Gauging Innovation in Pharmaceutical Development and Manufacturing

Innovation is the cornerstone of any industry, and Pharmaceutical Technology conducted a survey to determine the degree of, type of, and sources of innovation for pharmaceutical development and manufacturing. Key findings showed the level of innovation to be the highest in drug delivery, quality systems, and pharmaceutical analysis and the weakest in solid-dosage and small-molecule manufacturing. Respondents also said that quality by design (QbD) plays and will continue to play an important role in innovation, as will lean manufacturing and green chemistry.

Patricia Van Arnum

Level of innovation

The survey asked respondents to rate the level of innovation during the past year (see Figure 1). Respondents most frequently rated innovation high in drug delivery (24%), quality systems (21%), and pharmaceutical analysis (19%). Process development and manufacturing of biologic-based active pharmaceutical ingredients (APIs) and formulation development ranked in the middle. Fourteen percent of respondents rated innovation high in process development and manufacturing of biologic-based APIs, and 12% rated innovation high in formulation development.

Figure 1 Question: Rate the level of innovation during the past year for the following areas

Solid-dosage manufacturing, parenteral manufacturing, and process development and manufacturing of small molecules ranked fairly low. Only 6% of respondents said innovation was high in parenteral drug manufacturing, and 23% rated it as low. Only 10% said innovation was high in solid-dosage manufacturing, and 28% rated the level of innovation as low. Ten percent of respondents said innovation was high in process development for small molecules, and 9% said it was high for manufacturing of smallmolecule APIs. Eighteen percent said innovation was low in these areas.

Drug delivery and formulation

Nearly 64% of respondents ranked the level of innovation in drug delivery as either high or medium (see Figure 1). Looking at specific product forms, nearly 19% of respondents said innovation was high for respiratory (inhaled or nasal) delivery, making respiratory products the strongest product form for innovation in drug delivery. In contrast, only 12% of respondents rated innovation high for solid-dosage products, 7% did so for injectables, 4% for semisolids, and 3% for liquids.

The survey also examined the importance of innovation in formulation (see Figure 2). Respondents most frequently rated innovation very important in addressing the delivery of high-potency drugs (53%), poorly water-soluble drugs (52%), delivery of proteins and peptides (45%), and nanotechnology (37%).

Figure 2 Question: How would you rate the importance of innovation in addressing the following issues in formulation?

Innovation in delivering combination drugs, vaccines, and controlledrelease products also received fairly high marks. Roughly one-third of the respondents said that innovation was very important for controlled-release products. Nearly 31% of respondents said innovation for combination products was very important, and 27% said so for vaccine delivery (see Figure 2).

Capsules, tablets, and fast-melting products were areas in which respondents did not give innovation a priority. Nearly 22% of respondents said that innovation in capsule or tablet design was not important, and 12% said innovation for fastmelt release was not important.

Solid-dosage manufacturing

Although the level of innovation for solid-dosage manufacturing was ranked lower than for other areas, respondents pointed to the need for ore innovation in this area. Nearly 10% ranked the level of innovation in solid-dosage manufacturing as high, 34% ranked it as medium, and nearly 28% as low (see Figure 1).

But respondents were interested in seeing more innovation in solid-dosage manufacturing. Nearly one-quarter of respondents said innovation was very important in the areas of coating, granulation, compaction, milling, and drying. More than one-third said innovation was somewhat important for these areas.

Pharmaceutical analysis

Innovation in pharmaceutical analysis received moderate recognition. Nearly 19% of respondents said the level of innovation in pharmaceutical analysis during the past year was high, 43% said it was medium, and nearly 22% said it was low (see Figure 1). Looking at specific analytical techniques, innovation in high-performance liquid chromatography (HPLC) was ranked the highest. Nearly 32% of respondents said that innovation in HPLC was very important, and 43% said it was somewhat important. Respondents rated improvement in instrument design or application as very important in mass spectrometry (25%), and near-infrared (NIR) spectroscopy (24%), and 46% rated innovation as somewhat important in mass spectrometry and 47% for NIR. Seventeen percent rated innovation as very important for nuclear magnetic resonance (NMR) and also for Fourier transform infrared (FTIR) spectroscopy, and 14% did so for Raman spectroscopy. Respondents rated innovation as somewhat important for NMR (46%), FTIR (44%), and Raman (40%) spectroscopy.

Respondents profiles

Green chemistry

Although innovation for green chemistry in API synthesis and manufacturing was considered important by respondents, the degree of implementation of green chemistry was mixed. Thirteen percent of respondents said that using green chemistry in API synthesis and manufacture was extremely important, 34% said it was very important, and 29% said it was important.

The most frequently cited greenchemistry approaches used by respondents were reduction or prevention of waste (75%) and reduction, replacement, or elimination of solvents (61%). Other green-chemistry approaches in API synthesis and manufacturing were used less frequently. Nearly one-quarter of respondents increased energy efficiency by running reactions at ambient pressures and temperature. Roughly one-fifth of respondents either used renewable raw materials or analyzed a synthesis in realtime to minimize or reduce byproducts. Nearly 14% maximized atom economy in a synthesis to reduce waste and byproducts or used a structured mechanism to measure implementation of green chemistry. Roughly 12% eliminated stoichiometric reagents by using catalysts instead, and 7% used biocatalysts instead of chemical catalysts.

Disposables in bioprocessing

The survey also examined the prevalence and importance of disposable components in biologics manufacturing. Respondents' companies use disposable manufacturing components for bioprocessing for an average of 20% of their production. Breaking this number down, nearly 25% of respondents said that they do not use disposables. Nearly 40% said that disposables accounted for between 1 and 20% of their production, and roughly 20% said disposables accounted for between 21 and 40% of their production. Ten percent said disposables accounted for between 41 and 60% of their production, and 5% said disposables accounted for between 61 and 80% of their production.

Figure 3 Question: Are you or your company working on a project that incorporates quality by design?

For those respondents that do not use disposable components for bioprocessing, 24% say they are not considering their use, and 7% said they are considering disposables. The vast majority of respondents that do not use disposables, however, are undecided as to whether they will use them in the future. Sixty-nine percent say they do not know whether they will use disposables for bioprocessing.

Figure 4 Question: For which of the following areas are you or your company working on a project in quality by design?

Quality by design

More than half of the respondents said that they or their companies were working on projects that incorporated QbD initiatives and nearly one quarter are not (see Figure 3). Respondents who say they or their companies are working on QbD-related projects are most frequently doing so for the manufacturing of solid-dosage products (47%) and small-molecule drug substances (42%) (see Figure 4). A lower number of respondents are working on QbD projects in biologic drug substances (32%) and parenteral drug products (27%) (see Figure 4).

Figure 5 Question: What is the importance of quality by design for improving the efficiency and effectiveness of pharmaceutical manufacturing?

The survey examined how important QbD is for improving manufacturing efficiency and effectiveness (see Figure 5). Nearly 60% said QbD is either extremely or very important in doing so, and 28% said it was important. Following a similar trend, 65% of respondents say that implementing PAT was either extremely or very important, and 30% said it was important (see Figure 6).

Figure 6 Question: How important is process analytical technology (PAT) in advancing pharmaceutical manufacturing?

Reasons for innovation

The survey found that innovation was a critical tool for bettering human-resource development and for achieving cost efficiencies in manufacturing. Respondents most frequently rated innovation very important in finding skilled technicians and scientists to carry out process development and manufacture (48%), in improving cost efficiency in manufacturing and development (48%), and achieving greater predictability of biological processes, including improved scale-up and reproducibility (37%). Thirty-one percent said innovation was very important for improving product characteristics and reducing product heterogeneity. Twentyeight percent said innovation was very important for reducing bottlenecks in downstream processing or purification.

Figure 7 Question: Rate the importance of innovation in dosage-form manufacturing for the following during the next five years

Tools for innovation

Respondents also rated what was important to achieve innovation. Respondents most frequently rated management support (76%) and cross-functional teams (55%) as very important in realizing innovation. Team consensus, metrics, and reward systems were also considered. Forty-three percent said that team consensus was very important, and more than one-third said that both metrics to measure innovation and a reward system recognizing innovation were important.

The survey examined the barriers to innovation. Almost three-fourths of respondents said that they have encountered a lack of financial support, and 61% have experienced a lack of management support. Forty-six percent said that they do not have a structured mechanism to measure innovation, and 37% said they do not have a reward system in place. Other barriers to innovation encountered by respondents are an inability to build team consensus (30%), an inability to create cross-functional teams (29%), and an inability to access team members in locations outside a respondent's immediate workplace (22%).

For measuring innovation, respondents most frequently rated internal metrics designed by a project or department 50%) and peer recognition or awards 43%) as extremely or very useful. Respondents rated the number of publications (41%) and industry-wide metrics such as a balanced scorecard (32%) as useful. Only 22% rated the number of publications as extremely or very useful, and only 35% ranked industry-wide metrics as extremely or very useful in measuring innovation.

What's ahead in manufacturing

The survey examined the importance of innovation for certain manufacturing technologies or approaches during the next five years (see Figure 7). Respondents most frequently rated innovation during the next five years as very important in addressing implementation of QbD (47%) and adoption of lean manufacturing (41%). Nearly one-third said innovation was very important in the adoption of continuous processing and for implementing process simulation and predictive modeling.

Innovation for robotics, automation, and wireless technology was not given high priority during the next five years (see Figure 7). Only 20% said that innovation in robotics and automation was very important, and 15% said it was not important. Fourteen percent said innovation in wireless technology for pharmaceutical manufacturing was important, and nearly 19% said it was not.

Patricia Van Arnum is a senior editor at Pharmaceutical Technology, 485 Route One South, Bldg F, First Floor, Iselin, NJ 08830 tel. 732.346.3072, pvanarnum@advanstar.com