At the end of May, FDA
published its draft guidance, officially titled “Contract Manufacturing
Arrangements for Drugs: Quality Agreements”.
Here are some of the highlights.
First, a Quality Agreement
between a Sponsor and Contract Manufacturer has never been, nor is it now,
explicitly required by FDA regulations. However, responsibilities and
procedures of each company’s respective Quality Units are required to be documented, so a Quality Agreement that outlines
the responsibilities of each company is a logical next step.
Note that “Contract
Manufacturer” refers to any Contracted Facility that provides some or all
manufacturing services, including processing, packing, labeling, holding, or
testing.
In Europe, Sponsors (or, in
the vernacular of the draft guidance, “Owners”) can outsource the final product
release/rejection of finished goods for distribution. In the US, sponsors
always assume this responsibility and cannot delegate or outsource it.
Because Contracted Facilities
often provide services to multiple Sponsors, FDA advises that special
consideration be given to reporting information about objectionable conditions. Sponsors may wish to require that their
Contracted Facilities make them aware of manufacturing deficiencies that may
impact their products, even if the deficiencies were observed during an
inspection of another Sponsor’s product.
(Note, our consultants also suggest that the Quality Agreement require
that a Contracted Facility notify its Sponsor whenever the FDA inspects the
facility. The name of the inspected
product and its Sponsor would be kept confidential, but this reporting of
inspections tells a Sponsor how often FDA visits the site.)
FDA acknowledges that
processes can change at both Sponsor and Contracted Facility companies for a
variety of legitimate reasons, so communicating changes between the two
companies should be discussed in the Quality Agreement. Examples include
additional products brought into the line/facility, changes to key personnel
and suppliers, and changes resulting from stability studies, process
improvement projects, investigations into manufacturing deviations,
out-of-specification results, customer complaints, recalls, or adverse event
reports.
Finally, a Quality Agreement
does not exempt Contracted Facilities
from CGMP compliance. Regardless of the allocation of responsibilities in the
Quality Agreement, the Contracted Facility cannot essentially agree to manufacture
under non-CGMP conditions. Both companies could be held responsible – the
Contract Manufacturer for the non-compliance, and the Sponsor for lack of
oversight. FDA provided a few examples:
- The Contracted Facility receives a Warning Letter
for deficient maintenance of facilities and equipment. The Quality
Agreement specifies the Sponsor is responsible for this, yet the Owner has
failed to provide the requisite resources or carry out the necessary
upgrades and maintenance, and the Contracted Facility has continued to
operate under non-CGMP conditions. (Possible course of action: the Contracted
Facility could bear the costs of modifying operations in order to maintain
CGMP compliance, and then seek redress from the Sponsor later.)
- Batch records do not match the manufacturing
process of adding reclaimed powder, but the Contracted Facility claims
that this is just as the Sponsor specified. (Possible course of action:
the Contracted Facility could refuse to carry out the additional
manufacturing step without including it in the batch record).
The draft guidance concludes
by noting that “Owners and Contracted Facilities can draw on quality management
principles to carry out the complicated process of contract drug manufacturing
by defining, establishing, and documenting the responsibilities of all parties
involved in drug manufacturing, testing, or other support operations.”
by Laurie Meehan
We at Polaris hope you
find this information helpful. Contact us at info@polarisconsultants.com
with a question or post a comment.
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