Outsourcing Brings Complexity to the FDA and Industry
Outsourcing introduces considerable complexity into ensuring compliance with cGMPs. Outsourcing can result in having multiple
contractors involved in the manufacture of a single compound. Today, it is not uncommon for a biological product manufacturing
process to include more than 10 participant sites. This increase in participants translates into a commensurate increase in
Inspections have been expanding to include ex-US firms as manufacturers seek to reduce costs. This has resulted in an explosion
of travel time and expenses for inspection. Foreign manufacturing site inspections necessitate obtaining country-specific
clearances, multilingual staff to manage and control documentation, and increased interaction by the FDA inspection staff
with a variety of international business cultures.
In their interactions with foreign manufacturing sites, the FDA inspectors encounter different local regulatory requirements
and compliance expectations. These interactions also may entail translations of standard operating procedures (SOPs) into
multiple languages. The need to conduct foreign inspections of manufacturing sites has led to an increased dependence on information
technology and reliance on electronic meetings with new communication modalities for more effective communication.
Furthermore, interactions with more firms also translate into more reviews and inspections of manufacturing support sites.
These sites include laboratories, suppliers, labelers, storage sites, and packagers in and outside the US. Warehouses for
unlabeled products also may be inspected. (Warehouses for finished labeled and packaged material usually are not inspected
unless problems with the storage conditions exist.)
The complexities faced by the FDA translate into complications for the manufacturing firms. Each addition of a contract manufacturer
means another supplement to an existing biological license application. Additional inspections may be needed for these submissions,
depending on the manufacturing process or testing being contracted. For example, a contracted bulk manufacturer or a filling
manufacturer normally requires a prior approval supplement and a release testing laboratory generally requires a change-to-be-effected
in 30 days supplement.
The FDA encourages manufacturers to submit thorough and comprehensive submissions. To expedite the process, drug manufacturers
must follow the FDA regulations and guidelines as closely as possible. These guidelines are the basis for reviewing submissions
and are the documents most familiar to the FDA reviewers. Editing and organizing the material presented to the FDA in a coherent
document can pay huge dividends for the applicant. Effective communication facilitates understanding of the material presented
and saves review time. Using a table of contents and a list of acronyms minimizes misunderstandings. Furthermore, providing
background information with each submission clarifies the product's history and the company's future plans. Poor submissions,
like poor manufacturing compliance history, can slow the review and approval process of submissions.
Regular and timely communication with the regulatory project managers
The FDA encourages communication with the agency. Different avenues are available to manufacturing firms to accomplish this.
For example, alerting the regulatory project manager (RPM) responsible for a submission of any correspondence and amendments
being sent to the agency can be very useful both to the firm and to the FDA. This builds trust and enables both parties—the
RPM and applicant—to keep abreast of progress with each submission.
Meet with the agency
The FDA encourages meetings because carefully planned and well-run meetings facilitate understanding of the material being
presented to the agency. Teleconferencing is an option when a face-to-face meeting is not possible. Meetings facilitate a
mutual understanding of each party's needs.
Understand regulations and guidelines
Taking the time to understand how new regulations can affect manufacturing operations, and asking the FDA questions as needed
can help the company. Also, gaining an understanding of the regulations and guidelines can save time, money, and resources.
Visit the FDA web site and keep informed
The agency believes in clear and timely communication. The FDA's web site is therefore constantly updated with the most current
information available to the public. There are options to e-mail questions and to provide comments on regulatory policies.
Single-source editing of the submission
One of the most common mistakes made by firms is not having their submission edited by a single source. Reviewers often read
submissions containing sections written by different authors that do not agree among themselves. The sections sometimes are
incomplete or even contradictory. This is not only confusing for the FDA reviewers, but also wastes precious review time.
Such a lack of commitment in creating a quality submission could raise questions about the company's commitment to quality
Limit information to what is being requested
Manufacturing firms should be aware that providing more information than what is requested maybe unnecessary. More information
takes more review time and does not necessarily improve the quality of the information in the submission.
Learn from others' successes and failures
Firms need to be proactive and informed. The agency's web site gives access to current problems confronted by the FDA. News
about FDA actions is also available through various media outlets including professional journals. Firms must learn from examining
how the agency confronts emerging issues.