a regulatory for home infusion clinicians · 2016-03-10 · 3/10/2016 2016 nhia annual conference...

3/10/2016

2016 NHIA Annual Conference & Exposition 1

A Regulatory Update for Home Infusion

CliniciansCynthia Blankenship, Esq.

Of CounselRose Law Firm, Little Rock, AR

Mike Koch, RPh, MBASenior Vice President, Professional Services

Central Admixture Pharmacy Service (CAPS), Irvine, CA

Kendall Van PoolVice President of Legislative Affairs

NHIA, Alexandria, VA

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Speaker Disclosures

• Michael Koch is an employee of Central Admixture Services.

• Kendall Van Pool and Cynthia Blankenship have no potential conflicts of interest to disclosure.

• Off‐label and/or investigational drug uses will not be discussed during this presentation.

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Compounding Pharmacy RegulationKendall Van PoolVice President of Legislative AffairsNational Home Infusion Association

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Compounding Pharmacy Regulation• FDA DQSA

• Memorandum of Understanding (MOU)

• USP Chapters 800 and 797 • INS Infusion Nursing Standards of Practice• EPA Hazardous Waste Handling for

Pharmacies• IDSA Outpatient Antimicrobial Therapy

(OPAT) Guidelines

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Compounding Pharmacy Regulation• The Drug Quality and Security Act (DQSA) and 503A Pharmacies

• The Memorandum of Understanding (MOU)• NHIA’s Efforts

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History of Compounding Regulation• 503A originally passed in 1997 (Food and Drug Administration Modernization Act)

• Section was intended to regulate all compounding• Deemed unconstitutional due to advertising provisions

• Enforcement of portions of 1997 law halted –including MOU

• Remained partially enforced until NECC tragedy

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The Drug Quality and Security Act• Recodified 503A except for advertising provisions

• Including old MOU provision

• Created new entity – 503B outsourcing facilities• Presumably for the large scale outsourcing compounders

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The MOU503A statute (unchanged since 1997):

A drug product may be compounded under subsection (a) only if ‐ …

(B) such drug product is compounded in a State—

(i)that has entered into a memorandum of understanding with the Secretary which addresses the distribution of inordinate amounts of compounded drug products interstate and provides for appropriate investigation by a State agency of complaints relating to compounded drug products distributed outside such State; or

(ii)that has not entered into the memorandum of understanding described in clause (i) and the licensed pharmacist, licensed pharmacy, or licensed physician distributes (or causes to be distributed) compounded drug products out of the State in which they are compounded in quantities that do not exceed 5 percent of the total prescription orders dispensed or distributed by such pharmacy or physician. (Emphasis Added)

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MOU Statute Issues of Note• MOU required or 5% cap of products dispensed or distributed becomes standard

• No determination in statute of true oversight body – FDA or State?

• Unfunded mandate on FDA or States?

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NHIA Advocacy After Passage of DQSA

• Commented on the unreleased draft MOU twice before FDA’s release of the 2015 draft MOU

• Met with HELP and Energy and Commerce Committee Staff

• Met with other stakeholders on the issues

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2015 Draft MOU• 30% cap on compounded product over state lines• No state buffer zone• Dispensing over state lines included

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2015 Draft MOU• “For purposes of this MOU, a pharmacist, pharmacy, or physician has distributed an inordinate amount of compounded human drug products interstate if the number of units of compounded human drug products distributed interstate during any calendar month is equal to or greater than 30 percent of the number of units of compounded and noncompounded drug products distributed or dispensed both intrastate and interstate by such pharmacist, pharmacy, or physician during that month.” (emphasis added)

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2015 Draft MOU

Units of Compounded Product Over State Lines

Units of Compounded and Noncompounded products both interstate and intrastate

> 30% = Inordinate

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2015 Draft MOU• Issues of Concern

• Dispensing considered distribution• Unit definition lacking• > 30% ‐ is it really inordinate?

• Legal Remedies?• Legal challenge expected, perhaps alleging the MOU is arbitrary and capricious

• Question on who will file suit

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NHIA Advocacy Post 2015 Draft MOU Release• NHIA Presentation at FDA Listening Session• NHIA Concerns Raised on FDA Rollout Call• NHIA working coalition efforts – “DQSA Coalition”• NHIA comment letter to FDA in July, 2015• Appropriations report language in December, 2015

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Appropriations report language in December, 2015• Language creates legislative intent• Pharmacy Compounding.—

The Committee is very concerned with the draft MOU that the FDA has proposed under Section 503A of the FDCA. The proposed MOU would complicate patient and prescriber access to compounded medications, and may have a deleterious effect on small pharmacies. Under the draft MOU, the FDA attempts to describe `distribution' as occurring when `a compounded human drug product has left the facility in which the drug was compounded.' In the DQSA, Congress only allowed the FDA to regulate `distribution.' But the MOU appears to exceed the authority granted in the statue by redefining `distribution' in a manner that includes dispensing‐‐something unprecedented. This overreach could generate exactly the kind of costly and confusing litigation that Congress intended to avoid when it amended and reinstated Section 503A. The Committee expects that, when a final MOU is proposed as a model agreement for the states to consider, that distribution and dispensing are treated as the different and separate activities that they actually are.

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To watch for in 2016• Will FDA finalize the MOU as drafted?• Will states be inclined to sign the MOU?

• 5% cap if state boards don’t sign• Providers need to advocate at the state level

• Will there be a suit to stop the MOU’s enforcement?

• Will Congress intervene?

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Kendall Van Pool NHIA VP of Legislative Affairs

[email protected]

Office: 703.838.2664

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Is 503B Right for You?

Mike Koch, R.Ph., MBAMarch 21, 2016

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Are you Dispensing or Distributing?

• Download the FDA guidance documents related to the DQSA

• Operating a 503B Outsourcing Facility is very costly, time and labor intensive

• Ensure your practice meets the requirements in section 503A of the Federal Food Drug and Cosmetic Act (FFDCA) or be prepared for a big commitment

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Are you Dispensing or Distributing?

• Section 503A of the Federal Food Drug and Cosmetic Act• Establishes how a pharmacy needs to operate in order to be exempt from the NDA, Labeling, and cGMP provisions of the act

• Patient specific, licensed prescriber, using USP standards• If you do not meet the requirements in 503A and you want to remain legal, then you must register as a 503B Outsourcing Facility

• What are you planning on compounding?• Office use, distributing to health systems, product mix

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FDCA and DQSA Sections 503A – Traditional Compounder 503B – Outsourcing Facilities

•Exemptions from FFDCA •No NDAs, Labeling, or cGMP…If for individual patient, on Rx from licensed prescriber, filled by State licensed practitioner.

•No NDAs, Labeling, or Track and Trace (must meet cGMPs)

•Labeling Requirements •Per State Regs •Yes including “Office Use”, “This is a compounded drug”, “Not for Resale” www.fda.gov/medwatch•1‐800‐FDA‐1088

•Federal Registration •Not required if meet State regsand follow the rules in 503A

•Annually including notice of intention to compound drug shortage items, and drugs from bulk drug substances

•Public Notification of Registration

•NA •FDA will make public all 503B registrations, 483s, and Warning Letters

•Reporting Requirements •NA •Every June and December report for each drug compounded in prior six months

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FDCA and DQSA Sections 503A – Traditional Compounder

503B – Outsourcing Facilities

•Wholesaling •NA •Wholesaling is not allowed•Office Use and AC to Health System is OK

•Fees •NA •Annual Fee and “Re‐inspection Fee”

•Shipping across state lines •Restrictions for “inordinate amounts” TBD (MOU Pending)

•No federal restrictions•Some state issues with interstate shipments

•TBD through FDA guidance •Repackaging (draft guidance issued)•Biologicals (draft guidance issued)

•“Applicable” cGMPs (draft guidance issued)•Repackaging (draft guidance issued)•Biologicals (draft guidance issued)

•Office Use •Not allowed per FDA 503A guidance•Some state laws conflict

•Permitted

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cGMPs

• Very difficult to comply for traditional pharmacy practice• Garbing example

• USP <797> ‐ non shedding gowns*, sterile gloves, eye protection optional• cGMP – FDA expects all sterile gowning, sterile gloves, sterile eye shields sterile bouffants, masks, shoe covers, and no exposed skin

• Environmental monitoring example• Glove fingertip bioburden sampling

• USP <797> ‐ Initially, annually for low and med risk, Semi annually for high risk

• cGMP – All compounding personnel on every compounding shift

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*With sterile sleeve covers in most recent draft revision

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FDA cGMP Draft Guidance for Release Testing

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cGMPs• FDA is inspecting for every batch potency, sterility, and endotoxin testing

• Expect a 483 and follow up warning letter if you are not doing it

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Reporting Requirements

• Upon initial registration, twice each year (in June and December), report all drugs compounded during the previous six‐month:

• The active ingredient, strength, and source (bulk or finished drug)

• The National Drug Code (NDC) number of the source drug or bulk active ingredient, if available

• The dosage form and route of administration• The package description, # of units produced, NDC number of final product is assigned

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Labeling Requirements

• The label of the drug includes—• The name, address, and phone number of the OF, the lot or batch number, name of the drug, the dosage form and strength, quantity or volume, date that the drug was compounded; the expiration date, storage and handling instructions, the National Drug Code number, if available,

• The statements ‘This is a compounded drug.’, ‘Not for resale’, and ‘Office Use Only’

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Labeling Requirements

• The container from which the individual units of the drug are removed for dispensing or for administration (such as a plastic bag containing individual product syringes) shall include—

• www.fda.gov/medwatch, 1–800–FDA–1088, and directions for use

• Name and quantity of inactive ingredients can go on either the CSP label or the container label

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2016 Fees

• Annual registration fee• $16,465.30

• Reinspection fee• $15,610

• Discount for small business with annual sales of less than $1M

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State Regulations

• State have different requirement for OFs• Pharmacy registration

• Wholesaler registration

• Conflicting state regulations• Missouri and California

• Office use prohibition• Many states have defined pharmacy practice to include office use

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Contact Information

Mike Koch, R.Ph, MBASenior V.P. Professional ServicesCentral Admixture Pharmacy [email protected]

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References• Guidance For Entities Considering Whether to Register As Outsourcing Facilities Under Section 503B of the Federal Food, Drug, and Cosmetic Act

• http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM434171.pdf

• Pharmacy Compounding of Human Drug Products Under Section 503A of the Federal Food, Drug, and Cosmetic Act Guidance

• http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM469119.pdf

• Fees for Human Drug Compounding Outsourcing Facilities Under Sections 503B and 744K of the FD&C Act Guidance for Industry

• http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm391102.pdf

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References• Release testing language in FDA 483s:

• “Testing and release of drug product for distribution do not include appropriate laboratory determination of satisfactory conformance to the identity and strength of each active ingredient prior to release…Specifically, you release all products without any laboratory analysis”

• “Each batch of drug product purporting to be sterile and pyrogen‐free is not laboratory tested to determine conformance to such requirements. Specifically, you do not perform sterility and endotoxin testing on each lot of product prior to release and distribution.”

• http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/ucm378645.htm

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FDA’s Regulatory Authority and Current Trends with FDA Inspections and Findings

Cynthia Blankenship, Esq.March 21, 2016

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Overview

• FDA’s authority to inspect and what you can expect• FDA’s interpretation of DQSA is used to give additional

reasons for inspection• FDA’s use of their authorities, Adulterated products and

501(a)(2)(A)• 483 findings related to cGMP requirements

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FDA’s Authority to Inspect• Section 704 of the Federal Food, Drug, and Cosmetic Act

states that FDA has the authority to inspect all facilities where drugs are manufactured, prepared for sale or distribution, stored or inventoried.

• HOWEVER, this authority is limited. • The Courts have held that FDA inspections are “quite

limited and clearly does not extend to a pharmacy’s books and records.”

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Inspection Process

• FDA Form 482 – Notice of Inspection• Must be provided prior to the inspection• If no form 482, FDA is asking for your consent to inspect• Details certain rights and the records exemptions• Provides contact information to

• Office of Ombudsman• Small Business Administration

• FDA is entitled to samples of products and their accompanying labels. However, the investigator should issue a Form 484 when taking these samples.

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Records Exemption• Records exemption further limits this inspection authority.

• Unlike for manufacturers, FDA does NOT have the right to inspect items listed in Section 704(a) including “records, files, papers, processes, or controls”

• Court has held that §374(a)(2)(a) “prohibits the FDA from relying on the records inspection authority…in searching pharmacies that meet the requirements of these requirements…..[t]hus, if the pharmacy is a ‘compliant pharmacy’ – meaning that it meets the requirements of this section, it is exempt from the records provision.”

• For a compounding pharmacy to qualify for this exemption, it must meet the following criteria:

• Pharmacies which maintain establishments in conformance with any applicable local laws regulating the practice of pharmacy and medicine and which are regularly engaged in dispensing prescription drugs or devices, upon prescriptions of practitioners licensed to administer such drugs or devices to patients under the care of such practitioners in the course of their professional practice, and which do not, either through a subsidiary or otherwise, manufacturer, 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.

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Records Exemption• “We agree that the statute poses a dilemma of sorts in that it

will often be impossible to determine with precision whether a pharmacy qualifies for the §374(a)(2)(A) exception without first conducting an administrative inspection of that facility.”

• The court went on to call it “a statutory paradox” and stated “the exemption in §374(a)(2)(A) divests the FDA of authority to inspect in some limited fashion, but the FDA cannot establish whether or not the exemption applies without obtaining information.”

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The Former FDA CPG

• The former FDA CPG listed nine factors that the FDA will consider in deciding whether a pharmacy may be violating the Federal Food, Drug, and Cosmetic Act by engaging in manufacturing under the guise of compounding.

• The list included factors such as the volume of drugs that a pharmacy compounds, whether the pharmacy compounds in anticipation of prescriptions, except in limited quantities, and whether the pharmacy compounds copies of drugs that are otherwise available.

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Reasons for FDA Inspections• An adverse event report• A complaint from a prescriber, patient or competitor• Purchaser of a recalled API• Marketing materials/website• Follow-up to responses to warning letters, prior inspections, etc.• Current Trends

• Sterile compounding• Risk Based• All to be inspected within the next 18 months

• Compounding for office-use

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Current Inspection Trends• FDA has issued 483s based on cGMPs• FDA has then determined approximately half of the facilities

inspected are not under FDA authority and handed back to State Boards of Pharmacy even after issuing 483 based on cGMPs.

• Thus, FDA is going in and inspecting on cGMPs and then retroactively determining whether the facility is a pharmacy under State Boards of Pharmacy purview or a manufacturer.

• FDA generally does not show up with State Boards of Pharmacy. The State Boards have a right to be present, so get your State Board involved in the process.

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Current Inspection Trends

• Office-use compounding • FDA inspectors were instructed to review the firm’s complete

drug product list (sterile and non-sterile drug products) from the last 3 months and drug production logs to determine whether drug products were being produced by the firm were dispensed of distributed based on a patient-specific prescription. Instructed to collect examples.

• In addition, FDA inspectors were instructed to collect examples of documents that indicate interstate shipment for drug products produced without patient-specific prescriptions.

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Current Inspection Trends• Adulterated products and Insanitary Conditions - 501(a)(2)(A)

• Language in Warning Letter Jan. 2014 and Countless other Warning Letters• “FDA investigators noted that your sterile drug products were prepared, packed, or held

under insanitary conditions, whereby they may have become contaminated….FDA investigator also noted cGMP violations at your facility…..

• Warning Letter December 18, 2015• In your response to the Form FDA 483, dated March 12, 2015, you state that your firm

‘is a pharmacy that prepares doses pursuant to a valid prescription for an individual patient’ and ‘meets USP 797 guidelines.’ Please be aware that compounded drug products that qualify for the exemptions in section 503A remain subject to all other applicable provisions of the FDCA, including the requirement that the drug products are not prepared, packed, or held under insanitary conditions (section 501(a)(2)(A) of the FDCA).

• Once FDA has pulled a facility within its purview citing adulteration by insanitary conditions, FDA deems the facility a manufacturer, that facility loses all protections under the FDCA including the records exemption and is deemed in violation of the FDCA.

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Administration Inspection Warrants• Different standard from criminal warrants but there are limits

• Usually used when inspection request has been refused or if FDA has reason to believe the inspection request might be refused (this usually has to be based on the compliance record of the facility).

• FDA must verify three items:• FDA is “entitled by statute or regulation to inspect the facility and to have access to the

information which has been refused;”• There is a compelling FDA need for that information; and • The firm/individuals have refused to allow inspection or access to that information in

spite of a clear demonstration or explanation of appropriate statutory authority.

• FDA still ONLY has the authority to inspect as allowed under the FDCA.

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Future Solutions

• Congressional appropriations language regarding inspections

• Requirement to give all findings to State Boards where State law will be applied to determine whether the facility is a 503A pharmacy.

• Federal legislation on inspections

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Thank you!

Cynthia Blankenship, Esq.Rose Law Firm

[email protected]

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Regulatory GrassrootsKendall Van PoolVice President of Legislative AffairsNational Home Infusion Association

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Influence and the Regulatory Process• Regulatory process is more deliberative and structured

• Draft Guidances and Draft Rules• Public comment periods• Final Guidances and Final Rules

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Influence and the Regulatory Process• Comment opportunities (Federal Register, USP, Professional societies)

• FDA’s open docket• Impact of individual provider response• Professional and trade association responses• Public listening sessions• Capitol Hill directives / guidance to the FDA

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Thank you!

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a regulatory for home infusion clinicians · 2016-03-10 · 3/10/2016 2016 nhia annual conference...

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