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 FDA inspections.

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.

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.

FDA's Recommendations

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 in general.

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.