Seventy-five professionals representing a cross-section of the industry responded to Pharmaceutical Manufacturing’s first survey on process control and automation in the drug industry, providing a snapshot of control practices at many drug companies. Some respondents work at large, global corporations and others at smaller companies (one respondent describes his facility’s computers and IT systems as “vintage 1970s” technology).
While responses, so far, aren’t statistically significant (we will be updating and expanding this survey regularly), they still offer some insight into the industry’s changing approach to process analytical technology (PAT) and process control.
Interestingly, continuous processing is not the “blasphemy” that it might have been considered a decade ago by some drug industry professionals. Although respondents indicate that its use will depend closely on the chemistry involved in the specific process, they say that improvements in hardware and software make it more feasible, and that it would assure product quality and save money.
“Continuous control offers manufacturers a competitive advantage, but, at some point, FDA and other regulators will require it, as they see more MES (Manufacturing Execution System) implementations during plant inspections,” notes one respondent. Another, acknowledging that petrochemicals and electronics manufacturers have been using the methods successfully for so long, says, “It’s about time the pharma industry follows suit. FDA will determine the role that continuous processing and control play, as the Agency provides more or less freedom to manufacturers to improve their processes, continuously.”
Another respondent who may be representative of a large number of industry professionals at this point says, “It seems that continuous process control would fit nicely with the PAT initiative, but we’re not currently working on anything like this.”
Closed to Open Control
Despite more discussion of open control standards, and some staunch supporters within the drug industry, the survey indicates that professionals at many drug companies aren’t familiar with ISA/ANSI 95 or 88. “Ignorance is bliss,” says one.
Others describe them as too difficult to apply, given the array of automation systems and the even larger number of vendors that most drug manufacturing facilities must contend with. “At most facilities, it’s a real struggle even to discuss these standards,” another says.
One respondent was candid about S88. “We have attempted to use it in the past, but will avoid it moving forward.” Says another, “Each attempt at installing this method has proven too expensive, and counterproductive.”
However, the survey indicates that more drug companies are embracing PAT. 27% indicate that they’ve had PAT projects under way for a number of years, 13% have either started PAT projects recently or are just embarking on them now. 35% aren’t using PAT but plan to, while 20% aren’t interested in PAT (see Charts below).
Roughly 40% of those using PAT have just started projects or been working on them for less than a year, one quarter have been working on PAT for one to three years. Nearly 11% have been working with PAT for 10 years or more, another 11% for five to 10 years.
Staffing and Analytics
Of that same group, 40% say their facilities have only one PAT project under way, while 20% have three to five and 17% have five or more (see Chart above). Most companies (36% of respondents) have put a multidisciplinary, cross-departmental team in charge of their PAT projects, while 30% have charged their process engineering departments with PAT.
As far as the “analytics” portion of PAT is concerned, NIR appears to be the dominant technology being applied, with 54% of respondents using it (see Chart below). Chromatography is used in one-third of respondents’ projects, and Raman in 23%. Other technologies being used include in-situ particle size measurement using FBRM, laser diffraction and online NMR.
For data analysis, most respondents aren’t using principal component analysis or partial least squares methods, although one-third are using both methods. We also asked how routinely respondents use process capability analysis and statistical process control (SPC) methods at their facilities. Most (27.5%) say that they don’t typically use either method, although 18% say that they perform both methods routinely, and an equal number perform both occasionally.
Over half of respondents say that their facilities are using enterprise resource planning (ERP) software platforms; 17% indicate that they aren’t yet but may plan to, while 21% say they aren’t using it (see Chart at right).
Most respondents are not using manufacturing execution systems (MES) at this point, although 31% are using it and 27% plan to (see Chart at right).