	Tablet tooling, usually made from hardened and tempered tool steel, is subjected to a highly demanding process. The tooling is rotated through a cam track system at high speeds, exerting high friction forces. High cyclic compaction force is also applied to the punch heads via the precompression and main compression rollers to form what can sometimes be aggressive granules and powders into the final tablet. The delicate punch tips are extremely vulnerable to accidental damage at various stages of this process. This article highlights real-life examples of the more common types of damage or wear to the tooling and explains how these problems could be avoided. 


	One of the most common issues experienced is handling damage. This is usually accidental and can occur at several stages of the process such as: unpacking the tooling, loading/unloading the tools in or out of the tablet press, tool cleaning/maintenance procedures, and storage/transportation. If this damage occurs, usually in the form of nicks or burrs to the delicate punch-tip land area (see 

), it can lead to the production of poor quality tablets and probable further damage to both the tooling and the tablet press. With a better understanding and appreciation of the delicate nature of the tooling and with good tool care, maintenance, storage, and handling procedures, problems can be reduced.  


	Inappropriate operating conditions can occasionally lead to catastrophic failure during use of the punches and dies. Again, these issues relate to the delicate nature of the punch tip. The detail in the punch tip is usually described as the cup; this cup forms the profile of the tablet and can contain detail such as embossing or break lines, which effectively reduce the strength of the punch tips. Such problems can manifest themselves in small, difficult-to-detect cracks, chipping of the punch-tip edges, or even a full piece of the tip edge breaking away (see 

). These issues may look insignificant to the naked eye, but because high cyclic loading is applied to the cup many thousands of times per running hour, the tip edge is flexing and bending within the clearance between the punch tip and die bore. If the conditions are not optimized, this can eventually lead to fatigue or brittle fracture, causing the punch tip to fail. These types of failures can be avoided by careful punch and tablet design, correct metallurgical condition, and using the appropriate compaction force.


	Aggressive formulations can subject the punch tips to adverse effects such as abrasion, pitting, or corrosion when under compression, as shown in 

. The tools are manufactured from hardened and tempered tool steel, yet due to the demanding process, can deteriorate quickly if the tool material is not optimized to suit the formulation being compressed. Certain granules are extremely hard and abrasive and can scratch, wear, and impregnate the steel surface. Other granules can contain corrosive elements that react with the steel. Understanding the nature of the product to be compressed and carefully selecting a material and operating conditions can reduce these effects.


	Die wear is also quite a common occurrence, especially when compressing hard, abrasive granules and powders. Die wear is also known as “die ringing” because the wear takes place in the area of the die bore where the tablet is compacted. The wear appears in the bore as a double ring (see 

) due to the upper and lower punch tips flexing and bending within the clearance between the tips and the die bores during full compaction. The granule reacts between these surfaces leading to compressive and abrasive wear. When the wear becomes significant, it will lead to problems such as tablet capping or delamination and increased tablet ejection forces. This type of wear can be reduced by using different zones in the die bore where the tablet is compacted or by the selection of a harder, more wear-resistant die material.

	Incompatability of geometry between the punch-head profile and tablet-press cams will lead to premature head wear. The punch heads are subjected to high cyclic loadings, typically 20 kN to 50 kN, many thousands of times per hour of running. If the punches are running tight for any reason, there will be resistance between the punch heads and the cams and rollers, creating high frictional force. This will lead to premature wearing of the heads and eventual fatigue and total breakdown of the metal (see 

). An additional effect of this breakdown will be contamination in the tablet press by the metal particles, leading to expensive damage to tooling, press cams, and compression rollers. This type of damage can be avoided by close monitoring of the tooling condition and good tooling and tablet-press maintenance procedures.


	Another common sight is damage to punch keys (see 

), which is usually the result of handling damage during loading and unloading the tooling in or out of the tablet press. The punch key is an extra component fitted to punches for producing non-round tablets and for punches with multiple tips (usually upper punches) to facilitate accurate alignment of the upper punch tip into the die bore. The key is usually manufactured from a slightly softer material than the body of the punch, which may make it more prone to damage if not handled correctly during loading and unloading. Damage to keys can occur during storage and transportation of tooling, tool cleaning, repair and polishing, or wherever the keys can contact a hard surface. Damage to the keys can be reduced by having a good understanding and appreciation of its function and by taking extra care during the handling, maintenance, and setting processes.


	The problems discussed in this article are quite common, although the damage is not always to the extent shown in the images in this article. Damage and wear to tooling result in time-consuming and costly mistakes. If the correct procedures are put in place at the beginning of the process and the correct quality tooling is used, problems like the ones discussed will simply not happen. Employing good care and maintenance practices with both the tooling and the tablet press is crucial.


	Trevor Higgins is technical director at I Holland, trevor.higgins@iholland.co.uk, tel. +44 (0) 1159726153. All figures are courtesy of the author.      

When referring to this article, please cite as T. Higgins, “Preventing Tablet Tooling Problems,” 

Articles

Troubleshooting

Tooling can be damaged by poor handling or problems in process design or material choice.

Preventing Tablet Tooling Problems

	It’s not always feasible to package products in-house. A contract packager may be the answer to moving product out the door for low-volume runs, when specialized designs such as display packaging or single-dose, private-label pouches are needed, or in situations where capacity is constrained, equipment is unavailable, or specialized equipment must be acquired.

	“Contract packagers tend to be entrepreneurial organizations and specialists in what they do,” explained Chris Nutley, president of the Contract Packaging Association (CPA), during a webinar on Jan. 20, 2015 (1). For example, a contract packager may be set up to run parenteral products, but not solid-dosage forms or vice versa. A specialist in solid-dosage forms may not be equipped to handle both blister packaging and bottle formats.

	Contract packaging services also may be offered by vertically integrated CDMOs such as Aesica, which recently received continuing FDA approval of its bulk manufacture and packaging sites in Germany. “These approvals will allow Aesica to substantially grow its contract manufacturing and packaging services for supply of pharmaceutical products to the US market,” said Dr. Werner Schick, Aesica’s general manager, Germany, in a statement (2).

	Hiring a contract packager for projects such as test runs or pilot runs “allows you to keep your focus on your core competency,” John Mazelin, executive director of the CPA, told the webinar audience. “It also increases flexibility and [shrinks] time to market,” he said.

	There are dozens, if not hundreds, of service providers and many resources to identify potential candidates including CPA’s 

. Contract packagers also may be found via referrals, trade magazines, trade shows, Internet searches, Thomas Register, and the Yellow Pages.

	Once candidates have been identified, the selection process begins with a phone interview and written vendor survey, followed by an on-site visit/audit and final evaluation. “This research can’t be outsourced,” said Mazelin. “You have to do it yourself.”

	The written survey requests information such as mission statement, organization chart, safety record, warehouse-management system, and other business details. Mazelin told the audience members to meet staff, discern who is responsible for what, and gain an understanding of operating procedures during the on-site visit.

	Considerations include location, experience, cost, communication, controls, financial strength, ethics, size, quality, years in business, and full-time staffing. But perhaps most important, the contract packager should have a compatible culture. 

	Once the decision is made, “Begin with the end in mind,” advised Mazelin. “Know what you want.”

	“Communicate the values that are important to your process,” said Nutley. The contract packager needs to understand a brand owner’s expectations regarding quality standards, volumes, deadlines, lines of communications, nondisclosure agreements, reporting, and meetings. “Determine a single point of accountability in both companies,” added Mazelin. 

	Both parties also must agree on handling/service fees, payment terms, what happens when problems occur, and certifications. “Contract packagers are open to certification,” Nutley said. But considerable time and expense is involved when a brand owner requires its own certification rather than accepting an existing certification.  “Let the contract packager be part of the process. Involve them early and keep them informed of developments as quickly as possible. It’s difficult to be strategic if not involved early,” he explained. 


	1. Institute of Packaging Professionals, “Best Practices for Using Contract Packagers,” Webinar, Jan. 20, 2015.
	2. Aesica, “Aesica secures continuing FDA approval of its bulk manufacture and packaging sites in Germany,” Press Release, Feb. 2, 2015. 

Packaging

Careful selection of a contract packager should include interviews, surveys, and on-site visits.

Choosing a Contract Packager

	
	A transformation in thinking about how to manage data for controlling manufacturing processes is needed to obtain improvements in efficiency and quality in the pharmaceutical industry, said thought leaders at the International Society of Automation (ISA) Food and Pharmaceutical Industry Division (FPID) symposium on Automation & Serialization in the Pharmaceutical & Food Industry, held Feb. 10-11, 2015 in Philadelphia, PA. 

	Quality must be controlled throughout the supply chain by managing production information from the raw material through to the patient in a holistic, end-to-end process, said Paul McKenzie, currently vice-president of Ethicon global R&D and recently head of Janssen's Manufacturing and Technical Operations. One problem is that information management is often still paper and people based, rather than automated and electronic. Product lifecycle management (PLM) seeks to organize and automate product information handling end to end.  However, today’s systems are typically facility based, and various stages of a drug product may be manufactured at many different plants, including both internal facilities and external suppliers or contract facilities. In addition, different facilities may use different information management systems or applications. "We spend too much time recreating the same information in different systems, rather than having one, product and process data-based system," said McKenzie. The solution to the need to manage information from multiple plants, he proposed, is to base production information and recipes on the ISA S88 standard for batch process control, which provides an organized way of defining and describing processes and equipment.  Over the past year, Janssen implemented this standard for one of its products. Now, with fully integrated data that feed back in real time, process engineers can optimize the process with cycle-time analysis and troubleshoot out-of-specification deviations. "The key is expression of the product end-to-end, drilling down to the plant and back up with data," said McKenzie. The open S88 standard allows greater transparency with outside partners, because information can be communicated easily. With a standard "language" for data, all parties are seeing the "same truth," whether they are in different companies, at different facilities, or simply in different departments (e.g., quality control or process), he explained.

	The S88 recipe structure can also be applied to R&D. An R&D "data warehouse" that can hold data in a standardized recipe context can be used for knowledge management, and data can be drawn from it for data analysis or to compile regulatory filings, said Shaun McWeeney, principal engineer in the API large molecule group at Janssen, in a separate presentation. "Data warehousing makes it easier to analyze data. We don't need to waste time copying and pasting into spreadsheets to make graphs," he explained. Data warehousing is broadly used in other industries, such as retail, and it can help pharmaceutical companies be much more efficient, noted McWeeney. 

	Electronic production records (EPR) provide another tool for improving efficiency of data management in pharmaceutical manufacturing. Implementing EPR for a site-wide equipment monitoring system enabled electronic reports with review-by-exception and electronic signature approvals; saving several thousand hours per year of employee time previously spent manually logging parameter data and reviewing monthly reports fully paid for the infrastructure needed, noted Ken Kovacs, quality business systems manager at Fujirebio Diagnostics, in a presentation. The system was initially implemented using the ISA95 functional hierarchy model. That first project was completed three years ago, Kovacs said, and provided an infrastructure to add equipment both last year and this year. Having more accessible data allows the company to better analyze equipment performance. "We can address issues that weren't necessarily excursions, but that can be improved to make equipment more efficient. Looking at 24-hour, 7-day-a-week data also gives us a better understanding of the impact of equipment cycling," added Kovacs. The company is now applying the ISA88 process model to expand this system’s infrastructure for use in manufacturing operations management.

Production Trends

Advances in process modeling and use of open-architecture control models will lead to more efficient process control methods.

Equipment and Processing Report-02-18-2015

Preventing Tablet Tooling Problems

Choosing a Contract Packager

Forward Thinking in Data Management