Demonstrably Difficult to Demonstrably Difficult to Compound Drug ProductsCompound Drug Products

Kathleen Anderson, Pharm. D.Division of Prescription Drug Compliance and Surveillance

Office of Compliance

Center for Drug Evaluation and Research

Section 503A(b)(3)(A)Section 503A(b)(3)(A)

States that “a drug product may be compounded under subsection (a) only if such drug product is not identified by the Secretary by regulation as a drug product that presents demonstrable difficulties for compounding that reasonably demonstrate an adverse effect on the safety or effectiveness of that drug product.”

FactorsFactors

1. Drug Delivery System 2. Drug Formulation and Consistency 3. Bioavailability 4. Complexity of Compounding 5. Facilities and Equipment 6. Training 7. Testing and Quality Assurance

1. Drug Delivery System1. Drug Delivery System

Is a sophisticated drug delivery system required to ensure dosing accuracy and/or reproducibility?

2. Drug Formulation and 2. Drug Formulation and Consistency Consistency

Is a sophisticated formulation of the drug product required to ensure dosing accuracy and/or reproducibility?

Because of the sophisticated formulation, is product-to-product uniformity of the drug product often difficult to achieve?

Is the safety or efficacy of the product a concern if there is product-to product variability?

3. Bioavailability3. Bioavailability

Is it difficult to achieve and maintain a uniformly bioavailable dosage form?

Is the safety or efficacy of the product a concern if the bioavailability varies?

4. Complexity of 4. Complexity of CompoundingCompounding

Is the compounding of the drug product complex?

Are there multiple, complicated or interrelated steps?

Is there a significant potential for error in one or more of the steps that could affect drug safety or effectiveness?

5. Facilities and Equipment5. Facilities and Equipment

Are sophisticated facilities and/or equipment required to ensure proper compounding of the drug product?

Is there a significant potential for error in the use of the facilities or equipment that could affect drug safety or effectiveness?

6. Training6. Training

Is specialized, highly technical training essential to ensure proper compounding of the drug product?

7. Testing and Quality 7. Testing and Quality AssuranceAssurance

Is sophisticated, difficult to perform testing of the compounded drug product required to ensure potency, purity, performance characteristics, or other important characteristics prior to dispensing?

Is there a significant potential for harm if the product is compounded without proper quality assurance procedures and end-product testing?

FactorsFactors

1. Drug Delivery System 2. Drug Formulation and Consistency 3. Bioavailability 4. Complexity of Compounding 5. Facilities and Equipment 6. Training 7. Testing and Quality Assurance

ApproachApproach

Began a preliminary evaluation of products for inclusion on the list

Focusing on products with – evidence in the literature and – potential to affect the public health

ApproachApproach

Some products with similar characteristics raise similar concerns for pharmacy compounding

– tentatively proposing to include both specific drug products and categories of drug products that are grouped by relevant factors

ApproachApproach

Some products could raise concern for pharmacy compounding if minimum standards are not met

– tentatively proposing to include drug products that are demonstrably difficult to compound unless certain minimum standards are met

Preliminary FindingsPreliminary Findings

Our concept paper describes in detail our preliminary findings for tentatively including the following products on the demonstrably difficult to compound list:

Metered Dose Inhalers Dry Powder Inhalers

Preliminary FindingsPreliminary Findings

Transdermal Delivery Systems Sterile Products Compounded Under Procedures

Other Than Those Described in Chapter 1206 of the United States Pharmacopoeia (USP)

Preliminary FindingsPreliminary Findings

Scientific Rationales

Additional ProductsAdditional Products

We intend to identify and evaluate additional products and categories of drug products for the list