Published in the January 2014 issue of the American Journal of Obstetrics & Gynecology is a study finding that 17-hydroxyprogesterone caproate (“17P”), an injectable medication that is used to prevent prematurity, obtained from 15 compounding pharmacies throughout the United States “did not raise safety concerns when assessed for potency, sterility, pyrogen status, or impurities.”

4. Published in the January 2014 issue of the American Journal of Obstetrics & Gynecology is a study finding that 17-hydroxyprogesterone caproate (“17P”), an injectable medication that is used to prevent prematurity, obtained from 15 compounding pharmacies throughout the United States “did not raise safety concerns when assessed for potency, sterility, pyrogen status, or impurities.”  (17P is an unusual, possibly unique, case, in that it is a medicine that is FDA-approved–sold under the brand-name Makena–but also available in compounded form.  For background, see here.)   In an editorial accompanying the AJOG study, Arnold Parry and Samuel Cohen write that “it is critical for obstetrical providers to understand that the cost of compounded 17P is much lower than that of the FDA-approved product, and many patients will have limited access to the FDA-approved product based on their insurance coverage.”

quoted from here

 

Alabama Board of Pharmacy Statement on Compounding Hydroxyprogesterone Caproate

Board Statement on Compounding Hydroxyprogesterone Caproate
On June 15, 2012, Food and Drug Administration (FDA) issued a statement indicating it will apply its normal enforcement policies for pharmacies compounding hydroxyprogesterone caproate. In line with FDA’s statement, licensees are reminded that 20 CSR 2220-2.200(9) provides:
Compounding of drug products that are commercially available in the marketplace or that are essentially copies of commercially available Federal [Food and] Drug Administration (FDA) approved drug products is prohibited. There shall be sufficient documentation within the prescription record of the pharmacy of the specific medical need for a particular variation of a commercially available compound.
Accordingly, licensees must have sufficient documentation of a specific medical need prior to compounding hydroxyprogesterone caproate in the future.

Source found here

Pharmacy-made pregnancy drug under scrutiny after meningitis outbreak

By Julie Appleby, Kaiser Health News

When a brand-name drug to help prevent premature births was approved last year, its $1,500-a-dose-price alarmed state and private sector insurance officials.

Many restricted use of the FDA-approved Makena in favor of $20- to $40-a-dose versions that had been made for years by pharmacies, saying that would give more women access to the treatment. Federal officials, sympathetic to such arguments, allowed the pharmacies to continue making the unapproved drugs.

But those decisions are now getting a second look following a deadly meningitis outbreak linked to a different pharmacy-made drug that has sickened hundreds of people and killed more than 25. No one has been reported injured by the pregnancy drug knockoffs. But the judgments made about Makena offer a window into the difficult tradeoffs between cost, safety and access sometimes confronted by policymakers and insurers at a time of growing angst over drug prices.

continue reading article here

Missouri Board of Pharmacy Statement on Compounding Hyroxyprogesterone Caproate

In the August 2012 newsletter of the Missouri Board of Pharmacy the Board issued the following Statement on Compounding Hydroxyprogesterone Caproate:

In June 15, 2012, Food and Drug Administration (FDA) issued a statement indicating it will apply its normal enforcement policies for pharmacies compounding hydroxyprogesterone caproate.  In line with the FDA’s statement, licensees are reminded that 20

CSR 2220-2.200(9) provides:

Compounding of drug products that are commercially available in the marketplace or that are essentially copies of commercially available Federal [Food and] Drug Administration (FDA) approved drug products is prohibited.

There shall be sufficient documentation within the prescription record of the pharmacy of the specific medical need for a particular variation of a commericially available compound.  Accordingly, licensees must have sufficient documenation of a specific medical need prior to compounding hydroxypogesterone caproate in the future.

The newsletter can be found here.

FDA Issues More Guidance About Makena®

In the form of Questions and Answers issued on June 29, 2012, the FDA recommends healthcare providers prescribe FDA-approved Makena (hydroxyprogesterone caproate injection) made by K-V  Pharmaceutical Company as the first-line for clinically-indicated patients. The FDA has not determined any other form of progesterone to be effective for this medical condition. The FDA also explained its enforcement policy towards compounded formulations of hydroxyprogesterone caproate. The FDA Questions and Answers state:

The FDA Questions and Answers are as follows: 

What is pharmacy compounding?

The FDA regards pharmacy compounding as the combining or altering of the ingredients of a drug by a licensed pharmacist to produce a drug tailored to an individual patient’s particular medical needs, based on a valid prescription from a licensed medical practitioner. For example, compounding may occur if a patient needs a medication to be produced without a dye or preservative due to an allergy, or needs a medication in a liquid or suppository form because the patient cannot swallow a pill.

Should health care professionals prescribe and patients take the FDA-approved drug product rather than the compounded product?

If there is an FDA-approved drug that is medically appropriate for a patient, the FDA-approved product should be prescribed and used. Makena was approved based on an affirmative showing of safety and efficacy. The company also demonstrated the ability to manufacture a quality product. The pre-market review process included a review of the company’s manufacturing information, such as the source of the API used in the manufacturing of the drug, proposed manufacturing processes, and the firm’s adherence to current good manufacturing practice.
Compounded drugs do not undergo the same premarket review and thus lack an FDA finding of safety and efficacy and lack an FDA finding of manufacturing quality. Therefore, when an FDA-approved drug is commercially available, the FDA recommends that practitioners prescribe the FDA-approved drug rather than a compounded drug unless the prescribing practitioner has determined that a compounded product is necessary for the particular patient and would provide a significant difference for the patient as compared to the FDA-approved commercially available drug product.

How will a patient know if she is receiving Makena or a compounded product?

A patient can ask her health care provider what product is being administered. A label will also be visible on the vial or syringe with information such as the patient name, prescription number, and name of the product. Typically, if the pharmacy dispenses the FDA-approved product, it will have the brand name “Makena” on the label.

Will the agency take any enforcement action against pharmacies compounding versions of hydroxyprogesterone caproate products?

The FDA may take enforcement action against compounding pharmacies if warranted. The FDA makes its enforcement decisions about compounded products on a case-by-case basis after considering the particular facts at issue. As we explained in the June 15, 2012, statement¹, the compounding of any drug, including hydroxyprogesterone caproate, should not exceed the scope of traditional pharmacy compounding.

Are pharmacies free to compound large volumes of hydroxyprogesterone caproate as long as none of their drugs are tested and found to be unsafe?

No. The FDA does not consider compounding large volumes of copies, or what are essentially copies, of any approved commercially-available drug to fall within the scope of traditional pharmacy practice. One factor that the agency considers in determining whether a drug may be compounded is whether the prescribing practitioner has determined that a compounded product is necessary for the particular patient and would provide a significant difference for the patient as compared to the FDA-approved commercially available drug product.
The FDA may take enforcement action against pharmacies that compound large volumes of drugs that are essentially copies of commercially available products and for which there does not appear to be a medical need for individual patients to whom the drug is dispensed.

The FDA stated it is using a risk-based approach to enforcement action against compounding pharmacies. The FDA also stated that its investigation did not identify a major safety issue, so does that mean that the FDA does not intend to take enforcement action against the compounders of hydroxyprogesterone caproate?

No. A risk-based approach to enforcement relates to how the FDA generally prioritizes its enforcement efforts. The FDA’s June 15, 2012 statement should not be interpreted to mean that the FDA will take enforcement action only if the agency identifies a particular safety problem. We reiterate that the compounding of any drug, including hydroxyprogesterone caproate, should not exceed the scope of traditional pharmacy compounding.

Links on this page:

1. /NewsEvents/Newsroom/PressAnnouncements/ucm308546.htm

Page Last Updated: 06/29/2012 

IACP Responds to FDA's Makena(R) 17-P Update

IACP has responded to the FDA's Makena(R) 17-P update issued last week by stating FDA Study Affirms no Major Safety Issues with Compounded 17-P. To read an article about IACP statement click here.  To read additional articles click here, here and here.

Updated FDA Statement on Compounded Versions of hydroxyprogesterone caproate (the active ingredient in Makena)

For Immediate Release: June 15, 2012
Media Inquiries: Erica Jefferson, 301-796-4988, Erica.Jefferson@fda.hhs.gov

Updated FDA Statement on Compounded Versions of hydroxyprogesterone caproate (the active ingredient in Makena)

FDA (or the Agency) approved Makena (hydroxyprogesterone caproate) in February 2011 for the reduction of the risk of certain preterm births in women who have had at least one prior preterm birth. Beginning many years before Makena was approved, a version of the active ingredient of Makena has been available to patients whose physicians requested the drug from a pharmacist who compounded the drug.

As explained in a November 8, 2011 statement, in October 2011, FDA received information from Makena’s sponsor, K-V Pharmaceuticals, regarding the potency and purity of samples of bulk hydroxyprogesterone caproate active pharmaceutical ingredients (APIs) and compounded hydroxyprogesterone caproate products. The Agency explained that FDA had carefully reviewed the data K-V submitted and would conduct an on-site review of the laboratory analyses. The Agency also stated that FDA had begun its own sampling and analysis of compounded hydroxyprogesterone caproate products and the bulk APIs used to make them.

FDA has completed its review, and the Agency is now providing a brief summary of the results. FDA collected samples of compounded hydroxyprogesterone caproate products and hydroxyprogesterone caproate APIs. These samples generally were collected from compounding pharmacies, doctor’s offices, API distributors, and APIs offered for importation.

• FDA tested 16 samples of hydroxyprogesterone caproate API using the methods specified in the United States Pharmacopeia (USP) as well as the methods used in the Makena new drug application (NDA). 
  • All 16 API samples passed USP tests for potency (97-103 percent) and purity and all 16 API samples passed the potency tests in the Makena NDA.
  • All 16 of the API samples passed the total purity standard in the Makena NDA but failed the Makena NDA’s limit for unidentified impurities.
  • FDA also isolated and identified four impurities that appeared at levels above those permitted in the Makena NDA. Based on information available to FDA, the impurities observed in these samples do not raise safety concerns.  
• FDA also tested 13 samples of compounded hydroxyprogesterone caproate prepared by eight pharmacies.
  • One of 13 samples was subpotent and was in the range of 80 percent of declared potency. (The standard for potency is 90-110 percent). All 13 of the samples met the standard in the Makena NDA for total purity.
  • Two of the 13 samples failed to meet the standard for unidentified impurities in the Makena NDA.

FDA also obtained the available retained samples of compounded products from the laboratories that K-V hired to perform the tests on the compounded products that were submitted to the agency in October 2011. FDA’s testing of the retained samples found that three of 26 samples failed the standard for potency (90-110 percent) using the method in the Makena NDA. (The samples were not large enough for FDA also to test them using the USP method.)  The three products that failed potency testing were in the 115 percent range. Seven of 26 samples failed the standard for unidentified impurities in the Makena NDA.

Although the analysis of this limited sample of compounded hydroxyprogesterone caproate products and APIs did not identify any major safety problems, approved drug products, such as Makena, provide a greater assurance of safety and effectiveness than do compounded products. Before approving the Makena NDA, FDA reviewed manufacturing information, such as the source of the API used by its manufacturer, proposed manufacturing processes, and the firm’s adherence to current good manufacturing practice.

The drugs that pharmacists compound (including compounded hydroxyprogesterone caproate) are not FDA approved, which means they do not undergo premarket review nor do they have an FDA finding of safety and efficacy. Compounding large volumes of drugs that are copies of FDA-approved drugs circumvents important public health requirements, including the Federal Food, Drug, and Cosmetic Act’s drug approval provisions. Consumers and health professionals rely on the Act’s evidence-based drug approval process to ensure that drugs are safe and effective. For that reason, one factor that the agency considers in determining whether a drug may be compounded is whether the prescribing practitioner has determined that a compounded product is necessary for the particular patient and would provide a significant difference for the patient as compared to the FDA-approved commercially available drug product.  

FDA emphasizes that it is applying its normal enforcement policies for compounded drugs to compounded hydroxyprogesterone caproate. The compounding of any drug, including hydroxyprogesterone caproate, should not exceed the scope of traditional pharmacy compounding. As the Agency has previously explained, FDA generally prioritizes enforcement actions related to compounded drugs using a risk-based approach, giving the highest enforcement priority to pharmacies that compound products that are causing harm or that amount to health fraud.