Comments Re: “Questions for Stakeholders Regarding Appropriate Regulation of Pharmacy Compounding”

Chairman Tom Harkin                                      

731 Hart Senate Office Building                          

Washington, DC 20510                                     

Ranking Member Mike Enzi

379A Senate Russell Office Building

Washington, DC 20510

Comments from Members of the Patient, Consumer, and Public Health Coalition

Re: “Questions for Stakeholders Regarding Appropriate Regulation of Pharmacy Compounding”

Dear Chairman Harkin and Ranking Member Enzi,

Members of the Patient, Consumer, and Public Health Coalition welcome the opportunity to provide our views regarding pharmacy compounding.  Stronger regulations are clearly needed to prevent tragedies such as the contaminated steroid injections that have already resulted in 356 cases of fungal meningitis and 28 deaths.  Current laws and regulations regarding compounding pharmacies have resulted in giant loopholes that allow medical products that are neither safe nor effective to be sold throughout the country, putting patients’ lives at risk.

Changes to regulations should ensure that compounding pharmacies that operate as drug manufacturers are regulated by the FDA the same way as other drug manufacturers.  Pharmacies that engage in interstate commerce should be required to register with the FDA and comply with safety standards.  Compounding pharmacies should be required to report deaths and other serious adverse events to the FDA in a timely manner, so that other patients would not be harmed. There needs to be no question that the FDA has the authority to inspect pharmacy facilities. Legislation is also needed to require a warning to health professionals and patients that compounded drugs have not been approved safe and effective by the FDA.

Below, we address your specific questions:

Current Authorities FDCA 503A

The Federal Food, Drug, and Cosmetic Act could have and should have been used to prevent the New England Compounding Center tragedy from happening.

Section 503A of the FFDCA exempts compounded drugs from FFDCA requirements regarding drug adulteration, misbranding, and new drug approval, provided that certain conditions are satisfied.  NECC was manufacturing large quantities of the steroid.  This appears to be in violations of the FFDCA requirement that the company “does not compound regularly or in inordinate amounts (as defined by the Secretary) any drug products that are essentially copies of a commercially available drug product.”[1]

The uncertainty regarding the status of section 503A due to different interpretations of the law by the Fifth Circuit Court and the Ninth Circuit Court has led to non-uniform enforcement in the U.S.  Congress needs to take legislative action so that FDA has a clear, unambiguous law to There should not be one set of laws for Texas, Louisiana, and Mississippi (the Fifth Circuit), and another for the rest of the country.  Congress should absolutely clarify the legal status of section 503A, which should be revised to delete the unconstitutional advertising provision.

Regarding prescription language in (a)(2), the section on limited quantities must remain, but a more precise definition of “limited quantities” is needed.  The anticipatory language “based on a history of the licensed pharmacist or licensed physicians receiving valid prescription orders” would serve as a loophole that would make it too easy for companies to get around the prescription requirement.

The ban on compounding copies of commercially available drugs in (b)(1)(D) should be maintained.  As noted previously, NECC seems to have violated that restriction.

The 5% cap on interstate shipments in (b)(3) needs to be lowered.  Drug compounding has morphed from its original intention of preparing medications that are not commercially available, such as lower dosage drugs for children or drugs without dyes to prevent allergic reactions.  As a result, the restrictions on interstate shipments should be clearly stated and enforced. The Secretary should be able to develop a waiver process in case of drug shortages or to protect public health, but this must not serve as an easy loophole in the law.

As for retaining the memorandum of understanding, the question is: Has it been effective?  What is the MOU’s track record?  Has the MOU with the Secretary and individual states, which addresses “the distribution of inordinate amounts of compounded drug products interstate” resulted in investigations by state agencies?  It seems clear that it has not been effective, and therefore it is a moot point for The Secretary and the National Association of Boards of Pharmacy to develop a MOU to be used by the states to comply with the inordinate amounts provision.

Pharmacy licensing standards in states may or may not address compounding standards.  An important question is whether the states have the resources to enforce the standards.  Another problem is that a patchwork of 50 different standards, particularly when some companies are selling their products across state lines, makes it impossible to guarantee safety for all Americans, or to stop a bad actor from setting up a compounding business in the state with the weakest standards.

Good Compounding Practices

Federal requirements for compounding pharmacies should comply with United States Pharmacopoeia standards for compounding.   It seems obvious that there should be more stringent compounding practices for sterile compounding. Federal good compounding standards could be enforced with spot checks by the FDA and civil monetary penalties, or in major violations, the shutdown of production until the drug compounding company complies with the standards.

Scale of Compounding

Federal legislation should distinguish between traditional compounding (used for small quantities such as doses for specific children or preservative-free doses) and large-scale compounding that more closely approximates manufacturing.  As we stated earlier, by clearly defining the phrase “inordinate amounts,” the FDA should be able to distinguish between manufacturing and traditional compounding.  In addition, enforcing the requirement of individual prescriptions would also reduce the volume.  Volume, percentage of sales, standardization of drug products, and interstate sales should be part of the equation in determining whether or not a compounding company was a manufacturer.  FDA should also carefully scrutinize preservative-free doses, which have historically been defined as traditional compounding, and whether those might be more likely to become contaminated.  Earlier this week, FDA and CDC laboratories identified bacteria present in three separate lots of NECC-supplied preservative-free betamethasone, which is a topical steroid used for itching, inflammation, and sometimes as an intramuscular injection for allergic reactions.

Type of Compounding

The Federal legislation should differentiate between types of compounded products such as sterile and non-sterile, with sterile products subject to stricter standards and more frequent inspections.  Also, how the drug is used should be taken into account.  Drugs that are injected into the spine, which could travel throughout the nervous system, have a higher risk profile than drugs used to treat a specific area of the body such as a joint or a muscle area.  It is appropriate for facilities producing drugs with higher risks to be subject to more robust standards; however, all facilities should be subject to GMP.

Interstate Shipment

Interstate shipments should be regulated by the FDA.  We stated earlier that we question whether states have the resources to enforce regulations for compounding companies within their own borders.  It seems even less likely that states have the resources to ensure that out-of-state pharmacies comply with their laws.

Ingredients in Compounded Products

Federal regulations should require that bulk ingredients used in compounding come from FDA-registered establishments and with a certificate of analysis, or that the drug substance complies with the standards of the United States Pharmacopoeia or National Formulary monograph.

Registration of Listing

Most compounding pharmacies should be required to register with the FDA with an exception for pharmacies/pharmacists who prepare an extremely limited number of compounding drugs (doses for individual young patients/preservative-free doses).  Even compounding pharmacies that do not currently sell their products across state lines need to register with the FDA because they may well sell their products across state lines in the future, especially if they are compounding drugs that are in short supply.  Registration should cover the basic contact information and key information about the products compounded.  FDA has experience with registration of prescription drug companies and medical device companies that it can draw on to create a registration database for compounding companies.  Firms subject to registration should pay a modest user fee to cover FDA’s cost of establishing the registration program.  A registration program would not be overly burdensome for compounding companies and would allow the FDA to keep better track of compounding companies, which should improve public health.

The Prescription

It should be a federal requirement that compounded products be made in response to a prescription or in anticipation of a prescription (but only limited quantities) based on previous sales.  If there were a federal requirement that the prescription (or notation ordering a compounded drug product) explicitly called for the drug to be compounded, then that would eliminate any confusion by doctors or other health care professionals over whether the drug was compounded or not.  Did all of the physicians who ordered methylprednisolone acetate for their patients realize it was a compounded drug?  A related question is whether the doctors and medical facilities understood that compounded drugs were not tested to ensure that they were safe or effective.

Office Stock

There should be federal restrictions on compounding for office uses.  Ideally, the compounder should be required to reconcile prescriptions from the physician once the compounded product has been dispensed in the physician’s office, but will physicians actually take to time to do this?  The amount of compounded stock should be limited to match the number of prescriptions the physician has written.  Also, if it is a product that requires special handling (for example, refrigeration) its stock should be limited.  The labeling requirements for office use should mirror the labeling requirements for all compounded drugs, which should state explicitly that the FDA has not approved the safety or effectiveness of this drug.  There should be an allowance for compounding for research, teaching or chemical analysis as long as these products are not for sale or dispensing.

Standardized Drug Products

It may be appropriate for a pharmacy to compound standardized drugs products in the case of drug shortages, or to protect public health or well-being, or when a patient’s allergies require a preservative-free dose or when a small dose is needed for a child.  The drugs should not be copies of commercially available drugs.  Earlier this week, the FDA reported that the time-release method for a generic drug to treat depression did not work the same as the brand name drug and this compromised its effectiveness.  Any additional restrictions on compounded drugs that use standardized drug products would also apply to office stock.

Inspection Authority

FDA authority to inspect compounding pharmacies should be broadened and strengthened.  FDA should have access to all compounding records.  It is unacceptable that compounding pharmacists hindered FDA efforts to determine if an injectable drug used to reduce risks of premature birth was substandard and possibly made with unapproved Chinese ingredients.[2]  Compounding pharmacies should not be able to stonewall the FDA by stating that the compounding records are for state authorities. In addition, if compounding pharmacies ship products across state lines, then they should be inspected by the FDA, and they should also be inspected by the FDA if they are producing sterile drugs or drugs that have higher risks (such as drugs injected in to the spinal cord).  FDA should limit its inspections to larger compounding pharmacies and perhaps exempt pharmacies that only rarely compound products.

Compounded Product Labeling

There should be a disclaimer on the label of compounded drugs. We support the label requirements that were part of the 2007 Discussion Draft (Safe Drug Compounding Act). The label should state first and in bold letters: THIS DRUG IS NOT REQUIRED TO MEET THE SAFETY, EFFICACY, OR MANUFACTURING STANDARDS FOR FDA-APPROVED DRUGS.  It should then state that the drug was made specifically for the patient because a health care provider determined that no FDA-approved product is available for this specific need.  If it is a sterile product, the label should state: This drug was not prepared using FDA’s manufacturing standards for sterile drugs.  Additionally, the label should have the date when the drug was compounded, the name of the licensed compounding pharmacist or physician, and other relevant information from labeling including from medication guides.

Adverse Event Reporting

Compounding pharmacies should be required to report most adverse events to the FDA.  Exceptions could be made for minor side effects such as headache, upset stomach, dizziness, diarrhea, etc.  There should be special regulations for a subset of adverse events. For example, compounding pharmacies would have to report to the FDA within 5 work days from becoming aware of an event that required hospitalization or was a threat to health, since action would be needed to prevent an unreasonable risk of substantial harm to the public health.  They would have 10 days to report other adverse events. This is similar to the reporting requirements for medical device manufacturers.  The reporting requirements should not necessarily be limited to compounding pharmacies.  If a health care provider is aware of a significant A/E (major side effect, injury or death) caused by a compounded product they must report it also.

Federal and State Coordination and Communication

Based on the NECC tragedy, federal and state officials need to better coordinate their existing authorities.  The Massachusetts Department of Health recently released hundreds of pages of documents about violations at NECC going back to April 1999.[3]  Was FDA aware of all of these problems?  A related question is why the FDA did not follow up on their own warning to NECC in 2006, and whether they expected the state to do so.  If a specific federal requirement calls for coordinating enforcement and regulatory activities with state officials, it must be written in a clear manner and written so that FDA can pursue enforcement and regulatory activities with or without state officials.  We do not want an effort to coordinate enforcement to be a roadblock to enforcement.

Breast Cancer Action

Jacobs Institute for Women’s Health

National Consumers League

National Research Center for Women & Families

Union of Concerned Scientists



For more information, contact Paul Brown at (202) 223-4000 or


[1] 21 U.S.C. Sec. 353a (b)(1)(D) of the Federal Food Drug and Cosmetic Act.

[2] Bogdanich W, Tavernise S (October 23, 2012). U.S. Concern Over Compounders Predates Outbreak of Meningitis. New York Times.

[3] Tavernise S, Pollack A (October 23, 2012). Documents in Meningitis Case Show Complaints in 1999. New York Times.

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