We work with your

future in mind

Your leading excipient partner for continuous manufacturing

Continuous manufacturing (CM) is the future of pharmaceutical manufacturing. As well as having FDA backing, CM offers numerous advantages over batch production – not least higher product quality at lower manufacturing costs. At DFE Pharma, we have been at the forefront of driving this change for more than a decade. We have carried out detailed research on how the specific properties of excipients affect CM processes and we have partnered with leading pharmaceutical companies as they took their first steps into this new field.

Our expertise has informed the development of several CM-enabled excipients, all of which are now available as part of our portfolio. With our deep insights and ever-growing evidence base, DFE Pharma is more than an excipient supplier.

We are a CM formulation partner who can help secure the success of CM projects that deliver the benefits of this new, dynamic production paradigm. For more information on working with our dedicated CM team get in touch, or request a sample.

 

The future of pharma manufacturing

Continuous manufacturing (CM) is the future of pharmaceutical manufacturing, and the regulators, including the FDA and the EMA, agree. Continuous manufacturing is encouraged by the regulatory bodies since it is in line with the quality-by-design (QbD) paradigm for pharmaceutical development. To shift from batch to continuous production, the pharma industry has to invest in facilities and adapt the way it researches and develops formulations. It won’t happen overnight. DFE Pharma and our range of CM-enabled excipients stand ready to support our industry partners through this essential transformation.

A schematic illustration of continuous tablet manufacturing using direct compression, wet granulation, and roller compaction.

Source: Sebastian Escotet, Fernando Muzzio

Advantages of CM

Batch production has dominated the oral solid dose manufacturing landscape for decades. Now, both the FDA and the EMA have recognized the advantages of CM, and the regulatory barriers to using continuous processes, like feeding, blending, granulation and tabletting are coming down.

Developers are now free to reap the many rewards of CM:

  • Increased product uniformity and process optimization
  • Fewer bio studies and shorter registration batches
  • Safer, fully automated, unattended production
  • Integrated CIP/WIP, and a smaller physical footprint
  • Increased flexibility
  • Less waste
  • Reduced scale up and production/processing times

For all these reasons and more, DFE Pharma believes that CM reduces risks while increasing speed to market and product quality and significantly lowering manufacturing costs.

 

Specific properties of excipients in CM

Although traditional processes like direct compression, roller compaction, or wet granulation are used within continuous lines, the requirement for ingredients can differ from traditional batch processing. A better understanding of how products perform when used in continuous processes is required. This includes better control of all the key attributes of raw materials and how they impact the manufacturability and quality of the final drug product.

Understanding excipient variability is integral to the CM process but it is extremely complex. The parameters that dictate control vary from product to product, and even from grade to grade.

As experts in this field, DFE Pharma evaluated the behaviour of differing grades of our own excipients when applied to CM processes. We confirmed that varying intrinsic properties of the different grades of the well-established, regulatory-approved excipient had differing effects on equipment performance.

 

Specialized portfolio: CM-enabled excipients

While most of DFE Pharma’s products can be used in CM processes, our recent research has shown that certain key properties, like flow and particle size distribution optimize results. Flow properties are increasingly important in a continuous manufacturing line, as the feeding performance defines the content of components that end up in formulation. Any variation in how the material flows into the equipment can lead to quality failures, such as out of specification dosage form assay and content uniformity. 

Photo: Gericke

Electrostatic powder charging is an important consideration for the quality of the end-product as well, as it may lead to clogging and obstructions in your process. Lactose (depending on the particle size and type) has low charging potential behavior, MCC medium charging potential whereas other excipients have high charging potential.

Our heritage of understanding excipients in application has informed the development of our specialized portfolio of best-in-class, CM-enabled products. These excipients have been specifically designed to meet the requirements of future pharmaceutical manufacturing processes.

Our CM expert team can support in the selection of robust excipients based on your formulation needs. They include:

 

Continuous Direct Compression (CDC); for 

                                             Flow                       Compactability     
 SuperTab 30GR  ++ +
 SuperTab 22AN ++ ++
 SuperTab 24AN ++ +++
 SuperTab 40LL +++ ++++
 SuperTab 11SD ++ +
 Pharmacel sMCC90 ++ ++++

Superdisintegrants Primellose and Primojel can be used to support tablet disintegration.

 

Continuous Wet Granulation (CWG); for

                                            Flow                         Compactability    
 Pharmatose 200M +
 SuperTab 22AN ++ ++
 Pharmacel 101 ++++

Superdisintegrants Primellose and Primojel can be used to support tablet disintegration. It is adviced to add superdisintegrants at least 50% intra-granularly.

 

Continuous Dry Granulation (CDG); for


Flow                         Compactability     
 SuperTab 21AN             ++
 SuperTab 22AN ++ ++
 Pharmacel 102 ++++

Superdisintegrants Primellose and Primojel can be used to support tablet disintegration. It is adviced to add superdisintegrants at least 50% intra-granularly.

 

Case study: Partnering with DFE to accelerate time to market.

DFE Pharma has been working with a major pharmaceutical player to embed CM processes since 2015. The company, which planned to launch several new products using continuous production methods, utilized our signature Stretch Batch Approach.

The stretch batch approach uses multivariate analysis of large data sets to identify major sources of variation within our excipients. This facilitates a greater understanding of the relationships between all inputs – from the desired quality to process parameters and raw material attributes. Additionally, understanding the impact of the total historical batch to batch variation, allows de-risking the use of excipients.

For this DFE Pharma selects batches representative of a wide range of possible variation (batches near the Hotelling’s T2 95% confidence limit). Termed ‘Stretch Batches’, these application-specific batches of excipients, based on DFE Pharma historical data, are truly representative of the possible variation, while remaining well within the specification limits of the CoAs.

 

Example of MVA scoreplot of SuperTab® 30GR (M2, PCA-X). Coloured according to year. No trend is observed in the data over the years. MVA is utilized to gain insights in variation and to select Stretch Batches, batches near the Hoteling's T2 confidence limit.

Utilizing this information, our industry partner was able to accelerate their development process,  shortening  the route to market while safeguarding a smooth and risk-mitigated transfer of technology.

 

DFE Pharma: Your CM formulation partner

Using our deep insight into excipient dynamics, we work closely with industry partners to create high quality, innovative CM applications.

At DFE Pharma, we have developed a portfolio of robust, specialized excipients that act as an essential platform for your project. Combined with our expert knowledge on how they interact with processes and ingredients, including the API, they can help you achieve success. As your CM formulation partner, DFE Pharma can offer excipient advice throughout process development. 

We can:

  • Support the development with data insights by MVA
  • Supply of Stretch Batches
  • Advise in functional excipient selection

Sample request

Start off your development process on the right foot with robust, consistent, specialized DFE Pharma excipients. DFE Pharma’s decades of excipient knowledge have informed the development of excipients your API needs to become one of the greatest medicines in the world. Our solid oral dose excipient platforms are multi-use and have long been used and trusted by our pharmaceutical industry partners.

Talk to us during the formulation stage for support with trialing and testing, or request your samples here.

DFE Pharma is committed to supporting the shift to CM and has conducted a range of research projects to further the knowledge base. Our scientific researchers have worked with universities, consortia, and industry partners to deliver new insights in the benefits of CM and our CM-enabled excipients.

Related documents:
 ■
 White paper: understanding and accounting for excipient variability in continuous

tablet manufacturing

 ■ Article: Impact of excipients on batch and continuous powder blending

 ■ Article: Using Multivariate analysis of batch-to-batch excipient variation to reduce
risk

 ■ Poster: Continuous Feeding of excipients and excipient blends

 ■ Poster: Continuous Feeding of excipients

 ■ Poster: Continuous Twin Screw Granulation

 ■ Article: The flowability of lactose powders to optimize tableting process