2012 FDA Warning Letters: What Can Be Learned?

November 22, 2012

So far in 2012, the FDA has issued nearly 300 warning letters. More than half of those were sent to companies within the pharmaceutical, medical device and dietary supplement industries

he report states that in the first year of Dr. Margaret Hamburg’s tenure as FDA Commissioner, the number of warning letters increased 42 percent. In her second year, the number of warning letters rose a staggering 156 percent.

Labeling & Misbranding

One major responsibility of FDA is to ensure that the products it is in charge of regulating are correctly labeled and branded. The agency spells out specific labeling guidelines on its website and provides detail to the requirements that businesses must meet in order to be in compliance.

When browsing the various warning letters issued by FDA, a broad spectrum of labeling and misbranding issues are identified. This includes, but is not limited to:

• Failure to bear adequate directions for use on labeling for the purposes for which the product is intended;

• Failure to furnish material or information required by FDA; and

• Failure to provide adequate directions for use on labeling.

Reviewing FDA guidance and regulations affecting the labeling and branding of products will help businesses ensure compliance and ultimately prevent enforcement action from occurring.

Current Good Manufacturing Practice Violations

FDA ensures the quality of drug products, medical devices and dietary supplements by carefully monitoring compliance with Current Good Manufacturing Practice (CGMP) regulations. These regulations contain minimum requirements for the methods, facilities, and controls used in the manufacturing, processing and packing of a regulated product. In short, CGMP rules in essence ensure the safety of a product.

Some of the most common reasons identified for receiving warning letters over CGMP violations include, but are not limited to:

• Failure to establish and maintain adequate procedures for implementing corrective and preventive actions;

• Failure to establish a quality policy and quality objectives; and

• Failure to adequately conduct quality audits.

In many cases, CGMPs are straightforward. But, if such regulations are not implemented in a firm’s Standard Operating Procedure (SOP), they can be easily overlooked. All businesses should regularly review such plans and update them to ensure they are consistent with regulatory expectations.

Misleading Promotional Claims

FDA wants to ensure that a complete picture of each product is adequately conveyed to the public by the companies it regulates and will likely review such marketing materials during an inspection. Product claims made on a company’s website are also up for review by the agency.

Three of the most common reasons identified for receiving warning letters over promotional materials include, but are not limited to:

• False and misleading claims;

• Unapproved use of drugs (i.e., “off-label” claims); and

• Intentions to be used to cure, mitigate, treat, or prevent of disease.

Source: http://www.pharmpro.com/Articles/2012/10/2012-FDA-Warning-Letters–What-Can-Be-Learned/

 


FDA Rule and Companion Guidance Make Early Stage Clinical Drug Development Safe and Efficient

July 28, 2008

The U.S. Food and Drug Administration today issued a final regulation that makes early phase 1 clinical drug development safe and efficient by enabling a phased approach to complying with current good manufacturing practice (CGMP) statutes and FDA investigational requirements.

To facilitate this new approach, the regulation exempts most phase 1 investigational drugs from the requirements in 21 CFR part 211 — FDA will continue to exercise oversight of the manufacture of these drugs under FDA’s general statutory CGMP authority and through review of investigational new drug (IND) applications.

A companion guidance recommends an approach for complying with CGMP statutory requirements such as standards for the manufacturing facility and equipment, the control of components, as well as testing, stability, packaging, labeling, distribution, and recordkeeping.

“With this action, we are tailoring the CGMP requirements to make them appropriate to the earliest stages of drug development. This approach will ensure that these investigational products can be developed as efficiently as possible with the highest level of patient protection,” said U.S. Health and Human Services Deputy Secretary Tevi Troy.

When FDA originally issued CGMP regulations for drug and biological products (21 CFR parts 210 and 211), the agency stated that the regulations applied to all types of pharmaceutical production, but explained in the preamble to the regulations that FDA was considering proposing regulations more appropriate for the manufacture of drugs used in investigational clinical trials. The reason for this is that certain requirements in part 211 are directed at the commercial manufacture of products — such as repackaging and relabeling of drug products, rotation of stock, and maintaining separate facilities for manufacturing and packaging.  These types of requirements may be inappropriate to the manufacture of investigational drugs used in phase 1 clinical trials, many of which are carried out in small-scale, academic environments, typically involving fewer than 80 subjects.

“The new rule and guidance are intended to assure that manufacturers meet high standards for the safety of phase 1 drugs and biologics while removing unnecessary barriers that can slow the development of these potentially life-saving products,” said Rachel Behrman, M.D., associate commissioner for clinical programs and director of FDA’s Office of Critical Path Programs.

The guidance, CGMP for Phase 1 Investigational Drugs, describes an approach manufacturers can use to implement manufacturing controls that are appropriate for the phase 1 clinical trial stage of development. The approach described in this guidance reflects the fact that some manufacturing controls and the extent of manufacturing controls needed to achieve appropriate product quality differ among the various phases of clinical trials.

Manufacturers will continue to submit detailed information about relevant aspects of the manufacturing process as part of the IND application. The FDA may inspect the manufacturing operation, suspend a clinical trial by placing it on “clinical hold,” or terminate the IND if there is evidence of inadequate quality control procedures that would compromise the safety of an investigational product.

To find the Guidance for Industry, CGMP for Phase 1, Investigational Drugs, visit: http://www.fda.gov/cder/guidance/GMP%20Phase1IND61608.pdf

To find Current Good Manufacturing Practice and Investigational New Drugs Intended for Use in Clinical Trials/Final rule:  http://www.fda.gov/OHRMS/DOCKETS/98fr/oc07114.pdf