Law Week 6

Under 503A, traditional compounding is defined as

"...combining, admixing, mixing, diluting, pooling, reconstituting, or otherwise altering a drug or bulk drug substance to create a drug." Excluded, however, are such acts as mixing and reconstituting performed in accordance with the manufacturer's directions when performed on receipt of a prescription for a patient.

Neither 503A nor 503B allow an exemption to

501(a)(2)(A) related to insanitary conditions.

503A nor 503B allow an exemption to

5019(a)(2)(A) i.e. unsanitary conditions.

Discuss the relationship and applicability of USP standards to 503A compounding.

503A requires that drug products be compounded in compliance with the USP chapters on compounding, using bulk substances that comply with monograph standards, if one exists. 503A also requires that drug products be compounded with ingredients (other than bulk substances) that comply with USP standards. Compounding pharmacists must know the USP guidelines and follow them in the event that state requirements are not as comprehensive

violating the new drug provision of the FDCA, § 503A, and state law

A pharmacy that compounds an OTC product not pursuant to prescription would likely be violating

HDs

All healthcare entities, including pharmacies, whether they compound or not that handle ?, must follow the standards established in USP chapter <800>.

applicability of USP chapter <795>, <797>, and <800>

All healthcare entities, including pharmacies, whether they compound or not that handle HDs, must follow the standards established in USP Chapter <800>. USP 800 published in 2016 will become effective Decem- ber 1, 2019, and is intended to protect the healthcare worker, the environment, and the patient from the exposure of HDs. The chapter adds to the HD stan- dards contained in USP chapters <795> and <797> and to those from the Occupational Safety and Health Administration (OCSHA).

Bio-identical Hormone Replacement Therapy

BHRT

Beyond Use Date

BUD

Current Goods Manufacturing Practices

CGMP

certificate of analysis

COA

Compliance Policy Guide

CPG

Traditional compound pharmacist regulation

Compounding a "limited quantity" in anticipation of receiving a prescription o Compounding copies of commercially available products only occasionally and not in inordinate amounts Compounding in accordance to USP standards if in existence Compounding only with FDA approved drugs that have not been withdrawn or removed from the market because of safety and efficacy issues

Some of the conditions a § 503A pharmacy must meet to be exempt include

Compounding upon receipt of a prescription for an individual patient o Compounding a "limited quantity" in anticipation of receiving a prescription o Compounding copies of commercially available products only occasionally and not in inordinate amounts o Compounding in accordance to USP standards if in existence o Compounding only with FDA approved drugs that have not been withdrawn or removed from the market because of safety and efficacy issues

Drug Quality and Security Act of 2013

DQSA

Section 510(g): Exempt from registering as a manufacturer if they

Do not manufacture, prepare, propagate, compound or process drugs or devices for sale other than in the regular course of their business of dispensing or selling drugs or devices at retail. Repackage OTC products change the container, wrapper or labeling for resale. Important as if any of the following above is conducted pharmacies must obtain a license from the FDA and conform to CGMP (121) (Regulated by state law)

Food and Drug Administration Modernization Act of 1997

FDAMA

Compounding Pharmacies

FDCA exempts from registering as manufacturers when doing so in the regular course of dispensing and selling drugs or devices at retail.

Hazardous Drugs

HDs

USP Chapter 800

Hazardous drugs handling

Investigational New Drug

IND

Identify the impetus for the Drug Quality and Security Act of 2013.

In 2012, a Massachusetts pharmacy (New England Compounding Center [NECC]) compounded and shipped large batches of contaminated sterile injectables to hospital pharmacies, physicians' offices, and other licensed entities. The products killed 64 people and injured more than 700 others and highlighted the lack of clarity in the law regarding the FDA's authority over large batch compounders. Congress responded to this by enacting the DQSA of 2013.

Under 503B, a bulk drug substance cannot be used in compounding unless

It appears on a list established by the FDA identifying bulk drug substances for which there is a clinical need (Bulk List) or The drug compounded from the bulk drug substance appears on the drug shortage list

Long Term Care Facilities

LTCFs

Memorandum Of Understanding

MOU

National Institutes for Occupational Safety and Health

NIOSH

Nuclear Regulatory Commission

NRC

Occupational Safety and Health Administration

OSHA

USP Chapter 797

Sterile products

outsourcing facilities

The DQSA also created a new category of sterile compounding pharmacies under 503B. This is a status for which pharmacies could voluntarily register, an ? does not need to be a pharmacy.

List ways that traditional compounding pharmacists might be regulated

The answer is largely self-regulation to the USP standard, and Boards of Pharmacy that enforce the USP standard. Recognize the FDA will not act against a pharmacy or outsourcing facility that meets the conditions of its compliance guidance for non-exempted activities, such as repackaging and compounding of biologics and radiopharmaceuticals. If you follow FDA guidance, then the FDA will be happy!!!!

United States Pharmacopeia

USP

For compounding for "office use"

Under 503A, compounded drugs may not be supplied for "office use" to physician offices and other healthcare entities Under 503B, compounding products for "office use" is not prohibited

Under 503B, an outsourcing facility is defined as

a facility registered with the FDA that has one geographic location engaged in the compounding of sterile drugs and complies with all 503B requirements. An entity that only compounds nonsterile drugs does not meet the definition of an outsourcing facility. However, an outsourcing facility may compound nonsterile drugs, provided that it also compounds sterile drugs.

503A requirements

a pharmacy is exempt from adequate directions for use, CGMP, and new drug requirements, if the compounded drug product meets the following conditions: · compounding upon the receipt of a valid prescription for an individual patient · compounding a "limited quantity" in anticipation of receiving a prescription · compounding copies of commercially available products only occasionally and not in inordinate amounts · compounding in accordance to USP standards if in existence · compounding only with FDA approved drugs that have not been withdrawn or removed from the market because of safety and efficacy issues · compounding with bulk drugs that are manufactured by an entity registered with the FDA · compounding with ingredients (other than bulk substances) that comply with USP standards · compounder does not distribute more than 5% of the total prescriptions dispensed or distributed by the pharmacy absent a memorandum of understanding (MOU) between the pharmacy's state and the FDA

Recognize the FDA will not take action against

a pharmacy or outsourcing facility that meets the conditions of its compliance guidance for non-exempted activities, such as repackaging and compounding of biologics and radiopharmaceuticals.

NIOSH

defines, identifies, and maintains a list of HDs

"limited quantity"

for the purposes of anticipatory compounding.

FDA guidance

issued a guidance interpreting "limited quantity" for the purposes of anticipatory compounding.

DQSA created

new category of sterile compounding pharmacies under § 503B known as "outsourcing facilities," a status for which pharmacies could voluntarily register, although an outsourcing facility need not be a pharmacy.

The FDA will allow hospital or health system pharmacies to

perform some of the functions of outsourcing facilities by compounding drug products without a prescription, provided that certain conditions are met as established in its compliance guide

503A conditions

pharmacy must meet to be exempt include: Compounding upon receipt of a prescription for an individual patient

503B is primarily FDA regulated

registration as an outsourcing facility with the FDA is voluntary but there is no legal way for a pharmacy to compound outside of 503A requirements without registering as a 503B.

The DQSA of 2013 reinstated

reinstated the provisions of § 503A (less the unconstitutional provisions) and again stripped the FDA of its authority to declare exempt pharmacy-compounded drugs as new drugs.

The FDA will permit an outsourcing facility to

repackage radiopharmaceuticals, provided it complies with the conditions of the compliance guide

Sections 503A and 503B do not exempt

repackaged drugs from any provisions of the act, but if the pharmacies and outsourcing facilities meet the requirements of the FDA compliance guide, THE FDA WILL NOT TAKE ACTION AGAINST THEM.

What do 503a requirements fall under?

state regulatory authority.

Manufacturer patent rights

supersede the rights of a pharmacy to compound that product even pursuant to prescription.

Pharmacies may not supply

supply compounded drugs for "office use" to physician offices and other healthcare entities. However, this determination is controversial.

USP 800 requires at a minimum

that a healthcare entity handling HDs must maintain a list of HDs, proper facility and engineering controls, competent personnel, safe work practices, proper use of PPEs, and policies for HD waste segregation and disposal.

When the handling of an HD does not present a significant risk

the entity may make an assessment of risk and determine alternative containment strategies rather than have to comply with all the standards of the chapter

The DQSA of 2013 reinstated the provisions of

· 503A (less the unconstitutional provisions) and again stripped the FDA of its authority to declare exempt pharmacy-compounded drugs as new drugs.

There is additional incentive to register 503B because

· A drug product properly compounded at a registered outsourcing facility will be exempt from meeting the adequate directions for use labeling requirements and will not be considered a new drug. · The registered outsourcing facility can legally compound drugs and ship them interstate without receiving prescriptions for individual patients without quantity limitations. In contrast, an unregistered entity such as a 503A compounding pharmacy that does so will likely face misbranding, adulteration, and unapproved new drug charges.

USP 800 requires entities that handle HDs to maintain at a minimum the following

· A list of HDs · Proper facility and engineering controls · Competent personnel · Safe work practices · Proper use of appropriate Personal Protective Equipment (PPE) Policies for HD waste segregation and disposal

Major Similarities Between 503A and 503B requirements

· Neither 503A and 503B allow an exemption to repackaged drugs · However, if pharmacies and outsourcing facilities meet the requirements of the FDA compliance guide, the FDA will not take action against them

USP Chapter 795

· Non-sterile products

Sterile Drug products

· Pharmacists who prepare batches of sterile drug products are responsible for conforming to CGMP and for using safe packaging to ensure continued sterility during use.

List components of risk assessment and identify the reason for performing the risk assessment

· The assessment of risk must include at a minimum the type of HD, dosage form, risk of exposure, packaging, and manipulation. Each entity must have a designated person who is qualified and trained to be responsible for developing and implementing HD policies and procedures and complying with chapter.

Major differences in 503A and 503B requirements

· Under 503A, a compounded drug product can be identical or nearly identical if a prescriber makes a determination of significant or clinical difference · Under 503B, a prescriber's determination of significant or clinical difference does not matter - the product may not be compounded unless there is a drug shortage or if the drug was discontinued · For compounding using bulk drug substances: Under 503A, a bulk drug substance cannot be used in compounding unless: It meets USP or NF monograph standards or · It is a component of an FDA approved drug or · It appears on a list of bulk drug substances developed by the FDA by regulation

Neither 503A and 503B allow an exemption to 501(a)(2)(A)

· Which provides that a drug is deemed adulterated if it has been prepared, packed, or held under insanitary conditions

503B requirements

· complying with CGMP requirements · permitting FDA inspections according to a risk-based schedule · prohibiting sale or transfer of compounded products by an entity other than the outsourcing facility · compliance with the DQSA labeling requirements for each container · meeting certain other conditions such as reporting adverse events and providing the FDA with certain product-compounding information

FDA no action against

· nuclear radiopharmaceuticals to meet patient needs in violation of the FDCA provided the pharmacy meets the conditions in the compliance guide.

DQSA does not exempt

· the mixing, diluting or repackaging of biologicals BUT the FDA will not take action against a pharmacy or outsourcing facility that does so and meets the conditions of its compliance guidance.