A supplier's perspective

1. NEXT GENERATION PHARMACEUTICAL
Risk and quality management
– a supplier’s perspective
In September 2004, the FDA issued a final report on its Pharmaceutical Manufacturing Initiative
(PMI). The report includes steps the agency has taken and will take to develop and implement
a risk-based product quality regulatory system and quality systems management.
By Leonard J Goren and Kenneth P Clapp
I
ncluded in the report is draft guidance on the role of qual-
ity systems in the pharmaceutical cGMPs that enable
manufacturers to tailor their quality system to fit their
specific manufacturing environment. Per the final report, the
“intensity of FDA oversight needed will be related to several
factors, including the degree of a manufacturer’s product
and process understanding and the robustness of the qual-
ity system controlling their process.” Per the QSIT hand-
book, site inspections will utilize FDA’s system-based drug
inspection, which includes inspection of two or more sys-
tems, one being the quality system. One of the six addition-
al systems subject to inspection is the facility and equip-
ment system.
The focus herein is specific to the application of risk
management and quality systems management to facility
and equipment systems. From a packaged equipment sup-
plier’s point of view, the impact of a risk-based, quality man-
agement system ranges from minimal to severe. It’s been a
wild ride, and our goal is to share some of what we’ve
learned thus far.
Supplier qualification is mandated in the Code of Federal
Regulations (#21), but (until recently) has often been fol-
lowed only at a superficial level (i.e. a top line supplier audit).
FDA 483s have focused the ‘assumptions’ of quality versus
proof of quality. In practice (for example), the drug manufac-
turing specifications are often audited at the system (skid or
module) supplier level, but the specifications and quality
expectations, and proof of conformance, are rarely passed
down to sub-suppliers. As a result, FDA 483s can render the
equipment unusable for its intended purpose.
Managing the supply chain
Implementation of the PMI can cause certain areas of the
process, i.e. equipment such as the bioreactor, to be consid-
ered a critical, ‘high risk’ system. As such, the equipment
design and fabrication processes are subject to intense
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2. NEXT GENERATION PHARMACEUTICAL
scrutiny with the intent being to mitigate the risk. To meet the latest expec- each sources of error. Further complication occurs when a sub-supplier’s
tations of certain drug manufacturers, a supplier must invest in the per- front-end sales process uses one series of numbers to specify the com-
sonnel and procedures needed to dramatically redefine their supply chain ponent, but the manufacturing division uses another in its process. What
management (SCM). This includes development of a formal SCM program, shows up on the sub-supplier’s invoice rarely matches the supplier’s pur-
SOPs and training under the umbrella of a quality management program. chase order.
Sartorius BBI Systems selected ISO-9000:2000 as its quality management And what about acquisitions? Consolidations often lead to confusion.
system, which involved learning the ISO process, and auditing dozens of Besides the personnel issues and frequent loss of knowledge, a sub-sup-
sub-suppliers. The company learned that demonstrating traceability of plier’s attempt to merge product lines, part numbering systems and
every component requires a full-time QA/QC team working with constant processes causes the market to suffer, if even for a short time. One of our
vigilance to meet customer requirements. To understand the impact of the experiences involved a series of invoices containing a seemingly random
time, effort and cost – two years ago the SBBI staff included a 1:4 ratio of assortment of part numbers, descriptions and qualification data. In this
QA/QC to process personnel. Today, it’s 4:1. case, there were nearly 500 discrepancies. The documentation provided
was unclear, and traceability was compromised.
The price of quality
We also learned that sub-supplier compliance varies widely as does
the willingness to comply. As the requirements ratcheted up, only some FDA’s system-based drug inspection
sub-suppliers improved. The responses ranged from, “...that’s the way we
have been doing it for 10 years” to “Yes, we can do that; do you have a sug-
Laboratory control
gested format?” At this point, it is hard to say if sub-supplier responses system
were based on an understanding (or lack thereof ) of what benefit the end-
Personnel Production system
product – a vaccine or drug – will play in someone’s life, or if the motivation
was purely economic. We often had to deal directly with the highest levels
of management to gain the support needed. Our message was simple: Quality system
Those sub-suppliers willing to work with us to learn and comply with the
changing requirements were ensuring their future in this industry. Those Facility and equipment
Materials system
system
that could not or would not were replaced.
Not surprisingly, we learned that cooperation and compliance is not
Packaging and
free. The realization of a component, everything from material of construc- labeling system
tion to packaging, comes with a price tag. The more inspections needed,
the higher the cost. The more protection from dust, dirt and moisture need-
ed, the higher the cost. Labeling requirements cost more, too. And the doc-
umentation required to confirm and support the product attributes reads What’s better...paper-based or electronic records? One sub-supplier
like an expensive Chinese restaurant menu. transcribed original data from its sub-component manufacturer into its
For example, as recently as 2002, fittings were ordered by part number database. The documents provided with the parts had been generated from
and came with a material certificate. End of story. Today, the same fitting their database and contained various errors, including truncation of signif-
might require documentation consisting of datasheets, drawings, certifi- icant digits. To resolve this, the original sub-component manufacturer’s
cates of conformance, procedures, worker qualifications, etc. And the part documents had to be audited. This uncovered a number of other issues,
itself needs a description permanently stamped or etched on the exterior ranging from nearly illegible originals to unexplained annotations. The
(…of course, without diminishing its surface finish). Each document incre- result was a change in suppliers.
mentally adds to the cost of the delivered component. And the cost increas- Quality cannot be tested into a product; it must be designed and built
es depending on the number of copies needed. into the manufacturing process. Demonstration of such proof of quality
often relied on the interpretation of the cGMPs. Now, the Pharmaceutical
The part number jungle Manufacturing Initiative addresses manufacturing processes head-on.
For all the options associated with a given component, such as Regulators, according to the report, plan to reduce the frequency and scope
length, size, material of construction, finish and documentation, sub-sup- of inspections for “firms that FDA determines have acquired sufficient
pliers have created elaborate part numbering schemes. These intelligent process understanding and have succeeded in implementing effective
part-numbering systems create their own source of compliance issues. quality systems approaches.” As a result, the expectation of effective qual-
For example, a specification catalog may reference a part number: 11-A- ity systems must be passed down the supply chain to make this work. For
234-U700-M. Each of the alphanumeric characters possesses some criti- suppliers to survive they must accept and adapt, and the learning curve can
cally distinguishing feature. Data entry, omission and transposition are be expensive and severe.
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