FDA issues guidance for off-label communication

The FDA issued draft guidance this week clarifying conditions under which drug and medical device makers may provide information on off-label uses.  The draft guidance covers unsolicited requests for off-label information.  An unsolicited request is one not initiated in any form by the drug or device maker (or its affiliates) itself.

For a company's response to nonpublic (one-on-one communication) unsolicited requests, the agency has made the following 7 recommendations:

• Response information should be limited to the requestor and treated as private, one-on-one communication.
• Information should be limited to the scope of the initial question.
• Information should be "truthful, non-misleading, accurate, and balanced."
• Information should be scientific in nature.
• Information should be generated "by medical or scientific personnel independent from sales or marketing departments."
• Information should be accompanied by several documents, including a statement notifying the recipient that FDA has not approved the product for the specific off-label use.
• The responding firm should maintain required records, including any follow-up questions from the requester.

For a company responding in public to public (Web sites, discussion boards, and chat rooms that are created and maintained by people other than the manufacturer or its affiliates) unsolicited requests, FDA makes the following 4 recommendations:

• A firm should respond only to a request about its own named product and is not solely about a competitor's product.
• The firm's response "should be limited to providing [its] contact information and should not include any off-label information."
• Those responding on behalf of the firm should clearly disclose their specific involvement with that firm.
• Responses "should not be promotional in nature or tone."

Public comments and suggestions regarding the draft guidance should be submitted within 90 days its publication.

FDA to exempt certain devices from 510(k) process

The FDA released a guidance that will relax the agency's requirements for 510(k) clearance for some medical devices.

The FDA has identified certain class I and class II in vitro diagnostic and radiology devices that have established safety and effectiveness profiles and for which it intends to exempt from the 510(k) process.

While the FDA proposes and finalizes regulations for the down classification and exemption changes, the agency said it intends to exercise enforcement discretion with regard to 510(k) submission requirements for these devices.

FDA proposes regulation of mobile apps

The FDA announced its proposed regulatory approach for mobile medical applications, or apps, designed for smart phones and other handheld devices.

In a draft proposal, the agency defines a small subset of mobile medical apps that affect or may affect the performance or functionality of currently regulated medical devices.  This subset includes mobile medical apps that:

• Are used as an accessory to medical devices already regulated by the FDA (for example, an application that allows a health care professional to make a specific diagnosis by viewing a medical image from a picture archiving and communication system (PACS) on a smartphone or a mobile tablet); or
• Transform a mobile communications device into a regulated medical device by using attachments, sensors or other devices (for example, an application that turns a smartphone into an electrocardiogram machine to detect abnormal heart rhythms or determine whether a patient is experiencing a myocardial infarction). 

 The draft guidance excludes the following from regulation:

• Mobile apps that are electronic "copies" of medical textbooks, teaching aids or reference materials, or are solely used to provide clinicians with training or reinforce training previously received.
• Mobile apps that are solely used to log, record, track, evaluate, or make decisions or suggestions related to developing or maintaining general health and wellness. Such decisions, suggestions, or recommendations are not intended for curing, treating, seeking treatment for mitigating, or diagnosing a specific disease, disorder, patient state, or any specific, identifiable health condition.
• Mobile apps that only automate general office operations with functionalities that include billing, inventory, appointments, or insurance transactions.
• Mobile apps that are generic aids that assist users but are not commercially marketed for a specific medical indication.
• Mobile apps that perform the functionality of an electronic health record system or personal health record system.

The agency is seeking input from the public on its draft guidance.  Comments can be submitted for 90 days online or by writing to: Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Room 1061, Rockville, MD 20852. The FDA will update the guidance based on feedback received.

FDA to Exempt Certain Diagnostic (IVD) and Radiology Devices from 510(k) Requirements

The FDA has issued a draft guidance that would exempt 30 different device typess from 510(k) clearance requirements. These devices include common urine and blood tests, alcohol breath tests, blood clotting protein tests and radiology device accessories.

According to the draft guidance, the in vitro diagnostic (IVD) and radiology devices have well-established safety and effectiveness profiles, so the FDA plans to use its enforcement discretion to exempt the device from premarket notification requirements as long as those devices “do not exceed the limitations on exemption specified in the device classification regulations.” In the future, the FDA also intends to reduce the pre-market regulatory burden on additional IVDs and radiology device types.

The FDA said it intends to continue to enforce all other applicable requirements for the devices, including, but not limited to, registration and listing and current good manufacturing practice regulations as set forth in the quality system regulations.

FDA Issues Draft Guidance On New Dietary Ingredients

The FDA announced today that it has issued draft guidance clarifying agency expectations on new dietary ingredients (NDI) for industry.  The guidance addresses in question-and-answer format what qualifies as an NDI ("a dietary ingredient that was not marketed in the United States before October 15, 1994"), when an NDI notification is necessary, the procedures for submitting an NDI notification, the types of data and information that the FDA recommends manufacturers and distributors consider when they evaluate the safety of a dietary supplement containing an NDI, and what should be included in an NDI notification.

Dietary supplement manufacturers are required to notify the FDA in advance when they intend to add a NDI to their products.  However, in certain situations when the ingredient has been part of the food supply (and is still considered an NDI), an NDI notification to the FDA is not required if it has not been chemically altered for use in supplements.

Under the guidance, minor loss of volatile components, dehydration, lyophilization, milling, and formation of a tincture or a solution in water, a slurry, a powder, or a solid in suspension do not chemically alter an ingredient.

However, the following are examples of processes that the FDA would consider to involve chemical alteration:

• A process which makes or breaks chemical bonds such as hydrolysis or esterification, unless the bonds created by the process are reversed when the ingredient is dissolved in water (e.g., creation of a soluble salt) or during ingestion.
• Removal of some components of a tincture or solution in water (e.g., by chromatography, distillation or membrane filtration), which changes the chemical composition of the mixture.
• Use of solvents other than water or aqueous ethanol (tincture) to make an extract.
• High temperature baking or cooking of an ingredient that has not previously been baked or cooked, unless the process causes only minor loss of volatile components with no other changes to the chemical composition of the ingredient.
• Changing the manufacturing method for an ingredient such that the chemical composition is significantly different (e.g., changes that alter the composition of materials used to make the ingredient, use of a different solvent, use of a chromatographic matrix instead of a passive filter).
• Application of nanotechnology that results in new or altered chemical properties of the ingredient.
• Changing agricultural or fermentation conditions to alter the chemical composition of the ingredient, such as by sprouting garlic or fermenting yeast using a medium containing large amounts of sodium selenite to create large amounts of organic selenium compounds.
• Fermentation using a fermentation medium different from the one used to make conventional foods in the food supply (e.g., use of a defined commercial growth medium to produce a microorganism previously made by fermenting milk into dairy products like yogurt or cheese).
• Use of a botanical ingredient that is at a different life stage than previously used (e.g., making an extract from unripe instead of ripe apples or using the mycelium instead of the fruiting body of a fungus.)

The guidance also states that if the manufacturing process alter the chemical composition or structure of an "old" dietary ingredient, the resulting compound is probably an NDI and an NDI notification to the FDA would be required.  For example, using a solvent to prepare an extract from a "old" dietary ingredient creates a NDI because the final extract contains only a fractionated subset of the constituent substances in the original dietary ingredient.  In addition, changes that alter the composition of materials used to make the ingredient, such as using a different part of a plant (e.g., using an extract of plant leaves where the root extract from the same plant is an "old" dietary ingredient), would create a NDI.

The 53-page guidance document could greatly impact your business.  It is recommended that you read it carefully and discuss it with your legal and regulatory team. 

The FDA is inviting the public to submit comments about the draft guidance.  Although you can comment on any guidance at any time, to ensure that the agency considers your comments on the draft guidance before it begins work on the final version of the guidance, you should submit your comments by October 3, 2011.

For more information: Federal Register Notice for New Dietary Ingredient Notifications and Related Issues (link for submitting comments; Docket ID: FDA-2011-D-0376): http://www.regulations.gov/#!documentDetail;D=FDA-2011-D-0376-0001.

FDA Issues New Labeling Rules for Sunscreen

After 33 years of consideration, the FDA today announced new labeling requirements for sunscreen OTC drug products.  The new requirements are effective June 18, 2012.  However, the compliance date for products with annual sales less than $25,000 is June 17, 2013.

Under the new rules, sunscreens must protect equally against UVB and UVA to earn the designation of offering "broad spectrum" protection.   UVB causes burns, and UVA causes wrinkles.  Both forms of radiation can cause skin cancer.

Products that have SPF values between 2 and 14 may be labeled "broad spectrum" if they protect against both UVB and UVA, but only those with a SPF value of 15 or greater may state that they reduce the risk of skin cancer and early skin aging.  Products that are not broad spectrum, or that are broad spectrum but which don't have an SFP of at least 15, will have to carry a warning stating that they have not been shown to help prevent skin cancer or early skin aging.

The new rules will also bar the use of the terms “sun block,” “waterproof” and “sweatproof."  Instead, sunscreens can be labeled as “water resistant” and must specify if they work for 40 or 80 minutes. Those that are not water resistant must carry a warning label advising people to use a water resistant product if they are going to be exposed to water or sweat.

The agency also proposed a new regulation that would limit the maximum SPF value on sunscreen labels to “50 +.”  The agency said there is insufficient evidence to show that products with SPF values higher than 50 provide greater protection than those with SPF values of 50.

Sunscreen makers could, however, submit data to support including higher SPF values.

In addition, the agency will begin accepting data about the safety and effectiveness of sunscreen sprays and comments on possible warnings for sprays.

FDA Issues New Food-Safety Regulations

The FDA published two new rules on Wednesday designed to give the agency more power to detain unsafe food and identify potentially hazardous imported foods. 

Under the first rule, FDA will be able to seize food that agents believe could have been processed in unsanitary or unsafe conditions and hold it for up to 30 days.  Previously, the agency could only hold food products if there was specific evidence it was adulterated and presented a serious threat to life.

The second rule requires anyone importing food or animal feed into the United States to tell the FDA if any country has blocked importation of the same product. This requirement will give the agency more information about imported foods, improving its ability to target foods that may be hazardous, officials said. 

The new reporting requirement will be administered through the FDA's existing system requiring prior notice of incoming shipments of imported food, established under the Public Health Security and Bioterrorism Preparedness and Response Act of 2002.

The new rules were issued under the authority of the Food Safety Modernization Act, which was signed into law by President Obama in January.  The law gave the FDA greater authority to regulate the U.S. food supply. The law also gave the FDA the power to issue mandatory recalls for companies that did not voluntarily recall contaminated products.

Both new regulations are scheduled to take effect Jul 3, but the FDA will accept comments on them until Aug 3, according to notices published today in the Federal Register.

See:
May 5 Federal Register notice on new administration detention rule.

May 5 Federal Register notice on food import reporting rule

FDA Proposes Draft Menu and Vending Machine Labeling Requirements

The FDA releases documents today regarding proposed regulations for restaurants and vending machine operators to include nutrition details on their menus and vending machines, as part of a healthcare law passed last year.

The FDA proposed that certain restaurants and retail food establishments provide nutrition information for standard menu items, including food on display and self-service dishes.

The rules target restaurants with 20 or more locations, as well as other retail food outlets, coffee shops and convenience stores.  However, a notable exemption to the proposed rules are movie theaters.

The FDA also proposed that companies owning and operating 20 or more food vending machines would be required to provide calorie information in close proximity to the food item or selection button. 

The FDA is seeking public comment on the proposed rule for menu labeling for 60 days (until 06-06-2011). Comments on the proposed rule on vending machines may be submitted for 90 days (until 07-05-2011). The FDA plans to issue final rules before the end of 2011.

The documents may be downloaded here:
1. Food Labeling; Nutritional Labeling of Standard Menu Items in Restaurants and Similar Retail Food Establishments (pdf); docket number FDA-2011-F-0172

2. Food Labeling; Calorie Labeling of Articles of Food in Vending Machines (pdf); docket number FDA-2011-F-0171

FDA Clarifies Malfunction Reporting Requirements For Class I and Low-Risk Class II Devices

The FDA has issued a clarification regarding medical device manufacturers’ and importers’ compliance with malfunction report rules according to the agency’s Medical Device Reporting regulation.

The requirements temporarily cover not only high-risk devices but also Class I and II devices that are not permanently implantable, life-supporting or life-sustaining.

The Food and Drug Administration Amendments Act of 2007 (FDAAA) requires manufacturers and importers of Class III as well as permanently implantable or life-supporting Class II devices to submit malfunction reports unless granted exemptions by the US Secretary of Health and Human Services or FDA. The FDAAA changed such rules for Class I and low-risk Class II devices, requiring quarterly reporting of malfunctions in summary form, except in instances where the regulator deems a device subject to stricter reporting rules in order to protect public health. In such instances, the FDA will notify those device manufacturers or importers in writing—or post a Federal Register notice—that they would have to provide malfunction reports in a manner that fully complies with the FDA’s Medical Device Reporting rule.

For the time being, however, the FDA will now require all devices to malfunction reporting requirements previously targeting higher-risk devices. The agency plans to more clearly define which devices fall under the less rigorous quarterly malfunction reporting category. In the meantime, the FDA’s clarification states that the agency will subject all devices to more exacting reporting requirements “in order to protect the public health by ensuring that there is no gap in malfunction reporting for any device.”

Interested parties may submit written or electronic comments on the clarification until May 9.

Design-defect Claims Against Vaccine Makers Preempted, Supreme Court Rules

The Supreme Court on Tuesday shielded the nation's vaccine makers from being sued by parents who say their children suffered severe side effects from the drugs.

By a 6-2 vote, the court upheld a federal law that offers compensation to these victims through a special tribunal but closes the courthouse door to lawsuits.

The majority said that Congress found such a system necessary to ensure that vaccines remain readily available, and that federal regulators are in the best position to decide whether vaccines are safe and properly designed.

The National Childhood Vaccine Injury Act of 1986 "reflects a sensible choice to leave complex epidemiological judgments about vaccine design to the FDA and the National Vaccine Program rather than juries," Justice Antonin Scalia wrote, referring to the Food and Drug Administration.

Justices Sonia Sotomayor and Ruth Bader Ginsburg dissented, saying the threat of lawsuits provides an incentive for vaccine manufacturers to constantly monitor and improve their products.

The decision "leaves a regulatory vacuum in which no one - neither the FDA nor any other federal agency, nor state and federal juries - ensures that vaccine manufacturers adequately take account of scientific and technological advancements," Sotomayor wrote.

The case was brought by Russell and Robalee Bruesewitz on behalf of their daughter Hannah, 18. Hannah began to have seizures as an infant after receiving the third of five scheduled doses of Wyeth's Tri-Immunol diphtheria-pertussis-tetanus vaccine. The company, now owned by Pfizer, has taken the drug off the market.

The 1986 federal law said that all such claims must first go to a special tribunal commonly called the "Vaccine Court." The program has awarded nearly $2 billion for vaccine-injury claims in nearly 2,500 cases since 1989. It is funded by a tax on immunizations.

But the tribunal ruled against the Bruesewitzes, saying they had not proved that the vaccine harmed Hannah, who will need life-long care.

The couple then sued under Pennsylvania tort law. The company had the case moved to federal court, and judges have consistently ruled that the suit cannot proceed, because federal law prohibits claims against "design defects" in vaccines.

The justices at oral argument debated ambiguous wording in the federal law. It says that no vaccine maker can be held liable for death or injuries arising from "side effects that were unavoidable even though the vaccine was properly prepared and was accompanied by proper directions and warnings."

Scalia said the word "unavoidable" would be meaningless "if a manufacturer could be held liable for failure to use a different design."

Sotomayor read the language to mean the opposite, and said "text, structure and legislative history compel the conclusion that Congress intended to leave the courthouse doors open for children who have suffered severe injuries from defectively designed vaccines."

The case is Bruesewitz v. Wyeth.

FDA to reclassify Medical Device Data Systems

The FDA has published a final rule to reclassify Medical Device Data Systems (MDDS) from Class III devices requiring premarket approval to Class I devices regulated under much less stringent general controls.

“An MDDS is a device that is intended to transfer, store, convert from one format to another according to preset specification, or display medical device data,” according to the rule. “An MDDS acts only as the mechanism by which medical device data can be transferred, stored, converted or displayed. An MDDS does not modify the data or modify the display of the data. An MDDS by itself does not control the functions or parameters of any other medical device. An MDDS can only control its own functionality. This device is not intended to provide or be used in connection with active patient monitoring. Any product that is intended for a use beyond the use (or functions) identified in this final classification rule is not an MDDS and is not addressed by this rule.”

The final MDDS rule will apply to “all manufacturers,” the FDA says. Critically, this includes hospitals, health care facilities or any other organization that does any of the following:

• Makes any modifications to the MDDS that are outside the parameters of the original manufacturer’s specifications for the device, for purposes of the user’s clinical practice or otherwise for commercial distribution.
• Purchases hardware or software and modifies it to transfer, store, convert or display medical device data for clinical use.
• Develops in-house software with an intended use consistent with an MDDS.
• Develops an in-house system, using multiple components of devices, that has an intended use consistent with an MDDS.

Other key points from the preview to the MDDS final rule include the following:

• The rule does not apply to electronic health record (EHR), personal health record (PHR), computerized physician order entry (CPOE), e-prescribing or word processing systems. Laboratory information systems and picture archiving and communication systems (PACS) are not medical device data systems either.
• An MDDS can covert data to the HTML; PDF; or Health Level Seven International, or HL7, data formats. However, “an MDDS may not otherwise convert, alter, modify or interpret the data that is received from a medical device,” the FDA said.
• Devices that transfer information for the purpose of information exchange, or that can generate or manipulate data on their own, are not considered medical device data systems.
• Such devices as glucose monitors, blood pressure cuffs and active patient monitors are not MDDS. These are Class III devices because they directly support and sustain a patient’s life; as such, they remain subject to stricter regulatory control, as well as to premarket approval.
• Devices intended for use by people who are not health care professionals (data entry clerks, for example) count as MDDS, though the FDA reserves the right, “if, through normal reporting mechanisms or otherwise, FDA determines that the use of these devices by someone other than a health care professional poses an unreasonable risk of illness or injury.”

FDA to Revise Device Rules, but Most are Minor for Now

In a press release today, the FDA announced that it will be making 25 changes this year to its 510(k) medical device clearance program, but will hold off on any major moves until after the release of an Institute of Medicine (IOM) report scheduled for this summer.

The agency's Center for Devices and Radiological Health said it would implement changes including the streamlining of the "de novo" review process for lower-risk devices, more clarity on when medical device manufacturers must submit clinical data in a 510(k) submission, and the creation of a council to improve regulatory science.

Most of the controversial changes to the 510(k) program proposed by the agency last year were temporarily taken off the table until the release of the IOM review slated for this summer.  They include the ability to revoke 510(K) clearances, increased post-market surveillance, and the establishment of a new classification (IIb) for medical devices that would require the submission of clinical evidence.

The agency maintains that the changes (PDF) will be a boon for the process by which the vast majority of medical devices are cleared for the U.S. market, delivering "a smarter medical device program that supports innovation, keeps jobs here at home and brings important, safe and effective technologies to patients quickly," according to a statement by Shuren.

In order to facilitate innovation in medical devices, Shuren said the FDA will:

• Streamline the review process for innovative, lower-risk products, called the "de novo" process by Sept. 30.
• Publish guidance for industry to clarify when clinical data should be submitted to increase predictability and transparency on July 31.
• Develop a network of external experts who can use their knowledge and experience to help the agency address important scientific issues regarding new medical device technologies by Sept. 15.
• Establish a new Center Science Council of senior FDA experts within the agency’s medical device center to assure more timely and consistent science-based decision making. FDA will publish the charter for the council its website on March 31. The agency plans to publish initial results of a 510(k) audit by the council on June 15.

To bolster the safety of medical devices, Shuren said the FDA will:

• Establish a public database of important device information, such as medical device photographs, labeling and summaries of the basis for the FDA’s decision to clear specific devices. The database will be discussed at a public meeting taking place April 7 and 8.
• Require a brief description of scientific information regarding the safety and effectiveness known to the manufacturer for select higher-risk devices on a case-by-case basis through device-specific guidance.

President signs food safety legislation

President Obama signed into law Tuesday legislation that represents the first major overhaul of the nation's food-safety infrastructure since 1938.

The Food Safety Modernization Act moves the FDA away from its previous role of responding to adulterated food to a more modern one of requiring companies to stop contamination before it happens by looking for the places where things can go wrong and fixing them.

The Act also allows the agency to issue mandatory recalls and hire more food-safety inspectors.

The FDA will need to draft regulations to enforce the new law.

Some of the changes the Act puts into place:

	Before	Now
Surveillance	Under the FDA's original statute from 1938, the focus was on responding to adulterated food once it was discovered.	Under the new rules, the FDA's focus shifts to stopping outbreaks before they start, by requiring farmers to address places in production where contamination might occur and to require processors to implement written food-safety plans.
Enforcement	The FDA couldn't force a company to recall tainted food; it could only seek a voluntary recall.	When needed, the FDA can order the recall of tainted food.
Specific targets	The FDA had to treat all foods the same, despite the fact that some are more likely to become contaminated than others.	FDA can develop regulations that focus on the highest-risk foods, including fruits, vegetables and imports.
Inspections	The FDA was able to inspect fewer than 20% of domestic food facilities and 1% of foreign food imports. More than half of food facilities have gone five or more years without a federal inspection, according to a 2010 report from the Health and Human Services inspector general.	The FDA will be able to hire 2,500 more field safety inspectors and food-safety experts by 2014 and increase substantially domestic and foreign inspections. The riskiest domestic facilities will be inspected every three years, beginning in 2015.
Records checks	For most plants, when the FDA conducted an inspection, it could only require a spot check of what was happening that day.	The FDA will have access to the food-safety plan, records and test results that are linked to the safety plan.
Exemptions	Big and small farms and producers were treated the same under the statute.	Farmers who primarily sell to farmers' markets or to restaurants, and who sell less than $500,000 a year, don't have to follow the new regulations.