Neuland

Continuous Improvement in Drug Manufacturing – Still a Ways to Go

Posted on October 14, 2017 by

The healthcare industry is driven by scientific innovation, often in response to various public health crises. But while science & discovery often leap forward, the physical act of manufacturing a drug can lag behind.

A recent article at PharmTech (Breaking Through Obstacles to Improve Drug Manufacturing) bemoans the barriers to continuous process improvement.

“We saw what the industry can do and what regulators can support when the Ebola virus struck, and vaccines, which usually take over a decade to develop and approve, were developed and released in months,” says Maik Jornitz, CEO of G-CON.  “Why can’t we bring these approaches for the urgent to the normal, and create a more rapid approval approach?” he asks.

I made this point in a post on the Pharma Industry and Regulatory Agencies back in April – and it is still quite applicable. Fact is, technology is shifting faster than industry can keep up – let alone the regulators. And even with the best of intentions, the regulations themselves often arrive only after they are long overdue.

Because of the nature of our work and the fact that lives depend on us getting it right – both in terms of safety and efficacy – caution is, of course, absolutely critical.

There are times, though, when it feels like we’re talking about finally adopting flip phones as the world contemplates the eighth generation of smart phones.

Fractured Globalization
In the 30+ years we’ve spent developing APIs for drug companies, we’ve seen the pharma industry become globalized to a degree never even imagined. Our products alone end up in drugs spanning the globe – more than 85 countries at last count.

But, in light of the fractured regulatory standards worldwide, this globalization hasn’t streamlined manufacturing. Quite the opposite, in fact – as captured by this sentence in the PharmTech article: “One year, he says, Sanofi produced 83 batches of one of its vaccines according to 55 different configurations/variations, depending on the region involved.”

A More Agile Pharma Industry?
So what’s the answer? Pharma and its regulators need to become more agile – and as the article points out, it isn’t impossible, and it must be a collaborative effort between industry and regulators.

The FDA describes continuous improvement as “an essential element in a modern quality system and it aims at improving efficiency by optimizing a process and eliminating wasted efforts in production.” The challenge is getting the various parties on board with the overarching goal of modernization – refocusing from a mindset of ‘best historically-proven practices’ to ‘best available practices.’

The FDA is moving in this direction. Objectively, the FDA and other leading regulatory agencies have been enthusiastic supporters of improving pharma manufacturing processes. This has led to the widespread adoption of QbD, (LINK TO POST)  PAT and other innovative methodologies to enhance process control and quality.

The FDA is also evaluating how to best address changes to manufacturing processes post drug approval – reducing the need for multiple review cycles or CMC supplements. Again, this comes down to a collaborative effort: companies will need to be able to provide sufficient assurances that they understand how the changes they make will be controlled, and what the potential risk factors will be for both drug quality and efficacy.

The biggest challenge seems to be in harmonizing the view of process improvement globally. As the article notes, regulatory bodies tend to focus on the countries or regions for which they have responsibility, while pharma companies tend to consider a product’s markets.

If you have even a passing interest in drug manufacturing, the PharmTech article is worth a read: http://www.pharmtech.com/breaking-through-obstacles-improve-drug-manufacturing

 

 

 

 

 


How to Select a Peptide Synthesis Technique

Posted on October 1, 2017 by

Peptides are a complex drug class, and have historically proven challenging from a manufacturing standpoint. They are, however, experiencing a renaissance due to improvements in peptide synthesis, the development of high-throughput approaches and various innovations to overcome some of their traditional limitations, such as stability and half-life. These advances are expected to drive the peptide drug market to over $48 billion by 2025.

As we’ve discussed in earlier posts, there are three main strategies for synthesizing peptide active pharmaceutical ingredients (APIs):

  • Solid Phase
  • Liquid Phase
  • Hybrid Technology

The decision regarding which production technique to use is driven by three pivotal factors:peptide batch sizes

  • the size of peptide (meaning the number of amino acids)
  • the quantities needed at your current stage of development
  • the ultimate commercial launch quantities & batch sizes that will be required for manufacturing.

The latter two criteria go hand-in-hand: as a drug candidate progresses through development and clinical stages, the required volumes grow, as do batch sizes.

These three criteria – more than anything else – drive the peptide API synthesis strategy.

Shifting from Solid to Liquid Phase Synthesis
Transitioning from one synthesis to another often maximizes manufacturing efficiencies and minimizes unwanted substances in a peptide API.  The progression from one synthesis strategy to another typically flows like this:

Peptide Synthesis Selection Criteria

Solid Phase: 25 Amino Acids & Up|
Conventional wisdom suggests using a solid phase approach for peptides containing greater than 25 amino acids, for commercial quantities in the 1-10 kg range. Solid phase peptide synthesis utilizes an excess of protected amino acids to ensure as close to a 100% complete reaction as possible.

When larger quantities are needed, this can add considerable cost to the synthesis. However, a significant benefit of solid phase synthesis is the relatively shorter cycle time when compared to liquid phase synthesis. A secondary benefit: liquid phase synthesis of peptides larger than 15 amino acids is labor intensive.

Liquid Phase: 15 and Fewer Amino Acids
While the traditional approach to building peptides – liquid-phase peptide synthesis – has largely been succeeded by solid-phase synthesis, it remains useful for large-scale production. In fact, it’s an ideal strategy for peptides containing less than 15 amino acids and when commercial requirements range from 10+ kilograms to tons.

Hybrid Synthesis: More Than 25 Amino Acids & Larger Commercial Quantities
Today, a hybrid peptide synthesis strategy is generally chosen for peptides that are greater than 25 amino acids in length, and commercial requirements range from 10 to 200 kilograms. According to a recent market report, hybrid synthesis is expected to be a key driver of growth in the peptide drug market.

One notable success from hybrid synthesis was the pioneering work on Fuzeon, an approved 36 amino acid therapeutic for HIV-1.

Liquid Phase & Hybrid Synthesis for Improved API Substance Profiles
Whenever possible, transitioning from solid phase synthesis to a hybrid – and ultimately liquid phase – methodology is recommended due to the successive improvements in purification. With each change in strategy – from solid to hybrid, and from hybrid to liquid – significant improvements in the substance profile are observed with APIs.

Peptide APIs produced with a solid phase approach contain inherent deletion- and insertion-related substances. These substances decrease progressively with the transition to hybrid or liquid phase techniques. As peptide production progresses across these 3 distinct methods, the intervening purification steps increase – leading to fewer unwanted substances in the APIs.

As an example, Neuland experienced substantive improvements when we successfully used a liquid phase segment condensation strategy for the cGMP manufacture of 35 kilograms of a decapeptide NCE.

Exceptions to the Peptide Synthesis Selection Method Rule
While amino acid chain length and the need for various bulk quantities would seem to point to one synthesis technique over another, exceptions exist. Certain complex peptides such as Linaclotide are most conveniently produced by solid phase synthesis. In the case of Linaclotide, for example, Neuland – and others – have successfully leveraged this approach using 2-chlorotrityl resin.

Leveraging New Discoveries to Improve Peptide Synthesis
At Neuland, we routinely employ all three methods for the cGMP manufacture of peptides – solid phase, a hybrid strategy and liquid phase. We’ve also developed and patented a preparative HPLC technology which yields 10-12X higher output compared to classical Prep RP-HPLC. Among the advantages of our patented process (and the reason many of our peptide customers find it appealing), our Prep RP-HPLC technique results in reduced purification & post purification cycle times.

Learn more about Neuland’s peptide capabilities.


Leveraging QbD for API Scale Up

Posted on September 17, 2017 by

Earlier this month we wrote a piece on the Five Challenges Scaling Up an Active Pharmaceutical Ingredient (API). In the post’s conclusion, we discussed the role of QbD in aiding in scale-up:

Using QbD and a DoE approach, API manufacturers and CDMOs can reduce unanticipated challenges by developing deep process knowledge at lab scale – which aids in transfer to scale-up.

That isn’t just a random statement: QbD can radically transform the scale up process, and help companies avoid unforeseen complications.

Increased Regulatory Scrutiny and the Rise of QbD

Regulatory agencies are emphasizing the need for a more thorough understanding of products and processes prior to validating. This has led to widespread adoption of QbD (Quality by Design) approaches, which emphasize thorough process knowledge to avoid poorly-scaled processes.

QbD approaches typically use a Process Validation Lifecycle Approach, which is a holistic approach to development which supports and leverages:

  • Robust validation
  • Uni/multi variants
  • Use of modeling tools
  • Use of prior knowledge
  • Control strategy implementation
  • Proactive process monitoring, including PAT for trending, continuous verification and continuous proactive improvement.

Scale-up, which we previously discussed, is a critical link in this lifecycle. Without enough data, it can also be a ‘what if’ exercise. Bottom line: insufficient process knowledge can result in poorly scaled processes. This typically translates into more Out Of Specs (OOS), reduced process reliability, as well as higher production costs and a lower profit margin due to increased reprocessing.

With development and transfer to scale-up, the challenges which arise tend to be in a number of different categories: safety, environmental, health, quality and economics.

QbD Enables Robust Technology Development & Transfer to Manufacturing

With cause & effect analysis of Critical Process Parameters (CPP) on Critical Quality Attributes (CQA), QbD also aids in robust technology development & transfer at manufacturing plants. In order for QbD to aid in scale-up, an appropriate control strategy needs to be in place to ensure a focus on critical points.

Engineering API Scale-Up

The involvement of engineers in the laboratory during development and optimization of a process is the key to trouble-free scale up and technology transfer. The extent to which engineers need to address scale up of operations depends very strongly on the interaction between the chemist and the engineer, and the stage at which engineering became involved in the process.

While chemists tend to focus on process optimization, engineers focus on the scale- and hardware-dependent parameters, taking plant conditions under consideration. It is this dual approach that enables a ‘Right at First Time’ technology transfer. This can be achieved by adopting:

  • A scientific statistical approach (QbD-DOE, ICH Q8),
  • Simulation scale-up techniques (Dynochem / Visimix) for scale dependent parameters
  • Lab validation of process in conditions simulating the plant
  • The use of Quality Risk Assessment (ICH Q9) to evaluate each unit process and operations
  • Development and manufacturing (ICH Q10, 11) of robust/safe processes

Achieving successful technology transfer requires a robust manufacturing process, which – under QbD – is a collaborative effort, comprising Research and Development, Manufacturing Technical Operations, Quality and more.

The benefits of a QbD approach to scale-up are numerous:

  • Better manufacturing efficiencies
  • Higher yields
  • Superior quality
  • Enhanced process control
  • Higher design space, resulting in global regulatory flexibility
  • Fewer Deviations and a scientific rational for strong CAPA

QbD is an effective framework for bringing together a collaborative and inclusive team comprised of both chemists & engineers to ensure a successful API scale-up.


5 Common Challenges Scaling Up an API

Posted on September 3, 2017 by

While linear drug scale-up sounds great on paper, the reality is usually much different. In fact, scaling up an API can be challenging even under the best circumstances.

In fact, most scale-up challenges arise from the non-linear nature of shifting from the bench to the manufacturing plant. Not only do chemical reactions function differently at larger scales, but the environmental health & safety (EHS) issues can be enormous. (How enormous? Well, just how do you safely store – and eventually dispose of – millions of gallons of potentially highly-toxic chemicals each day?)

Here are 5 Common Challenges in API Scale-up our scientists frequently confront:

  1. Reactions
    In Unit Processes, reactions may poorly impact product selectivity during scale up if they are not properly understood at the lab scale. This can result in an increase in impurities – impacting both yield and quality.A thorough working knowledge of the chemical reactions includes the effects of scale-dependent factors (such as mixing, mass transfer and heat transfer). Using simulation software (for example, Dynochem or Visimix), the effects of mass, heat transfer and mixing changes can be predicted at larger scales.

    Design of Experiment (DoE) should be followed at lab scale to develop a robust process, including the time, temperature and mixing scale criticalities. This exercise will provide adequate Design Space for variability, and avoid surprises during scale up & technology transfer.The lab process validation & qualification to be done in the manufacturing plant should mimic the conditions at the lab scale. For example, switching to cylindrical reactors during manufacturing may mean the slower addition of reagents, a slower rate of heat increase and decrease and more.

  1. Safety Data Generation
    Runaway reactions are a challenge during scale-up. Generating safety data at lab scale can potentially help in designing the hardware for pilot or commercial scale batches – leading to inherently safer process technology.
    This typically involves Reactions hazards and Thermal hazards studies. These are performed using Reactor calorimeters, Thermal Screening units (TSu),  or Rapid Screening Devices (RSD) to monitor:
  • reaction heat
  • reaction initiation temp
  • adiabatic temp rise
  • gas evolution rate.
  1. Crystallization
    Crystallization often causes problems if the Critical Process Parameters and their impacts on Critical Quality Attributes (CQA) have not been adequately studied.
    Crystallization can negatively impact solubility and dissolution rates. Changes in crystal habit (the external structure) or the crystal form (polymorphism – in which the internal arrangement of atoms is different) can have wider impacts on ease of filtration, washing and drying. 

    These changes, in turn, can impact the Particle Size Distribution and bulk density, porosity, surface area or polymorph-pseudo polymorph (solvates/hydrates) to ultimately affect the formulated product’s drug activity.Process Analytical Techniques (PAT) can be used during lab development to understand the impact of process parameters on physicochemical properties.

  1. Drying
    Drying APIs at larger scales – much as with crystallization – can be complicated. It is common to use an NIR probe to perform an on-line moisture checks.
    Residual solvents are a frequently-encountered problem during drying, and they are mainly the result of the crystallization process.When crystallization solvent is trapped in the lattice, it is difficult to remove it to a level that meets solvent limits during drying. Crystallization process parameters should be studied at the lab scale, including the super saturation driving force and its impact of residual solvent.
  1. Particle Size
    An APIs’ particle size has become increasingly important – down to the micron level. Equally as important, however, is the Particle Size Distribution (PSD) – essentially, how wide the range of particle sizes in a given sample. Common size reduction techniques to meet today’s small, tightly-banded distributions include multi-milling, micronization or other size reduction (or sometimes enlargement) techniques & systems. 

    Where particle size matters (and when doesn’t it?) Particle Engineering studies should be performed for both drying and crystallization using focused beam reflectance measurement (FBRM) and particle vision and measurement (PVM) probes to understand the impact of process parameters on target particle size and shape distribution.

Determining the proper parameters for API scale-up can be difficult. Using QbD and DoE approaches, API manufacturers and CDMOs can reduce unanticipated challenges by developing deep process knowledge at lab scale – which aids in transfer to scale-up.


Neuland, Corporate Responsibility & the Movement to Eradicate Hunger

Posted on August 28, 2017 by

As a pharmaceutical company, Neuland has always been committed to impacting life positively across the globe. Whether it is manufacturing products to improve health, or improving the life of its employees, the Company’s focus on ‘quality’ reigns supreme – and is reflected in our Corporate Social Responsibility activities as well.

The Company recently turned its attention to the issue of food waste and how we can help reduce it in order to contribute towards the global movement to eradicate hunger.

In R&D and each of Neuland’s other facilities, a set of Food Waste Awareness posters were recently displayed.

A ‘conversation-over-tea’ session was then conducted on 3rd July in our R&D center by Senior HR Manager, Mr. Shiva Kumar. During this interactive session which aimed to create awareness among Neulanders, participants discussed some of the facts and data about food waste, and shared their thoughts on the topic.

A Commitment to Good Corporate Stewardship

The result of Neuland’s collective effort was an astounding 75% reduction in food waste, beginning the very next day!

Thanks to everyone who came together to fight food-waste and contribute to ending hunger.


Medicine & Science: Keeping Up with the Pace of Change

Posted on August 20, 2017 by

The changes we’ve witnessed in the fields of science and medicine over the last decade or two have been truly astonishing. When we stood at the beginning of the ‘omics revolution two short decades ago – long before the advent of Big Data or precision medicine – protease inhibitors and plasma TVs were just launching. It would have been nearly impossible to see what lay down the road 20- or even a scant 10 years ago.

Shrinking Planet, Increasing Opportunity
The typical business desktop computer in 1997 had significantly less computing power and storage space than an entry-level phone does today. And all of those technologies involved in developing a drug – chromatography, mass spec, imaging, data collection and analysis, and much more – have seen equal or even greater shifts.

Even within Neuland’s microcosm of the scientific world – advanced drug chemistry, peptides, contract pharm and APIs – the world has undergone massive shifts. Outsourcing, once an obscure option, has become the standard business model for research and drug manufacturing – thanks to rapid (and far-reaching) globalization. Supply chains have grown far more convoluted and complex, thanks to more efficient & faster manufacturing coupled with better infrastructure.

In the same timeframe, peptides shifted from a drug class of the past (insulin was discovered in 1922) to an up-and-coming drug class of the future.

APIs have also grown increasingly complex, with techniques unimaginable a handful of years ago now considered standard practice. Issues such as drug solubility, drug delivery, and the ability to process potent, very-low-volume compounds are seeing barriers drop rapidly (while new ones undoubtedly emerge).

Underlying all of this change has been technology. We’ve experienced this change as we do all changes: incrementally, and not as a single breakthrough. When taken in historical context, however, the two decade long change has been astounding in its breadth.

Drug APIs – More Complex, But Simpler to Make?
It’s hard to fathom what technology will look like or be capable of 20 years from now. What we know is that technology has allowed us to develop drugs that are far more complex than anything seen before. At the same time, however, technology has simplified things enormously.

That’s the key – we are able to perform much more complex tasks with greater simplicity and less effort or expense. Thus, tomorrow’s drug chemistry might very well make our current efforts look like the discovery of germs, or hygiene. These technology advances will have enabled medicine and science advances, further pushing out the boundaries of our knowledge.

Science constantly amazes me, so it is likely that the future of medicine – while perhaps somewhat unknowable – will certainly change how we look at treating human health issues in another decade or two.

What has amazed you the most about science advances in the latest 10 or 20 years? Join the conversation on Facebook, Twitter or LinkedIn using the hashtag #AmazingScience.

 

 


Inside Look: The Role of the IPR Department

Posted on August 5, 2017 by

Intellectual Property Rights and its Importance in Research, Business & Industry

We wrote a post on the patent cliff issue back in 2015. The patent cliff has served to further highlight intellectual property’s (IP) growing importance as a tool to maintain a competitive edge in the pharmaceutical and biotechnology markets.

IP has fostered a redefinition of strategy, a focus on constant innovation, and a complete restructuring & diversification of businesses. In that earlier post, we wrote that an essential aspect of newer strategies is to ignore the patent cliff and focus on filling product pipelines.

I.P. – The Power Behind Growth

While frequently an intangible asset, intellectual property has always been a powerful driver for company growth. And while this is true almost regardless of industry, virtually the entire drug sector revenue model is constructed around IP rights. In fact, IP is likely the single most important factor in securing capital and developing partnerships in the life sciences industry.

Pharma and biopharma firms leverage intellectual property rights (IPR) in a number of ways to maximize business value – from out-licensing to partnering to the outright sale of IP.

Neuland’s Track Record of IP Innovation

Located at our Bonthapally R&D Center, Neuland’s Intellectual Property Rights Group manages all of Neuland’s and its client’s IP-related matters.

Our IPR department performs a number of critical functions. One key task is to create and maintain our value proposition. The department also focuses on adding capabilities to APIs that differentiate them from competitor APIs.

In most cases, this entails supporting Neuland’s Research & Development teams by identifying whitespace in each portfolio API molecule and converting the whitespace into commercial advantage.

Neuland has a 30+ year track record of innovation. We have filed 172 patent applications around the world,  including: the USA, Europe, China, Canada, Japan and India. We have been granted 48 patents, and we have an extensive portfolio of patent applications in different stages of examination. We have been the recipient of the Silver Award for Patents under the category of Bulk Drugs/API by PHARMEXCIL (Pharmaceuticals Export Promotion Council, 8th Edition of Patents Award, 2015-2016).

IP Rights & Neuland’s Unique Non-Compete Approach

One key Neuland differentiator (We’ve blogged about it before here and here) LINKS TO POSTS is our no-compete approach to APIs, which you can read about here: The Contract Manufacturing & Intellectual Property Challenge: Solution? Don’t Compete With the Customer.

By using a unique client-focused approach to I.P., we remove IP as an issue between us and you, the client. We’ve found this fosters the scientific creativity needed to develop better, faster, safer, less-expensive drug manufacturing processes. Our clients benefit from Neuland’s expertise & innovation, and we benefit by building successful, long-term customer relationships.

An Active Intellectual Property Group

Our intellectual property team performs a whole host of other tasks aimed at strengthening Neuland’s competitive differentiators. Here are some of the other Neuland IPR Group responsibilities:

  • Monitoring and managing IP administration
  • Providing vital input for IP-driven product selection
  • Assisting and guiding scientists in designing potentially patentable inventions
  • Supporting the Business Development and Marketing teams with IP-related issues
  • Resolving all IP-related customer queries
  • Maintaining a strong and focused patent portfolio
  • Identifying Paragraph 4 (IV) & early launch opportunities
  • Drafting, filing, prosecuting and maintaining worldwide patent grants & patent applications
  • Providing IP clearance reports, These may include:
  • Patent Landscape Reports
  • Competitive Intelligence Reports
  • Patentability Search Analysis Reports
  • Infringement Analysis Reports
  • Freedom-To-Operate Analysis Reports for different regions
  • Patent Invalidity Studies
  • Whitespace Analysis Reports
  • Providing IP due diligence & IP compliance
  • Conducting IP awareness programs in-house

Want to learn more about Neuland’s Intellectual Property Rights Group, or the Company’s strict no-compete approach to clients? Visit our website or contact us.


Reflections on DCAT Week 2017 & AsiaTIDES, Japan

Posted on July 23, 2017 by

This year’s DCAT Week saw a new format and setting, while Neuland’s first AsiaTIDES show demonstrated the growing importance of peptides to the Japanese & Asian pharma industries. Here are brief recaps of these two global shows:

DCAT 2017
We have historically been a sponsor at DCAT Week, and this year was no exception. We did expand our sponsorship activities this year to include the DCAT mobile app. This proved an excellent choice, given that DCAT changed venues this year for the first time in its history. With events spread out across New York City, the app enabled participants to navigate different events & suites and schedule meetings, while also learning more about Neuland and its various contract pharma products & services.

This year’s DCAT show began on a Monday, as opposed to previous years in which it was a mid-week show. It was one of many changes – notably, the venue shift from the venerable Waldorf Astoria to the Hotel Continental Barclay. From our standpoint, it actually worked out for the better. There just generally seemed to be more cross-pollination of people from other hotels – leading to better attendance at various events – including our own.

A little more than two-thirds of our meetings across the three days were focused on Neuland’s Generic Drug Substances (GDS) business.

AsiaTIDES
AsiaTIDES – held earlier this year in Kyoto, Japan’s oldest city (and former capital city) – is a conference focused exclusively on peptides and oligonucleotides (hence the ‘tides’). The last ten years has seen growing research, deal-making and clinical activity in peptide and oligo therapeutic programs, and AsiaTIDES represents one of the key events focused on oligonucleotide and peptide research and commercialization.

At the show, our team did an excellent job promoting Neuland’s advanced capabilities in the peptide space. Neuland – with expertise in both solution phase and solid phase synthesis methodologies – offers a full range of peptide synthesis services. These include the production of peptides from milligrams to multi-kilogram scale by standard sequential chemical peptide syntheses and segment condensation strategies.

Among the services our team discussed with attendees were our proprietary Prep-HPLC technique to increase throughput during peptide purification 10-20 fold, our large-scale manufacturing capabilities for complex amino acids & Fmoc-building blocks, and our peptide regulatory support services.

It was a well-attended show, which speaks highly of the therapeutic potential for the growing ‘-tides industry.

Thanks to all of our team members who helped make both shows a success!


5 Variables Shaping the Contract Pharma-Client Relationship

Posted on July 9, 2017 by

Several posts ago, I discussed an article on the ‘shifting sands’ of contract provider/pharma relationships, and how smart providers were responding to pharma’s needs, rather than establishing fixed models of business.

I wanted to expand on that a bit, since it recently came up in a discussion with a major pharma company exec who was just a wee bit exasperated at being told precisely how a relationship would be structured by what amounted to a secondary supplier.

Business & Relationship Models
As far as relationship models are concerned, at Neuland we’re very flexible, because the best model to apply depends on the project or product type.

For example, with life cycle extension of APIs, we find a conventional business model is favored in which contract pharma clients prefer to outsource the products to meet their quality and regulatory requirements while sourcing at a competitive price. This kind of business model is exclusive in nature, and historically offered a guaranteed volume uptake on an annual basis. Taking market dynamics in consideration, it’s clear that guaranteed annual volumes for procurement is a largely extinct model.

In fact, many of the models we encounter these days are geared more and more towards encouraging a CMO to improve cost in order to compete against generic pressures. This is becoming increasingly common in situations where innovator firms rely heavily on CMOs such as Neuland for better delivery at the most competitive pricing under standard quality norms.

Here are five more observations on what we’re seeing impact the provider-sponsor (or innovator) relationships:

  1. More Contract Pharma Sponsor Audits
    One aspect of the relationship that has received some coverage is the increasing number of audits of CMO firms by the sponsor companies. While this may have its origins in the revised FDA standards assigning responsibility for manufacturing to the sponsor company, one particular positive consequence has been to help contract pharma providers improve their overall quality systems.
  2. QbD Drawing More Attention
    Quality by Design (QbD) is standardizing across the industry in the development phase to ensure that manufacturing is done to meet consistent quality in deliveries of drugs. With the adoption of QbD, the processes relating to yield, quality and impurity profiling are increasingly drawing more regulatory attention. This has led pharma sponsors & innovator companies to seek out relationships with firms that are ‘QbD-enabled,’ for lack of a better term, in order to best address the regulatory concerns raised by the growing complexity of today’s drug science.

 

  1. Large Molecules Draw Innovation, Small Molecules Draw Competition
    The innovator’s focus is – and has been, for some time – shifting towards large molecule development. In the interim, the small molecule space has become increasingly competitive. This is highlighted by the decreasing number of approvals for small molecules drugs over the last decade. The reduction in value for small molecules has led to market erosion, and is forcing CMOs to upgrade the technology platforms to remain competitive. It is also driving a restructuring of contract pharma-client relationships, with an emphasis on competitive processes & technologies. The innovators are stressing development in the areas of mAb and proteomics, as well as peptides
  2. Old Drugs Seek New Life
    Pharma companies are looking for new indications for old drugs. There is a trend in replacing some of the active side elements with isotopes to enhance efficacy. It is also opening up new avenues for contract manufacturing as CMOs begin to work on drug repurposing on behalf of clients.

 

  1. The Growing Role of I.P.
    Intellectual property has always played a major role in the contract pharma-drug company relationship. The importance of I.P. (and rights ownership) is taking on an even larger role with the passage of time. This is due – in large part – to the increasing complexity of drugs and their respective processes, which has led to highly-specialized CROs/CMOs with the ability to produce critical I.P. Relationships are now often structured around the presumed I.P. innovations that will emerge, and in many cases both parties work jointly to generate new IP innovations.

 

Just as every contract manufacturing project differs in its details, so – too – do the relationships between providers and clients. It is important to view the entire scope of the project, taking into account the variables that will have a bearing on the contract research or manufacturing agreement. Flexibility in designing the client relationship to meet the needs of the drug firm is the key to building a successful long-term alliance.


Defining the Contract Pharma Provider Relationship

Posted on June 18, 2017 by

I read an article at Pharmaceutical Manufacturing earlier this year (Inking the Deal: Mastering the art of lasting outsourcing relationships in the pharmaceutical industry) on the nature of contract pharma relationships with customers, and some of the points really struck home.

The limits of describing the relationship between supplier and sponsor are perhaps best captured in the article by the popular contract manufacturer statement: “it depends.”

It’s a truism: many different factors affect and impact how the relationship will come to be defined.

The VP of Global Business Development for one firm explained it nicely in relation to their CDMO services:

“I think it’s important for our potential customers to keep in mind why they went to a CDMO in the first place. Was it speed or technical advancements or a specific delivery platform, for example. If they keep that in the forefront of their minds, they will find a partner that is a good fit.”

At Neuland, we’ve found similar rationales behind a customer’s driving motivation. It may be that timelines are the key driver. It might be regulatory track record, or experience with a given technology or capability. In some cases, the interpersonal relationship might be a key deciding factor.

And just as those drivers vary with each client, so too does each client’s conception of what the relationship should look like – and how it should function. The Pharmaceutical Manufacturing article stated:

Much has been written about the role of contract manufacturers evolving from an “extra set of hands” to a more high-level, strategic partnership. But is the term “strategic partnership” truly the best way to describe the contract organization/drug manufacturer relationship? Again, the answer is: it depends.

Karen Langhauser, author of the article, goes on to point out that the term ‘strategic partnership’ is widely – and perhaps erroneously – used in the bio/pharma outsourcing industry. This may just be linguistic nuance. Most CMOs, CROs or CDMOs would acknowledge that the relationship isn’t exactly a partnership in traditional terms of shared risk/reward, but rather a partnership in the sense of long-term collaboration to create a successful drug product.

Regardless, the point that effective contract firms adapt to the desires of the sponsor drug company are spot-on, and much of this comes down to culture.

One last point from the article dovetailed nicely with our approach here at Neuland: “Building a good outsourcing relationship is the responsibility of both parties, and the best relationships have these three things in common: communication, flexibility and planning.”

Interested in some of the nuance of contract pharma-drug company relationships? Read the full article here: http://www.pharmamanufacturing.com/articles/2017/inking-the-deal/