QRM Process

BioManufacturers Do More Supplier Auditing

Quality management is part of an increased focus on productivity and performance.

By Eric S. Langer, President, BioPlan Associates

Auditing of suppliers is a universal practice among biomanufacturers. As the industry matures, however, we are seeing an increase in the amount and types of auditing being done, as a result of the industry’s increased focus on productivity and performance. In the 8th Annual Report and Survey of Biopharmaceutical Manufacturing Capacity and Production [1], we found that almost half of biomanufacturers are auditing more of their suppliers and secondary suppliers (with nearly all presumably already auditing key vendors). 

We studied the quality management techniques being used by global biomanufacturers to assure quality of supply. Today’s evolving biopharma environment requires that biologics developers pay increasing attention to quality management issues to avoid production problems, capacity bottlenecks, and failures. An integral facet of this oversight is the supply chain: End-users are seeing more importance in supply chain management, and are increasingly attempting to take control through managing, assessing and protecting their supply of materials.

Our annual survey, with responses from 352 global biomanufacturers, asked respondents to identify what, in the past 12 months, their organization had done to assure consistent quality in raw materials and ingredient supply. Not far behind “audited more of our suppliers,” which was cited by 49% of respondents, was “audited our suppliers more frequently,” at 45% of respondents.

These numbers are not entirely unexpected—supply chain management and oversight are becoming more essential, particularly as the industry continues to adopt single-use/disposable bioprocessing equipment. Here, bioprocessing equipment is repeatedly purchased, used and disposed of, rather than being permanently installed and recycled. These repeated purchases place more stress and importance on the supply chain. Vendors and equipment suppliers (and, in turn, their materials, parts and component suppliers), must be in full compliance with regulatory and related documentation requirements. (See Figure 1.)

Bioplan
In addition to these data, our study shows that biomanufacturers:
-    Specifically identified secondary suppliers (e.g. those who supply our suppliers)
-    Implemented more dual-sourcing
-    Held more frequent meetings between quality staff and manufacturing staff
-    Manufactured some ingredients in-house

CMO Trends
We also compared biomanufacturers’ responses to contract manufacturing organizations, and found that CMOs, by nearly 10 percentage points, are more actively auditing their suppliers and secondary vendors (47% for biologics developers vs 56% for CMOs). They are also auditing suppliers more frequently (50% of CMOs vs 43% for biologics developers), and they are far more likely to test individual ingredients (44% for CMOs vs. 16%).

Biomanufacturers, however, are more active in demanding suppliers demonstrate higher levels of GMP (43.7% vs. 31.3% for CMOs). They are also more apt to develop new, more rigorous tests for incoming materials (34.5% for developers vs. 18.8% for CMOs). Communication tools are clearly preferred by biomanufacturers, with double the amount of biomanufacturers holding more frequent meetings or calls between quality staff compared to CMOs. (25.3% vs. 12.5%). According to Thomas E. Colonna, Biotech Consultant LLC and Associate Director of Regulatory Affairs at Johns Hopkins University, “Communication throughout the global manufacturing supply chain continues to be a key component in quality assurance” [1].

US vs. Western Europe Auditing
We compared U.S. and Western European responses to see how they differed in their approach. We found that U.S. respondents audited their suppliers more frequently than their Western European counterparts, by a considerable margin (55.7% to 37.5%). U.S. respondents also implemented significantly more comprehensive audits (52.5% for U.S. vs. 37.5% for W. Europe) and demanded suppliers demonstrate higher levels of GMP/GLP compliance (49.2% vs. 31.3%).

Strikingly, U.S. respondents were more likely to implement quality assurance measures almost across the board. The only areas that Western European respondents implemented at a greater rate than the U.S. were “manufacturing some ingredients in house” (21.9% for W. Europe vs. 6.6% U.S.) and “verified vendors’ Certificates of Analysis” (37.5% W. Europe vs. 34.4% U.S.). This may suggest that U.S. manufacturers employ audits of suppliers as their preferred method of assuring quality, while Western Europeans prefer less subcontracting in the manufacturing process as a method of assuring higher quality. It also may be due to audits simply being adopted more regularly as good business, in response to vendor-associated problems.

Vendors Blamed for Quality Problems
In addition, we evaluated seven key areas where respondents felt vendors have created quality problems. This year, making the top of the list of quality problems resulting from vendors, was vendors making promises they cannot keep (noted by 49.1% of respondents), poor product quality followed a close second, with poor service quality, inexperience with regulatory requirements, and inadequate certificates of analysis, record keeping or others (Figure 2).



Where vendors, particularly sales reps, make promises they cannot keep and/or provide defective or inadequate products, it can be presumed that their customers will seek out other vendors with more documented up-front product claims and better follow-through and quality products. To some extent, vendors not meeting their promises may be due to vendor-customer communication problems and customers taking in only the positive information supporting their purchase decisions. It is interesting to note that, when looking at the data compared to 2010, more respondents pointed to vendors making promises they could not keep, but less complained of poor product and service quality. Even though these latter issues appear to be on the decline, they continue to be key issues in need of attention.

To mitigate product quality issues, biomanufacturers need to develop better relationships with suppliers. Probably the greatest issue for industry with vendors is the unanticipated change that was not communicated to the manufacturer. Many times the vendor will not realize that a change they are making will result in a problem for the manufacturer until after the fact. This problem is a critical reason why clear quality agreements should be in place. More frequent audits, to be certain that suppliers understand what industry expects (and vice versa), will also contribute to better long term relationships. According to our study, these audits are indeed becoming more regular, and it will be interesting to see if this contributes to a continued downward trend of product quality complaints through 2012.

The data also show a definite trend in the reduction of vendors’ inexperience with industry regulatory requirements, from 46.3% in 2008 to 30.8% in 2010 and 28.1% this year. This suggests that both industry vendors and buyers are becoming more experienced with regulatory requirements, and suggests that it is learning from mistakes. It also may reflect the increased regulatory enforcement or perception in increased enforcement, and the necessity of understanding requirements. Vendors seem to be adapting to the needs of this highly-regulated industry. Vendor learning and adaptation presumably includes many well-established and new vendors expanding their single-use/disposable bioprocessing product lines. The relatively rapid adoption of single-use equipment is a major change in bioprocessing. To continue this positive trend, vendors should place increasing emphasis in staff training on the regulatory aspects of their products, and how they integrate them into regulated manufacturing processes.

Is Cost-Cutting Affecting Quality Standards?
Surprisingly, we found that only one in six (17.5%) respondents agreed or strongly agreed that manufacturing quality has suffered as a result of cost-cutting. As the current economic stress is causing many vendors to focus on cost cutting, conventional wisdom suggests this would manifest itself in increased quality problems and resulting concern from customers regarding both poor product and service quality. Our survey indicates this may not be the case (Figure 3).



We compared the responses from U.S. and Western European biomanufacturers, and found that a higher percentage of U.S. biomanufacturers feel that cost-cutting is affecting their ability to focus on quality manufacturing—19.8% of U.S. companies vs. only 10.5% that “agree” (none “strongly agree”) that cost cutting is creating a quality pinch. 

In comparing the responses from global CMOs and biomanufacturers, we found that a much higher percentage of CMOs feel that cost-cutting is affecting their ability to focus on quality manufacturing. This is possibly due to the fact that CMOs may perceive themselves as vendors. In a high-cost, labor-intensive service, cost-cutting invariably will affect quality. Clients of CMOs may need to put more emphasis on vigilance in investigating and confirming CMO standards, SOPS, documentation and quality-related practices and policies. This may include investigations regarding changes in corporate policy and cutbacks likely affecting quality and performance. Although CMOs are typically used for research and clinical trials-scale manufacturing, rather than commercial manufacturing, this remains a concern.

Although perceptions of decreased quality standards are much lower among commercial product manufacturers, it is important that the industry pay attention to CMO concerns. In particular, as vendors are forced to be cost-competitive just to survive, the potential exists for more stress and limitations on their ability to proactively deal with quality issues.


References
1. 8th Annual Report and Survey of Biopharmaceutical Manufacturing Capacity and Production:  A Survey of Biotherapeutic Developers and Contract Manufacturing Organizations, BioPlan Associates, April 2011, 490 pages.

About the Author
Eric S. Langer is president and managing partner at BioPlan Associates, Inc., a biotechnology and life sciences marketing research and publishing firm established in Rockville, MD in 1989. He is editor of numerous studies, including “Biopharmaceutical Technology in China,” “Advances in Large-scale Biopharmaceutical Manufacturing”, and many other industry reports.  elanger@bioplanassociates.com  301-921-5979. 

Survey Methodology: The 2011 eighth Annual Report and Survey of Biopharmaceutical Manufacturing Capacity and Production in the series of annual evaluations by BioPlan Associates, Inc. yields a composite view and trend analysis from 352 responsible individuals at biopharmaceutical manufacturers and contract manufacturing organizations (CMOs) in 31 countries. The methodology also encompassed an additional 186 direct suppliers of materials, services and equipment to this industry. This year's survey covers such issues as: new product needs, facility budget changes, current capacity, future capacity constraints, expansions, use of disposables, trends and budgets in disposables, trends in downstream purification, quality management and control, hiring issues, and employment. The quantitative trend analysis provides details and comparisons of production by biotherapeutic developers and CMOs. It also evaluates trends over time, and assesses differences in the world's major markets in the U.S. and Europe.

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