a saying that goes: “If it’s left up to two people to water the horse, the horse
will go thirsty.” So when it comes to the shared responsibilities between the
sponsor and their contract manufacturer, it’s important to ensure that the
product does not die of thirst.
growing trend toward outsourcing has not been lost on Rick Friedman, Director
FDA Division of Manufacturing & Product Quality. From all indications, it is
one of his inspection priorities to ensure the sponsor is carrying the water
emphasized at the 2010 PDA/FDA meeting mid-September
in Washington, DC, that sponsors should expect to hear questions during
inspections about how their companies are making sure that their CMOs are
actually being monitored.
are tools at the sponsor’s disposal to help ensure that both parties are going
into the relationship with their eyes open and to establish expectations. These
diligence audits to identify potential risks up front
Agreements to establish who does what and whose procedures and standards
Agreements to establish the business requirements and financial
after the dance is done and the CMO is integrated into the supply chain,
remember “they” are “you,” and “you” are ultimately responsible for product
was made clear in the “lecture” portion of the Warning Letter to River’s
you have agreements with other firms that may delineate specific
responsibilities to each party (e.g., quality control responsibilities), you are
ultimately responsible for the quality of your products. Regardless of who
manufactures your products or the agreements in place, you are required to
ensure that these products meet predefined specifications prior to distribution
and are manufactured in accordance with the Act and its implementing
regulations, including CGMP regulations for Finished Pharmaceuticals, Title 21,
Code of Federal Regulations, Part 211.
in addition to the tools that initiate the relationship, there are also tools to
ensure the sponsor exercises ultimate responsibility for product quality—and
these must not be delegated:
(GMP) the contract manufacturing facility
of product quality data and quality system performance
changes that potentially affect the validated process and
batch rework, reprocessing, culling/inspection
your product being manufactured
the final batch disposition (accept or reject)
ultimate responsibility makes sense. After all, CMOs have their own problems.
Their problems become incremental problems to you.
the most recent example of Contract Pharmacal Corporation2, a
full-service contract manufacture.
firm received a Warning Letter on October 14 that ran the gamut and also cited
repeated violations from previous inspections. FDA recommended that they
a third party consultant having appropriate CGMP experience to assess their
facility, procedures, and systems on a routine basis to ensure their drug
products have their appropriate identity, strength, quality, and purity. (See
The QA Pharm 9/25/10, When FDA Recommends
a Consultant—Implications for the Pharma QCU.)
be involved and develop not only a legal relationship, but also an active
partnership that works well together all the way down to the shop
can there ever be “too involved, or too controlling?” That depends.
worst case I ever saw was the outright bullying of a CMO by a big name, global
pharma company—because they could. The CMO that was hungry for business took
their regular beating—because they had to.
to the sponsor who likes to throw his weight around, I say—Be careful what you
ask for, you might get it. Demanding unreasonable launch dates; constantly
making last minute schedule changes; and insisting that it be your exact SOPs
adopted as their quality system infuse volatility throughout the CMO. For this
you get happy smiles and unwanted variation in the form of half-baked processes,
last-minute training of the operators, and complexity due to “one more
difference” in the way something has
to be done at the CMO.
the CMO, I say—Be careful what you promise. You may get the business, but are
you truly engineered for the sponsor’s products? Does the sponsor expect
shortcuts? Are you staffed to deal with the inefficiencies as a result of
mercurial sponsors that make demands much better than they can forecast and
way, you are in it together—but the sponsor is the “Responsible
Edge Pharmaceuticals, LLC, Warning Letter 10-ATL-05, May 20, 2010.
Pharmacal Corporation, Warning Letter 10-ATL-15, October 14,
About The QA Pharm:
“I am an observer of the pharmaceutical industry from inside and out with
over 30 years experience from the lab bench to the management board. If you have
a passion for the value and the direct relationship that quality assurance and
current Good Manufacturing Practices have to your patients and your business,
you will find a kindred spirit here.” For more insight from The QA Pharm visit
his blog here.
Pharmaceutical Processing has been given
permission to reprint The QA Pharm’s blogs as long as his identity remains a