Neuland has recently welcomed the addition of a new, dedicated Process Engineering Lab to its R&D Center. The lab opened in March, and supports operations and safety studies via a Quality by Design (QbD) approach.
Three Keys to QbD Success
The success of a QbD approach hinges on three fundamental elements. First, the target product profile must be clearly understood. This involves the second key element, determining the critical quality attributes (CQAs) that must be within a certain range limit or distribution according to the ICH guideline governing the product.
The third and final phase of QbD centers on the process needed to deliver the product. In this phase, risk assessments are used to gauge the impact of the raw material attributes and process parameters on the CQAs. Based on this, a design space is developed, and a control strategy is conceived and implemented.
The product lifecycle is then actively managed, with continual improvements made along the way, as shown in the flow chart below:
Taking Advantage of the Latest Equipment
In addition to a full range of state-of-the-art instrumentation and systems, the Process Engineering Lab features several innovative devices essential to the work it performs. An HEL reaction calorimeter and TSu (thermal screening unit) increases safety while enabling risk analysis and evaluation.
The reaction calorimeter is a stirred and controlled reactor that measures the rate of heat release as the reaction is conducted under controlled conditions. The TSu uses only approximately 0.5 to 5g of a sample, and provides clear data concerning hazards, including pressure. Specifically, the TSu indicates the thermal stability of chemicals, the safe process/handling temperature, and any potential temperature/pressure rise following exotherm.
The HEL automated parallel reactors in the lab allow one chemist to perform multiple experiments, in parallel. Benefiting from precise stirring and temperature control, each experiment can be conducted at a separate temperature from -60 to 225C, and stirred separately, with different sized containers and different applications.
In addition, Design of Experiments software and Design Space methodology are used to create an optimal design.
The Process Engineering Lab will enable Neuland to continue meeting regulatory requirements, and providing quality products using cost-effective procedures. Through a scientific, risk-based approach, the work achieved in the Process Engineering Lab yields greater insight into active drug substance manufacturing process. The result includes improved scale-up efficiency and speed, and faster time to market.
The 2016 Barcelona CPhI show (CPhI Worldwide) was an excellent opportunity for Neuland to set in place some strengthened internal sales team processes. These processes allowed us to better capture and understand the concerns, issues and challenges of both our customers and attendees in general. A bit more about what seems to be on everyone’s mind in the industry a little later…
But first, back to Barcelona. It’s a remarkable city – cosmopolitan and modern, yet bursting with history. It served as an excellent backdrop for the conference. Barcelona has historically been a key trading connection between Europe, Africa and the East – so it was the perfect venue to discuss the increasingly global pharma API industry.
Neuland held nearly 150 meetings over the course of the three-day show – keeping the booth’s 5 meeting rooms in constant use.
Pradeep Jain, Neuland’s Head of Manufacturing Operations, was one of the team who also had the opportunity to attend technical seminars and other exhibitions to gain knowledge about the latest advances in containment systems, and clean room & micronization technologies. (Pradeep’s personal show highlight actually happened away from the conference: visiting the stadium of FC Barcelona – a mecca for football – where diehard fans purchase samples of the stadium’s grass field.)
Neuland’s CPhI Mixer Held Atop Roman Ruins
Neuland held its VIP event at the History Museum in the medieval quarter of Barcelona. In our internal Company newsletter – Neuworld – Pradeep Jain described the setting:
The museum event organized by Neuland was held in the Casa Padellàs – a 15th century Gothic palace that in 1931 was transported stone by stone from its original location on the Carrer dels Mercaders to the Plaça del Rei. The palace has a typical Catalan Gothic architecture, with a small inner courtyard and external staircase. During the excavation work necessary to build the new foundations for the palace, remains of the old Roman city were uncovered. To better preserve these remains it was decided to move Barcelona’s city museum to this site, which opened in 1973.
What Were Attendees at CPhI Talking About?
Many of the questions we encounter as an API manufacturer were fairly conventional, and recur at every show. Among them:
Topics related to classes of compounds Neuland works with (e.g., amino acids, nucleosides, steroids, heterocyclics, quinolones, FMOC building blocks)
Project management-related topics: timelines, cost, IP, regulatory track record
Capabilities-related topics: route scouting & development, micronization, manufacturing scales (e.g., lab, pilot, kilo, production), process optimization, etc.
Aside from these customary questions, regulatory and supply chain queries seemed to grow as topics of discussion at this year’s show. These are two issues to which we happen to have an unrelenting commitment (and we’ve written about them frequently).
It’s fair to say that both of these issues are on everyone’s mind. There is a perception that the global economy is threatened by the possible rise of trade barriers. Combined with recent FDA guidance on Quality Agreements referencing the legal responsibilities of suppliers & pharma companies regarding cGMP manufacturing, both regulatory & supply chain issues should be expected to be a principal concern. (And truly, when hasn’t regulatory been a top issue for pharma, anyway?)
All in all, it was a successful show in a great city, and it was wonderful to catch-up with our customers and engage with those in our industry.
CPhI North America 2017
In you are in Philadelphia (or headed there) for the 2017 CPhI North America show, be sure to stop by the Neuland booth (#2059) and learn more about our API, Peptide and Contract Manufacturing services.
I read an article at PharmTech at the tail end of 2016 that I thought was quite interesting, and it reflects Neuland’s position on regulatory agencies & issues. The article – Nurturing the Relationship Between Industry and Regulators – emphasized the need for the pharma industry to partner with regulatory agencies to provide safe and effective therapeutics.
In the PharmTech article, author Susan Haigney, points out:
“It’s a partnership that can sometimes be contentious but is, ultimately, beneficial to all.”
To me, the relationship between regulators and the life sciences industry is (or, at least, should be) fairly straightforward: regulators hold us – as an industry – to uniform and consistent standards…and that’s a plus for us. And we – the industry – have the ability to deliver the tools and know-how to help regulators in their efforts.
The life sciences industry also has an obligation to inform regulatory agencies when we think they are off-base. Analytical standards are an excellent example in which industry often provides information, data and feedback about the widespread use of newer technologies that have come to replace older, potentially less accurate standards.
The article references this, as well: “international standard-setting organizations emphasize the importance of industry input. USP encourages pharma companies to participate in the development of public standards.”
The Industry-Regulatory Relationship: ‘It’s Complicated.’
The piece at Pharmtech also brought to mind an editorial I’d seen at DDNews on the 21st Century Cures Act, pointing to the at-times conflicting relationship industry and regulators tend to have:
“As chief editor of this magazine, I have an emotional and intellectual relationship with the FDA that would, were it a Facebook status, be ‘it’s complicated.’
On the one hand, the part of me that deals with pharma and biotech business issues knows that it would be nice to trim the costs of clinical trials and other aspects of the approval process. Unlike most of the American population, I know that high drug prices are often at least as much due to the economic necessity of recouping R&D costs as they are to do with greed.
On the other hand, I also deal with the academic and clinical researcher side of the news and a lot of the people on that side (and me, too) would like to see rigorous scientific study of potential drugs. I was happy in the early talk of 21st Century Cures to hear about working in “real world” results as part of the review/approval process and possibly streamlining some FDA processes.”
Finding Common Ground: Collaborating to Improve Patient Health
Back to the PharmTech article for a moment – it pointed out some key areas (beyond standards development) in which collaborative (or at least non-combative!) efforts can make some inroads towards improving patient health in ways that benefit industry participants, as well.
A big piece of the growth trend, however, will be driven by high-potency APIs (a “staggering increase,” as the report puts it) and their increasing role in cancer therapeutics. The rise of peptide drugs also drew a mention, but came with some manufacturing and regulatory caveats:
“Popularity of peptide-based drugs and the patent expiry of blockbuster branded drugs in the near future is also expected to boost the growth of the market. Complex manufacturing guidelines and stringent regulatory processes will continue to pose challenges to widespread adoption of peptide-based drugs.”
This is Eroom’s law in practice. (Eroom’s law – Moore’s law spelled backwards – posits that pharmaceutical R&D costs go up while drug approvals fall.)
This is also something that has been mentioned elsewhere. In a January piece at PharmTech, the editors referenced the growing imbalance between investment in – and sales of – a new drug:
“Since 2015, the report states, the costs of launching a new drug have remained near where they were during the heyday of the blockbuster, at $1.539 billion, 30% above where they were six years ago. A three-fold improvement in productivity would be needed to restore balance the imbalance between investments and sales.”
Specialty APIs Driving Growth
Back to the API report: it rightfully, in my opinion, points out the nuance in the sector’s projected growth. Bottom line: As pressure mounts to streamline & increase the efficiency of traditional API production, especially in the generic space, newly-emerging compounds (e.g., peptides, HPAPIs) are beginning to shift the balance in the wider market – hence the still-quite-respectable projected growth rates.
Specialty API projects tend to be more complex, requiring extensive process discovery and development across multiple scales. With high-potency APIs, additional containment and infrastructure adds to the challenge, while peptides have their own complexities.
In response to the increasingly specialization-driven nature of the pharma manufacturing space, most manufacturers have evolved their own respective knowledge sets and expertise. In the case of Neuland, we bring mastery of complex chemistry to bear on small molecule drug manufacturing challenges, with an emphasis on regulatory excellence.
API Geographical Market Segmentation
In terms of the API Market report’s segmentation into North America, Europe and Rest of World (ROW), the breakdown seems broadly (and very generally) accurate. [Of course, we do take issue with ROW CMOs reportedly focusing on bulk manufacturing versus quality…the implication being that ‘bulk’ and ‘quality’ are somehow mutually exclusive. Neuland has been a bulk ROW manufacturer focused almost exclusively on the U.S., E.U. and Japanese markets for over 30 years with a spotless regulatory record. Our focus is on quality, high-purity and, yes, also bulk APIs that meet the most stringent global regulatory standards. It is just a long-time point of pride for us!]
A pharmaceutical manufacturer is only as good as its supply chain. Supply chain management and strategic sourcing are the key drivers which keep operations running smoothly.
Set the Right Inventory Targets
When planning for the coming quarter, you need to ensure capacities are fully met. Adequate inventory of required items and at right quantities ensures continuous production thereby exploiting capacities to the maximum.
An OTIF – or ‘On Time in Full’ – calculation with a target of 95% is measured against pre-agreed benchmark lead-times. Here at Neuland we treat all User Departments requesting consumables as internal customers. Against agreed timelines, timeliness of deliveries is measured based on which all OTIF calculations are recorded. To achieve a high OTIF score means to balance the cost of disservice with the cost of carrying more inventories.
Choose Pharma Supplier Sources with Care
It is critical to identify reliable sources that meet all aspects of your company’s requirements. When qualifying API supplier sources, consider among others:
route of synthesis
At each stage of the process, look for sources who meet your expectations for the supply of drug intermediates and key starting materials (KSM) for new products.
Line Up Multiple Sources
Once you’ve determined how to seek out and qualify your sources, you can use that same process to secure as many sources as possible for each KSM.
Remember, sources can suddenly be disqualified or lost without warning due to unforeseen issues—anything from pollution to business viability to regulatory issues or other problems which might prompt closures or supply chain constraints. While being caught in a single-source situation may be unavoidable (due to specific expertise or infrastructure), new alternate suppliers should be continuously sought and added to your source base. The more trusted sources you can enlist, the more your company’s reputation (or reliability) is potentially safeguarded.
Aim High, with First Time Right Approach
With the goal of continuous improvement, employ a First Time Right (FTR) approach. The FTR thinking focuses on suppliers and helping them to avoid potential rejections – internally though, it aims to focus and attack wherever gaps exist in specifications, methods and analyses. Striking a balance between supplier focus and internal accountability, such an approach can extend to everything from alignment of test methods including HPLC/GC columns and release procedures to pre-shipment clearance of CoAs. It can also be used to verify the recentness of production batches with select Suppliers of your KSM and Intermediates, to confirm the quality of incoming materials is in line with expectations.
Ensure Regulatory Compliance of the Supplier Base
A compliance program designed for KSM and Intermediate Suppliers can keep your supplier base audit-ready. Such a program should emphasize traceability, and clearly demonstrate that all processes are performed in compliance with relevant regulatory standards and the quality agreements made with Suppliers.
To improve supplier performance on commercial and technical parameters, you can measure and score:
speed of supplier response
All of these can be measured on an objective pre-determined scale, plotting supply base performance on two different axes of a Supplier Performance Dashboard. From there, Supplier Improvement Actions can be devised with the goal of moving the suppliers from three different sub-optimal quadrants (Q1, Q2 and Q3) to a more desirable fourth quadrant (Q4) [see image, at right].
Buying competitiveness can be measured using relevant benchmarks. Via a transparent RFQ process, you can invite multiple quotes, and then fine-tune the results based on Commodity Price Trends.
Deliver On Time
A manual tracking program can be used to track outbound cargo from origin to destination, per delivery terms. The Outbound Delivery OTIF, which is an effectiveness metric, (at Neuland, the target is >=95%) should reflect successful delivery lead-times vis-à-vis pre-determined target lead-times taking into account mode of transport and destination. Good performance in OTIF is a key indicator (barometer) of an end-to-end supply chain that’s working effectively.
By effectively pursuing and gaining visibility of demand to plan inventory, choosing and guiding sources that meet your expectations for quality, and keeping everything on track with an OTIF that makes sense for your business, you can manage your supply chain and sources with greater efficiency – improving your bottom line and benefiting your customers.
For us at Neuland quality is an obsession, as the article points out. As global pharma suppliers, we don’t put much stock into the perception that Indian pharma – or Chinese pharma (or any other particular region, for that matter) – is necessarily weak or subpar. For us, it’s a supplier issue…not a geopolitical issue.
The Cost of Outsourcing
The decision to outsource in the pharma and biopharma business is driven by one factor, and one factor only: cost. Everything else – from facilities & infrastructure, to developing & implementing a quality-driven mindset, to the collective team experience of having worked with hundreds or thousands of diverse compounds – all of those things can be acquired, given enough resources. It often simply isn’t cost-effective to do so.
So the decision to outsource is virtually always cost-driven.
But choosing who – which contract pharma provider – to turn to is driven by all of those other things that I mentioned above:
Does the provider have sufficient facilities?
Do they have the technical processes needed?
Do they have deep working knowledge of my class or specific type of compound?
What are the timelines?
Floating above all of these questions aimed at finding the supplier who is a good fit is quality:
What is the supplier’s regulatory track record?
How robust are their quality systems?
What is their quality adherence mindset?
So yes – the supplier must be able to scale a product accordingly. They must have the infrastructure and skills needed in whatever niche space the sponsor occupies. But the number one most important factor, given the highly-regulated environment we operate in? Quality.
That’s been our experience as a global provider. Since 99% of our products are exported to the U.S., Europe and Japan, we’ve always been keenly aware of quality. Our earliest FDA inspection occurred in 1997 – one of the first in India. In the article, our head of manufacturing operations – Pradeep Kumar Jain – is quoted at referring to Neuland as “a non-compromising organization” when it comes to quality. That mentality – at the core of what we do – is a key reason we’ve never once received a critical observation from any regulatory or customer audit.
Pradeep also said “production done without GMP compliance and quality in mind does not have any value to Neuland Labs or our customers” – a great reflection of our absolute insistence on quality.
With the cost pressures of today’s competitive market, active pharma ingredient (API) sales profit margins are continuously falling. As a result, pharmaceutical manufacturers find themselves under pressure to cut production costs to sustain market share and maintain position.
One particular source of production inefficiencies – current batch manufacturing and manual process control using traditional equipment – has limitations in terms of capacity and process variation. In addition to this, Deviation closure and reprocessing both increase overhead, by cutting into plant productivity and ultimately raising production costs.
A Few Techniques to Boost Your Bottom Line, Instead of Your Costs
In the process development stage of R&D, the concept of Quality by Design (QbD) can be used to understand and control processes, based on sound science and quality risk management. Design of Experiments (DOE) is very useful in optimizing & validating processes, creating accurate design space, with flexibility for operability at plant scale. The processes operating in the defined design space have more consistency and are less likely to be prone to OOS and deviations.
Plant automation can reduce human error by controlling the process parameters and ensuring consistency (e.g., temperature control, pH adjustment, rate of additions, quenching time, etc.) This also improves process safety, and semi-batch mode operation can make exothermic reactions inherently safer. Automation includes feedback control loops and special utilities, along with heating and cooling.
Automated crystallizers can offer built-in flexibility for temperature control, supersaturation, nucleation, crystal growth, and the other parameters that affect particle size distribution.
Solvent/reagent recovery and recycling during processes is a very effective and modern way to lower solvent consumption and costs, while reducingenvironmental pollution at the same time. You can also design a synthesis route (LINK TO POST ON SCOUTING) that does not generate pollutants, thereby reducing the hydraulic load sent to effluent treatment plants.
Getting More from Less
As an API producer who never competes with customer formulations, we provide continuous API manufacturing to reduce costs and meet market requirements of high throughput and process intensification. By doing so, you can get more from less.
Specifically, you can take advantage of more:
Safety in processes, with less chemicals handled per unit of time
Flexibility in production throughout product lifecycle
While also benefiting from less:
Inventory, with less money tied up in investment
Time to market
Reprocessing, resulting in less overhead and less expense for raw materials
Square footage needed for your manufacturing plant, and thus, a smaller environmental footprint
Another technique employed at Neuland is to increase productivity and yield using the most efficient equipment available in current batch processes. For example, by using a rising/falling-film evaporator or wiped film evaporator for distillation, less time is needed and quality is improved through less exposure to higher temperatures.
Putting PAT to Work for You
One final step is using PAT, or Process Analytical Techniques, during lab development and plant implementation. Using PAT tools enables a shift from Quality by Analysis to Quality by Design. This brings continuous process validation to a plant via key monitoring of critical on-line processes and operations rather than the current one-time process validation (3 to 5 batches).
PAT tools are especially useful for:
Reaction studies, using On-lineReactIR, a full-featured reaction analysis system for reaction conversion
Crystallization/Drying, via Particle Engineering studies where focused beam reflectance measurement (FBRM) and particle vision and measurement (PVM) probes are used to achieve a target particle size and shape distribution
Drying, using an NIR probe to perform an on-line moisture check or NVM (residual solvent)
At Neuland, our R&D department is establishing a dedicated research team with expertise in continuous processes, flow chemistry and particle engineering. Our research team is a QbD group supported by state-of-the-art technology and infrastructure.
With a now-established track record of successful implementations, it is clear that PAT tools and innovative automation result in cost-effective drug products while providing robust quality assurance in real time. Going forward, partnering with manufacturers who take advantage of these measures will keep your business at the forefront of pharmaceutical manufacturing.
What new techniques or technologies are you considering to increase your profit margin?
One portion of an article at PharmTech (Five Themes That Will Drive the CMO Industry) discussing opportunities for smaller CMOs recently caught my eye. It mentioned that those aforementioned opportunities for smaller service providers have been rapidly expanding, that they are a reflection of “the growing number of niche products that are getting commercial approval.”
This is certainly a very real trend in the niche spaces, and one which we are witnessing in the High Potency (HPAPI) and orphan drug spaces, to name a few.
The article (rightfully, I believe) points out the growing need for CDMO scalability – a contract provider’s ability to grow capacity in-line with client needs. But at the same time, smaller niche products are on the rise…both in terms of development as well as regulatory approvals.
Smaller CDMOs, as the article points out, tend to be more agile and responsive to client needs – and have capabilities that tend to better align with products that – at their height – still only require small batch production. Much as smaller pharma and biotech firms tend to be innovation-centric, smaller CDMOs likewise have very concentrated – and often very advanced – knowledge of specific fields.
At Neuland, we tend to play on both sides of the proverbial river. We enjoy the challenges of working at smaller scales in our research and pilot lab facilities, with an emphasis on advanced chemistry process development & optimization. Those capabilities have served us well in the orphan drug API market, a topic I wrote about earlier this year.
But we also pride ourselves for having the capabilities and expertise needed to bring early-stage compounds through to eventual commercialization at the bulk scale – effectively & economically.
The challenge for mid-sized CDMOs who handle projects that start at the bench and eventually transition to commercial scale can be integrating the different approaches such circumstances call for. On the one hand, there’s innovation and agility, while on the other hand, commercialization-focused resources & robust infrastructure come to bear.
CDMOs: In Depth Knowledge There’s no doubt your typical team at a CDMO will see far more diverse project types and process experiences than a drug manufacturer’s team would. A major strength of virtually all contract pharma partners, and (aside from cost) perhaps the biggest allure of contract research and manufacturing is the in-depth experience in one (or multiple) specific areas of scientific knowledge. In an interview on contractpharma.com (CMOs, Pharma and Outsourcing: Perception vs. Reality) Stuart Needleman mentioned that “the high level of competence that CMO scientists bring to the table is often underrated.” He goes on:
“Many CMO scientists choose the pharmaceutical discovery and development industry because they appreciate the number and variety of active programs and proposals that will regularly come their way. In most cases, this is a far larger number than they would experience if they worked at a pharma company, where the focus on individual therapeutic specialty areas can limit a wider breadth of experience.”
Small CDMOs: An Attractive Acquisition Target
As the article states, such innovative & agile small firms have become attractive fodder for the pharma acquisition machine. See a capability that clients want? Simple – acquire it. The unfortunate byproduct of this is that those capabilities can be diluted by the very act of acquisition. Agility tends to evaporate when new layers of decision-making are suddenly present. And the flame of innovation that made the small CDMO an attractive target in the first place can sputter in a strictly profit-driven and budget-centric environment.
Protecting Mindset During Company Expansion & Growth
It’s a wider, global business issue, beyond CDMOs. How does a firm stay responsive and engaged with the customer while growing to a mid-sized or larger company – either organically (as Neuland has) or through M&A?
Bottom line: it is fundamentally important to remember there are reasons small CDMOs are sought after, both as suppliers and as M&A targets. Those which grow successfully always remember that, and they embed it deep into the company mindset. Food for thought.
In today’s pharmaceutical industry, Quality by Design (QbD) has become an essential – instead of optional – tool.
In fact, the phrase, “essential instead of optional” reminds me of the Crabtree ad stating, “A switch is a switch.” (The ad emphasizes the importance of quality in a lighthearted way.) Pharma’s quality requirement has a much more serious significance, as it directly affects consumers’ health.
In a pharmaceutical context, QbD is a systematic approach to development that starts with predefined objectives. It emphasizes product & process understanding and process control, based on sound science and quality risk management.
QbD focuses on Quality planning, Quality control and Quality improvement (the J.M. Juran approach) which, further strengthened by Six Sigma – DMAIC (Define, Measure, Analyze, Improve, Control) methods, has helped advance various industries over the past 60 years. These methodologies eventually took hold in the pharma industry about 15 or 20 years ago.
At Neuland, we view QbD as a way to ensure we remain a good, sustainable business. We treat it, however, as a regulatory requirement.
Benefits of Quality by Design
When implemented properly, the various characteristics of QbD—knowledge capture, risk management and quality systems—offer a number of advantages to both sponsors and contractors…and ultimately benefit the patient.
More accurate planning allows greater supply chain reliability and predictability, which drive down the cost of goods. This can result in better product pricing and increased availability.
Faster time to market and reduced rework, resulting in lower costs and higher revenues.
Increased assurance of product quality.
Better-defined processes lead to better facilities, which can improve product reliability and reproducibility.
Potential compliance actions are reduced or eliminated.
Effective knowledge management makes it possible to work smarter and faster to make new therapies available sooner.
More opportunities for first-cycle approval.
Improved scale-up efficiency and speed.
Streamlines post-approval changes and regulatory procedures.
Allows for more focused inspections.
Offers opportunities for continual improvement.
The ability to use innovative new technologies accelerates change and enables a proactive product lifecycle marketing plan.
Builds a scientific knowledge base for all products.
Allows better interaction with industry on science issues.
QbD generates better results – not only in terms of a product’s “processability,” but also by eliminating potentially problematic unknowns when the time comes to scale up production.
Since QbD is a science-based approach, it provides a basis for optimizing and improving manufacturing without having to deal with additional regulatory filings or scrutiny. And when it comes to technology transfer, QbD-generated process understanding can smooth the transition.
Regulatory authorities feel that carrying out incremental, unsystematic improvement in unit operations in isolation ultimately has little effect on overall process performance or quality. To ensure product quality, a more holistic QbD approach should be adopted.
Throughout the process, providing explicit knowledge in a clear, concise, systematically catalogued format with the help of QbD adds a new dimension to customer service and allows companies to differentiate themselves.
Areas of Impact
It encompasses various functions such as technology transfer, control checks, deviation reduction and analytical methods development and improvement. With such a wide scope of impact, QbD renders regulatory authorities more comfortable approving the drug application.
QbD is an essential tool that fosters process understanding, and has proven to be pivotal in ensuring product quality and performance. In fact, with new guidelines in place to facilitate its use, recent NDAs at Neuland have provided numerous opportunities to demonstrate successful implementation of QbD.
Harmonizing Industry and Regulation
Full implementation of QbD is a win-win situation for pharmaceutical companies. The key issue is to understand the scientific principles of QbD and how to correctly implement it. Regulatory authorities also need to harmonize the requirements and understanding across their departments. Only with clear communication between the industry and regulatory bodies can the challenges and concerns associated with implementation be successfully resolved.