This week, we will continue looking at the current Draft Memorandum of Understanding recently issued by the FDA for public comment; specifically the highlighted portion below.

3. Substance of Agreement
   1. Investigation of Complaints Relating to Compounded Drug Products Distributed Outside the State
   2. Distribution of Inordinate Amounts of Compounded Drug Products Interstate
   3. Submission and Disclosure of Information

There are seven items in this section of the proposed agreement.

1. Appropriate agencies of [Your State] will investigate complaints received relating to drug products compounded by a pharmacist and distributed outside [Your State] by a pharmacy. The primary responsibility for investigating complaints will be with the State Board of Pharmacy or other appropriate state agency.
   
   
2. Complaints related to compounded drugs by a pharmacist that will be investigated include:
   • Adverse drug experiences, or
   • Product quality issues
   
   
3. The investigations will include, but not be limited to assessing:
   • Whether or not there is a public health risk, and
   • Whether any public health risk is adequately contained.
   
   
4. If the complaint is found to be valid, the State will take appropriate and warranted action to ensure that the compounding pharmacy investigates the root cause of the problem and takes corrective action.
   
   
5. The State will notify the FDA via an email with the information as soon as possible, but no later than 3 business days after receiving any complaint involving a compounded drug distributed outside the State involving a serious adverse drug experience or serious product quality issue.
   
   
6. If compounded by a physician and distributed out of state, the State will notify the appropriate regulator of the physician compounding within the State. FDA notification is the same as in step 5.
   
   
7. The State will maintain:
   • Records of the complaint,
   • Investigation of the complaint, and
   • Any response to or action taken as a result of the complaint.

Beginning when the State receives notice of the complaint, the records will be maintained for at least 3 years.

Next week, we will look at:

"b. Distribution of Inordinate Amounts of Compounded Drug products Interstate."

Loyd V. Allen, Jr., PhD, RPh
Editor-in-Chief
International Journal of Pharmaceutical Compounding
Remington: The Science and Practice of Pharmacy Twenty-second edition

News

S.2553–Know the Lowest Price Act of 2018 and S.2554–Patient Right to Know Drug Prices Act
Congress passed and the President signed the above two bills this week, prohibiting pharmacy "gag clauses" that may result in patients being charged inflated prices for their medications and provide pharmacists more flexibility in informing patients they could pay less out of pocket for a prescription than by using their health insurance.
https://www.nytimes.com/2018/10/10/us/politics/trump-health-insurance-drug-costs.html

Did You Know ...

�that a question that has arisen many times over the years concerns the water of hydration when compounded in a non-aqueous vehicle and the current 6-month BUD; will the water cause a problem and require a shorter BUD?

Tip of the Week

Concerning the above question�probably not. As we know, according to USP Chapter <1112>, bacteria, yeast, and fungi will not grow and proliferate below a water activity (a_w) of 0.60. What is an approximate "a_w" of an example formulation using the worst-case scenario for demonstration purposes? Let's look at the actual percentage of water in the following formula, which is related to an approximate "a_w".

Rx Morphine Sulfate Pentahydrate 50 mg/g in Nonaqueous Vehicle, Disp. 100 g

Note: The "g" was used in this example in place of "mL" as the specific gravity of the vehicle(s) will vary. If this was an actual formula, mL would be used and calculated appropriately.

(C₁₇H₁₉NO₃)₂.H₂SO₄.5H₂O       MW 758.83

MW of water = 18

18 � 5 = 90 = Weight of water in MS molecule

758.8 - 90 = 668.8 = Weight of MS without water

90/758.8 = 11.86% = % of water in molecule

However, the USP allowable range for Morphine Sulfate Loss on Drying is 10.5% to 13.4%, so we will use the worst-case scenario of 13.4%.

Morphine Sulfate 50 mg/g, 100 g Nonaqueous Preparation

50 mg/g � 100 g = 5,000 mg or 5 g Morphine Sulfate required

5000 mg � 0.134 = 670 mg water (max allowed by the USP in that quantity of morphine sulfate)

0.670 g / 100 g of mixture = 0.67% water present

Conclusion: The amount of water contributed by the pentahydrate in the morphine sulfate pentahydrate is negligible, and a 6-month BUD can currently be assigned to the formulation.

At issue is in the "proposed" USP <795>. This BUD will be reduced to 3 months, but the rationale is not explained. If the API is stable, and there will be no microbial growth, why not continue with the 6-month BUD?

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