-based systems may retain drug through partitioning, slow dissolution, matrix reorganization, or combinations of these processes. The term long-acting therefore describes the intended exposure profile rather than a single formulation technology.^1–3

Selecting among these approaches begins with the therapeutic objective. The desired onset, maintenance exposure, dosing interval, route of administration, and acceptable degree of pharmacokinetic fluctuation all influence the target product profile. Those clinical requirements must then be reconciled with the amount of drug that must be delivered, the volume or dimensions available for the dosage form, and the conditions the molecule can tolerate during processing and residence in the body. A platform that is suitable for a potent small molecule may not be suitable for a peptide or protein that requires a much larger mass, has limited stability, or is vulnerable to interfaces and solvents.^4–6

Months-long release is consequently an emergent property of the entire system. It depends on how the active ingredient, excipients, internal structure, manufacturing history, administration method, and biological environment interact over time. A formulation may contain an established biodegradable polymer and still fail to deliver the intended profile if the drug is distributed unevenly, the particle structure changes during scale-up, the depot forms inconsistently after injection, or the test method does not detect a meaningful process shift.^7–9

The Molecule and the Release Mechanism Define the Design Space

The active ingredient establishes the practical boundaries of long-acting formulation development. A months-long product must contain enough drug to maintain exposure throughout the intended interval, but the available space is limited by injection volume, suspension concentration, implant dimensions, and the amount of release-controlling material needed to construct a functional dosage form. Increasing drug loading may reduce the quantity of polymer or lipid that must be administered, but it can also change internal structure, drug distribution, and release behavior. The relationship among dose, loading, and duration must therefore be evaluated within the specific formulation rather than treated as a simple proportional calculation.^7,8

Solubility and solid-state properties influence both platform selection and release. A drug may be dissolved in a vehicle, suspended as solid particles, dispersed through a polymer matrix, or held within a reservoir. In some systems, dissolution of the drug is itself a rate-limiting step. In others, the drug dissolves readily after water enters the dosage form, and transport through the surrounding material becomes more important. Low aqueous solubility can help sustain release from certain depots, but it does not by itself ensure a predictable, months-long profile. The size, form, and distribution of the solid drug phase may still affect loading, local concentration, and the rate at which the payload becomes available for transport.^2,7

Stability requirements become more demanding as the intended release interval increases. The active ingredient must survive manufacturing and storage, remain intact within the depot, and retain its intended activity as the surrounding material hydrates, reorganizes, or degrades. Peptides and proteins can be particularly sensitive to organic solvents, shear, temperature changes, water–oil interfaces, adsorption, and the evolving microenvironment within a biodegradable polymer matrix. These stresses can affect encapsulation, conformation, aggregation, and biological activity before the drug reaches the patient or while it remains within the formulation.^4,5

Once the molecule’s constraints are defined, the formulation scientist must determine which physical processes can generate the desired release curve. Water entry is often the first step. Incoming fluid may dissolve the drug, hydrate a polymer, create aqueous channels, or initiate degradation. The dissolved payload can then diffuse through pores, a swollen matrix, or a rate-controlling membrane. In biodegradable systems, cleavage of polymer chains and progressive erosion can alter porosity and transport pathways. In swelling-controlled matrices, solvent penetration and polymer relaxation affect mobility. Osmotic implants use a different principle: water enters through a semipermeable membrane, generates pressure, and drives drug through a defined outlet.^2,7

Several of these mechanisms may operate within the same product. Early release can arise from drug located near the surface or within readily accessible pores. A slower interval may follow as diffusion occurs through a hydrated but still-intact structure. Later, polymer degradation, pore expansion, or loss of structural integrity may become more influential. The relative contribution of each process changes as the dosage form ages, which is why release cannot always be represented as a single, constant rate.^2,7,10

Polymeric Microspheres Build Release into the Particle

Biodegradable microspheres divide the dose among particles that can be suspended and injected. After administration, water penetrates the particles, the drug dissolves or redistributes, and the payload exits through pathways created by diffusion and progressive changes in the polymer matrix. Product performance depends not only on the behavior of an individual microsphere but also on the consistency of the entire particle population. Variability in size, internal structure, or drug content can broaden or distort the collective release profile.^4,8

Poly(lactic-co-glycolic acid) (PLGA) is widely used in long-acting microspheres because its properties can be varied through molecular weight, lactide:glycolide ratio, end-group chemistry, and molecular architecture. Formulations may use one polymer grade or combine grades with different characteristics. These variables influence hydration, drug–polymer interactions, degradation, and release, but their effects cannot be reduced to universal rules. The same change in polymer properties may produce different outcomes depending on the drug, loading, manufacturing process, particle structure, and release environment.^4,7,8

Drug distribution within the particle is equally important. The active ingredient may be dispersed throughout the matrix, concentrated in discrete domains, or enriched near internal and external interfaces. Drug located near the surface can contribute to early release, while material embedded more deeply may remain dependent on water penetration, diffusion, or structural changes in the polymer. Encapsulation efficiency also affects the total amount of material that must be injected. A low-loading formulation may require more polymer and a larger suspension volume to deliver the intended dose.^7,10

The microsphere manufacturing process creates the structure that governs these events. Emulsion-based processes form droplets that are subsequently hardened through solvent extraction or evaporation. Double-emulsion methods are often used for hydrophilic peptides and proteins, while single-emulsion approaches may be suitable for selected small molecules. Coacervation relies on controlled phase separation, and spray drying creates particles through atomization and rapid removal of solvent. Each method exposes the formulation to a different combination of interfaces, mixing forces, temperatures, and solidification conditions.^4,8

Process choices affect particle-size distribution, surface morphology, internal porosity, pore connectivity, drug distribution, residual solvent, moisture, and payload integrity. A change in mixing intensity may alter initial droplet size. A different solvent-removal rate may change how rapidly the polymer hardens and whether the drug migrates during solidification. Washing and drying can further modify particle structure. As a result, two formulations with similar ingredient lists can exhibit different release behavior if they were manufactured through different process histories.^8–10

Raw-material comparability presents a related challenge. PLGA materials with similar nominal descriptions or certificate values may differ in molecular characteristics that affect processing and performance. A supplier or lot change cannot be evaluated solely by confirming that the replacement material carries the same general polymer designation. Developers need to understand which material attributes are linked to particle formation, degradation, and release in the specific product.^11,12

Peptide and protein microspheres add another layer of complexity. The manufacturing process must encapsulate the molecule while preserving its structure and activity. Exposure to organic solvents, shear, temperature changes, and aqueous–organic interfaces can destabilize the payload. After administration, adsorption to the polymer and changes in the local environment can further affect recovery and activity. Successful development therefore requires simultaneous control of the polymer matrix, the process, and the molecular state of the drug.^4,5

Injectable Depots and Preformed Implants Control Release at a Larger Scale

In situ–forming depots are administered in a flowable form and develop their release-controlling structure after injection. In phase-inversion systems, a biodegradable polymer and drug are dissolved or dispersed in a suitable vehicle. Contact with tissue fluid initiates water entry and solvent exchange, causing the polymer to precipitate and form a semisolid or solid depot. The kinetics of this transition influence the structure that develops at the injection site and the amount of drug released before the depot fully consolidates.^7,13

Burst release is a central formulation concern for these systems. Drug may escape rapidly during solvent exchange, particularly if it remains mobile while channels and pores are forming. Drug located near the formulation–tissue interface may also be released before the polymer structure becomes an effective barrier. Polymer concentration, solvent selection, formulation viscosity, drug solubility, additives, and the rate of phase inversion can all influence this process, although their effects vary among formulations.¹³

The structure of an in situ depot is formed under physiological conditions rather than entirely within manufacturing equipment. This provides the practical advantage of needle-based administration but introduces sources of variability that are difficult to observe directly. Depot geometry may depend on how the formulation disperses at the injection site, how quickly solvent and water move across the interface, and how surrounding tissue constrains the material. Development must therefore connect the properties of the pre-injection formulation with the post-injection structure that controls release.^6,13

Preformed implants shift more of that structural control into the manufacturing process. In a matrix implant, the drug is distributed through the polymer body and released through diffusion, swelling, and, for biodegradable materials, changes associated with degradation and erosion. In a reservoir implant, the drug occupies a distinct compartment surrounded by a rate-controlling membrane. Osmotic implants use water entry and pressure to move drug through a defined outlet. These architectures allow the release path to be engineered through geometry, membrane properties, material selection, and drug distribution.²

Biodegradable implants are designed to lose structural integrity over time and may avoid a separate removal procedure. Non-biodegradable implants retain their material and often require removal or replacement, but an accessible device may allow delivery to be stopped by removing it. Neither approach is inherently superior. The choice depends on the treatment duration, payload, desired release mechanism, administration procedure, and need for reversibility.^2,6

Implant manufacture can involve extrusion, molding, compression, or assembly of reservoirs and membranes. Dimensions, mechanical strength, matrix uniformity, and membrane integrity must support both insertion and controlled release. The applicator and insertion procedure are also part of the product design. An implant that performs consistently in vitro but is difficult to place reproducibly would not meet the practical requirements of a long-acting therapy.^2,6

Lipid and Nanoparticle Systems Expand the Formulation Toolkit

Lipid-based depots include oil solutions and suspensions, liposomes, solid lipid systems, and formulations that reorganize or form structured phases after administration. These systems can retain drug through slow dissolution, partitioning between phases, diffusion through a lipid matrix, or gradual structural change. The relevant mechanism depends on the composition and architecture of the formulation rather than on the presence of lipid alone.³

Nanoparticles can play several roles within extended-release systems. They may carry the drug directly, protect a labile payload, alter local interactions, or function as components of a larger depot. In hybrid systems, particles may be embedded within a hydrogel, polymer matrix, or structured lipid phase. This arrangement can separate functions: the particle can protect or bind the payload, while the surrounding depot limits movement away from the administration site.^1,3

The term nanoparticle does not describe a release mechanism. Nanoscale size does not by itself produce months-long exposure. Performance also depends on composition, surface properties, particle-size distribution, encapsulation, aggregation, physical stability, and interactions with proteins, cells, and tissue. A nanoparticle formulation intended for prolonged local delivery may require a separate retention mechanism to prevent rapid dispersion or clearance from the site.¹⁴

Hybrid systems offer additional design flexibility but introduce more structural levels that must be controlled. Developers may need to characterize the drug within the particle, the particle within the surrounding matrix, and the evolution of both components during release. Manufacturing must reproduce particle properties, loading, matrix formation, and the interaction between the two. This complexity can be justified when the separate elements address different formulation problems, such as protecting a sensitive molecule while also retaining it locally.^3,14

The Entire Release Curve Must Be Designed

A long dosing interval is only one feature of a successful release profile. The timing and magnitude of exposure throughout that interval are equally important. Initial burst, lag time, maintenance release, and terminal behavior must be evaluated as connected parts of the product rather than as isolated measurements.

Initial burst commonly reflects drug that is accessible before the main release-controlling structure becomes fully effective. In microspheres, that fraction may be located near the surface or within connected pores. In an in situ–forming depot, drug may escape during solvent exchange and polymer precipitation. In an implant, early diffusion may be influenced by the initial distribution of drug and the hydration of the matrix or membrane. Some initial exposure may support rapid onset, but excessive release can create a peak that is inconsistent with the intended profile.^10,13

A lag phase may occur when water must penetrate the dosage form, the drug must dissolve, or the polymer must swell or degrade before additional transport pathways develop. Whether a lag is acceptable depends on the therapeutic context. A product intended to replace an existing therapy immediately may require sufficient early exposure, while another may be administered with an oral or injectable loading strategy. The formulation must be designed around the intended clinical sequence rather than optimized for a mathematically smooth curve in isolation.

During the maintenance phase, the dosage form is continually changing. Drug concentration falls, polymer molecular weight may decline, pores expand or connect, and diffusion distances shift. The formulation must compensate for these changes well enough to maintain the intended exposure. A structure that releases appropriately during its first weeks may behave differently as degradation becomes more extensive or the remaining payload becomes concentrated in less accessible regions.^7,10

Late-stage release also requires attention. Accelerated erosion, structural collapse, or opening of new pathways can change the release rate near the end of the dosing interval. Conversely, a residual fraction may remain trapped if the structure does not evolve as expected. Characterizing only the early and middle portions of the profile can therefore conceal problems that emerge after prolonged residence.^2,7

Loss of release control, including dose dumping, should be treated as a failure of the intended product design. Prevention depends on material consistency, structural integrity, process control, and analytical methods that can identify changes associated with altered release. Claims about the frequency or cause of dose dumping must remain product-specific, but the broader development principle is clear: duration cannot be separated from the shape and stability of the entire curve.

Formulation, Device, and Manufacturing Must Be Developed Together

A long-acting formulation must be deliverable as well as pharmacologically effective. Microsphere and particle suspensions may settle during storage or after reconstitution. They must redisperse sufficiently to provide a uniform dose and pass through the selected needle without unacceptable aggregation or blockage. The time between preparation and administration, the mixing method, and the properties of the diluent can all affect delivery performance.^4,6

Viscosity creates another trade-off. Increasing polymer concentration, particle concentration, or drug loading may reduce the required injection volume, but it can also increase injection force. An in situ–forming formulation must remain flowable before administration while still producing a stable depot afterward. Testing should use the intended syringe, needle, injection rate, and preparation procedure because a formulation’s behavior cannot be separated from the system used to deliver it.⁶

Manufacturing determines whether the release-controlling structure can be produced reproducibly. Critical material attributes may include polymer molecular-weight distribution, monomer composition, end-group chemistry, drug particle size, solid state, lipid composition, and solvent or excipient quality. Critical process parameters vary by platform but can include mixing energy, phase ratios, addition rate, temperature, solvent extraction, particle hardening, washing, drying, extrusion, molding, filling, and assembly.^4,7,8

Scale-up changes more than batch volume. Equipment geometry can alter mixing, droplet formation, heat transfer, mass transfer, solvent removal, and solidification. A larger process may reproduce the same formulation composition while producing particles or implants with different internal structures. Scale-up studies must therefore show that the commercial process recreates the material attributes and microstructure associated with the intended release profile.^8,10

Technology transfer presents the same challenge. A receiving site needs more than a formula and a sequence of operating steps. It needs an understanding of which material and process variables affect particle formation, depot behavior, implant structure, and release. That knowledge supports rational adjustment when equipment, scale, raw materials, or facility constraints differ from those used during development.

The control strategy should connect measurable product attributes with performance. Depending on the platform, relevant endpoints may include particle-size distribution, morphology, porosity, drug distribution, loading, encapsulation efficiency, residual solvent, moisture, polymer properties, membrane integrity, in vitro release, and device-delivery performance. No single measurement establishes equivalence. The objective is to build a set of controls that collectively demonstrate that the process continues to create the intended release-controlling structure.^7,9,10

This need for integration gives contract development and manufacturing organizations (CDMOs) a significant role in long-acting product development. Formulation science, process engineering, analytical development, sterile-product operations, device expertise, scale-up, and technology transfer must be coordinated early. Specialized capabilities may also be required for solvent handling, particle manufacture, implant processing, aseptic operations, and structural characterization. Bringing these disciplines together before the formulation is locked can reduce the risk that a promising laboratory concept proves difficult to manufacture or administer.

Testing a Product Designed to Release for Months

The defining performance characteristic of a long-acting formulation may unfold over weeks or months, creating an immediate analytical challenge. Real-time release tests can slow formulation screening, process optimization, stability assessment, and investigations of material or manufacturing changes. Developers need methods that are sensitive enough to distinguish meaningful differences while remaining practical for development and quality control.^9,11

Accelerated tests attempt to shorten the observation period by changing conditions, such as temperature, medium composition, pH, or agitation. Acceleration must be applied carefully. A faster test is useful only if it preserves sensitivity to the structural and formulation differences that matter under physiological conditions. Conditions that force rapid release through an artificial mechanism may conceal differences in polymer degradation, pore development, drug distribution, or membrane transport.

A discriminatory method should detect changes associated with raw materials, particle size, internal structure, loading, manufacturing process, and storage. It does not need to reproduce every aspect of the injection site to provide value, but its purpose must be defined clearly. A method that detects process differences is not automatically capable of predicting clinical performance.^9,14

Establishing an in vitro–in vivo correlation (IVIVC) is especially difficult for complex long-acting products. Multiple mechanisms may contribute to release, the dosage form evolves over time, and the local biological environment is difficult to reproduce in a laboratory vessel. Clinical pharmacokinetic studies may also extend over long intervals, limiting the speed with which formulation changes can be evaluated. An IVIVC must therefore be demonstrated with appropriate evidence rather than assumed from similarity between an in vitro curve and a plasma profile.^4,11

Bioequivalence assessment presents related problems. A comparative product may need to match an early burst, a possible lag, the maintenance phase, and the terminal portion of the profile. Similar active and inactive ingredients do not establish equivalent microstructure, and equivalent average exposure may not capture differences in the timing of release. These challenges explain why regulators continue to study material attributes, manufacturing variables, dissolution methods, modeling, and relationships between in vitro and in vivo performance for long-acting injectables and implants.^9,12,14

Choosing the Right Platform and Moving Toward Predictive Development

Platform selection should begin with the dose and exposure profile rather than with a preferred technology. Developers must determine how much drug must be delivered, how much carrier material can be administered, and whether the required loading is compatible with the intended particle, depot, or implant. They must also evaluate what the molecule can tolerate during solvent exposure, mixing, drying, sterilization, storage, and prolonged residence within the dosage form.

The desired release mechanism should then be matched to the clinical objective. A poorly soluble drug may be suitable for a suspension depot. A molecule that can be dispersed within a biodegradable matrix may support a microsphere or implant approach. A drug requiring membrane-controlled output may favor a reservoir architecture. A sensitive payload may require a hybrid system that separates protection from local retention. The preferred route and administration setting further narrow the options by imposing constraints on volume, viscosity, needle compatibility, reconstitution, insertion, and removal.

Manufacturability and testability must be considered before a platform is selected. A formulation that reaches the desired duration in a small laboratory study may still be unsuitable if its structure cannot be reproduced at scale, its raw materials cannot be controlled adequately, or its release profile requires an impractically long test for every development decision. The strongest platform is the one that combines the required exposure with a controllable process, a practical delivery system, and an analytical strategy capable of monitoring performance.

Future progress will depend on improved understanding of the connections among materials, structure, and release. Average particle size and total loading provide useful information, but they may not reveal differences in internal porosity, pore connectivity, drug distribution, or polymer evolution. More detailed structural characterization can help identify which attributes govern burst, maintenance, and terminal release.

Mechanistic and computational models may further support development by integrating transport, degradation, and material properties. Their immediate value lies in testing hypotheses, organizing experimental data, and guiding formulation studies rather than replacing in vivo evidence. Quality-by-design approaches can provide a framework for defining the target release profile, identifying the variables likely to affect it, and establishing links among process inputs, dosage-form structure, and performance.

Hybrid delivery systems and closer formulation–device integration will continue to broaden the design space. Combining particles, hydrogels, lipids, and polymers may allow different components to address payload protection, local retention, and release control. At the same time, every additional structural level creates new requirements for manufacturing and characterization. Formulations, containers, needles, applicators, and insertion systems must therefore be developed as connected parts of the same product.

Months-long delivery is achieved by engineering a dosage form that changes in a controlled manner. Polymers, lipids, microspheres, implants, and nanoparticles provide distinct tools, but the intended interval emerges only when the molecule, material, structure, process, device, and test strategy function together. The objective is not simply to slow the movement of drug. It is to create a reproducible exposure profile that remains controlled from manufacture and storage through administration and residence in the body.

References

1. Shi, Yujie, et al. “A Review of Existing Strategies for Designing Long-Acting Parenteral Formulations: Focus on Underlying Mechanisms, and Future Perspectives.” Acta Pharmaceutica Sinica B. 11: 2396–2415 (2021).

2. Stewart, Sarah A, et al. “Implantable Polymeric Drug Delivery Devices: Classification, Manufacture, Materials, and Clinical Applications.” Polymers. 10: 1379 (2018).

3. Rahnfeld, Lisa, and Paola Luciani. “Injectable Lipid-Based Depot Formulations: Where Do We Stand?” Pharmaceutics. 12: 567 (2020).

4. Butreddy, Arun, et al. “PLGA/PLA-Based Long-Acting Injectable Depot Microspheres in Clinical Use: Production and Characterization Overview for Protein/Peptide Delivery.” International Journal of Molecular Sciences. 22: 8884 (2021).

5. Schwendeman, Steven P, et al. “Injectable Controlled Release Depots for Large Molecules.” Journal of Controlled Release. 190: 240–253 (2014).

6. Alidori, Simone, Raju Subramanian, and René Holm. “Patient-Centric Long-Acting Injectable and Implantable Platforms—An Industrial Perspective.” Molecular Pharmaceutics. 21: 4238–4258 (2024).

7. Lim, Yi Wen, et al. “Challenges and Complications of Poly(lactic-co-glycolic acid)-Based Long-Acting Drug Product Development.” Pharmaceutics. 14: 614 (2022).

8. Park, Kinam, et al. “Formulation Composition, Manufacturing Process, and Characterization of Poly(lactide-co-glycolide) Microparticles.” Journal of Controlled Release. 329: 1150–1161 (2021).

9. FY2015 Regulatory Science Research Report: Long-Acting Injectable Formulations. U.S. Food and Drug Administration. 9 May 2017.

10. Wang, Mengdi, et al. “Microstructure Formation and Characterization of Long-Acting Injectable Microspheres: The Gateway to Fully Controlled Drug Release Pattern.” International Journal of Nanomedicine. 19: 1571–1595 (2024).

11. FY2016 Regulatory Science Report: Long-Acting Injectable Formulations. U.S. Food and Drug Administration. 28 Mar. 2017.

12. FY2018 Regulatory Science Report: Long Acting Injectables and Implants. U.S. Food and Drug Administration. 2018.

13. Bakhrushina, Elena O, et al. “Burst Release from In Situ Forming PLGA-Based Implants: 12 Effectors and Ways of Correction.” Pharmaceutics. 16: 115 (2024).

14. “FY 2025 Generic Drug Science and Research Initiatives Public Workshop: Session 2 Transcript.” U.S. Food and Drug Administration. 6 Aug. 2025.

Originally published on PharmasAlmanac.com on July 9, 2026.

A truly integrated CDMO with the right structural foundation and top-down commitment can provide tremendous benefits to biopharmaceutical customers.

Rising Demand for Contract Services

The value of the global pharmaceutical contract manufacturing market is expected to reach $95.9 billion by 2025, with the API segment accounting for the largest share but the final drug formulation segment growing at the fastest rate.¹ Growth overall is being driven by rising demand for medications around the world, due to the aging population, increases in chronic diseases and growing wealth in emerging economies. Pharmaceutical companies are increasing their dependence on outsourcing partners to achieve increased efficiencies and gain access to advanced technologies.

Renewed Interest in the One-Stop Shop

Over the past decade, innovation in the pharmaceutical industry has shifted to emerging pharma and biotech companies that lack the infrastructure, capabilities and resources necessary to support the entire drug development and commercialization cycle. For these smaller companies that must rely heavily on outsourcing partners, it is much more efficient to develop strategic relationships with integrated CDMOs.

Larger pharmaceutical companies are also realizing that, by working with a company like Piramal Pharma Solutions, it is possible to take a candidate from post-discovery to commercialization with one point of contact and without the need to manage multiple suppliers or the cost and time delays associated with tech transfer between different service providers. Product knowledge and expertise are retained throughout the project lifetime, facilitating collaboration and process scale-up.

Time is of the Essence

There has never been more pressure for pharmaceutical companies to develop new drugs more quickly and at lower cost. Integrated CDMOs that operate as true one-stop shops help sponsors reduce time to the clinic and the market while also controlling costs and often providing access to unique, advanced capabilities. With one contract, one global master service agreement and one quality agreement, integrated providers help simplify the drug development process.

Integration is Essential

Integrated offerings are only effective, however, if all of the services are harmonized and presented to the customer as a single system. An integrated offering must not simply be different businesses linked together, but a single business at the operational level. Commitment must come from the top down, with establishment of a company philosophy and systems that create a single customer-facing solution that facilitates easy customer interaction.

Piramal does not consider integrated projects as projects, but as programs. We have installed software to manage our integrated programs and hired experts to serve as program managers. All interactions with clients from verbal to written communications follow the same protocols. The technology transfer process is headed by the program manager, who ensures that all necessary documents are exchanged, goals and timelines are agreed upon and met and routine communications, both internal and external, are managed effectively.

Understand Your Value Proposition

Choosing a service provider ultimately comes down to risk tolerance, which is different for every pharma company. It is therefore essential for integrated CDMOs to have a clear understanding of their value propositions and clearly communicate those benefits to potential clients. Commitment to the company’s mission must also be embedded in the hearts and minds of all employees.

Piramal has grown through acquisition, building capabilities in drug substance and drug product development and manufacturing. Our leaders have experience in integrated offerings and leverage our global network to provide maximum efficiency and productivity. We have facilities for the production of drug substances in lower-cost countries and sites in the West with specialized capabilities for drug product manufacturing, including solutions for highly potent products and antibody–drug conjugates. We are one of the few CDMOs able to offer integrated services for oncology candidates, as well as for candidates targeting other indications.

At present, Piramal is evaluating how to further expand upon our existing capabilities, including the addition of oral solid dose development and manufacturing services. We have the necessary organizational structure in place and are excited to build on our early success as a truly integrated CDMO.

References

1. $95.94 Bn Pharmaceutical Contract Manufacturing Market, 2025. Research and Markets. 21 2019. Web.

Originally published on PharmasAlmanac.com on October 28, 2019.

The pandemic has significantly affected the pharmaceutical industry, including the contract manufacturing segment. CMOs with flexibility, agility, and speed combined with the ability to form strategic partnerships have been best positioned to support customers going forward. Avara’s Liscate sterile injectables facility has these attributes and continues to pursue investments in equipment and technology — including digitalization solutions for documentation, remote auditing, training, and more — and is exploring the introduction of development capabilities to enhance its ability to support customers from late-stage clinical trials through commercialization.

Pandemic Impacts

As with most sectors within the pharmaceutical industry, contract manufacturing has been strongly impacted by the COVID-19 pandemic. These impacts have been significant, even unprecedented, and many of the changes that have evolved will remain even after we move on from the pandemic.

One of the biggest changes to this segment of the industry was the transition from steadier market demand to a situation characterized by spikes and troughs as the world responded to waves of infections caused by new variants of the SARS-CoV-2 virus. This dynamic and unpredictable situation was challenging for everyone, including contract manufacturers, to manage. Procurement difficulties and significantly extended lead times heightened these challenges.

Customers have responded by seeking to reduce the number of contract manufacturing partners with whom they work, as well as to form deeper and more strategic relationships that are better positioned to respond to such challenges. Meanwhile, lockdowns and limited travel within and across borders created the need for digital solutions to facilitate internal and external communications — from personnel training and remote work to sales and marketing efforts to auditing and inspections. The advent of mRNA vaccines, meanwhile, reflects a general trend in sterile injectables toward more personalized products.

Those companies that were sufficiently flexible and agile to survive the COVID-19 pandemic did so in part because they rapidly adopted new ways of communicating with their stakeholders — employees, suppliers, customers, and regulators.

Importance of Speed, Flexibility, and Agility

The sudden changes in demand that occurred during the COVID-19 pandemic required contract manufacturers to offer a higher level of flexibility and speed, and this has now become a customer expectation. In the sterile injectable sector, flexibility and the ability to respond quickly to the unexpected have become even more important. The supply of critical drugs to patients on time and without interruption is of the highest priority. CMOs with these attributes built in are most able to rise to this challenge, even during crises, as Avara Liscate continues to do.

Strategic Partnerships Increasingly Important

The supply chain issues highlighted by the pandemic have led many branded biopharmaceutical manufacturers to seek ways to reduce the complexity of their supply chains. They are doing so by reducing the number of suppliers they use and concentrating their attention on building solid, stronger relationships with a limited number of strategic partners.

The sterile injectable CMOs with which Big Pharma companies are forming those strategic partnerships are top-performing, customer-oriented organizations that are focused on manufacturing and share three important attributes: they make the right investments, have the right organizational structure (e.g., flexibility, agility, and personalized customer service), and possess the specialized skills and equipment needed to reliably supply high-quality products with assured sterility.

In addition to branded biopharma companies, many small startups — often spinoffs from universities — are seeking partners that can help them advance their candidates from preclinical development to market. These emerging biotechs are a main driver of growth in the sterile injectables market, so successful CMOs must have the capability to form long-term partnerships with these firms.

Trend Toward More Dedicated Sterile Products

An overarching trend in the pharmaceutical industry today is the shift away from blockbusters and toward more niche, targeted, and personalized or precision medicines. That is certainly true in the sterile injectables sector. Autologous cell therapies, gene therapies, and immuno-oncology treatments are all prime examples of patient-specific medicines. The successful development of mRNA vaccines against COVID-19 has also opened the door for future development of novel therapeutics in this space. Most pharmaceutical companies have programs exploring new mRNA treatments against other infectious diseases, as well as many types of cancer and numerous other disorders. CMOs must develop the capabilities — facilities, equipment, processes, and expertise — to support the manufacture and packaging of small-volume precision medicines, as well as new therapies that require specialized production and fill/finish technologies, such as viral vectors for gene therapies and mRNA treatments prepared using lipid nanoparticles or other novel delivery vehicles.

Making the Right Investments is Essential

That ties into the next important trend, which is a growing emphasis on making the right investments in equipment, infrastructure, and personnel. Sterile injectable manufacturing is complex and challenging because the products are injected or infused into the blood of patients. It therefore requires not only the right type of equipment but also the right-sized equipment to ensure the production of sterile drug products of the highest quality. It is absolutely imperative that capital investments be made appropriately and directed toward the right product areas and the appropriate, state-of-the-art equipment that will ensure sterile injectable manufacturing.

Acceleration of Digitalization

Those companies that were sufficiently flexible and agile to survive the COVID-19 pandemic did so in part because they rapidly adopted new ways of communicating with their stakeholders — employees, suppliers, customers, and regulators, among others. Digital technologies made that possible. While digitalization of the pharmaceutical industry did not start during the pandemic, that unexpected and complicated period certainly accelerated the rate at which digital transformation is occurring — a rate that has not and likely will not decline going forward.

Given that speed is of the essence in drug development, efficiency and productivity are two crucial objectives for pharmaceutical manufacturers. Digitalization is an enabler of both. It facilitates the management and analysis of large quantities of data, contributes to increased quality, and helps to reduce the risk of error.

Digital tools leveraged during the pandemic included software for data sharing to enable remote working, video conferencing, and online meeting software; solutions for the remote monitoring of production operations with real-time data access from mobile phones, laptops, and other devices; and video streaming for remote audits, to name just a few.

Going forward, these technologies, and many more — such as artificial intelligence, robotics and other automation solutions, cloud computing, and so on — will be used to further boost efficiency and productivity and allow for a good balance of on-site and remote work to support the needs of manufacturers and their employees.

De­spite the extraordinary situation that the COVID-19 pandemic present­ed, Avara was able to build on our strong rela­tionships with customers and stay on track with the delivery of needed medicines.

Rapid Pandemic Response at Avara

The COVID-19 pandemic placed everyone in the pharmaceutical industry in a dramatically unfamiliar environment unlike anything previously experienced. Everything was new and in flux, with sudden changes that had to be managed. Contract manufacturers that could adapt to those sudden changes and then continue to meet customer needs not only kept those customers happy but often built stronger relationships with them.

Avara took many measures to ensure the ongoing supply of sterile injectable products for our customers. These products included several drugs used to treat intensive-care patients, such as anesthesia medications. We focused resources on increasing the manufacturing of existing products while also accelerating the transfer of critical new products for the treatment of patients with COVID-19 and other diseases.

New product transfer activities were made possible by implementing the latest communication technologies that enabled close interaction with our customers despite lockdowns and travel bans. For instance, real-time video streaming during audits and during pilot and engineering batch runs ensured business continuity and adherence to very tight timelines.

To overcome equipment shortages, Avara identified opportunities to use — after requalification — existing equipment and components to support product transfers. We were also very open and transparent with our customers about other supply chain issues. In particular, there have been shortages of vials and stoppers, with lead times of 9–12 months. For these materials, we worked closely with our customers to develop specific assessments in support of the use of equivalent commodities.

The preparation of GMP documentation was accelerated by creating parallel work streams and simplifying document storage and access, all while maintaining full compliance with quality and other regulatory requirements. Our project management system was also modified, with the key change being a move to quick, daily meetings with customers to address the various constraints and problems that continually arose and had the potential to impact timelines.

At Avara, we always keep in mind that the final customer is the patient and that our products help alleviate suffering. That was true during the pandemic as well, and, despite the extraordinary situation it presented, we were able to build on our strong relationships with customers and stay on track with the delivery of needed medicines.

A good example of a collaborative effort with a Big Pharma customer involved an Italian hospital. The hospital identified Avara as the manufacturer of an important product used for intensive-care patients for which they were out of stock and needed to receive more immediately. We dedicated a team to this issue, who worked closely with the pharmaceutical company for which the product is made. It was very gratifying to see the aircraft leave our site and head to the hospital with that much-needed medicine. Ultimately, our customer and Avara elected to donate a portion of the volume of this product that we had in stock to the pandemic effort. This was an experience that not only underscored the types of partnerships Avara has with its customers but touched all of us working at the Liscate facility.

As a medium-sized CMO, Avara is appreciated for the focus and dedication that we offer our partners. We are a very customer-centric CMO, with each customer valued highly and appreciated individually. At Avara Liscate, operating in this mode gives confidence to customers with respect to the customer service they receive and the quality of the sterile injectable products we manufacture.

Investing in Stronger Relationships

To meet the increasing needs of customers who require support earlier in their projects — at clinical rather than commercial phase — is a key strategic objective for Avara Liscate. Supporting customers with their clinical trial, product and process development, and dossier creation efforts will allow for the establishment of stronger customer relationships and the building of trust, both of which are crucial as a project advances to the commercial phase. The goal is to help develop the right processes and the right products that will find success in the pharmaceutical market.

To that end, Avara Liscate is investing in the construction of a new department within the facility that will be fully dedicated to product process and development, as well as clinical trial material production.

A Customer-Oriented CMO Partner

As a medium-sized CMO, Avara is appreciated for the focus and dedication that we offer our partners. We are a very customer-centric CMO, with each customer valued highly and appreciated individually. At Avara Liscate, operating in this mode gives confidence to customers with respect to the customer service they receive and the quality of the sterile injectable products we manufacture.

By taking this approach, we continually work to make our company stronger within the CMO world and to ensure the growth of the company. With the right investments, organization, and quality, we can ensure ongoing regulatory compliance, on-time delivery, and excellent customer service.

Creating partnerships with customers involves much more than establishing basic relationships with them. Partners work closely together to resolve any issues that arise and leverage innovative technologies to improve all aspects of performance — flexibility, efficiency, productivity, quality, and pricing.

Ultimately, the most important element that emerges from successful strategic partnerships is trust. Trust is fundamental to the deeper relationships needed for both suppliers and customers today. By engendering trust with our customer partners, Avara Liscate helps them accelerate the commercialization of their sterile injectable products, which translates to greater access to medicines for patients. At the same time, it supports Avara’s goal of becoming a CMO recognized for meeting the current and future expectations of all of our stakeholders.

Originally published on PharmasAlmanac.com on June 16, 2022.

With mutual respect and a shared commitment to high quality standards and sustainable value creation, Vetter and Rentschler Biopharma began exploring ways to build upon our respective service portfolios and draw from synergies between our companies to provide valuable market foresight. In mid-2020, Vetter and Rentschler Biopharma announced a strategic collaboration aimed at achieving long-term value for clients through the alignment of manufacturing approaches, combining Vetter’s drug product manufacturing expertise with Rentschler Biopharma’s drug substance manufacturing expertise, to optimize time-to-market and simplify processes. The relationship allows Vetter and Rentschler Biopharma to leverage complementary skills and experience along the biopharmaceutical value chain, with the aim to better serve our clients and, by extension, their patients, more efficiently.

A Dynamic Global Market

The global pharmaceutical market and larger global healthcare ecosystem continue to experience rapid and expansive growth, albeit with increasing costs and complexities. Contract development and manufacturing organizations (CDMOs) must continually find new ways to better support their clients as they work to develop new therapies to treat patients with serious and rare diseases. In order to maintain safety and efficacy standards while simultaneously reducing costs and time to market, CDMOs must innovate while demonstrating flexibility and adaptability to maintain competitive advantages and provide first-class client service. Biopharmaceutical companies must streamline their products’ path to market and optimize efficiency and simplicity. To do so, CDMOs must think outside the box to set new standards and benchmarks as they continue to refine best practices. The collaborative alliance between Vetter and Rentschler Biopharma aims to mutually enhance our respective services to provide our clients and their patients with the best possible outcomes.

Defining and Refining — Progress in the Framework

Vetter and Rentschler Biopharma have marked an important milestone since the initial collaboration announcement, taking key steps forward to further strengthen and define our collaboration through validation of previously identified opportunities to simplify structures and processes, as well as sharing visibility into manufacturing requirements early on. This has led to an active exchange of best practices that may benefit both companies and our respective clients.

The alliance has progressed with the establishment of a governance structure in addition to the implementation of guidelines for a joint approach across functions. The framework for contributions from both organizations was established in a collaboration agreement, including operational agreements and guidelines between various departments spanning quality, development services, and logistics. These guidelines delineate key standards for joint approaches and core inputs, aligning interfaces and optimizing services for client convenience and long-term planning.

The formation of the mutual agreements and alignment on a client approach were foundational steps that both Vetter and Rentschler Biopharma identified early in our exploration of this strategic alliance. We look forward to the new progress that this step will facilitate.

Having more narrowly defined some of the finer details of the alliance, Vetter and Rentschler Biopharma anticipate the possibility of reduced project timelines, adding value to our respective clients and their patients around the world. Some of the joint measures include the orchestration of logistics processes to minimize efforts for active pharmaceutical ingredient (API) shipments, thereby reducing transportation risks. Additionally, joint organization and client-audit management should help coordinate a seamless exchange of information and client requests and the creation of an aligned client questionnaire for early information sharing. The collaboration is further enhanced through the coordination of processes and materials from Rentschler Biopharma on the drug substance side and Vetter on the drug product side. We have also been working to fast-track various options and boost technology concepts. 

Our efforts include collaboration across our business development teams, where we have clearly defined target markets with a focus on Europe, the United States, Asia-Pacific, and emerging markets. The teams are working closely to identify clients who would likely benefit from our collaboration, with each organization introducing the other to our respective clients to demonstrate the collaborative benefits. We have successfully initiated our first joint-client projects, with additional projects in various phases of discussion; however, each company will remain fully independent without an obligation for clients to work with both organizations.

“We are very interested to see how the experience gained in these initial projects will further enhance our strategic alliance,” commented Dr. Frank Mathias, CEO of Rentschler Biopharma. “These client engagements will provide valuable insights for our teams to leverage in refining the alignment of our processes and approaches.”

Both organizations remain steadfast in their commitment to simplify and accelerate product path-to-market for propitious new therapies for patients, and we will continue to pursue strategies and initiatives aimed at supporting the continued refinement of this collaboration.

About Vetter

Headquartered in Ravensburg, Germany, Vetter is a global leading CDMO with production facilities in Germany and the United States. Currently employing 5,500 individuals worldwide, the company has long-term experience in supporting biotechnology and pharmaceutical customers both large and small. Vetter services range from early-stage development support, including clinical manufacturing, to commercial supply and numerous packaging solutions for vials, syringes, and cartridges. As a leading solution provider, Vetter appreciates its responsibility to support the needs of its customers by developing devices that contribute to increased patient safety, convenience, and enhanced compliance. Great importance is also given to social responsibility, including environmental protection and sustainability.

About Rentschler Biopharma SE

Rentschler Biopharma is a leading CDMO focused exclusively on client projects. The company offers process development and manufacturing of biopharmaceuticals as well as related consulting activities, including project management and regulatory support. Rentschler Biopharma’s high quality is proven by its long-standing experience and excellence as a solution partner for its clients. A high-level quality management system, a well-established operational excellence philosophy, and advanced technologies ensure product quality and productivity at each development and manufacturing step. In order to offer best-in-class formulation development along the biopharmaceutical value chain, the company has entered into a strategic alliance with Leukocare AG. Rentschler Biopharma is a family-owned company with about 1,000 employees headquartered in Laupheim, Germany, with a second site in Milford, MA. In Stevenage, UK, Rentschler Biopharma has launched a company dedicated to cell and gene therapies, Rentschler ATMP Ltd.

Originally published on PharmasAlmanac.com on June 9, 2021.

Complex injectable products, including those based on liposomes, microspheres, micelles, and submicron crystals, are attractive formulation solutions for many challenging new active pharmaceutical ingredients (APIs) and for unique life cycle management strategies. Few CDMOs have the knowledge, expertise, and appropriately designed manufacturing facilities to support these highly advantageous drug delivery technologies. New Jersey–based ForDoz Pharma is changing that.

Growing Interest in Complex Products

Complex products under the Generic Drug User Fee Amendments (GDUFA II) are defined as products with complex active ingredients; complex mixtures of APIs; complex formulations, including liposomes, suspensions, emulsions and gels; complex routes of delivery, such as locally acting dermatological and inhalation drugs; complex dosage forms including long-acting injectables and implantables; and complex drug–device combinations.

Water-insoluble APIs, which make up a growing percentage of drugs in development, may be highly potent or cytotoxic, and many have solubility issues. Particle-based drug delivery systems, such as liposomes, microspheres, and micelles and submicron crystals in suspensions or emulsions, can address these issues and facilitate delivery to target sites.

The emerging technologies for complex and innovative drug delivery have wide applications in the design of sustained-release dosage forms, such as long-acting injectables, improving therapeutic index by reducing toxicity and enhancing efficacy of APIs and facilitating reformulation of existing pharmaceutical products with limited clinical utility. As a result, the demand for complex products is particularly high in drug delivery technologies for complex injectable products, due to the rapidly expanding market for biologic drugs, which are often unstable and are prone to degradation in vivo and thus require stabilization and delivery to specific target organs.

Many Types of Complex Injectable Products

Complex injectable products include liposomes, microspheres, micelles and submicron crystals in suspensions, and emulsions.

Liposomes are microscopic vesicles comprising an aqueous solution core surrounded by a hydrophobic membrane of carefully selected phospholipids. Both hydrophobic and hydrophilic small molecule and biologic (e.g., proteins, plasmids, nucleic acids) drug substances can be carried in liposomes and delivered to targeted sites of action by modifying the surfaces of the vesicles. They are also useful for sustained-release drug delivery, reducing toxicity, improving efficacy, enhancing drug solubility, and improving the activity of vaccine adjuvants.^1–6

Microspheres range in size from approximately one to several hundred micrometers and consist of the active drug substance dispersed in a matrix comprising biodegradable synthetic polymers, most commonly PGLA or PLA. They can be delivered via several routes of administration, including parenterally. Microspheres are ideal for delivering drugs at a sustained and controlled rate, which can significantly improve patient compliance.^7–10

A polymeric micelle, which typically exists on the nanoscale, is a supramolecular assembly of surfactant molecules dispersed in a liquid with the hydrophilic “head” regions in contact with surrounding solvent, sequestering the hydrophobic single-tail regions inside the micelle center. Unlike microspheres, they can adopt a number of different shapes, including rods, tubules and filaments, as well as vesicles and spheres. Various polyamides, polyesters, and lipids are employed for micelle generation. Micelles are typically attractive for the delivery of poorly soluble drug substances. Many water-insoluble drugs, including proteins and gene therapy drugs, can be encapsulated in the hydrophobic core during the formation of the micelle core. Many micelle pharmaceuticals demonstrate favorable stability and pharmacokinetics properties.^11–14

Emulsions are thermodynamically stable isotropic systems in which two immiscible liquids are mixed to form a single phase by means of an emulsifying agent, and are suitable for the delivery of both hydrophilic and hydrophobic drugs. The droplets in the emulsion have a large degree of dispersion and a large total surface area, which can promote the absorption of drugs and improve the bioavailability.^15,16

A suspension is a coarse dispersion of insoluble solid particles in a liquid medium with a particle size in the low micron range. Suspension dosage forms can incorporate significantly higher concentration of poorly water-soluble and lipid-soluble drugs.^17–19 Submicron crystals in suspension also provide a method for enhancing the bioavailability of poorly soluble drugs, but do so in a carrier-free manner. The drug substance is formulated in a colloidal delivery system with a particle size ranging from 100 to 1000 nm. Compared with traditional formulations, submicron crystals in suspension can significantly improve drug solubility and prolong adhesion and the retention time of the drug in biological tissues. When injected into the muscle, submicron crystals can be slowly released over a prolonged period, reducing dosing frequency.^20,21

ForDoz Pharma is a technology-based company focusing on the development and commercialization of complex injectable products.

Benefits of Complex Injectable Products

Encapsulation provides greater control over the pharmacokinetic and pharmacodynamic properties of the API, leading to one or a combination of positive improvements, including reduced toxicity, increased solubility, enhanced bioavailability, and improved activity against intra- and extracellular pathogens. Additional benefits include targeted delivery, which is achieved through careful design of the liposome, microsphere,  micelle, or other system. Controlled release over extended periods of time, which allows for reducing dosing frequency, is also possible with these systems.

Specialized Expertise Required for Drug Development and Manufacturing

The therapeutic efficacy of complex injectable products is directly correlated with their stability during manufacturing, storage, and delivery, as well as their ability to deliver the active drug substance to the right target. If these special particles are not produced properly, they will disassociate and not function as intended, and the drug substance may leach out into the bloodstream, potentially causing toxic side effects.

It is therefore necessary to understand the chemistry and physics of the formation processes involved for each specific type of complex injectable form and the biochemical processes contributing to their biodistribution and to be able to translate that knowledge into formulations that are manufacturable and scalable.

Specialized equipment and manufacturing systems are required to ensure that complex injectable products are produced with the desired properties. Careful selection and pre-processing of raw materials can reduce the likelihood of physical and chemical degradation. For particulate forms that are difficult to maintain in suspension, lyophilization (freeze-drying) is often used to extend shelf stability.

Sterilization for some complex injectables, notably liposomes, can also be challenging, due to the sensitive nature of the components with respect to exposure to high temperatures and radiation. Typical sterile filtration methods may also not be applicable for complex injectables based on larger particles. For some products, the entire production process must be performed under aseptic conditions.

It is also essential to develop production processes that provide high encapsulation efficiencies for liposomes and micelles, uniform distribution of APIs for microspheres, and the appropriate crystalline form for submicron crystals.

Production of liposomes, microspheres, and submicron crystals involves very high-energy processes to ensure that the right particle sizes are obtained. High entrapment efficiency must also be achieved. Off-the-shelf equipment is generally not suitable; specially designed, purpose-built systems combined with deep knowledge of processing parameters are needed to ensure that processes are established that consistently and reproducibly generate particles of the correct size. For microspheres, it is also important to remove the organic solvent used to solubilize the starting polymers without impacting the particle integrity.

Characterization of these different particle types is also challenging and requires specialized analytical technologies. It is also necessary to conduct in vivo studies to understand how these particles behave in the body.

Specialized Particle Technology Platform at ForDoz Pharma

ForDoz Pharma is a technology-based company focusing on the development and commercialization of complex injectable products. Our proprietary particle-based drug delivery technology platforms enable us to develop and manufacture innovative and superior complex products with particle sizes ranging from 10 nm to several hundred µm that improve patient care. These technologies include, micelles (~10–30 nm), liposomes (~100 nm), nanoemulsions (~200 nm), submicron crystals in suspension (~100–1000 nm), micron suspensions (~1000–3000 nm) and microspheres (~100 µm).

New State-of-the-Art Facility

In 2016, ForDoz Pharma acquired LaviPharm’s campus in East Windsor, New Jersey. At this 27-acre property, we established our own R&D labs and cGMP analytical labs. From 2017 to 2019, we successfully constructed, validated and qualified a complex product manufacturing facility that complies with U.S. cGMP standards. Overall, we have invested significant funds in this new, state-of-the-art, purpose-built facility.

The plant includes two unique, specially designed suites dedicated to liposome processing, one of which can handle cytotoxic APIs. The third process suite is reserved for microspheres, designed to operate at up to the 1000-L scale (1000 kg output).

Our filling line for liquids can process up to 100 vials per minute for vial sizes ranging from 2 to 100 mL. The completely automated line is installed within an isolator to minimize the risk of contamination. No direct human contact occurs from vial loading, vial washing and depyrogenation, filling, stoppering, and crimping; any manual interventions take place using a glove box. In the future, we will be adding a second filling line for powders and pre-filled syringes.

At ForDoz Pharma, we also have the capability for lyophilization, with two large-scale (10 m²) lyophilizers. Vial loading, washing and depyrogenation, filling, loading, and unloading of the two units is fully automated and is performed inside the isolator.

Extensive Generics Pipeline of Complex Injectables

ForDoz Pharma has established a diversified product pipeline of investigational drug products to benefit patients and ensure continuous growth of our company. We are actively pursuing additional growth opportunities for our pipeline through a combination of internal development and external licensing.

Our proprietary technologies include NanolipoDoz™ Technology, a phospholipid-based nanotechnology designed to improve therapeutic index and enhance solubility, and NanopolyDoz Technology™, a polymer-based nanotechnology in which APIs are encapsulated in polymeric matrices to control drug delivery rates and enhance drug stability.

These technologies are being used to develop generic versions of the complex existing injectable drug products. In all but one case, the drug is produced only by the innovator. By offering a generic alternative in the future, we are reducing supply chain risk and providing a more cost-effective option for important medicines. Currently, we have four products in our pipeline for which we are ready to produce FDA submission batches for the clinical trial bioequivalence stage, including anticancer and antifungal agents and a treatment for schizophrenia and emesis. The first two approvals are expected in 2022–2023, with additional approvals expected in 2024–2025.

We also have seven additional products in different stages of development in our pipeline: three are microsphere injectable products, which are used for treatment of pain, Alzheimer’s disease, and infertility; one micellar anticoagulant product; and one submicron suspension anti-inflammatory product. Patents for the five products have been filed, and regulatory submission will be filed via the 505(b)(2) route. Further, we are currently developing processes for two ANDA products based on submicron crystal technology.

Now Offering CDMO Services

We have always provided contract services for partners with whom we have had long-standing relationships. With our facility in place and our pipeline of late- and early-stage candidates well established, we are in a position to begin offering CDMO services to the pharma community at large.

ForDoz Pharma is looking to evolve by offering our platform liposome, microsphere, micelle, and submicron suspension technologies to customers seeking differentiating drug delivery technologies for their NCEs. We hope to work with customers that have candidates at the IND phase or that are in early-phase clinical development and can benefit from improved drug delivery solutions.

As projects scale, we have room to expand our production capacity and are willing to invest to meet growing demand. We are also happy to sign a no-compete agreement for all our CDMO clients; ForDoz has no interest in developing similar products that would be direct competitors of our customers’ products. We are, however, committed to partnering with pharmaceutical companies in the fight against serious illness with improved formulations.

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Originally published on PharmasAlmanac.com on March 19, 2020