Dispensing and Compounding att Sit Sites Gerald E. Finken CEO CSM 342 42nd Street South  Fargo, ND 58103 g , GCSG 2011 Conference: April 4-6, 2011 www.mygcsg.org Global Clinical Supplies: New Thinking, New Decade

Dispensing and Compounding at Sites Workshop Learning Objectives: „

Understand difference between compounding and manufacturing

„

Understand regulations

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Identifyy issues to be addressed when compounding and dispensing

GCSG 2011 Conference: April 4-6, 2011 www.mygcsg.org Global Clinical Supplies: New Thinking, New Decade

Dispensing and Compounding at Sites What is your understanding? What q questions do yyou have? What are your issues? GCSG 2011 Conference: April 4-6, 2011 www.mygcsg.org Global Clinical Supplies: New Thinking, New Decade

Defining Compounding USP 795 The preparation, mixing, assembling, altering, packaging, and labeling of a drug drug, drug-delivery drug delivery device device, or device in accordance with a licensed practitioner’s prescription, medication order, or initiative based on the practitioner / patient / pharmacists / compounder relationship in the course of professional practice. Note: Compounding p g includes reconstitution of commercial products

GCSG 2011 Conference: April 4-6, 2011 www.mygcsg.org Global Clinical Supplies: New Thinking, New Decade

Defining Compounding Tennessee Pharmacy Laws “Compounding” Compounding means the preparation, mixing, assembling, packaging, or labeling of a drug or device: (A)

(B)

(C)

As the result of a prescription order or initiative based on the prescriber patient pharmacist relationship in the course of prescriber-patient-pharmacist professional practice; In anticipation of prescription orders based on routine, regulatory observed prescribing patterns; or For the purpose of, or as an incident to, research, teaching or chemical analysis and not for sale for dispensing.

GCSG 2011 Conference: April 4-6, 2011 www.mygcsg.org Global Clinical Supplies: New Thinking, New Decade

Defining Compounding Arkansas Pharmacy Laws “Compounding” means the preparation, mixing, assembling, packaging, and labeling g of a drug g or device as the result of a duly y authorized practitioner’s prescription drug order or initiative based on the prescriber-patient-pharmacist relationship in the course of professional practice: (A)

(B)

(C)

Compounding may also be for the purpose of, or as an incident to, research, teaching, or chemical analysis. Compounding includes the preparation of drugs or devices in anticipation of prescription i ti d drug orders d b based d on routine, ti regulatory l t observed b d prescribing ibi patterns. Reconstitution of commercial products is not considered compounding for the purposes of this regulation.

GCSG 2011 Conference: April 4-6, 2011 www.mygcsg.org Global Clinical Supplies: New Thinking, New Decade

Defining g Manufacturing g Drug manufacturing is the process of industrial-scale synthesis of pharmaceutical drugs by pharmaceutical companies i

Governed by GMP „ 21CFR 211 21CFR 211 „ EudraLex Volume 4 „ ICH Guidelines Q7 I GCSG 2011 Conference: April 4-6, 2011 www.mygcsg.org Global Clinical Supplies: New Thinking, New Decade

Defining g Compounding/Manufacturing g g NOTE: „ „

Compounding C di requires i a pharmacist h i t Manufacturing requires training

GCSG 2011 Conference: April 4-6, 2011 www.mygcsg.org Global Clinical Supplies: New Thinking, New Decade

Review of Compounding Regulations USP 1075 – Good Compounding Practices „ Combined with 795 (Revised April 2010) „ Changed from informational to enforceable (if adopted by State Board of Pharmacy) „ Outlines Risk Levels and the need for training ‰ ‰

Simple: Mixing 2 or more commercial products Complex: Compounding with bulk drug or calculations required

GCSG 2011 Conference: April 4-6, 2011 www.mygcsg.org Global Clinical Supplies: New Thinking, New Decade

Review of Compounding Regulations USP 795 – Pharmaceutical Compounding – N Nonsterile t il P Preparations ti „

Guidance document very similar to GMP regulations: documentation facilities, documentation, facilities equipment; responsibilities; QC; etc.

GCSG 2011 Conference: April 4-6, 2011 www.mygcsg.org Global Clinical Supplies: New Thinking, New Decade

Review of Compounding p g Regulations g USP 795 – Pharmaceutical Compounding – Nonsterile Preparations p Notable Sections: „ Beyond Use Dating – date after which preparation is not to be b used d • Must be noted on label „ Patient Counseling • GCP inclusion • Use, storage and instability GCSG 2011 Conference: April 4-6, 2011 www.mygcsg.org Global Clinical Supplies: New Thinking, New Decade

Review of Compounding Regulations USP 797 – Pharmaceutical Compounding – Sterile Preparations (Updated in 2008) „

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Guidance document very similar to GMP regulations: documentation, facilities, equipment; responsibilities; QC; etc., AND Environmental Controls and Quality, AND Beyond Use dating

GCSG 2011 Conference: April 4-6, 2011 www.mygcsg.org Global Clinical Supplies: New Thinking, New Decade

Review of Compounding Regulations USP 797 – Pharmaceutical Compounding – Sterile Preparations (Updated in 2008) Notable Sections: „

CSP (compounded sterile preparations) microbial contamination risk levels • Low-risk level CSP’s: aseptic manipulations using only sterile ingredients • Medium-risk Medium risk level CSP’s: CSP s: low low-risk, risk preparing bulk • High-risk level CSP’s: nonsterile ingredients

GCSG 2011 Conference: April 4-6, 2011 www.mygcsg.org Global Clinical Supplies: New Thinking, New Decade

Review of Compounding Regulations State Laws ƒ Regulated by the state board or ƒ

pharmacy, or state medical board Each state creates their own laws |

Many states follow USP/NF

|

Some states restate USP/NF

|

Some states combine

|

Pharmacist taught to use the more strict law

GCSG 2011 Conference: April 4-6, 2011 www.mygcsg.org Global Clinical Supplies: New Thinking, New Decade

Review of Compounding Regulations PCAB Standards ƒ PCAB is a voluntary system of standards for ƒ

compounding pharmacies PCAB has created stringent g standards and the accreditation process is underway

GCSG 2011 Conference: April 4-6, 2011 www.mygcsg.org Global Clinical Supplies: New Thinking, New Decade

Review of Compounding Regulations

21 CFR 211 and d 312

No specific regulations governing compounding for investigational drug product GCSG 2011 Conference: April 4-6, 2011 www.mygcsg.org Global Clinical Supplies: New Thinking, New Decade

Review of Compounding Regulations 21 CFR Sec. 216.24 Drug products withdrawn or removed from the market for reasons of safety or effectiveness: The following drug products were withdrawn or removed from the market because such drug gp products or components p of such drug g products were found to be unsafe or not effective. The following drug products may not be compounded under the exemptions provided by section 503A(a) ( ) of the Federal FD&C Act. GCSG 2011 Conference: April 4-6, 2011 www.mygcsg.org Global Clinical Supplies: New Thinking, New Decade

Review of Compounding Regulations FD&C Act – Sec. 503A (Modernization Act) Describes the circumstances under which compounded drugs may qualify for exemption from the requirements of the Act To qualify T lif ffor th the exemption ti (501 (501, 502 and d 505) 505), a pharmacist h i t or physician must meet statutory conditions for compounding, including the following: ƒ ƒ ƒ ƒ

A prescription must exist Quantity is limited Drug product must be listed in USP-NF g etc. No marketing,

GCSG 2011 Conference: April 4-6, 2011 www.mygcsg.org Global Clinical Supplies: New Thinking, New Decade

Review of Compounding Regulations Compounding Confusion Thompson v. v Western States Medical Center ƒ 1992 FDA issues compliance policy guide on pharmacy compounding ƒ 1997 FDA Modernization Act (section 503A) ƒ 2001 Supreme Court ruled 503A invalid ƒ 2002 FDA reissues Compliance Policy Guides Manual on compounding

GCSG 2011 Conference: April 4-6, 2011 www.mygcsg.org Global Clinical Supplies: New Thinking, New Decade

Review of Compounding Regulations FDA Compliance Policy Guides Manual Manual, Sec Sec. 460 460.200, 200 Pharmacy Compounding (2002): FDA recognizes g that p pharmacists traditionally y have extemporaneously compounded and manipulated reasonable quantities of human drugs upon receipt of a valid prescription for an individually identified patient from a licensed practitioner. This traditional activity is not the subject of this guidance.

GCSG 2011 Conference: April 4-6, 2011 www.mygcsg.org Global Clinical Supplies: New Thinking, New Decade

Review of Compounding Regulations FDA Compliance Policy Guides Manual Manual, Sec Sec. 460 460.200 200 Pharmacy Compounding: ƒ Describes the difference between manufacturing g and compounding. ƒ Also provides list of drugs that are no longer safe and cannott be b compounded. d d

GCSG 2011 Conference: April 4-6, 2011 www.mygcsg.org Global Clinical Supplies: New Thinking, New Decade

Review of Compounding Regulations FDA Guidance for Industry, y, CGMP for Phase I Investigational Drugs ƒ 2008 FDA issues new guidance document for Phase I manufacturing practices ƒ Updates 1992 guidance document ƒ Purpose is to control Investigator-Own Investigator Own INDs ƒ Indirectly has impact on compounding GCSG 2011 Conference: April 4-6, 2011 www.mygcsg.org Global Clinical Supplies: New Thinking, New Decade

Review of Compounding Regulations EudraLex Volume 4 No exceptions whether IMPs are prepared in the pharmaceutical plant or in a pharmacy Annex 13 Section 42 Where, permitted in accordance with local regulations, Where regulations packaging or labelling is carried out at the investigator site by, or under the supervision of a clinical trials pharmacist, or other health care professional as allowed in those regulations, the Qualified Person is not required to certify the activity in question. The sponsor is nevertheless responsible for ensuring that the activity is adequately documented and carried out in accordance with the principles of GMP and should seek the advice of the Qualified Person in this regard. GCSG 2011 Conference: April 4-6, 2011 www.mygcsg.org Global Clinical Supplies: New Thinking, New Decade

Compounding and Dispensing Issues „ „

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Pharmaceutical industry is governed by FDA/EMEA Pharmacists who compound and dispense are governed by State Boards Wh t regulations What l ti d do we ffollow ll when h a pharmacist h i t compounds and dispenses IDP?

GCSG 2011 Conference: April 4-6, 2011 www.mygcsg.org Global Clinical Supplies: New Thinking, New Decade

Compounding p g and Dispensing p g Issues FDA Approved Compounding

ƒ ƒ ƒ

IF an IND is submitted and approved (FDCA Section 505) IF a valid prescription is written for an individually identified patient (FDA 2008 Guidance Document) THEN the drug should be able to be compounded?

GCSG 2011 Conference: April 4-6, 2011 www.mygcsg.org Global Clinical Supplies: New Thinking, New Decade

Compounding and Dispensing Issues State Approved Compounding

ƒ ƒ ƒ ƒ

If a valid prescription is written for an individually identified patient, then the drug should be able to be compounded All state requirements for prescriptions and labeling must be met Pharmacy/pharmacist licensure required Follow USP 795 and USP 797

GCSG 2011 Conference: April 4-6, 2011 www.mygcsg.org Global Clinical Supplies: New Thinking, New Decade

Compounding p g and Dispensing p g Issues Dispensing considerations: ƒ Use By Date vs. Beyond Use Date ƒ Labeling - Prescription - Investigational - FDA/State Board of Pharmacy/PCAB/Clinic

GCSG 2011 Conference: April 4-6, 2011 www.mygcsg.org Global Clinical Supplies: New Thinking, New Decade

Compounding p g and Dispensing p g Issues Dispensing considerations PCAB Required Compounded Prescription Statement: „

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Pursuant to PCAB Standard 8.20, the primary label of each compounded d d medication di ti prepared d iin response tto a prescription i ti ffor a specific patient shall include a statement notifying the patient that the medication has been compounded. “Thi medicine “This di i was specially i ll compounded d d in i our pharmacy h for f you at the direction of your prescriber.” 2

GCSG 2011 Conference: April 4-6, 2011 www.mygcsg.org Global Clinical Supplies: New Thinking, New Decade

Compounding p g and Dispensing p g Issues Dispensing considerations: ƒ Hospital vs. Clinic ƒ Patient counseling

GCSG 2011 Conference: April 4-6, 2011 www.mygcsg.org Global Clinical Supplies: New Thinking, New Decade

Compounding p g and Dispensing p g Issues How would you handle compounding and what considerations should be g given? ƒ Weighing of oral powder ƒ Simple p reconstitution (nonsterile/sterile) ( ) ƒ Sterile dilution to achieve dose or to delivery dose ƒ Mixing API with excipients and encapsulating GCSG 2011 Conference: April 4-6, 2011 www.mygcsg.org Global Clinical Supplies: New Thinking, New Decade

Questions? Gerald E. Finken CEO CSM 342 42nd Street South  a go, N 58 03 Fargo, ND 58103 GCSG 2011 Conference: April 4-6, 2011 www.mygcsg.org Global Clinical Supplies: New Thinking, New Decade