Strategic concerns
Consider the following situation: Your company registered a new finished product in various markets worldwide. The applications
are pending. Your purchasing department wants to change the supplier of either an active or key inactive ingredient because
it found a new supplier who can give a per kilogram price that is 30% of the current cost. How will you handle the change?
ICH Q10 Pharmaceutical Quality System, finalized in June 2008, states: "The change management system ensures continual improvement is undertaken in a timely and
effective manner while providing a high degree of assurance there are no unintended consequences of the change."
In the current commercial environment, companies are constantly looking for ways to cut costs. One of the areas where, at
first glance, substantial savings might be made is in sourcing of active and inactive ingredients. Your purchasing department,
for example, may find from a quick Internet search that there is no shortage of suppliers, including manufacturers and, of
still greater concern, brokers or distributors. The quality department, understanding that cost savings cannot be calculated
by a price-per-kilogram comparison, is in a dilemma as to how to manage such a request. The request cannot be ruled out without
investigation. A risk assessment might be a useful approach. A better option may be a product control strategy that assesses
the hazards associated with changing a manufacturer of a raw material on a product-by-product basis during development, identifies
potential points of entry for counterfeits, and aggressively designs controls into the supply chain.
A product control strategy, according to ICH Q10, is defined as:
A planned set of controls, derived from current product and process understanding, that assures process performance and product
quality. The controls can include parameters and attributes related to drug substance and drug product, materials and components,
facility and equipment operating conditions, in-process controls, finished product specifications, and the associated methods
and frequency of monitoring and control.
Figure 1
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Using the Ishikawa (fishbone) diagram, an initial identification of risk associated with sourcing of raw materials can be
constructed. Figure 1 provides one example of a partial assessment. To conduct a complete analysis, a multifunctional team
should be established, preferably including persons from the development, production, quality assurance/quality control, laboratory,
and purchasing departments. The diagram can then serve as a basis for performing a risk assessment such as the failure mode
and effects analysis (FMEA) technique, for each point that was identified or for those points which the team designates as
significant concerns. For example, microbial issues might be related to potential uses of an API by the end-user. Therefore,
as a purchaser, one of the questions to ask the supplier or manufacturer is whether it has performed a risk assessment for
microbial control of its process. ICH Q6: Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products provides decision trees for setting microbial specifications, so this could help the API vendor in performing its risk assessment.
However, your company may need the vendor to refine the assessment based on your intended use (e.g., their current customers
have used the product in solid oral dosage forms but your company plans to use it for parenteral administration; therefore,
your microbial requirements will be more stringent).
An initial questionnaire can provide useful insight into the quality system of the vendor and regarding other products manufactured
by the vendor at the same site. For example, does the vendor have a risk management policy? Does it produce beta-lactam products,
potent hormones, or pesticides? Ask about nonpharmaceutical activity at the same site. What type of quality system does it
have in place and who releases batches? The initial decision to continue to investigate or reject the supplier out of hand
should be based on the outcome of this initial risk assessment.
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