Compounding Pharmacy Regulation. A Regulatory Update for Home Infusion Clinicians. Speaker Disclosures 3/9/2016

Transcription

1 A Regulatory Update for Home Infusion Clinicians Kendall Van Pool Vice President of Legislative Affairs NHIA, Alexandria, VA Cynthia Blankenship, Esq. Of Counsel Rose Law Firm, Little Rock, AR Mike Koch, RPh, MBA Senior Vice President, Professional Services Central Admixture Pharmacy Service (CAPS), Irvine, CA 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. 2 Compounding Pharmacy Regulation Kendall Van Pool Vice President of Legislative Affairs National Home Infusion Association NHIA Annual Conference & Exposition 1

2 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 4 Compounding Pharmacy Regulation The Drug Quality and Security Act (DQSA) and 503A Pharmacies The Memorandum of Understanding (MOU) NHIA s Efforts 5 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 NHIA Annual Conference & Exposition 2

3 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 7 The MOU 503A 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) 8 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? NHIA Annual Conference & Exposition 3

4 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 Draft MOU 30% cap on compounded product over state lines No state buffer zone Dispensing over state lines included 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) NHIA Annual Conference & Exposition 4

5 2015 Draft MOU Units of Compounded Product Over State Lines Units of Compounded and Noncompounded products both interstate and intrastate > 30% = Inordinate 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 14 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, NHIA Annual Conference & Exposition 5

6 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. 16 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? 17 Kendall Van Pool NHIA VP of Legislative Affairs kendall.vanpool@nhia.org Office: NHIA Annual Conference & Exposition 6

7 Is 503B Right for You? Mike Koch, R.Ph., MBA March 21, 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 20 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 NHIA Annual Conference & Exposition 7

8 22 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 FDA 1088 Federal Registration Public Notification of Registration Not required if meet State regs and follow the rules in 503A NA Annually including notice of intention to compound drug shortage items, and drugs from bulk drug substances 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 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 TBD through FDA guidance Office Use Restrictions for inordinate amounts TBD (MOU Pending) Repackaging (draft guidance issued) Biologicals (draft guidance issued) Not allowed per FDA 503A guidance Some state laws conflict No federal restrictions Some state issues with interstate shipments Applicable cgmps (draft guidance issued) Repackaging (draft guidance issued) Biologicals (draft guidance issued) Permitted 23 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 * With sterile sleeve covers in most recent draft revision NHIA Annual Conference & Exposition 8

9 FDA cgmp Draft Guidance for Release Testing 25 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 26 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 NHIA Annual Conference & Exposition 9

10 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 28 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 FDA 1088, and directions for use Name and quantity of inactive ingredients can go on either the CSP label or the container label 29 Annual registration fee $16, Reinspection fee $15, Fees Discount for small business with annual sales of less than $1M NHIA Annual Conference & Exposition 10

11 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 31 Contact Information Mike Koch, R.Ph, MBA Senior V.P. Professional Services Central Admixture Pharmacy Services 32 References Guidance For Entities Considering Whether to Register As Outsourcing Facilities Under Section 503B of the Federal Food, Drug, and Cosmetic Act ulatoryinformation/guidances/ucm pdf Pharmacy Compounding of Human Drug Products Under Section 503A of the Federal Food, Drug, and Cosmetic Act Guidance ation/guidances/ucm pdf Fees for Human Drug Compounding Outsourcing Facilities Under Sections 503B and 744K of the FD&C Act Guidance for Industry tion/guidances/ucm pdf NHIA Annual Conference & Exposition 11

12 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. harmacycompounding/ucm htm 34 FDA s Regulatory Authority and Current Trends with FDA Inspections and Findings Cynthia Blankenship, Esq. March 21, 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 NHIA Annual Conference & Exposition 12

13 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. 37 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. 38 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 NHIA Annual Conference & Exposition 13

14 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. 40 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. 41 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 NHIA Annual Conference & Exposition 14

15 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. 43 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. 44 Current Inspection Trends Adulterated products and Insanitary Conditions - 501(a)(2)(A) Language in Warning Letter Jan 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 NHIA Annual Conference & Exposition 15

16 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. 46 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 47 Thank you! Cynthia Blankenship, Esq. Rose Law Firm cblankenship@roselawfirm.com NHIA Annual Conference & Exposition 16

17 Regulatory Grassroots Kendall Van Pool Vice President of Legislative Affairs National Home Infusion Association 49 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 50 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 NHIA Annual Conference & Exposition 17

18 Thank you! NHIA Annual Conference & Exposition 18