Auditing a firm's complaint and out-of-specification systems have always been favorite areas for regulators to assess to determine
the compliance, effectiveness, and adherence of a company's quality system to the regulations.
Susan J. Schniepp
In today's regulatory environment, it is important for organizations to know the regulations with the same depth of knowledge
and understanding as regulators. If an organization happens to be a contract manufacturer, it might also find itself in the
position of providing that in-depth regulatory expertise to customers. In either case, the contract manufacturer and its customers
must be able to work with each other and within the regulatory requirements to assure that the product manufactured and released
for patients is of the highest quality. The partnership between the contract provider and contract giver must reflect the
requirements and time commitments as defined in the regulations.
Potential out-of-spec and adverse event reports
In situations where more than one organization is involved in the complaint and out-of-specification (OOS) processes for the
product, all participating organizations must be harmonized in their approach for handling customer complaints and OOS results.
In this author's opinion, it is the responsibility of the license holder (i.e., the NDA holder) to make sure its contract
providers have the necessary processes and timelines in place to meet the necessary regulatory expectations. Likewise, it
is up to the contract providers to make sure their internal systems meet regulatory expectations for all their clients.
These systems should have established, agreed-to turnaround times regardless of whether the organization manufactures its
own products or contracts the manufacturing and testing to external organizations. Complications can arise when more than
one organization is involved in the processes and timelines for handling complaints and OOS results.
The parties involved therefore must establish internal requirements that are consistent with the regulatory guidelines and
give both parties sufficient time to conduct the needed activities required for the investigation into the complaint or OOS.
The processes and timelines for handling complaints should be defined in a Quality Agreement and the related SOPs of the respective
organizations and should include a clear delineation of which organization is responsible for various aspects related to the
Contract organizations should establish timeframes for completing certain investigation activities, which may vary from client
to client, but are usually completed within 30 days. The internal SOPs for handling complaints should be robust enough to
be able to handle various clients' needs without creating multiple SOPs on the same topic. The process for investigating and
handling OOS results should be similarly defined.
The complaint SOP and the Quality Agreement also should address the turnaround requirements needed to investigate complaints
associated with adverse or serious unexpected adverse events. For these complaints, the turnaround time must be able to accommodate
tighter regulatory requirements. The license holder (i.e., the client) is required to submit a Field Alert within 3 working
days after becoming aware of a reported problem either through a complaint or internal testing.
In these cases, the complaint must be investigated quickly by the contract manufacturer. The turnaround time for these types
of investigations should be defined in the Quality Agreement and subsequent SOPs and must be more expeditious than the timelines
for handling routine investigations. OOS reports also require an expedited timeline for communicating confirmed results to
the client because of the potential impact to product already distributed for use.
In some cases, there may be more than two organizations involved in product manufacturing. These relationships can be complicated
and communication lines blurred. The license holder must make sure through its various Quality Agreements that compliance
to the regulations is met and responsibilities are clearly defined and adhered to.